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The detailed chemical investigations of the South China Sea soft corals Sinularia tumulosa and Sinularia depressa, yielded two new compounds, namely tumulosterol A (1) and 11’-hydroxy-α-tocopherylquinone (3), along with four related known ones (2, 5–7). Their structures were determined by extensive spectroscopic analysis and comparison with the spectral data previously reported in the literature. In bioassays, compound 1 displayed significant cytotoxic effects against H1975 and MDA-MB-231 cells with IC50 values of 6.0 and 6.3 µM, respectively. In addition, compound 3 exhibited interesting inhibitory effect on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells with IC50 value of 9.5 µM.

Fifteen new diterpenoids, namely xishaklyanes A-O (1–15), along with three known related ones (16–18), were isolated from the soft coral Klyxum molle collected from Xisha Islands, South China Sea. The stereochemistry of the new compounds was elucidated by a combination of detailed spectroscopic analyses, chemical derivatization, quantum chemical calculations, and comparison with the reported data. The absolute configuration of compound 18 was established by the modified Mosher’s method for the first time. In bioassay, some of these compounds exhibited considerable antibacterial activities on fish pathogenic bacteria, and compound 4 showed the most effective activity with MIC of 0.225 μg/mL against Lactococcus garvieae.

Two novel diterpenoids, sinuaustones A (1) and B (2), featuring an unprecedented tricyclo[9.3.1.03,15]tetradecane carbon framework were isolated from the South China Sea soft coral Sinularia australiensis.

Applying the emerging molecular networking strategy, an uncommon cembranoid orthoester, sarcotortin A (1), featuring a 3/14/8/5-fused scaffold, an unusual eunicellane-type diterpenoid, sarcotorolide A (2), and two new biscembranoids, ximaolides M and N (7 and 8), along with nine known terpenoids 3-6 and 9-13 were isolated from the Hainan soft coral Sarcophyton tortuosum. The structure and absolute configuration of all new compounds were established by a combination of spectroscopic data, X-ray diffraction analysis, and/or quantum chemical computational approaches. The plausible biogenetic relationship among these skeletally different terpenoids was proposed and discussed. In in vitro bioassay, new compound 7 exhibited a remarkable inhibitory activity against protein tyrosine phosphatases 1B (PTP1B) with the IC50 value of 8.06 μM. In addition, compounds 4 and 10 displayed significant inhibitory effects on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophages cells with the IC50 values of 19.13 and 16.45 μM, respectively. Compound 9 showed interesting cytotoxicity against H1975, MDA-MB231, A549, and H1299 cancer cell lines with IC50 values of 31.59, 34.96, 43.87, and 27.93 μM, respectively.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs. However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000 single-nucleus transcriptomes of the lung, liver, kidney, and cerebral cortex in rhesus macaques (新型冠状病毒（SARS-CoV-2）感染可以造成多种临床表现和多种器官的组织损伤。但是对于新冠病毒感染相关的病理和免疫防御特征的细胞和分子水平的理解还不完善。该研究中，我们对感染新冠病毒的猕猴及健康对照个体的肺脏、肝脏、肾脏、大脑皮层进行单细胞核转录组测序和分析，共获得了约77 000个单细胞核的转录组数据。多器官数据集整合分析结果表明肝脏具有最强的全局转录改变。我们发现肺脏中的上皮细胞，尤其是AT2细胞和纤毛细胞，存在突出的损伤特征，在成纤维细胞中纤维化迹象明显。肺部的这些损伤特征与新冠肺炎（COVID-19）病人中报道的结果很相似。此外，我们发现肺中的主要组织相容性复合体（MHC）I/II类分子活性下调，肝脏中存在炎症反应和犬尿氨酸通路的激活，它会诱导免疫抑制性微环境的发展。对肾脏数据集的分析发现肾小管上皮细胞对新冠病毒具有更强的趋向性，同时发现了感染猕猴出现了由足细胞失调引起的膜性肾病(一种自身免疫疾病)。另外，我们还识别到了大脑皮层中星形胶质细胞和少突胶质细胞的病理状态，为新冠肺炎相关的神经学影响提供了分子洞察。总之，此项对新冠病毒感染的猕猴模型多器官进行单细胞核转录组研究的工作拓宽了我们对新冠病毒感染造成的疾病特征和机体抗病毒免疫缺陷的理解，这可能促进新冠肺炎治疗干预手段的开发。.

A detailed chemical investigation of the South China Sea soft coral Sarcophyton ehrenbergi has yield seven undescribed cembranoids, namely isoehrenbergol D and sarcoehrenolides F-K embodying a rare α,β-unsaturated-lactone moiety at C-6 to C-19, along with two known related compounds, ehrenbergol D and sarcoehrenolide A. Their structures and absolute configurations were unambiguously established in the light of extensive spectroscopic data analysis, modified Mosher's method, X-ray diffraction analysis, and quantum chemical computation method. In a bioassay for α-glucosidase inhibition, ehrenbergol D was evaluated as α-glucosidase inhibitor with an IC

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19.

This study aims to explore the efficacy of Chinese medicine injections( CMIs) for promoting blood circulation and removing blood stasis for acute cerebral infarction from the perspectives of clinical medication and mechanism of action based on two complex network analysis methods. Firstly,the current 13 kinds of CMIs for acute cerebral infarction were obtained from 2019 List of medicines for national basic medical insurance,industrial injury insurance and maternity insurance with the method of network Meta-analysis. Secondly,with the use of network pharmacology,the mechanisms of top 2 CMIs with the highest therapeutic effect for acute cerebral infarction were explored from two levels including core target and network function enrichment. The result of network Meta-analysis showed Mailuoning Injection was superior to Danhong Injection in terms of total effectiveness rate for neurological deficit score and NIHSS score. The network pharmacology results showed that Mailuoning Injection had more core targets,interaction networks,enriched biological functions and more signaling pathways than Danhong Injection for cerebral infarction. Both two CMIs can play a role in treating cerebral infarction through core targets such as TP53 and NOS3,biological processes such as fibrinolysis,nitric oxide biosynthesis,nitric oxide-mediated signal transduction,negative regulation of apoptosis in endothelial cells and apoptosis process,as well as the signaling pathways such as PI3 K-Akt signaling pathway,HIF-1 signaling pathway and cell apoptosis signaling pathways. The results of pharmacological studies explained their differences in clinical efficacy to a certain extent. A research strategy based on curative effect should be advocated in efficacy evaluation of traditional Chinese medicine,where comparative research on clinical efficacy can be conducted firstly,and then mechanism research based on outstanding effective drugs to better provide references and basis for selection of similar competitive drugs for one disease in the clinical practice.

Introduction Chinese medicine injections (CMIs) are widely applied to the treatment of acute cerebral infarction (ACI) in China. However, there are very few head-to-head comparative trials to determine the relative efficacy between different CMIs. It is reported that 20 kinds of CMIs are often used for treating cerebral infarction. Due to the fact that various CMIs are used in clinic, it’s difficult for clinicians to choose the optimal CMIs for patients with ACI. We plan to conduct a network meta-analysis (NMA) to compare the efficacy of 12 kinds of different CMIs, including direct and indirect comparisons between CMIs, aiming to provide the best currently available evidence base to guide the choice about CMIs treatment for patients with ACI. Methods A systematic and comprehensive search will be performed from inception to August 2018 in both English and Chinese databases, involving PubMed ,Cochrane Library, Embase, China National Knowledge Infrastructure Database (CNKI), Wanfang Database, Chongqing VIP information (CQVIP), and SinoMed. Randomized controlled trial (RCT) related to CMIs in the treatment of ACI will be included. Quality of included literature will be assessed according to the risk of bias tool of Cochrane Handbook 5.1.0. The GRADE approach will be used to rate the quality of evidence of estimates derived from NMA. Data analysis will be conducted by using STATA 13.1. Results This systematic review and NMA is to summarise the direct and indirect evidence for 12 kinds of different CMIs to manage ACI, and to rank these CMIs for CMIs treatment of patients with ACI. The findings of this NMA will be reported according to PRISMA-NMA statement. Conclusion This study will offer helpful and informative evaluations of current CMIs for ACI. The results will inform clinicians, provide optimal CMI, establish evidence gaps, and identify promising CMIs for evaluation in future trials.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used solely for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLN. A low dose of I-R-F induces not only high titer long-lasting neutralizing antibodies but also comprehensive T cell responses than RBD, and even provides comprehensive protection in one dose without adjuvant. This study shows that the I-R-F vaccine provides rapid and complete protection throughout upper and lower respiratory tracts against high dose SARS-CoV-2 challenge in rhesus macaques. Due to its potency and safety, this engineered vaccine may become one of the next-generation vaccine candidates in the global race to defeat COVID-19.

To systemically evaluate the clinical efficacy and safety of oral preparation of Xiakucao with levothyroxine(LT4) on Hashimoto's thyroiditis(HT), so as to provide the evidence for its clinical application in the future. All the included studies were retrieved from four Chinese databases and three English databases from their inception to December 2019. ROB assessment tool of cochrane system and the evidence classification recommended by GRADE were used to evaluate the quality of evidences in all included studies. RevMan 5.3 was used for Meta-analysis of the outcomes. Software TSA 0.9(trail sequential analysis) was used to estimate the sample size for Meta-analysis. The results showed that 11 randomized controlled trials and totaling 1 215 patients were included. Preparation of Xiakucao combined with LT4 was adopted as intervention in experimental group, while patients in control group were treated with LT4 alone. Meta-analysis results showed that as compared with control group, the rate of total efficacy in experimental group was significant improved, including improvement of thyroid function and thyroid autoantibodies, shrinkage of thyroid gland and nodule, and improvement of clinical symptoms such as fatigue and cold intolerance(RR=1.15, 95%CI[1.09, 1.21]). The experimental group significantly decreased the serum level of thyroperoxidase antibody TPO-Ab(SMD=-0.91, 95%CI[-1.40,-0.41]), and reduced the size of left thyroid lobe(MD=-1.46, 95%CI[-1.82,-1.11]), right thyroid lobe(MD=-1.45, 95%CI[-1.96,-0.94]) and isthmus of thyroid gland(MD=-1.08, 95%CI[-1.20,-0.95]). After evaluation based on GRADEpro, the results showed that the evidence quality of all included studies was low or very low. The result of TSA showed that the cumulative sample size had reached the expected value. However, the pooled results may be affected by one study with high bias risk, with not so high effect intensity of evidences. From this review, we can see that in treatment of HT, intervention of preparation of Xiakucao combined with LT4 has advantages on improvement of clinical efficiency, decreasing serum level of TPO-Ab and shrinkage of thyroid gland. However, due to the quality of evidence, more rigorously designed and high-quality trials are needed in the future to verify the clinical efficacy and safety of preparation of Xiakucao in treating HT.

To systematically evaluate the efficacy and safety of Xiangsha Yangwei Pills in the treatment of chronic gastritis. Compu-ter retrieval was performed for Cochrane Library, Medline, EMbase, China Knowledge Network Database(CNKI), China Biomedical Literature Service System(SinoMed), Chongqing Weipu Chinese Science and Technology Journal Database(VIP) and WanFang Database(WanFang) randomized controlled trials about Xiangsha Yangwei Pills combined with Western medicine in the treatment of chro-nic gastritis. The retrieval time ranged from the establishment of the library to April 26, 2019. Meta-analysis was performed by RevMan 5.3 software after two independent researchers conducted literature screening, data extraction and quality evaluation according to inclusion and exclusion criteria. A total of 1 720 patients were enrolled in 18 RCT. According to the classification of chronic gastritis, they were divided into three subgroups: chronic gastritis, chronic atrophic gastritis and chronic superficial gastritis. The results of Meta-ana-lysis showed that the efficacy of Xiangsha Yangwei Pills combined with Western medicine in treating chronic gastritis was higher than that of Western medicine. As for the recurrence rate, Xiangsha Yangwei Pills combined with Western medicine was lower than Western medicine. And there was no statistical difference about helicobacter pylori(Hp) eradication rate between Xiangsha Yangwei Pills combined with Western medicine as well as Western medicine. In terms of the incidence of adverse reactions, Xiangsha Yangwei Pills combined with Western medicine was lower than Western medicine, and no serious adverse reaction was reported. The results of this systematic review showed that compared with the conventional Western medicine group, Xiangsha Yangwei Pills combined with Western medicine can significantly alleviate clinical symptoms of chronic gastritis, with fewer adverse reactions. However, due to the low methodological quality of the included studies and the reliability of the impact conclusions, high-quality multi-center, large-sample, randomized, double-blind controlled trials are needed for validation.

The purpose of this study was to evaluate the selection situation of outcome indexes in randomized controlled trials of traditional Chinese medicine(TCM) in the treatment of acute ischemic stroke and to provide suggestions for future research. In this study, four Chinese databases and three English databases were searched from January 2017 to June 2019. The randomized controlled trials of traditional Chinese medicine in the treatment of ischemic stroke were selected according to the pre-established selection criteria. Cochrane bias risk assessment tool was used to evaluate the quality of the included studies. A total of 20 651 related articles were searched, and 11 662 ones were left after eliminating the repetitions. Finally, 42 articles were included, including 36 articles in Chinese and 6 articles in English, 40 randomized controlled trials and 2 registration schemes of randomized controlled trials. The results showed that the outcome indexes of 42 randomized controlled trials were mainly divided into seven categories, that is clinical outcome index, blood biochemical index, mental state evaluation index, cerebral hemodynamics index, index of evaluating the degree of carotid artery stenosis, safety indicators and other indicators. The blood biochemical index was the one with highest frequency, followed by the clinical outcome index. TCM syndrome score was used as an indicator of curative outcome in 17 studies. After the analysis, it was found that there were many problems in selecting the outcome indexes for the randomized controlled trials of traditional Chinese medicine in the treatment of cerebral apoplexy. For example, the end point index and hard index were rarely selected as the main outcome indicators, and the vast majority of them were intermediate alternative indexes; recognized curative effect could not be obtained; there were too many kinds of outcome indicators and excessive heterogeneity, hindering the promotion of superior treatment measures of traditional Chinese medicine in clinical practice. Therefore, we should draw lessons from the establishment method of the international core index outcome index set, construct the core index outcome index set of traditional Chinese medicine in the treatment of ischemic stroke, and develop the outcome index set which accords with the curative effect characteristics of traditional Chinese medicine treatment mea-sures to solve the problems effectively.

To assess the clinical efficacy of Chinese patent medicine for bradyarrhythmia(BA) by using network Meta-analysis method. Relevant randomized controlled trials(RCTs) of Chinese patent medicine for BA were retrieved from China National Knowledge Infrastructure(CNKI), WanFang Database, VIP database, SinoMed, PubMed and Cochrane Library. The retrieval time ranged from the commencement of each database to February 2019. We completed the literature screening and data extraction according to the pre-determined inclusion and exclusion criteria. The quality of inclusion studies was assessed using the bias risk assessment tool recommended by the Cochrane Handbook of Systematic Review 5.3. The data were analyzed by WinBUGS, and STATA software was used for plotting. Finally, 46 RCTs were included, involving 4 Chinese patent medicines and 3 306 patients. According to the network Meta-analysis, the total effective rate in alleviating BA symptoms had 7 direct comparisons and 3 indirect comparisons. The efficacy of the 4 Chinese patent medicines combined with routine therapy was superior to that of routine therapy, with statistically significant differences. The order of the four Chinese patent medicines by efficacy was as follows: Shenxian Shengmai Oral Liquidgt;Shensong Yangxin Capsulesgt;Xinbao Pillsgt;Ningxinbao Capsules. The average heart rate had 7 direct comparisons and 3 indirect comparisons. The efficacy of Shenxian Shengmai Oral Liquid and Shensong Yangxin Capsules combined with routine therapy was superior to that of routine therapy, with statistically significant differences. The order of the four Chinese patent medicines by efficacy was as follows: Shenxian Shengmai Oral Liquidgt;Shensong Yangxin Capsulesgt;Xinbao Pillsgt;Ningxinbao Capsules. The results showed that the Chinese patent medicines combined with routine therapy were effective in the treatment of BA. Due to the differences in the quantity and quality of the included studies on different Chinese patent medicines, the sequencing results of Chinese patent medicines need to be further verified.

To systematically review the effectiveness and safety of Tanreqing Injection in treating acute exacerbation of chronic bronchitis( AECB). CNKI,Wan Fang,VIP,CBM,Medline,Cochrane Library,EMbase and Web of Science were retrieved,and randomized controlled trials for the effect of Tanreqing Injection in the treatment of acute exacerbation of chronic bronchitis were screened. The quality of the included studies was evaluated according to the Cochrane Handbookapos;s evaluation criteria. The data was analyzed by RevMan 5.3. Totally 23 RCTs involving 1 901 patients were included,including 952 in the experimental group and 949 in the control group. The Meta-analysis demonstrated that in terms of the disappearance time of fever,the group of Tanreqing Injection combined with the conventional therapy was superior to conventional therapy group( RR =-1. 03,95%CI[-1. 45,-0. 62],Plt;0. 000 01); compared with the conventional therapy group,the group of Tanreqing Injection combined with conventional therapy had a higher cure rate for AECB( RR = 1. 17,95% CI[1. 13,1. 23],Plt; 0. 000 01). The group of Tanreqing Injection combined with levofloxacin had a higher cure rate for AECB than the levofloxacin group( RR = 1. 23,95% CI[1. 08,1. 41],P = 0. 002). The group of Tanreqing Injection combined with cefuroxime had a higher cure rate for AECB than the cefuroxime group( RR = 1. 22,95%CI[1. 05,1. 42],P = 0. 01).The group of Tanreqing Injection combined with cefoperazone sodium and sulbactam sodium had a higher cure rate for AECB than the group of cefoperazone sodium and sulbactam sodium( RR = 1. 22,95% CI[1. 04,1. 44],P = 0. 02). The outcomes of disappearance time of cough and expectoration had a huge heterogeneity,so were used for descriptive analysis. The adverse reactions mainly included skin rash,dizziness,gastrointestinal reactions. Based on the available data and the results of the analysis,the group of Tanreqing Injection combined with Western medicine has a higher cure rate for acute exacerbation of chronic bronchitis,and the effect in reducing symptoms disappearance time. In view of the limited number of included studies,small sample size and low methodological quality,the results of this study need to be confirmed with high-level clinical trials.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate post-transcriptional gene expression via binding to the 3'-untranslated region (3'-UTR) of targeted mRNAs. They are reported to play important roles in tumorigenesis and progression of various cancers. Among them, miR-149 was confirmed to be aberrantly regulated in various tumors. In this review, we provide a complex overview of miR-149, particularly summarize the critical roles of it in cancers and expect to lay the foundation for future works on this important microRNA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19.

A novel 3D interactive painting method for Chinese calligraphy and painting based on force feedback technology is proposed. The relationship between the force exerted on the brush and the resulting brush deformation is analyzed and a spring-mass model is used to build a model of the 3D Chinese brush. The 2D brush footprint between the brush and the plane of the paper or object is calculated according to the deformation of the 3D brush when force is exerted on the 3D brush. Then the 3D brush footprint is obtained by projecting the 2D brush footprint onto the surface of the 3D object in real time, and a complete 3D brushstroke is obtained by superimposing 3D brush footprints along the painting direction. The proposed method has been successfully applied in a virtual 3D interactive drawing system based on force feedback technology. In this system, users can paint 3D brushstrokes in real time with a Phantom Desktop haptic device, which can effectively serve as a virtual reality interface to the simulated painting environment for users.

To investigate above- and belowground biomass allocation patterns and the relationship of root distribution between different functional groups (shrubs vs. herbs) along a groundwater depth gradient, an experiment was carried out in a Haloxylon persicum woodland. Four sites were selected along the groundwater depth gradient. At each site, five sample plots (20 × 20 m) and 15 subplots (1 × 1 m) were established for a vegetation inventory of Haloxylon persicum and the herbaceous layer. The vegetation inventory included plant density, canopy coverage, height, and basal stem diameter of H. persicum . Allometric equations were established for H. persicum based on the biomass of 22 excavated trees, which were then applied to inventory data to provide stand estimates of aboveground biomass (AGB), belowground biomass (BGB), and total biomass (TB) of H. persicum. The AGB of the herbaceous layer was measured in subplots (1 × 1 m) and BGB was excavated and measured to a depth of 100 cm at 10-cm intervals. Our results indicated that the BGB-to-AGB ratio at the community level in the herbaceous layer increased notably along the gradient of declining groundwater depth. The depth of the soil horizon that contained 65% of the root surface area and 85% of the root biomass was shallower (0–2.5 m) in the deep end of the groundwater depth gradient than in the shallow end (0–3 m) of the gradient. H. persicum adjusted root distribution to capture water in the upper soil layers in response to the decline in groundwater depth. However, this adjustment was not sufficient to compensate for the decline in the water table: the BGB-to-AGB ratio showed no significant increase as AGB declined. On the contrary, herbaceous plants seemed better adapted to changes in the water table by effectively adjusting their BGB-to-AGB ratio. Use of BGB-to-AGB ratios that are specific to groundwater tables will significantly improve our estimates of BGB carbon stocks in these woodlands. Considering the scarcity of information on biomass stocks and partitioning in desert woodlands, our results might be applicable to other desert regions in Central Asia dominated by H. persicum .

To systematically review the efficacy and safety of Huoxiang Zhengqi Pills combined with Western medicine in the treatment of acute gastroenteritis. Four Chinese databases( CNKI,VIP,Wan Fang,Sino Med) and three English databases( Cochrane Library,Medline,EMbase) were systematically and comprehensively searched from the database establishment to April 2019 to collect the randomized controlled trials( RCTs) about the treatment of acute gastroenteritis with Huoxiang Zhengqi Pills combined with Western medicine. Two investigators independently performed literature screening,data extraction and bias risk assessment. Rev Man 5. 3 software was used for data analysis. A total of 316 articles were retrieved and finally 44 studies were included in this study,involving 4153 patients. The overall quality of the included studies was generally low. Meta-analysis results showed that in the total clinical effective rate,Huoxiang Zhengqi Pills combined with conventional treatment or norfloxacin tablets was superior to conventional treatment or norfloxacin tablets alone. In terms of the time for improving clinical symptoms,Huoxiang Zhengqi Pills combined with conventional treatment or norfloxacin tablets could better relieve fever than conventional treatment or norfloxacin tablets alone. In terms of incidence of adverse reactions,there was no statistical difference between Huoxiang Zhengqi Pills combined with conventional treatment and conventional treatment alone. Other outcome measures were affected by various factors( such as inclusion of only 1 study or excessive heterogeneity among studies) and could not be concluded. Due to the limitations of the quality and quantity of included studies,this conclusion still needs to be verified by more high quality researches.

Expert consensus statement on Diemailing Kudiezi Injection in clinical practice was approved on April 17,2019 by the Standardadization Office of the Chinese Association of Chinese Medicine. This project,which started in November 2017,has been developed and completed in accordance with the standard developing procedure. This paper will give a detailed introduction to the compilation process about the consensus. The aim is to enable readers to understand the background,purpose and basis of this consensus in a timely manner. Readers can learn about diffferent stages of develping process,including project management system,drafting,consulting,expert consensus,as well as current problems and shortcomings. Such an editorial explanation is just a dynamic follow-up of the whole consensus-making process. It also plays a good supervisory role in the whole consensus-making. It could be a guarantee for the quality of the consensus. There is no doubts that the editorial explanation is an important auxiliary document in the process of consensus-making. It is the extension and supplement of consensus content and a basis for fully understanding the technical content of this consensus. Therefore it is an indispensable document in the process of consensus-making.

To systematically review the effectiveness and safety of Kudiezi Injection in treating patients with acute cerebral infarction( ACI). Four Chinese databases( CNKI,VIP,Wan Fang,Sino Med),three English databases( Cochrane Library,EMbase,Medline)and Clinical Trail.gov were systematically and comprehensively retrieved. The retrieval time was from the establishment of each database to November 2017. Randomized controlled trials( RCTs) for the treatment of acute cerebral infarction with Kudiezi Injection were screened out according to pre-established inclusion criteria and exclusion criteria. The quality of the included studies was assessed using the Cochrane Risk Assessment Tool,and the included studies were put into descriptive analysis or Meta-analysis using the Rev Man 5. 3 software. A total of 932 articles were retrieved,and finally 14 studies were included. Except for 2 multi-arm trials,the total sample size was 1 244 in the experimental group and 638 in the control group. The overall quality of the included studies was not high. The results of Meta-analysis showed that Kudiezi + conventional therapy for acute cerebral infarction was superior to conventional therapy in total effective rate( RR = 0. 86,95% CI[0. 77,0. 96],P = 0. 006); Kudiezi + conventional therapy for acute cerebral infarction was superior to conventional therapy in serum inflammatory factors( MDhs-CRP=-3. 77,95% CI[-4. 17,-3. 37],P0. 000 01; MDIL-18=-16. 18,95% CI[-19. 26,-13. 11],P0. 000 01); Kudiezi + conventional therapy was superior to conventional therapy in Barthel index( MD = 12. 52,95%CI[8. 93,16. 10],P0. 000 01). Adverse reactions included in the study reports showed mild adverse reactions. Based on the results of this study,Kudiezi Injection combined with conventional therapy or other Western medicine had a certain curative effect on acute cerebral infarction,with no serious adverse reactions. However,due to the low quality of the included research methodology,the conclusions of this study were not recommended. In addition,in order to produce high-quality evidence for the clinical application of Kudiezi Injections,more randomized controlled trials with a large sample size,scientific design and strict implementation were required to study the effectiveness and safety of Kudiezi Injection in the treatment of cerebral infarction.

microRNAs (miRNAs) are small noncoding RNAs that could regulate post-transcription level through binding to 3' untranslated region (3'UTR) of target messenger RNAs (mRNAs), which were reported to be related with the incidence and development of diverse neoplasms. Among them, miR-197 was confirmed to play a vital role of oncogene or anti-oncogene in different cancers via targeting key tumorigenic or tumor-suppressive genes. Additionally, miR-197 had extensively been studied in carcinogenesis progression of cancers through various mechanisms, including apoptosis, proliferation, angiogenesis, metastasis, drug resistance and tumor suppressor, and also played a role in prognosis of cancers. In this review, we summarized the roles of miR-197 in cancers and considered it as a potentially novel biomarker for different cancers, offering an alternatively secure and effective tool in molecular targeting cancer treatment.

A disintegrin and metalloproteinase (ADAM) family members are known to process the target membrane-bound molecules through the quick induction of their protease activities under interaction with other molecules, which have diverse roles in tissue morphogenesis and pathophysiological remodeling. Among these, ADAM17 is a membrane-bound protease that sheds the extracellular domain of various receptors or its ligands from the cell membrane and subsequently activates downstream signaling transduction pathways. Importantly, breast cancer remains a mainspring of cancer-induced death in women, and numerous regulatory pathways have been implicated in the formation of breast cancer. Substantial evidence has demonstrated that an obvious increased in ADAM17 cell surface expression has been discovered in breast cancer and was shown to be associated with mammary tumorigenesis, invasiveness, and drug resistance. Over the last decades, it has received more than its share of attention that ADAM17 plays a potential role in breast cancer, including cell proliferation, invasion, angiogenesis, apoptosis, and trastuzumab resistance. In our review, we discuss the mechanisms through which ADAM17 acts on breast cancer tumorigenesis and progression. Thus, this will provide further impetus for exploiting ADAM17 as a new target for breast cancer treatment.

Liver X receptor (LXR) has been exploited widely as a drug target in breast cancer treatment, and various mechanisms underlying the effects of LXR in this area are well studied. The activated LXR plays important roles in estrogen receptor α (ERα) breast cancer cells, such as reducing cell proliferation and arresting cell cycle progression. Different LXR ligands have diverse effects on the development of breast cancer, such as the inhibitory effect of oxysterol, which can return cells to normocholesterol conditions and target other metabolic genes. Moreover, 27-hydroxycholesterol, a locally produced cholesterol metabolite, reportedly promotes the proliferation of ERα breast cancer cells in vitro and facilitates tumor metastasis with other LXR ligands. Moreover, the expression of LXR also exerts potential effects on immune surveillance, tumor immunity, and tumor microenvironment. These advances in breast cancer research indicate that LXR may be a new therapeutic target to treat the refractory or drug-resistant subtypes of breast cancer.

The biological behaviors of hepatocellular carcinoma (HCC) are complex mainly due to heterogeneity of progressive genetic and epigenetic mutations as well as tumor environment. Hepatocyte growth factor (HGF)/c-Met signaling pathway is regarded to be a prototypical example for stromal-epithelial interactions during developmental morphogenesis, wound healing, organ regeneration and cancer progression. And p53 plays as an important regulator of Met-dependent cell motility and invasion. Present study showed that 2 HCC cell lines, Hep3B and HepG2, displayed different invasive capacity when treated with HGF which was secreted by hepatic stellate cells (HSCs). We found that HGF promoted Hep3B cells invasion and migration as well as epithelial-mesenchymal transition (EMT) occurrence because Hep3B was p53 deficient, which leaded to the c-Met over-expression. Then we found that HGF/c-Met promoted Hep3B cells invasion and migration by upregulating Snail expression. In conclusion, HGF/c-Met signaling is enhanced by loss of p53 expression, resulting in increased ability of invasion and migration by upregulating the expression of Snail.

To evaluate the effectiveness and safety of Kudiezi injection in the treatment of angina pectoris of coronary heart disease. Four Chinese databases (CNKI, VIP, WanFang, and SinoMed) and three English databases (Cochrane Library, Medline, and ClinicalTrail.gov) were systematically and comprehensively searched from the establishment of each database to March 2018. Randomized controlled trials (RCTs) on the treatment of angina pectoris of coronary heart disease with Kudiezi injection (KDZ) were screened according to the pre-established inclusion criteria and exclusion criteria. The quality of the included studies was evaluated by using the ROB tool developed by the Cochrane Collaboration, and RevMan 5.3 software was used for Meta-analysis. A total of 712 articles were retrieved and finally 38 studies were included. The total sample size was 3 812 cases, 1 945 in the experimental group and 1 867 in the control group. The overall quality of the included studies was generally low. The results of Meta-analysis showed that: KDZ combined with conventional or western medicine was superior to conventional or western medicine alone in the effectiveness and electrocardiogram efficacy of angina pectoris and unstable angina. The descriptive analysis showed that KDZ combined with conventional treatment group was superior to conventional treatment group in agina pectoris associated indicators of angina pectoris and unstable angina. Other outcome measures were easily affected by various factors (such as too large heterogeneity of outcome indicators) and could not be concluded. Adverse reactions included in the study report were all mild adverse reactions and did not affect treatment. Based on the results of this study, it can be seen that Kudiezi injection had a certain effect on the treatment of angina pectoris of coronary heart disease, especially with significant positive effect on the improvement of the curative effect for angina pectoris and the effect of electrocardiogram. No serious adverse reactions occurred. However, due to the limited number of studies included, the generally low quality of the included studies, and the existence of published biases, the quality of the evidence in this study was low, so that caution should be taken to apply this conclusion. The effectiveness and safety of Kudiezi injection in the treatment of angina pectoris of coronary heart disease remained to be confirmed in the future with a well-designed and rigorous multi-center randomized controlled trials with standardized report, large sample, and enough follow-up time.

To systematically evaluate the efficacy and safety of breviscapine injection in the treatment of unstable angina pectoris (UAP). Eight electronic databases and clinical trials registries were searched to collect randomized controlled trials on breviscapine injection in the treatment of UAP. According to the evaluation standards in Cochrane Handbook 5.1, two independent reviewers screened out the literature, extracted data and assessed the quality of the studies included. RevMan 5.3 software was used for Meta quantitative analysis and corresponding description analysis. A total of 36 studies involving 3 058 patients were included, 1 552 cases in the trial group, 1 506 cases in the control group, 1 846 males and 1 212 females. All the clinical studies showed a low quality. Meta-analysis results showed that the combination of breviscapine injection and conventional therapy was superior to conventional therapy in angina pectoris efficacy (RRangina pectoris efficacy=1.29, 95%CI[1.23,1.35]

Previous studies concerning the association between aspirin use and breast cancer risk yielded inconsistent results. We aimed to investigate the association by meta-analysis. PubMed and EMBASE were searched for relevant studies. We calculated the summary relative risks (RR) and 95% confidence intervals (CI) using random-effects models. Seventeen cohort studies and 15 case–control studies were included. The overall result showed that aspirin use decreased risk of breast cancer (RR, 0.90; 95% CI, 0.85–0.95). However, there was evidence of publication bias and heterogeneity and the association disappeared after correction using the trim-and-fill method. When stratified by study design, a significant benefit for aspirin users was only found in population-based and hospital-based case–control studies but not in cohort or nest case–control studies. Further subgroup analyses showed that aspirin use could decrease risk of in situ breast tumors or hormone receptor–positive tumors and reduce risk of breast cancer in postmenopausal women. Aspirin use may not affect overall risk of breast cancer, but decrease risk of in situ breast tumors or hormone receptor–positive tumors and reduce risk of breast cancer in postmenopausal women. Considering between-study significant heterogeneity and publication bias, confirmation in future studies is also essential. Cancer Epidemiol Biomarkers Prev; 24(11); 1645–55. ©2015 AACR.

The major objective of this work was to establish a structural state-space model to estimate the dynamic origin-destination (O-D) matrices for urban rail transit network, using in- and out-flows at each station from automatic fare collection (AFC) system as the real time observed passenger flow counts. For lacking of measurable passenger flow information, the proposed model employs priori O-D matrices and travel time distribution from historical travel records in AFC system to establish the dynamic system equations. An arriving rate based on travel time distribution is defined to identify the dynamic interrelations between time-varying O-D flows and observed flows, which greatly decreases the computational complexity and improve the model’s applicability for large-scale network. This methodology is tested in a real transit network from Beijing subway network in China through comparing the predicted matrices with the true matrices. Case study results indicate that the proposed model is effective and applicative for estimating dynamic O-D matrices for large-scale rail transit network.