In Vitro Insights into the Role of 7,8-Epoxy-11-Sinulariolide Acetate Isolated from Soft Coral Sinularia siaesensis in the Potential Attenuation of Inflammation and Osteoclastogenesis.

The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is essential for the process of bone remodeling. Excessive osteoclast differentiation plays a pivotal role in the pathogenesis of bone diseases such as rheumatoid arthritis and osteoporosis. In the present study, we examined whether 7,8-epoxy-11-sinulariolide acetate (Esa), a marine natural product present in soft coral Sinularia siaesensis, attenuates inflammation and osteoclastogenesis in vitro. The results indicated that Esa significantly inhibited lipopolysaccharide (LPS)-induced inflammation model of RAW264.7 cells and suppressed receptor activator for nuclear factor-κB ligand (RANKL)-triggered osteoclastogenesis. Esa significantly down-regulated the protein expression of iNOS, COX-2, and TNF-α by inhibiting the NF-κB/MAPK/PI3K pathways and reducing the release of reactive oxygen species (ROS) in RAW264.7 macrophages. Besides, Esa treatment significantly inhibited osteoclast differentiation and suppressed the expression of osteoclast-specific markers such as NFATC1, MMP-9, and CTSK proteins. These findings suggest that Esa may be a potential agent for the maintenance of bone homeostasis associated with inflammation.

Chemistry, Chemo-Ecology, and Biological Activities of Uncommon and Structurally Diverse Sesquiterpenoids from the Sanya Bay Nudibranch Hexabranchus sanguineus.

A detailed chemical investigation of the Sanya Bay nudibranch Hexabranchus sanguineus yielded thirteen new sesquiterpenoids, namely sanyagunins A-H, sanyalides A-C, and sanyalactams A and B, along with eleven known related ones. Sanyalactams A and B feature an unprecedented hexahydrospiro[indene-2,3'-pyrrolidine] core. The structures of new compounds were established by a combination of extensive spectroscopic data analysis, quantum mechanical-nuclear magnetic resonance methods, the modified Mosher's method, and X-ray diffraction analysis. Based on analysis of NOESY correlations and the modified Mosher's method, the stereochemistry of two known furodysinane-type sesquiterpenoids were revised. A plausible biogenetic relationship between these sesquiterpenoids wasproposed and discussed, and a chemo-ecological relationship of the title animal and its possible sponge preys has been analyzed. In bioassays, sanyagunin B showed moderate antibacterial activity, whereas 4α-formamidogorgon-11-ene exhibited potent cytotoxicity with IC50 values ranging from 0.87 to 1.95 µM.

Guided Isolation of An Uncommon Cembranoid Orthoester, Sarcotortin A, and Three Skeletal Diverse Terpenoids from the Hainan Soft Coral Sarcophyton tortuosum Based on Molecular Networking Strategy.

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.

New Antibacterial Diterpenoids from the South China Sea Soft Coral Klyxum molle.

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.

Structurally Diverse Diterpenes from the South China Sea Soft Coral Sarcophyton trocheliophorum.

The present investigation of the South China Sea soft coral Sarcophyton trocheliophorum resulted in the discovery of six new polyoxygenated diterpenes, namely sartrocheliols A-E (1, 3, 5-8) along with four known ones, 2, 4, 9, and 10. Based on extensive spectroscopic data analysis, sartrocheliol A (1) was identified as an uncommon capnosane diterpene, while sartrocheliols B-E (3, 5-8) were established as cembrane diterpenes. They displayed diverse structural features not only at the distinctly different carbon frameworks but also at the various types of heterocycles, including the epoxide, γ-lactone, furan, and pyran rings. Moreover, their absolute configurations were determined by a combination of quantum mechanical-nuclear magnetic resonance (QM-NMR) approach, modified Mosher's method, and X-ray diffraction analysis. In the anti-tumor bioassay, compound 4 exhibited moderate cytotoxic activities against A549, H1975, MDA-MB-231, and H1299 cells with the IC50 values ranging from 26.3 to 47.9 µM.

Oxygenated Cembrane Diterpenes from the South China Sea Soft Coral Sinularia tumulosa.

The chemical investigation of the rarely studied soft coral Sinularia tumulosa resulted in the discovery of five oxygenated cembrane diterpenes 1-5, including two new compounds situmulins A (1) and B (2). The structures of 1 and 2 were established through the extensive analyses of 1D and 2D NMR spectral data together with the comparisons with the known compounds. Furthermore, the absolute configuration of 1 was determined by the time-dependent density functional theory (TDDFT) ECD approach, while the relative configuration of 2 was assigned via the quantum mechanical-NMR (QM-NMR) calculations. It might be worth to point out it is the first time to disclose the presence of cembrane diterpenes in the title species. In the bioassays, compound 2 not only showed strong antibacterial activities against fish pathogenic bacteria Streptococcus parauberis FP KSP28 and Phoyobacterium damselae FP2244 with both minimum inhibitory concentration for 90 % (MIC90 ) values of 25 µM, but also demonstrated substantial inhibitory efficacy against vancomycin-resistant Enterococcus faecium bacteria G1, G4, G7, G8 and G13 from several individuals, with MIC90 values of 25, 50, 100, 50 and 25 µM, respectively.

Two New Cembranoids from the Chinese Soft Coral Sarcophyton boettgeri.

Two new cembranoids, namely sarcoboettgerols D and E, together with four known related ones, have been isolated from the soft coral Sarcophyton boettgeri collected from Weizhou Island in the South China Sea. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance methods, time-dependent density functional theory-electronic circular dichroism calculations, as well as comparison with the reported data in the literature. A plausible biogenetic relationship of four cembranoids was proposed. In bioassays, sarcomililatin B exhibited cytotoxic activity against H1299 cell (IC50 =35.0 µM), whereas sarcomililatin B and sarcomililatin A displayed moderate antibacterial activities (MIC 17.4-34.8 µg/mL).

Antitumor Cembrane Diterpenoids from the South China Sea Soft Coral Lobophytum sp.

Two new highly functionalized cembrane diterpenoids named ximaolobophytolides A (1) and B (2) as minor components, together with seven related known compounds (3-9), have been isolated and identified from the Ximao soft coral Lobophytum sp. They were characterized by the presence of an α-methylene-γ-lactone moiety. Based on the comprehensive analyses of 1D and 2D NMR spectroscopic data, the absolute configurations of these two new compounds were elucidated by the combination of quantum mechanical (QM)-NMR and time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculation approaches. In the anti-tumor bioassays, compounds 3-9 showed moderate to significant inhibitory effects (IC50 values ranging from 29.66 to 0.39 µM) against the proliferations of five tumor cells HEL, A549, H1975, MDA-MB-231, and H1299. It might be worthy to point out that compounds 4, 7, and 8 exhibited better anti-tumor activities than that of the positive control Doxorubicin.

Two new compounds from the Hainan Soft Corals Sinularia tumulosa and Sinularia depressa with their anti-inflammatory or cytotoxic activities.

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.

Four New Diterpenoids from the South China Sea Soft Coral Sinularia nanolobata and DFT-Based Structure Elucidation.

Three new cembranoids (1-3) and a new casbanoid (4), along with three known analogues (5-7), have been isolated from the soft coral Sinularia nanolobata collected off Ximao Island. The structures, including the absolute configurations of new compounds, were established using extensive spectroscopic data analysis, time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculations, and the comparison with spectroscopic data of known compounds. In the in vitro bioassay, compounds 1 and 5 exhibited moderate cytotoxic activities against human erythroleukemia (HEL) cell lines, with IC50 values of 37.1 and 42.4 µM, respectively.

[Exploring efficacy of Chinese medicine injection for promoting blood circulation and removing blood stasis in treatment of acute cerebral infarction based on two complex network analysis methods].

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.

Long noncoding RNA TCL6 binds to miR-106a-5p to regulate hepatocellular carcinoma cells through PI3K/AKT signaling pathway.

Long noncoding RNAs (lncRNAs) have been reported to dysregulate and involve in the pathology of hepatocellular carcinoma (HCC). Nonetheless, the functional role of lncRNA T cell leukemia/lymphoma 6 (TCL6) and its underlying mechanism in HCC remain unclear. Herein, we analyzed the expression of TCL6 and elucidated its mechanistic involvement in HCC. Bioinformatics analyses indicated TCL6 was evidently downregulated in HCC tissues compared with normal controls. TCL6 was downregulated while microRNA-106a-5p (miR-106a-5p) was upregulated in HCC cell lines. Moreover, knockdown or overexpression of TCL6 significantly raised or diminished the expression level of miR-106a-5p in HCC cells, similar to the effect of miR-106a-5p on TCL6 expression. Functionally, TCL6 inhibited the proliferative, migratory, and invasive potentials of HCC cells as analyzed by cell counting kit-8, scratch wound healing, and transwell assays, respectively. Conversely, miR-106a-5p exerted an opposite effect on the proliferative, migratory, and invasive potentials of HCC. RNA immune precipitation and luciferase reporter assays revealed TCL6 directly bound to miR-106a-5p and luciferase reporter assay verified phosphatase and tensin homolog (PTEN) was a target gene of miR-106a-5p. Mechanistically, TCL6 knockdown evidently reduced PTEN expression at both messenger RNA and protein levels, and miR-106a-5p inhibitor partially rescued this reduction effect in HCC cells. Additionally, western blot assays demonstrated miR-106a-5p downregulation or TCL6 overexpression promoted the protein level of PTEN, and suppressed the phosphorylation level of AKT, the protein level of phosphatidylinositol 3-kinase (PI3K). Collectively, these results revealed TCL6 as a tumor-suppressive lncRNA regulates PI3K/AKT signaling pathway via directly binding to miR-106a-5p in HCC. This mechanism provides a theoretical basis for HCC pathogenesis and a potential therapeutic strategy for HCC treatment.

[Network Meta-analysis of oral Chinese patent medicine in treatment of acute cerebral infarction].

The efficacy of oral Chinese patent medicine in the treatment of acute cerebral infarction was systematically evaluated by network Meta-analysis. The literature search was conducted in three English databases(Medline, EMbase and Cochrane Library) and four Chinese databases(CNKI, VIP, WanFang and SinoMed) from inception to June 2018, and the randomized controlled trials of acute cerebral infarction were screened out according to the pre-set criteria. Two reviewers independently screened out the literature by using pre-specified eligibility criteria, and assessed the quality of included studies according to the risk of bias tool of Cochrane Handbook 5.1.0. Data analysis was conducted by using Stata 13.0 and WinBUGS 1.4.3 software. Finally, 52 RCT were included, involving 11 kinds of oral Chinese patent medicines. The results of the network Meta-analysis showed that in terms of the total effective rate, the order of efficacy was as follows: Naomaitai Capsules>Xiaoshuan Changrong Capsules>Angong Niuhuang Pills>Yangxue Qingnao Granules>Compound Danshen Dripping Pills>Naoxintong Capsules>Tongxinluo Capsules>Naoxueshu Oral Liquid>Zhuyu Tongmai Capsules>Yinxingye Tablets>Compound Danshen Tablets; in terms of neurological deficit scores, the order of efficacy was: Tongxinluo Capsules>Angong Niuhuang Pills>Compound Danshen Dripping Pills>Xiaoshuan Changrong Capsules>Yangxue Qingnao Granules>Zhuyu Tongmai Capsules>Naoxintong Capsules>Naoxueshu Oral Liquid; in terms of Barthel index score, the order of efficacy was: Xiaoshuan Changrong Capsules>Naomaitai Capsules>Naoxueshu Oral Liquid>Angong Niuhuang Pills>Tongxinluo Capsules>Zhuyu Tongmai Capsules. Although different oral Chinese patent medicines can improve these outcomes, the difference in efficacy ranking was relatively large. Because of the small number and low quality of research literature, the conclusion still needs to be proved by multi-center, large-sample, and double-blind randomized trials.

[Systematic review and Meta-analysis of efficacy and safety of Xiangsha Yangwei Pills in treatment of chronic gastritis].

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.

[Systematic review and trail sequential analysis of preparation of Xiakucao for Hashimoto's thyroiditis].

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.

[Network Meta-analysis of randomized controlled trials of Chinese patent medicine for bradyarrhythmia].

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 Liquid>Shensong Yangxin Capsules>Xinbao Pills>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 Liquid>Shensong Yangxin Capsules>Xinbao Pills>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.

[Analysis of status quo of RCT outcome indexes in treatment of acute ischemic stroke with traditional Chinese medicine].

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.

[Efficacy and safety of Breviscapine Injection in treatment of diabetic nephropathy: systematic review and Meta-analysis of randomized controlled trials].

This study aimed to systematically evaluate the efficacy and safety of Breviscapine Injection in the treatment of diabetic nephropathy( DN). Eight electronic databases and Clinical Trials.gov were searched to collect randomized controlled trials on Breviscapine Injection in the treatment of DN. According to the Cochrane Handbook 5. 1,two independent reviewers screened out the literatures,extracted data and assessed the quality of the studies included. Rev Man5. 3 software was used for the data analysis. A total of 29 studies containing 37 trials were included,involving 2 097 patients,1 054 cases in test groups and 1 043 cases in control groups. The clinical studies included had a low overall quality. According to Meta-analysis: ①Conventional therapy plus breviscapine injection was superior to conventional therapy in total efficiency rate,24 h UTP,SCR,BUN,UEAR,ALB and m ALB during DN stage Ⅲ( RRtotal effective rate=1. 60,95%CI [1. 32,1. 93],P<0. 000 01; SMD24 h UTP=-1. 21,95%CI[-1. 56,-0. 87],P<0. 000 01; MDSCR=-6. 33,95%CI[-9. 20,-3. 46],P<0. 000 1; MDBUN=-6. 6,95%CI[-1. 10,-0. 22],P = 0. 003; MDUEAR=-20. 30,95%CI [-28. 14,-12. 46],P<0. 000 01; MDALB= 0. 47,95%CI[0. 42,0. 52],P<0. 000 01; MDmALB=-10. 03,95%CI[-10. 62,-9. 46],P<0. 000 01). ②Conventional therapy plus Breviscapine Injection was better than conventional therapy in total efficiency rate( only 1 study),24 h UTP,SCR and BUN during DN stage Ⅳ( RRtotal effective rate= 1. 57,95% CI[1. 10,2. 25],P = 0. 01; SMD24 h UTP=-0. 52,95% CI [-0. 71,-0. 33],P<0. 000 01; MDSCR=-35. 38,95%CI[-48. 57,-22. 19],P<0. 000 01; MDBUN=-1. 89,95%CI [-3. 01,-0. 77],P<0. 000 01). ③Conventional therapy plus Breviscapine Injection was better than conventional therapy in SCR( MD =-26. 35,95% CI[-47. 45,-5. 24],P= 0. 01),but with no significant difference in 24 h UTP,BUN and ALB during DN stageⅤ. ④It was impossible to obtain the specific judgment information on the adverse reactions of Breviscapine Injection in the treatment of the disease from the existing evidences. The current evidences suggest that the combination of Breviscapine Injection and conventional therapy had a certain curative effect in the treatment of DN,especially in stages Ⅲ and Ⅳ. The safety of Breviscapine Injection needs to be further explored.Because the low quality of the study impacted the accuracy of the result,more rigorous,high-quality,multi-center,randomized doubleblind controlled trials are required to increase the support of the evidences in the future.

[Editorial explanation for Expert consensus statement on Diemailing Kudiezi Injection in clinical practice].

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.

[Meta-analysis of randomized controlled trials on effect of Tanreqing Injection combined with Western medicine on acute exacerbation of chronic bronchitis].

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 Handbook'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],P<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],P < 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.