Integrative Medicine

Danshensu Ameliorates Cardiac Ischaemia Reperfusion Injury through Activating Sirt1/FoxO1/Rab7 Signal Pathway Abstract Objective: To explore the specific molecular mechanisms of Danshensu (DSS) in the treatment of ischemia reperfusion injury (IRI). Methods: IRI model was established with isolated rat hearts by performing global ischaemia for 30 min, and then followed by 60 min reperfusion. Also, H9C2 cells were subjected to 4-h hypoxia followed by 3-h reoxygenation. Then 10 μmol/L DSS were added in the reperfusion/reoxygenation step to intervene IRI. Cardiac function, structural change and apoptosis were respectively tested by Langendorff System, hematoxylin and eosin (HE) and terminal-deoxynucleotidyl transferase mediated nick endabeling (TUNEL) stainings. Then lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide gasififi cation enzyme (SOD) and glutathione peroxidase (GSH-PX) were detected by enzyme-linked immunosorbent assay (ELISA). Sirt1/FoxO1/Rab7 Signal Pathway was monitored at both protein and mRNA levels. Results: The results showed that IRI not only greatly attenuated cardiac function (LVDP and ±dp/dtmax, P<0.01, P<0.05) and increased the level of the marker enzymes (cardiac troponin T, LDH, P<0.01) from the coronary effluents, but also markedly induced changes in the structure of cardiomyocytes and contributed to apoptosis, which were mediated by boosted endogenous ROS. However, after treatment with DSS all above indexes were improved, which was related to activating Sirt1/FoxO1/Rab7 signal pathway accompanied with the enhancement of antioxidant defense system, such as superoxide gasififi cation enzyme and glutathione peroxidase. Conclusion: DSS is able to protect hearts from IRI, which may be attributable to inhibiting excessive ROS through Sirt1/FoxO1/Rab7 signaling.

Effects and Mechanism of Action of Artemisinin on Mitochondria of Plasmodium berghei Abstract Objective To study the antimalarial effects and mechanisms of artemisinin (Qinghaosu in Chinese, QHS) on mitochondria in mice infected with Plasmodium berghei. Methods A total of 108 C57 mice infected with Plasmodium berghei were randomly divided into 3 groups by weight: the control group, 200 and 400 mg/kg QHS groups. The two QHS treatment groups were further divided into 4 sub-groups with 12 animals each time according to the treatment time, 0.5, 1, 2, and 4 h. Normal saline was intragastrically (i.g.) administered to the control group. The other two groups received different doses of QHS by i.g. administration. Animals were treated once with QHS for different detection time as follows: 0.5, 1, 2, and 4 h. The mitochondrial energy metabolism, oxidative damage, membrane potential, and membrane permeability and other indexes were detected. Results After administration of 200 and 400 mg/kg QHS, adenosine triphosphate (ATP) levels in Plasmodium and its mitochondria were reduced (P<0.05), the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were increased (P<0.05), and the activity of superoxide dismutase (SOD) was also increased (P<0.05). At the same time, the membrane potential of the mitochondria was reduced and the degree to which the membrane permeability transition pore was opened was irreversibly increased (P<0.05). Conclusions Mitochondria in Plasmodium were the targets of QHS, which can adversely affect mitochondrial energy metabolism, oxidative damage, membrane potential, and membrane opening, and ultimately exert an antimalarial effect.

Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System Abstract Objective To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (通心络胶囊, TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI). Methods Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group, MIRI group, low- and high-dose TXL (0.5 and 1 g·kg-1·d-1, respectively) groups, atorvastatin (ATV) group (7.2 g·kg-1·d-1), chloroquine (CQ) group (10 g·kg-1·d-1), and highdose TXL + CQ group. After pharmacological administration for 7 days, rats underwent left anterior descending artery ligation surgery to establish the MIRI models with 50 min ischemia followed by 4 h reperfusion. Blood was taken for cardiac troponin I (cTnI) detection and hearts were harvested for infarct staining and apoptosis detection. The autophagy or mitophagy proteins and ubiquitinated proteins were detected by Western blotting. Results Compared with the sham group, the MIRI group exhibited a larger infarcted area (27.13%±0.01%, P<0.01), a higher apoptotic index (34.33%±2.03% vs.1.81%±0.03%, P<0.01), and higher cTnI expression (14.18±1.01 vs. 7.96±0.32, P<0.01). The mitochondrial integrity was damaged in the MIRI group, while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58 vs. 4.33±1.15, P<0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (P<0.05). The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group (P<0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL. Conclusions TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.

Oral Chinese Herbal Medicine for Depressive Disorder in Patients after Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis Abstract Objective: To evaluate the effectiveness and safety of oral Chinese herbal medicines (CHMs) on post-percutaneous coronary intervention (PCI) patients with depressive disorder in coronary heart disease (CHD). Methods:A literature search was conducted through databases including PubMed, Cochrane Library, Chinese National Knowledge Infrastructure Databases (CNKI), Chinese Biomedical Literature Database (SinoMed), Chongqing VIP Chinese Science and Technology Periodical Database (VIP) and Wanfang Database up to August 2018. Randomized controlled trials (RCTs) comparing CHMs with placebo or no additional treatments on the basis of standard conventional pharmacological therapies were included. Data extraction, analyses and quality assessment were performed according to the Cochrane standards. RevMan 5.3 software was used to synthesize the results. Results: A total of 16 RCTs enrolling 1,443 participants were included in this systematic review. When compared with antidepressants alone, CHMs showed similar benefits with less side effects [risk ratio=0.54, 95% confidence interval (CI) 0.43 to 0.69, 582 patients]; meanwhile, the combination therapy may have more advantages than antidepressants alone [mean difference (MD)=–1.03, 95%CI–1.81 to–0.25, 267 patients). When identified with placebo, CHMs seem to have more advantages in relieving depressive symptoms (MD=–19.00, 95%CI–20.02 to–17.98, 189 patients). However, when compared with basic treatment of post- PCI, CHMs showed different results in two trials. In terms of post-PCI related clinical symptoms, CHMs seem to have more advantages in relieving chest pain and other general clinical symptoms. However, the heterogeneity in this review was generally high, it may be caused by different interventions used in each trial and the low quality of the trials. Conclusions: In total, CHMs showed potentially beneficial effects on depressive symptoms and post-PCI related clinical symptoms. However, because of small sample size and potential bias of most trials, this result should be interpreted with caution. More rigorous trials with larger sample size and higher quality are warranted to give high quality of evidence to support the use of CHMs for CHD complicated with depression.

Comparative Studies of Two Major Sets of Tibetan Medical Paintings: A Historical Perspective Abstract Tibetan medicine, one of the time-honored medical systems in the world, has increasingly been receiving attention the world over. Tibetan medical paintings (TMP, tib. Sman thang) has become one of the focal points in the studies of this medical system. To date, there are many atlases and publications on TMP, which are principally based on the two major sets of TMP series existing today in the world, the Lhasa set and the Buryat set. It has been found that the Buryat set is based on the Lhasa set, which was brought in late 19th to the first half of the 20th century from Tibet to Buryatia, Russia. A careful investigation on the basic structure of the two sets reveals that there are many differences between the two sets of paintings, including the total number of the paintings involved, of which some are missing in one set, the details of the captions of some of the paintings, the existence of the 80th painting and its supervisor, and the overall order of the entire set, etc. The details of the differences are elaborated and discussed, and the prospective of developing the research to arrive at a standard and perfect TMP set in the future is also analyzed and anticipated.

Effect of Shexiang Baoxin Pill (麝香保心丸) in Alleviating Early Hypertensive Renal Injury in Rats Abstract Objective To investigate the effect of Shexiang Baoxin Pill (麝香保心丸, SBP) on early hypertensive renal injury in rats and to explore the possible mechanism. Methods Twelve-week-old spontaneous hypertensive rats (SHRs) with high-salt diet (dietary containing 8% NaCl) were randomized into the SBP group [40 mg/(kg·d)], losartan potassium group [20 mg/(kg·d)] and saline group by stratified random sampling method, 12 in each group. Blood pressure and urea albumin creatinine ratio were measured. After 10 weeks, the expression levels of serum creatinine (Scr), hypersensitive C-reactive protein (hs-CRP), interleukin (IL)-1 β, IL-6, tumor necrosis factor α (TNF-α), and transforming growth factor β (TGF-β) in serum were assessed. Kidney pathology periodate-schiff staining was performed. Semi-quantitative count of macrophage infiltration was determined by immunochemistry of CD68 staining. Real-time quantitative polymerase chain reaction and Western blot were performed to examine the mRNA and protein expressions of Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), monocyte chemokine peptide (MCP-1), inducible nitric oxide synthase (iNOS), and arginase-1 (Arg-1). Results SBP did not affect the mortality of SHR (P<0.05). SBP significantly reduced the level of elevated blood pressure of SHRs, but the effect was less significantly than that of losartan potassium. SBP decreased urine protein (P<0.01) and the expression levels of IL-1 β, IL-6, TNF-α, and TGF-β in serum. The 22-week-old SHRs showed mild proliferation of glomerular endothelial cells, glomerular ischemic lesions, inflammatory cell infiltration in renal tubular interstitium and arteriosclerosis. Both SBP and losartan potassium had alleviated renal pathological change, and significantly reduced the infiltration of macrophage (P<0.05, P<0.01). SBP and losartan potassium decreased the expressions of TLR4, NF-κB, MCP-1, iNOS, and Arg-1. Conclusion SBP significantly modified the early hypertensive renal injury by reducing inflammation, and the effect was similar to losartan potassium.

Changes of Intestinal Microecology in Patients with Primary Sjogren's Syndrome after Therapy of Yangyin Yiqi Huoxue Recipe (养阴益气活血方) Abstract Objective To explore the change of intestinal microecology in patients with primary Sjogren's syndrome (pSS) and correlation with disease activity, and also discuss the therapy effect of Yangyin Yiqi Huoxue Recipe (养阴益气活血方, YYHD). Methods Sixteen pSS patients were enrolled in the present study, who received 3-month treatment of YYHR, 200 mL orally twice daily. Their pre-and post-test ESSDAI scores, erythrocyte sedimentation rate (ESR) and serum immunoglobulin G (IgG) levels were measured respectively. The 16SrDNA metagenomic sequencing was used to detect and analyze the abundance and diversity of intestinal bacteria flora and the proportion of bacteria at the levels of phylum, family, and genus, in comparision with those of 6 healthy subjects in the control group. Results The abundance and diversity of intestinal bacteria flora in pSS patients were lower than those of healthy subjects (P<0.05). After the treatment with YYHD, patients' ESSDAI score and levels of IgG and ESR have decreased significantly (P<0.05). At the phylum level, the proportions of Actinobacteria, Firmicutes, Fusobacteria and Proteobacteria have reduced sharply, while the proportions of Bacteroidetes, Teneriquetes and Candidate-division-TM7 have increased significantly by treatment (all P<0.05). At the classification level, such treatment has caused a significant decrease in the proportions of Bacteroidaceae, Ruminococcaceae, Veillonellaceae, and Enterobacteriacea (all P<0.05), but a significant increase in the proportion of Lachnospiraceae (P<0.05). At the genus level, the treatment has significantly decreased the proportions of Bifidobacterium, Bacteroides, Escherichia-Shigella, Faecalibacterium and Prevotella (all P<0.05), but significantly increased the proportion of Clostridia (P<0.05), close to the levels of healthy subjects (P>0.05). Conclusions There exists an imbalance of intestinal microecology in pSS patients, which can be improved through the treatment with YYHD. Besides, such treatment can also improve the disease activity and adjust the diversity of intestinal bacteria flora, the composition and the abundance of intestinal flora.

Anticancer Effects of Constituents of Herbs Targeting Osteosarcoma Abstract Osteosarcoma is a rare primary malignancy of bone that is prone to early metastasis. Resection surgery and chemotherapeutic regimens are current standard treatments for osteosarcoma. However, the long-term survival rate of patients with osteosarcoma is low due to a high risk of metastasis. Hence, a new approach is urgently needed to improve the treatment of osteosarcoma. Compared with chemotherapy, natural active constituents isolated from herbs exhibit less adverse effects and better anti-tumor effects. This study aimed to summarize the anticancer effects of constituents of herbs on the progression and metastasis of osteosarcoma cells. It showed that many constituents of herbs inhibited osteosarcoma by targeting proliferation, matrix metalloproteinases, integrin and cadherin, and angiogenesis. The findings might be beneficial for the development of new drugs and treatment strategies.

Is Acupressure Useful for Alleviating Hyperventilation Syndrome?

Embolic effects of Bletilla striata microspheres in renal artery and transplanted VX2 liver tumor model in rabbits Abstract Objectives To evaluate the characteristics of Bletilla striata microspheres (BSMs) and its effects as an embolic agent in a rabbit model. Methods BSMs were prepared with an emulsification-cool condensation-chemical cross-linking method. The characteristics of BSMs in vitro were observed. Embolization experiments were performed in renal artery of rabbit and in a rabbit liver VX2 carcinoma model. Seventy-two New Zealand rabbits were divided into 2 groups, and the right renal artery was embolized with BSMs (200 μm in diameter) in the experimental group and with polyvinyl alcohol (PVA) of the same size in the control group. The pathological findings were examined with hematoxylin-eosin and Masson stainings. Liver and renal functions were tested before and after embolization. VX2 tumor was transplanted in 15 New Zealand rabbits, which were randomly divided into 3 groups (n=5). Group A were treated with saline, group B with a mixture of doxorubicin and lipiodol, and group C with hepatic arterial infusion of BSMs (200 μm in diameter). Tumor growth rate was evaluated by magnetic resonance imaging scan. Apoptosis-related factors (bax, bcl-2) and tumor vascular endothelial cell growth factor (VEGF) were evaluated through immunohistochemical staining. Results The characteristics of BSMs in vitro were in full compliance with the requirements for use in interventional procedures. In the renal artery embolization experiment, after BSMs intervention, it was more difficult to form collateral circulation than that with PVAs, and the kidney manifested atrophy and calcification. There were no significant difference of liver and renal functions in rabbits between groups. In the liver VX2 carcinoma embolization experiment, compared with group A, the growth rate of VX2 liver tumor and Bcl-2 levels was reduced, while apoptosis index, Bax, and VEGF were increased in group B (P<0.05). There were no significant difference between groups B and C (P>0.05). Conclusions The characteristics of BSMs in vitro and in vivo meet the requirements for its use as an embolic agent in interventional approaches.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Philosophical Studies

Prioritizing Platonism Abstract Some see concrete foundationalism as providing the central task for sparse ontology, that of identifying which concreta ground other concreta but aren't themselves grounded by concreta. There is, however, potentially much more to sparse ontology. The thesis of abstract foundationalism, if true, provides an additional task: identifying which abstracta ground other abstracta but aren't themselves grounded by abstracta. We focus on two abstract foundationalist theses—abstract atomism and abstract monism—that correspond to the concrete foundationalist theses of priority atomism and priority monism. We show that a consequence of an attractive package of views is that abstract reality has a particular mereological structure, one capable of underwriting both theses. We argue that, of abstract foundationalist theses formulated in mereological terms, abstract atomism is the most plausible.

Naïve realism: a simple approach Abstract Naïve realism is often characterized, by its proponents and detractors alike, as the view that for a subject to undergo a perceptual experience is for her to stand in a simple two-place acquaintance relation toward an object. However, two of the leading defenders of naïve realism, John Campbell and Bill Brewer, have thought it necessary to complicate this picture, claiming that a third relatum is needed to account for various possible differences between distinct visual experiences of the same object (for example, differences that result from changes in the object's spatial orientation relative to the subject, or from changes in the intensity with which the subject focuses her attention on the object). This, I argue, is a mistake. Once it is acknowledged that a subject's visual experience acquaints her with more than just a single object, all of the relevant facts can be explained from within the simpler naïve realist framework.

Moral pickles, moral dilemmas, and the obligation preface paradox Abstract This paper introduces and defends a new position regarding the question of whether it is possible to have conflicting moral obligations. In doing so, it focuses on what I call a moral pickle. By "moral pickle" I mean a set of actions such that you ought to perform each and cannot perform all. Typically, when people discuss conflicting moral obligations, they focus on the notion of a moral dilemma, which is a type of moral pickle involving two conflicting actions. In other words, a moral dilemma is a pair of actions such that you ought to perform each and cannot perform both. As of yet, there is no debate about the possibility of moral pickles over and above the possibility of moral dilemmas. But as I show, there is good reason to think that moral pickles are possible and moral dilemmas are not.

Against epistemic partiality in friendship: value-reflecting reasons Abstract It has been alleged that the demands of friendship conflict with the norms of epistemology—in particular, that there are cases in which the moral demands of friendship would require one to give a friend the benefit of the doubt, and thereby come to believe something in violation of ordinary epistemic standards on justified or responsible belief (Baker in Pac Philos Q 68:1–13, 1987; Keller in Philos Pap 33(3):329–351, 2004; Stroud in Ethics 116(3):498–524, 2006; Hazlett in A luxury of the understanding: on the value of true belief, Oxford University Press, Oxford, 2013). The burden of this paper is to explain these appearances away. I contend that the impression of epistemic partiality in friendship dissipates once we acknowledge the sorts of practical and epistemic reasons that are generated by our values: value-reflecting reasons. The present proposal has several virtues: it requires fewer substantial commitments than other proposals seeking to resist the case for epistemic partiality (in particular, it eschews both Pragmatic Encroachment and Epistemic Permissivism); it is independently motivated, as it cites a phenomenon—value-reflecting reasons—we have independent reasons to accept; it provides a single, unified account of how various features of friendship bear on belief-formation; and makes clear how it is the very value we place on friendship itself that ensures against epistemic partiality.

Weak speech reports Abstract Indirect speech reports can be true even if they attribute to the speaker the saying of something weaker than what she in fact expressed, yet not all weakenings of what the speaker expressed yield true reports. For example, if Anna utters 'Bob and Carla passed the exam', we can accurately report her as having said that Carla passed the exam, but we can not accurately report her as having said that either it rains or it does not, or that either Carla passed the exam or pandas are cute. This paper offers an analysis of speech reports that distinguishes weakenings of what the speaker expressed that yield true reports from weakenings that do not. According to this analysis, speech reports are not only sensitive to the informational content of what the speaker expressed, but also to the possibilities a speaker raises in making an utterance. As I argue, this analysis has significant advantages over its most promising competitors, including views based on work by Barwise and Perry (J Philos 78(11): 668–691, 1981), views appealing to recent work on the notion of content parthood by Fine (J Philos Log 45(2):199–226, 2016) and Yablo (Aboutness. Princeton University Press, Princeton, 2014), and Richard's (Mind Lang 13(4): 605–616, 1998) proposal appealing to structured propositions.

Second best epistemology: fallibility and normativity Abstract The Fallibility Norm—the claim that we ought to take our fallibility into account when managing our beliefs—appears to conflict with several other compelling epistemic norms. To shed light on these apparent conflicts, I distinguish two kinds of norms: norms of perfection and norms of compensation. Roughly, norms of perfection tell us how agents ought to behave if they're to be perfect; norms of compensation tell us how imperfect agents ought to behave in order to compensate for their imperfections. I argue that the Fallibility Norm is a norm of compensation, and that thinking of it like this helps us make progress in debates surrounding disagreement, higher-order evidence, and coherence.

Against reductive ethical naturalism Abstract This paper raises an objection to two important arguments for reductive ethical naturalism. Reductive ethical naturalism is the view that ethical properties reduce to the properties countenanced by the natural and social sciences. The main arguments for reductionism in the literature hold that ethical properties reduce to natural properties by supervening on them, either because supervenience is alleged to guarantee identity via mutual entailment, or because non-reductive supervenience relations render the supervenient properties superfluous. After carefully characterizing naturalism and reductionism, we will present, explain, and raise objections against each of the main reductionist arguments: (a) that supervenience does not support the claim that ethical properties and their subvenient natural properties are mutually entailing; (b) that reductive views undermine the claim that ethical properties yield resemblance; and (c) that supervenience does not entail that non-descriptive ethical properties are superfluous in the most fundamental sense.

The epistemic significance of political disagreement Abstract The degree of doxastic revision required in response to evidence of disagreement is typically thought to be a function of our beliefs about (1) our interlocutor's familiarity with the relevant evidence and arguments, and their intellectual capacities and virtues, relative to our own, or (2) the expected probability of our interlocutor being correct, conditional on our disagreeing. While these two factors are typically used interchangeably, I show that they have an inverse correlation in cases of disagreement about politically divisive propositions. This presents us with a puzzle about the epistemic impact of disagreement in these cases. The most significant disagreements on (1) are the least significant disagreements on (2), and vice versa. I show that assessing the epistemic status of an interlocutor by reference to either (1) or (2) has uncomfortable consequences in these cases. I then argue that this puzzle cannot be escaped by claiming that we usually have dispute-independent reason to reject the significance of politically charged disagreement altogether.

Imprecise lexical superiority and the (slightly less) Repugnant Conclusion Abstract Recently, Derek Parfit has offered a novel solution to the "Repugnant Conclusion" that compared with the existence of many people whose quality of life would be very high, there is some much larger number of people whose existence would be better but whose lives would be barely worth living. On this solution, qualitative differences between two populations will often entail that the populations are merely "imprecisely" comparable. According to Parfit, this fact allows us to avoid the Repugnant Conclusion without violating the transitivity of better than. In this paper, I argue that Parfit's view nevertheless implies two objectionable conclusions. The first is an alternative version of the Repugnant Conclusion that, Parfit suggests, may not be all that repugnant. The second is a revised version of the first that is nearly identical to the Repugnant Conclusion. I conclude that Parfit's view offers no escape from repugnance.

Saying and believing: the norm commonality assumption Abstract One very popular assumption in the epistemological literature is that belief and assertion are governed by one and the same epistemic norm. This paper challenges this claim. Extant arguments in defence of the view are scrutinized and found to rest on value-theoretic inaccuracies. First, the belief-assertion parallel is shown to lack the needed normative strength. Second, I argue that the claim that assertion inherits the norm of belief in virtue of being an expression thereof rests on a failed instance of deontic transmission. Third, the inheritance argument from the norm for action is proven guilty of deontic equivocation. Last but not least, it is argued that, on a functionalist normative picture, assertion and belief are governed by different epistemic norms, in virtue of serving different epistemic functions.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Neuro-Oncology

Correction to: Phase I-II trial of imatinib mesylate (Gleevec; STI571) in treatment of recurrent oligodendroglioma and mixed oligoastrocytoma. North central cancer treatment group study N0272 (ALLIANCE/NCCTG) The last author's first name was truncated in the initial online publication. The original article has been corrected.

Nomograms for predicting the overall and cause-specific survival in patients with malignant peripheral nerve sheath tumor: a population-based study Abstract Background Malignant peripheral nerve sheath tumor (MPNST) is extremely rare in soft tissue sarcoma, with a high rate of recurrence and metastasis. Due to its rarity, the epidemiological features and prognostic factors are still uncertain. Moreover, nomograms for patients with MPNST have not been constructed and validated until now. Patients and methods Patients diagnosed with MPNST between 1973 and 2014 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis, machine learning and Lasso regression were used to identify the prognostic factors for overall survival (OS) and cause-specific survival (CSS). Significant prognostic factors were integrated to construct nomograms and then the nomograms were validated externally with a separate cohort from our own institution. Results A total of 689 patients were included in the training set and 42 patients in the validation set. Multivariate analysis suggested that age, histology, historic stage and chemotherapy were independent prognostic factors for OS and primary site, surgery, historic stage and chemotherapy for CSS. The nomograms based on multivariate models were developed and validated for predicting 3- and 5-year OS and CSS, with a C-index of 0.686 and 0.707, respectively. In the external validation set, the C-index was 0.700 for OS and 0.722 for CSS. Conclusion ICD-O-3 histology, historic stage and chemotherapy were independent prognostic factors for OS and primary site, surgery, historic stage and chemotherapy for CSS. The constructed nomograms could provide individual prediction for MPNST patients and assist oncologists in making accurate survival evaluation.

Health-related quality of life of patients with brain metastases selected for stereotactic radiosurgery Abstract Purpose Information on health-related quality of life (HRQoL) of patients with brain metastases (BM) before stereotactic radiosurgery (SRS) is very relevant to improve communication between patients and clinicians and to be able to interpret changes in HRQoL after SRS. The aim of this study was to evaluate the prevalence and severity of complaints on different aspects of pre-SRS HRQoL among patients with BM and to identify predictors thereof. Methods Patients with 1–10 newly diagnosed BM, expected survival > 3 months, Karnofsky Performance Status ≥ 70, and scheduled to undergo SRS were included. HRQoL was measured with the Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. One-sample z-tests were conducted to analyze differences between patients with BM and published normative data of a general adult sample and of an adult cancer sample. Multiple regression analyses were run to identify predictors of pre-SRS HRQoL. Results On the individual level, most patients with BM (57.6% of 92 included patients) reported complaints regarding emotional well-being. As a group, patients with BM reported significantly lower emotional well-being compared to both control groups and significantly higher social well-being compared to the general population. Worse psychological factors, e.g. physical fatigue, depression, mental fatigue and anxiety, predicted aspects of pre-SRS HRQoL. Conclusions An increased understanding of pre-SRS HRQoL and predictors hereof, provides us with more insight into the well-being of our patients with BM and is necessary for the interpretation of (changes in) HRQoL after SRS.

Spinal location is prognostic of survival for solitary-fibrous tumor/hemangiopericytoma of the central nervous system Abstract Background Prior studies have highlighted infratentorial tumor location as a prognostic factor for solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) of the central nervous system (CNS), and spinal location is considered a positive prognostic factor for other tumors of the CNS. While SFT/HPC of the CNS is known to frequently arise from the spinal meninges, there are no case series that report outcomes for spinally located CNS tumors, and their prognosis in relation to intracranial and other CNS-located tumors is unknown. Objective To investigate outcomes for patients with SFT/HPC of the spinal meninges. Methods The Surveillance, Epidemiology, and End-Results Program was used to identify patients with SFT/HPC within the CNS from 1993–2015. We retrospectively analyzed the relationship between tumor location (spinal vs. Brain and other CNS) and survival. Results We identified 551 cases of CNS SFT/HPC, 64 (11.6%) of which were primary tumors of the spinal meninges. Spinal tumors were more likely than brain and other CNS tumors to be SFT vs. HPC (37.5 vs. 12%, p < 0.001), benign (42.2 vs. 20.3%, p < 0.001), and less than 5 cm (53.1 vs. 35.7%, p < 0.001). The 10-year survival rates for spinal and brain/other CNS tumors were 85 and 58%, respectively. Median survival time was significantly longer for spinal tumors (median survival not reached vs. 138 months, p = 0.03, HR = 0.41 [95% CI 0.18–0.94]). On multivariable analysis, spinal tumor location was associated with improved survival over tumors located in the brain and other CNS (HR = 0.36 [95% CI 0.15–0.89], p = 0.03). Conclusion Spinal tumor location is associated with improved survival in patients with SFT/HPC of the CNS. Larger institutional studies are necessary to characterize the relationship between tumor location and other relevant factors such as presentation and amenability to gross-total resection and adjuvant radiotherapy. Future studies exploring optimal management of spinally located tumors are also needed.

Gliosarcoma: distinct molecular pathways and genomic alterations identified by DNA copy number/SNP microarray analysis Abstract Purpose Gliosarcoma is a histologic variant of glioblastoma (GBM), and like GBM carries a poor prognosis. Median survival is less than one (1) year with less than 5% of patients alive after 5 years. Although there is no cure, standard treatment includes surgery, radiation and chemotherapy. While very similar to GBM, gliosarcoma exhibits several distinct differences, morphologically and molecularly. Therefore, we report a comprehensive analysis of DNA copy number changes in gliosarcoma using a cytogenomic DNA copy number (CN) microarray (OncoScan®). Methods Cytogenomic DNA copy number microarray (OncoScan®) was performed on 18 cases of gliosarcoma. MetaCore™ enrichment was applied to the array results to detect associated molecular pathways. Results The most frequent alteration was copy number loss, comprising 57% of total copy number changes. The number of losses far exceeded the number of amplifications (***, < 0.001) and loss of heterozygosity events (***, < 0.001). Amplifications were infrequent (4.6%), particularly for EGFR. Chromosomes 9 and 10 had the highest number of losses; a large portion of which correlated to CDKN2A/B loss. Copy number gains were the second most common alteration (26.2%), with the majority occurring on chromosome 7. MetaCore™ enrichment detected notable pathways for copy number gains including: HOXA, Rho family of GTPases, and EGFR; copy number loss including: WNT, NF-kß, and CDKN2A; and copy number loss of heterozygosity including: WNT and p53. Conclusions The pathways and copy number alterations detected in this study may represent key drivers in gliosarcoma oncogenesis and may provide a starting point toward targeted oncologic analysis with therapeutic potential.

Sporadic and Von-Hippel Lindau disease-associated spinal hemangioblastomas: institutional experience on their similarities and differences Abstract Introduction Hemangioblastomas are uncommon tumors of the central nervous system that can be seen in Von Hippel-Lindau (VHL) disease. Despite their benign histology, hemangioblastomas can cause substantial morbidity due to involvement of critical structures. In order to better understand the clinical behavior of spinal cord hemangioblastomas, we have analyzed the clinical, pathologic, radiologic characteristics and management of sporadic and VHL-associated cases at our institution. Methods We performed a database search to identify all spinal hemangioblastomas at our institution between 1997 and 2016. Tumor characteristics were analyzed for sporadic and VHL-associated tumors separately in order to understand the differences in groups. Results We included 20 patients with VHL-associated spinal hemangioblastomas, and 22 patients with sporadic spinal hemangioblastomas. VHL-associated patients were significantly younger at time of presentation compared to sporadic patients (p < 0.0025). Thirty-two patients (76.2%) presented with focal weakness, 34 (81.0%) with sensory loss, and 22 (52.4%) with pain. VHL patients were more likely to present with multiple symptoms (p < 0.001). Median follow-up time was 20.9 months, during which 17 tumors recurred. The median recurrence free interval was 44 months. There were no differences in gross total resection rates between sporadic and VHL-associated cases (p = 0.197). VHL-associated cases had a higher rate of repeat surgery for recurrence (14 patients-73.6%) compared to sporadic cases (3 patients-13.6%; p < 0.001). Conclusion VHL-associated spinal hemangioblastomas differ from sporadic tumors in terms of age, presenting symptoms, multifocality, and rate of recurrence. Recurrences seem to be unrelated to the extent of resection, indicating the need for life-long follow up for VHL patients.

Comparative analysis of intracranial meningiomas in patients younger than 40 years Abstract Purpose Intracranial meningiomas are relatively rare in young adults, and their specific clinical features remain unclear. The authors analyzed the clinical characteristics of intracranial meningioma in patients younger than 40 years. Methods Consecutive patients younger than 40 years with meningioma (n = 223) who underwent surgical treatment at our hospital from 2010 to 2018 were retrospectively reviewed. The study cases was further divided into a younger group (≤ 30 years old; n = 63) and an older group (31–40 years old; n = 160). The clinical information, radiological characteristics, intraoperative findings, and pathological outcomes were extracted from the patients' records and statistically analyzed. Results Intracranial meningioma is uncommon in patients younger than 40 years (8.6%). The study group's most common symptoms at presentation were headaches (46.7%), visual impairment (27.8%), limb weakness (20.6%), and epilepsy (13.5%). The mean tumor size was larger (51.47 ± 50.36 cm3) in the younger group than in the older group (22.94 ± 27.20 cm3). According to multivariate analyses, young age was an independent predictor of large tumor size, and large tumor size was significantly associated with peritumoral brain edema and intraoperative blood loss. Conclusion Intracranial meningiomas in younger adult patients may have special complexity and perioperative risk due to large tumor sizes. Therefore, individualized treatment strategy is recommended, and the appropriate caution should be taken during surgery.

Multisession radiosurgery for perioptic meningiomas: medium-to-long term results from a CyberKnife cooperative study Abstract Purpose Most recent literature has confirmed the efficacy of single-session radiosurgery (sRS) in the treatment of intracranial meningioma. Unfortunately, sRS is not always applicable due to large tumor volume and the proximity of the tumor to critical structures. When sRS is not recommended, multi-session radiosurgery (mRS) can be the solution. The best treatment schedule for mRS, however, is not well established. The aim of the present retrospective study is to validate the effectiveness of one approach, 25 Gy delivered in 5 fractions in 5 consecutive days, to treat skull base meningiomas. Methods This is a retrospective multicenter study. Patients with an anterior or a medium skull base meningioma that could not be treated by sRS due to large volume or proximity to the anterior optic pathways (AOPs) underwent 5-fraction mRS. Only patients with at least 36 months follow-up were included in the analysis. Local control and visual outcomes were investigated. Results One-hundred-sixty-seven patients were included in the analysis. One-hundred-one patients underwent RS as a primary indication and 66 were treated after a previous surgery. The median follow-up period was 51 months (range 36–129 months). Progression-free survival at 3, 5 and 8 years were, respectively, 98%, 94% and 90%. Excluding the progressive disease patients, the visual worsening rate was 3.7%. The 42% of the patients with a pre-treatment visual deficit experienced improvement in vision. Conclusion 25 Gy delivered in 5 fractions is an effective modality for meningiomas that are near the AOP or are too large to be treated by sRS. The treatment schedule controlled the tumors while sparing visual function.

Hypofractionated radiation therapy versus chemotherapy with temozolomide in patients affected by RPA class V and VI glioblastoma: a randomized phase II trial Abstract Introduction In RPA V-VI glioblastoma patients both hypofractionated radiotherapy and exclusive temozolomide can be used; the purpose of this trial is to compare these treatment regimens in terms of survival and quality of life. Methods Patients with histologic diagnosis of glioblastoma were randomized to hypofractionated radiotherapy (RT–30 Gy in 6 fractions) and exclusive chemotherapy (CHT–emozolomide 200 mg/m2/day 5 days every 28 days). Overall (OS) and progression free survival (PFS) were evaluated with Kaplan Maier curves and correlated with prognostic factors. Quality- adjusted survival (QaS) was evaluated according to the Murray model (Neurological Sign and Symptoms–NSS) Results From 2010 to 2015, 31 pts were enrolled (CHT: 17 pts; RT: 14pts). Four pts were excluded from the analysis. RPA VI (p = 0.048) and absence of MGMT methylation (p = 0.001) worsened OS significantly. Biopsy (p = 0.048), RPA class VI (p = 0.04) and chemotherapy (p = 0.007) worsened PFS. In the two arms the initial NSS scores were overlapping (CHT: 12.23 and RT: 12.30) and progressively decreased in both group and became significantly worse after 5 months in CHT arm (p = 0.05). Median QaS was 104 days and was significantly better in RT arm (p = 0.01). Conclusions The data obtained are limited by the poor accrual. Both treatments were well tolerated. Patients in RT arm have a better PFS and QaS, without significant differences in OS. The deterioration of the NSS score would seem an important parameter and coincide with disease progression rather than with the toxicity of the treatment.

First report of quality of life in adults with neurofibromatosis 2 who are deafened or have significant hearing loss: results of a live-video randomized control trial Abstract Purpose To test the feasibility, acceptability, and preliminary efficacy of a mind–body program for patients with neurofibromatosis 2 (NF2) who are deaf or have significant hearing loss (d3RP-NF2) against an attention placebo control (dHEP-NF2) in a single-blind randomized control trial. Both were delivered using Communication Access Real-Time Translation and live group videoconferencing. Methods Forty-five adults with NF2 were randomized. Co-primary outcomes were physical quality of life (QoL) and psychological QoL and secondary outcomes were social QoL and environmental QoL, all measured with the World Health Organization Quality of Life Abbreviated Instrument (WHOQOL-BREF). Assessments were conducted at baseline, post-treatment, and six-month follow-up. Results Forty-one participants (91%) completed the intervention, and 29 (64%) completed the six-month follow up. Participants in the d3RP-NF2 showed significantly greater improvements from baseline to post-treatment on physical QoL (14.79, 95% CI 5.41–24.18; p ≤ 0.001), psychological QoL (18.77, 95% CI 7.09–30.44, p ≤ 0.001), and environmental QoL (13.25, 95% CI 1.10–25.39, p = 0.03) compared to the dHEP-NF2. Social QoL also significantly increased in the d3RP-NF2 (16.32, 95% CI 6.66–25.97, p = 0.001), but improvement was not beyond the dHEP-NF2. Gains in QoL were clinically meaningful and maintained at the 6-month follow-up for d3RP-NF2 participants across all QoL domains. There were more treatment responders in the d3RP-NF2 compared to the dHEP-NF2. Conclusions The d3RP-NF2 was well accepted, highly feasible, and resulted in sustained improvements in QoL in patients with NF2 who are deaf or have significant hearing loss.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Integrative Medicine

Danshensu Ameliorates Cardiac Ischaemia Reperfusion Injury through Activating Sirt1/FoxO1/Rab7 Signal Pathway Abstract Objective: To explore the specific molecular mechanisms of Danshensu (DSS) in the treatment of ischemia reperfusion injury (IRI). Methods: IRI model was established with isolated rat hearts by performing global ischaemia for 30 min, and then followed by 60 min reperfusion. Also, H9C2 cells were subjected to 4-h hypoxia followed by 3-h reoxygenation. Then 10 μmol/L DSS were added in the reperfusion/reoxygenation step to intervene IRI. Cardiac function, structural change and apoptosis were respectively tested by Langendorff System, hematoxylin and eosin (HE) and terminal-deoxynucleotidyl transferase mediated nick endabeling (TUNEL) stainings. Then lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide gasififi cation enzyme (SOD) and glutathione peroxidase (GSH-PX) were detected by enzyme-linked immunosorbent assay (ELISA). Sirt1/FoxO1/Rab7 Signal Pathway was monitored at both protein and mRNA levels. Results: The results showed that IRI not only greatly attenuated cardiac function (LVDP and ±dp/dtmax, P<0.01, P<0.05) and increased the level of the marker enzymes (cardiac troponin T, LDH, P<0.01) from the coronary effluents, but also markedly induced changes in the structure of cardiomyocytes and contributed to apoptosis, which were mediated by boosted endogenous ROS. However, after treatment with DSS all above indexes were improved, which was related to activating Sirt1/FoxO1/Rab7 signal pathway accompanied with the enhancement of antioxidant defense system, such as superoxide gasififi cation enzyme and glutathione peroxidase. Conclusion: DSS is able to protect hearts from IRI, which may be attributable to inhibiting excessive ROS through Sirt1/FoxO1/Rab7 signaling.

Effects and Mechanism of Action of Artemisinin on Mitochondria of Plasmodium berghei Abstract Objective To study the antimalarial effects and mechanisms of artemisinin (Qinghaosu in Chinese, QHS) on mitochondria in mice infected with Plasmodium berghei. Methods A total of 108 C57 mice infected with Plasmodium berghei were randomly divided into 3 groups by weight: the control group, 200 and 400 mg/kg QHS groups. The two QHS treatment groups were further divided into 4 sub-groups with 12 animals each time according to the treatment time, 0.5, 1, 2, and 4 h. Normal saline was intragastrically (i.g.) administered to the control group. The other two groups received different doses of QHS by i.g. administration. Animals were treated once with QHS for different detection time as follows: 0.5, 1, 2, and 4 h. The mitochondrial energy metabolism, oxidative damage, membrane potential, and membrane permeability and other indexes were detected. Results After administration of 200 and 400 mg/kg QHS, adenosine triphosphate (ATP) levels in Plasmodium and its mitochondria were reduced (P<0.05), the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were increased (P<0.05), and the activity of superoxide dismutase (SOD) was also increased (P<0.05). At the same time, the membrane potential of the mitochondria was reduced and the degree to which the membrane permeability transition pore was opened was irreversibly increased (P<0.05). Conclusions Mitochondria in Plasmodium were the targets of QHS, which can adversely affect mitochondrial energy metabolism, oxidative damage, membrane potential, and membrane opening, and ultimately exert an antimalarial effect.

Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System Abstract Objective To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (通心络胶囊, TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI). Methods Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group, MIRI group, low- and high-dose TXL (0.5 and 1 g·kg-1·d-1, respectively) groups, atorvastatin (ATV) group (7.2 g·kg-1·d-1), chloroquine (CQ) group (10 g·kg-1·d-1), and highdose TXL + CQ group. After pharmacological administration for 7 days, rats underwent left anterior descending artery ligation surgery to establish the MIRI models with 50 min ischemia followed by 4 h reperfusion. Blood was taken for cardiac troponin I (cTnI) detection and hearts were harvested for infarct staining and apoptosis detection. The autophagy or mitophagy proteins and ubiquitinated proteins were detected by Western blotting. Results Compared with the sham group, the MIRI group exhibited a larger infarcted area (27.13%±0.01%, P<0.01), a higher apoptotic index (34.33%±2.03% vs.1.81%±0.03%, P<0.01), and higher cTnI expression (14.18±1.01 vs. 7.96±0.32, P<0.01). The mitochondrial integrity was damaged in the MIRI group, while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58 vs. 4.33±1.15, P<0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (P<0.05). The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group (P<0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL. Conclusions TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.

Oral Chinese Herbal Medicine for Depressive Disorder in Patients after Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis Abstract Objective: To evaluate the effectiveness and safety of oral Chinese herbal medicines (CHMs) on post-percutaneous coronary intervention (PCI) patients with depressive disorder in coronary heart disease (CHD). Methods:A literature search was conducted through databases including PubMed, Cochrane Library, Chinese National Knowledge Infrastructure Databases (CNKI), Chinese Biomedical Literature Database (SinoMed), Chongqing VIP Chinese Science and Technology Periodical Database (VIP) and Wanfang Database up to August 2018. Randomized controlled trials (RCTs) comparing CHMs with placebo or no additional treatments on the basis of standard conventional pharmacological therapies were included. Data extraction, analyses and quality assessment were performed according to the Cochrane standards. RevMan 5.3 software was used to synthesize the results. Results: A total of 16 RCTs enrolling 1,443 participants were included in this systematic review. When compared with antidepressants alone, CHMs showed similar benefits with less side effects [risk ratio=0.54, 95% confidence interval (CI) 0.43 to 0.69, 582 patients]; meanwhile, the combination therapy may have more advantages than antidepressants alone [mean difference (MD)=–1.03, 95%CI–1.81 to–0.25, 267 patients). When identified with placebo, CHMs seem to have more advantages in relieving depressive symptoms (MD=–19.00, 95%CI–20.02 to–17.98, 189 patients). However, when compared with basic treatment of post- PCI, CHMs showed different results in two trials. In terms of post-PCI related clinical symptoms, CHMs seem to have more advantages in relieving chest pain and other general clinical symptoms. However, the heterogeneity in this review was generally high, it may be caused by different interventions used in each trial and the low quality of the trials. Conclusions: In total, CHMs showed potentially beneficial effects on depressive symptoms and post-PCI related clinical symptoms. However, because of small sample size and potential bias of most trials, this result should be interpreted with caution. More rigorous trials with larger sample size and higher quality are warranted to give high quality of evidence to support the use of CHMs for CHD complicated with depression.

Comparative Studies of Two Major Sets of Tibetan Medical Paintings: A Historical Perspective Abstract Tibetan medicine, one of the time-honored medical systems in the world, has increasingly been receiving attention the world over. Tibetan medical paintings (TMP, tib. Sman thang) has become one of the focal points in the studies of this medical system. To date, there are many atlases and publications on TMP, which are principally based on the two major sets of TMP series existing today in the world, the Lhasa set and the Buryat set. It has been found that the Buryat set is based on the Lhasa set, which was brought in late 19th to the first half of the 20th century from Tibet to Buryatia, Russia. A careful investigation on the basic structure of the two sets reveals that there are many differences between the two sets of paintings, including the total number of the paintings involved, of which some are missing in one set, the details of the captions of some of the paintings, the existence of the 80th painting and its supervisor, and the overall order of the entire set, etc. The details of the differences are elaborated and discussed, and the prospective of developing the research to arrive at a standard and perfect TMP set in the future is also analyzed and anticipated.

Effect of Shexiang Baoxin Pill (麝香保心丸) in Alleviating Early Hypertensive Renal Injury in Rats Abstract Objective To investigate the effect of Shexiang Baoxin Pill (麝香保心丸, SBP) on early hypertensive renal injury in rats and to explore the possible mechanism. Methods Twelve-week-old spontaneous hypertensive rats (SHRs) with high-salt diet (dietary containing 8% NaCl) were randomized into the SBP group [40 mg/(kg·d)], losartan potassium group [20 mg/(kg·d)] and saline group by stratified random sampling method, 12 in each group. Blood pressure and urea albumin creatinine ratio were measured. After 10 weeks, the expression levels of serum creatinine (Scr), hypersensitive C-reactive protein (hs-CRP), interleukin (IL)-1 β, IL-6, tumor necrosis factor α (TNF-α), and transforming growth factor β (TGF-β) in serum were assessed. Kidney pathology periodate-schiff staining was performed. Semi-quantitative count of macrophage infiltration was determined by immunochemistry of CD68 staining. Real-time quantitative polymerase chain reaction and Western blot were performed to examine the mRNA and protein expressions of Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), monocyte chemokine peptide (MCP-1), inducible nitric oxide synthase (iNOS), and arginase-1 (Arg-1). Results SBP did not affect the mortality of SHR (P<0.05). SBP significantly reduced the level of elevated blood pressure of SHRs, but the effect was less significantly than that of losartan potassium. SBP decreased urine protein (P<0.01) and the expression levels of IL-1 β, IL-6, TNF-α, and TGF-β in serum. The 22-week-old SHRs showed mild proliferation of glomerular endothelial cells, glomerular ischemic lesions, inflammatory cell infiltration in renal tubular interstitium and arteriosclerosis. Both SBP and losartan potassium had alleviated renal pathological change, and significantly reduced the infiltration of macrophage (P<0.05, P<0.01). SBP and losartan potassium decreased the expressions of TLR4, NF-κB, MCP-1, iNOS, and Arg-1. Conclusion SBP significantly modified the early hypertensive renal injury by reducing inflammation, and the effect was similar to losartan potassium.

Changes of Intestinal Microecology in Patients with Primary Sjogren's Syndrome after Therapy of Yangyin Yiqi Huoxue Recipe (养阴益气活血方) Abstract Objective To explore the change of intestinal microecology in patients with primary Sjogren's syndrome (pSS) and correlation with disease activity, and also discuss the therapy effect of Yangyin Yiqi Huoxue Recipe (养阴益气活血方, YYHD). Methods Sixteen pSS patients were enrolled in the present study, who received 3-month treatment of YYHR, 200 mL orally twice daily. Their pre-and post-test ESSDAI scores, erythrocyte sedimentation rate (ESR) and serum immunoglobulin G (IgG) levels were measured respectively. The 16SrDNA metagenomic sequencing was used to detect and analyze the abundance and diversity of intestinal bacteria flora and the proportion of bacteria at the levels of phylum, family, and genus, in comparision with those of 6 healthy subjects in the control group. Results The abundance and diversity of intestinal bacteria flora in pSS patients were lower than those of healthy subjects (P<0.05). After the treatment with YYHD, patients' ESSDAI score and levels of IgG and ESR have decreased significantly (P<0.05). At the phylum level, the proportions of Actinobacteria, Firmicutes, Fusobacteria and Proteobacteria have reduced sharply, while the proportions of Bacteroidetes, Teneriquetes and Candidate-division-TM7 have increased significantly by treatment (all P<0.05). At the classification level, such treatment has caused a significant decrease in the proportions of Bacteroidaceae, Ruminococcaceae, Veillonellaceae, and Enterobacteriacea (all P<0.05), but a significant increase in the proportion of Lachnospiraceae (P<0.05). At the genus level, the treatment has significantly decreased the proportions of Bifidobacterium, Bacteroides, Escherichia-Shigella, Faecalibacterium and Prevotella (all P<0.05), but significantly increased the proportion of Clostridia (P<0.05), close to the levels of healthy subjects (P>0.05). Conclusions There exists an imbalance of intestinal microecology in pSS patients, which can be improved through the treatment with YYHD. Besides, such treatment can also improve the disease activity and adjust the diversity of intestinal bacteria flora, the composition and the abundance of intestinal flora.

Anticancer Effects of Constituents of Herbs Targeting Osteosarcoma Abstract Osteosarcoma is a rare primary malignancy of bone that is prone to early metastasis. Resection surgery and chemotherapeutic regimens are current standard treatments for osteosarcoma. However, the long-term survival rate of patients with osteosarcoma is low due to a high risk of metastasis. Hence, a new approach is urgently needed to improve the treatment of osteosarcoma. Compared with chemotherapy, natural active constituents isolated from herbs exhibit less adverse effects and better anti-tumor effects. This study aimed to summarize the anticancer effects of constituents of herbs on the progression and metastasis of osteosarcoma cells. It showed that many constituents of herbs inhibited osteosarcoma by targeting proliferation, matrix metalloproteinases, integrin and cadherin, and angiogenesis. The findings might be beneficial for the development of new drugs and treatment strategies.

Is Acupressure Useful for Alleviating Hyperventilation Syndrome?

Embolic effects of Bletilla striata microspheres in renal artery and transplanted VX2 liver tumor model in rabbits Abstract Objectives To evaluate the characteristics of Bletilla striata microspheres (BSMs) and its effects as an embolic agent in a rabbit model. Methods BSMs were prepared with an emulsification-cool condensation-chemical cross-linking method. The characteristics of BSMs in vitro were observed. Embolization experiments were performed in renal artery of rabbit and in a rabbit liver VX2 carcinoma model. Seventy-two New Zealand rabbits were divided into 2 groups, and the right renal artery was embolized with BSMs (200 μm in diameter) in the experimental group and with polyvinyl alcohol (PVA) of the same size in the control group. The pathological findings were examined with hematoxylin-eosin and Masson stainings. Liver and renal functions were tested before and after embolization. VX2 tumor was transplanted in 15 New Zealand rabbits, which were randomly divided into 3 groups (n=5). Group A were treated with saline, group B with a mixture of doxorubicin and lipiodol, and group C with hepatic arterial infusion of BSMs (200 μm in diameter). Tumor growth rate was evaluated by magnetic resonance imaging scan. Apoptosis-related factors (bax, bcl-2) and tumor vascular endothelial cell growth factor (VEGF) were evaluated through immunohistochemical staining. Results The characteristics of BSMs in vitro were in full compliance with the requirements for use in interventional procedures. In the renal artery embolization experiment, after BSMs intervention, it was more difficult to form collateral circulation than that with PVAs, and the kidney manifested atrophy and calcification. There were no significant difference of liver and renal functions in rabbits between groups. In the liver VX2 carcinoma embolization experiment, compared with group A, the growth rate of VX2 liver tumor and Bcl-2 levels was reduced, while apoptosis index, Bax, and VEGF were increased in group B (P<0.05). There were no significant difference between groups B and C (P>0.05). Conclusions The characteristics of BSMs in vitro and in vivo meet the requirements for its use as an embolic agent in interventional approaches.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Medicina Interna

Irma Elizabeth Gonzalez Curiel

LOS PÉPTIDOS ANTIMICROBIANOS Y SUS BENEFICIOS EN EL TRATAMIENTO DE LAS ÚLCERAS DE PIE DIÁBETICO

En la presente revisión se analiza, sobre la base de los estudios realizados tanto in vivocomo in vitro el posible uso de péptidos antimicrobianos y sus inductores en el tratamiento de úlceras de pie diabético.

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Vivian Molina

TRATAMIENTO DE LA ISQUEMIA CEREBRAL GLOBAL EN JERBOS DE MONGOLIA

El tratamiento con dosis orales únicas de las combinaciones policosanol (100 mg/kg) más aspirina (60 mg/kg) y policosanol (100 mg/kg) más atorvastatina (20 mg/kg) redujo marcada y significativamente la isquemia cerebral global en jerbos de Mongolia, con una eficacia muy similar entre ellos, pero ligeramente superior a la obtenida con la monoterapia con aspirina. Además, ambas combinaciones presentaron efectos antioxidantes, a diferencia de la monoterapia con aspirina, lo que les proporciona un beneficio adicional.

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Cristina Chirico

EL AMPARO ECONÓMICO PARA MEJORAR EL TRATAMIENTO DE LA TUBERCULOSIS

El objetivo de nuestro estudio es analizar las diferencias de los datos clínicos y epidemiológicos entre pacientes con y sin inclusión en el régimen de amparo, y si el subsidio fue un factor de éxito en el tratamiento.

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Fernando Ricardo Racca Velásquez

PAQUIMENINGITIS HIPERTRÓFICA POSINFECCIOSA: PRESENTACIÓN DE CASO CLÍNICO

La paquimeningitis hipertrófica es una entidad infrecuente que puede ser idiopática o secundaria, y dado que incluso un diagnóstico acertado y un correcto tratamiento pueden dejar secuelas neurológicas graves o incluso producir la muerte, presentamos este caso en el que consideramos que la causa fue una meningitis que no recibió tratamiento adecuado al inicio de los síntomas y que tuvo una respuesta satisfactoria al tratamiento con corticoides inicialmente en altas dosis.

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Glaucio De Moraes Paula

FATORES ASSOCIADOS A DISPLASIA BRONCOPULMONAR EM RECÉM-NASCIDOS EGRESSOS (EN LOS RECIÉN NACIDOS) DE GESTAÇÃO COM AMNIORREXE PREMATURA NO PRÉ-TERMO (EN EL PRETÉRMINO)

O (El) estudo teve por objetivo identificar fatores obstétricos e neonatais associados à ocorrência da (a la aparición de) displasia broncopulmonar

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