Problems and thoughts in clinical safety evaluation of traditional Chinese medicine / 中国中药杂志

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Evaluation methods of clinical efficacy of traditional Chinese medicine / 中国中药杂志

Clinical efficacy is the basis for the development of traditional Chinese medicine(TCM), and the evaluation of clinical efficacy of TCM has always been the focus of attention. The technical and methodological difficulties in the evaluation process often restrict the generation of high-level evidence. Therefore, methodological research should be deepened and innovative practice should be carried out to study the application of scientific research methods in the evaluation of the advantages of TCM. After more than ten years of development, the clinical efficacy evaluation of TCM, on the basis of the initially classic placebo randomized controlled trials, has successively carried out a series of meaningful attempts and explorations in N-of-1 trials, cohort studies, case-control studies, cross-sectional studies, real world studies, narrative medicine studies, systematic evaluation, and other aspects, laying the foundation for the transformation of TCM from "experience" to "evidence". This paper focused on the clinical efficacy evaluation of TCM, summarized the main connotation and development status of efficacy evaluation indicators, standards, and methods, and put forward corresponding countermeasures and suggestions for the problems of indicator selection, standard formulation, and methodology optimization in the research process. It is clear that scientific and objective evaluation of the efficacy of TCM is an urgent problem to be solved at present.

Strategy and challenge of innovative drug research and development from clinically effective ingredients of traditional Chinese medicine / 中国中药杂志

Novel drug discovery from the active ingredients of traditional Chinese medicine is the most distinctive feature and advantageous field of China, which has provided an unprecedented opportunity. However, there are still problems such as unclear functional substance basis, action targets and mechanism, which greatly hinder the clinical transformation of active ingredients in traditional Chinese medicine. Based on the analysis of the current status and progress of innovative drug research and development in China, this paper aimed to explore the prospect and difficulties of the development of natural active ingredients from traditional Chinese medicine, and to explore the efficient discovery of trace active ingredients in traditional Chinese medicine, and obtain drug candidates with novel chemical structure, unique target/mechanism and independent intellectual property rights, in order to provide a new strategy and a new model for the development of natural medicine with Chinese characteristics.

Role and mechanism of miR-548-3p/ DAG1 in the occurrence and malignant transformation of laryngeal carcinoma / Papel y mecanismo de miR-548-3p/DAG1 en la aparición y transformación maligna del carcinoma de laringe

Abstract The AMC-HN-8 cell line and the primary human laryngeal epithelial cell lines were utilized in this work to explore the molecular mechanism of miR-548-3p regulating the gene DAG1 to induce the occurrence and malignant transformation of laryngeal carcinoma. Non-coding RNA miR-548- 3p overexpression plasmid, interference plasmid and blank plasmid were constructed, and the plasmids were transfected into AMC-HN-8 cells, respectively. Meanwhile, a non-transfected plasmid group and a human laryngeal epithelial primary cell group were set up. Five groups of cells were named as NC (Normal control), Model, Ov-miR-548-3p, Sh-miR-548-3p and Blank-plasmid group. The luciferase reporter experiment was used to analyze the regulation characteristics of hsa-miR-548-3p on dystrophin-associated glycoprotein 1 (DAG1). Immunofluorescence was used to analyze the relative expression characteristics of the protein DAG1. The cell cloning experiment was used to analyze the proliferation characteristics of AMC-HN-8. The scratch healing test was used to analyze the migration ability of AMC-HN-8. The transwell test was used to analyze the invasion ability of AMC-HN-8. The RT-PCR was used to analyze the expression level of miR-548-3p. Western blot experiments were used to analyze the expression of protein DAG1, laminin α2 (LAMA2) and utrophin (UTRN). The luciferase report experiment and immunofluorescence test found that the expression of DAG1 and miR-548-3p are positively correlated. Cell cloning, scratching and migration experiments identified that the activity of laryngeal cancer cells was positively correlated with the expression of DAG1. The results of Western blot analysis further strengthened the above conclusions. Through carrying out research on the cellular levels, our work has demonstrated that miR-548-3p regulated the content of protein DAG1, and then further induced malignant transformation of laryngeal carcinoma.

Resumen En este trabajo se utilizaron la línea celular AMC-HN-8 y la línea celular epitelial laríngea humana primaria, para explorar el mecanismo molecular regulador del miR-548-3p sobre el gen DAG1 para inducir la aparición y la transformación maligna del carcinoma laríngeo. Se construyeron el plásmido de sobreexpresión de miR-548-3p de ARN no codificante, el plásmido de interferencia y el plásmido en blanco, y los plásmidos se transfectaron en células AMCHN-8 respectivamente. Mientras tanto, se establecieron un grupo de plásmidos no transfectados y un grupo de células primarias epiteliales laríngeas humanas. Se nombraron cinco grupos de células como NC (control normal), modelo, OvmiR-548-3p, Sh-miR-548-3p y grupo de plásmido en blanco. El experimento indicador de luciferasa se utilizó para analizar las características de regulación de hsa-miR-548-3p en la glicoproteína 1 asociada a distrofina (DAG1). Se utilizó inmunofluorescencia para analizar las características de expresión relativa de la proteína DAG1. El experimento de clonación celular se utilizó para analizar las características de proliferación de AMC-HN-8. Se utilizó la prueba de cicatrización por rascado para analizar la capacidad de migración de AMC-HN-8. La prueba de transwell se utilizó para analizar la capacidad de invasión de AMCHN-8. Se utilizó RT-PCR para analizar el nivel de expresión de miR-548-3p. Se usó un experimento de transferencia Western (Western blot) para analizar las expresiones de la proteína DAG1, laminina α2 (LAMA2) y utrofina (UTRN). El experimento de reporte de luciferasa y la prueba de inmunofluorescencia encontraron que la expresión de DAG1 y miR-548-3p están positivamente correlacionadas. Los experimentos de clonación celular, rascado y migración, identificaron que la actividad de las células cancerosas de laringe se correlacionó positivamente con la expresión de DAG1. Los resultados del análisis de transferencia Western fortalecieron aún más las conclusiones anteriores. A través de la investigación a nivel celular, nuestro proyecto ha demostrado que miR-548-3p regula el contenido de la proteína DAG1 y luego induce la transformación maligna del carcinoma de laringe.

Discovery of a small-molecule inhibitor of carbamoyl phosphate synthase 1 and its anti-colorectal cancer mechanism / 药学学报

The carbamoyl phosphate synthase 1 (CPS1) enzyme is involved in the first phase of the urea cycle, providing a prerequisite molecule for pyrimidine synthesis, as well as promoting tumor cell proliferation and growth. Studies have found that CPS1 is highly expressed in a variety of tumors, including colorectal cancer, lung cancer, etc. and its overexpression is related to the poor prognosis of tumors. Thus, small molecules targeted to inhibit the function of CPS1 in tumors may provide therapeutic benefits for cancer patients who overexpress CPS1. In this study, the function of CPS1 was investigated in vitro, and we found that overexpression of CPS1 can enhance the migration ability of colorectal cancer cells HCT15. Here, based upon the existing crystal structure, combined with high-throughput virtual screening, we obtained 8 candidate small molecule compounds. In vitro activity evaluation, we found that compound 3 has good anti-HCT15, HCT116 cell proliferation activity (HCT15, IC50, 7.69 ± 1.10 μmol‧L-1, HCT116, IC50, 13.53 ± 0.46 μmol‧L-1). Subsequently, molecular docking and molecular dynamics (MD) simulation analysis showed that, compound 3 could target and inhibit the activity of CPS1. In vitro studies showed that compound 3 could inhibit the migration of HCT15 cells, as well as induced cell cycle arrest and apoptosis. Taken together, this study found that compound 3 is a potential small molecule inhibitor that targets CPS1, which provides the experimental basis and theoretical basis for the development of targeted intervention small molecule therapeutic drugs. Based upon the chemical structure of compound 3, we will shed new light on further optimizing its activity and therapeutic potential, which may provide a therapeutic benefit to the patients with CPS1-related tumors.

Genomic Epidemiology of Imported Cases of COVID-19 in Guangdong Province, China, October 2020 - May 2021 / 生物医学与环境科学（英文）

Objective@#The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been engendering enormous hazards to the world. We obtained the complete genome sequences of SARS-CoV-2 from imported cases admitted to the Guangzhou Eighth People's Hospital, which was appointed by the Guangdong provincial government to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 diversity was analyzed, and the mutation characteristics, time, and regional trend of variant emergence were evaluated.@*Methods@#In total, 177 throat swab samples were obtained from COVID-19 patients (from October 2020 to May 2021). High-throughput sequencing technology was used to detect the viral sequences of patients infected with SARS-CoV-2. Phylogenetic and molecular evolutionary analyses were used to evaluate the mutation characteristics and the time and regional trends of variants.@*Results@#We observed that the imported cases mainly occurred after January 2021, peaking in May 2021, with the highest proportion observed from cases originating from the United States. The main lineages were found in Europe, Africa, and North America, and B.1.1.7 and B.1.351 were the two major sublineages. Sublineage B.1.618 was the Asian lineage (Indian) found in this study, and B.1.1.228 was not included in the lineage list of the Pangolin web. A reasonably high homology was observed among all samples. The total frequency of mutations showed that the open reading frame 1a (ORF1a) protein had the highest mutation density at the nucleotide level, and the D614G mutation in the spike protein was the commonest at the amino acid level. Most importantly, we identified some amino acid mutations in positions S, ORF7b, and ORF9b, and they have neither been reported on the Global Initiative of Sharing All Influenza Data nor published in PubMed among all missense mutations.@*Conclusion@#These results suggested the diversity of lineages and sublineages and the high homology at the amino acid level among imported cases infected with SARS-CoV-2 in Guangdong Province, China.

Molecular Mechanism of Resveratrol Against NAFLD Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo predict the molecular mechanism of resveratrol against non-alcoholic fatty liver disease （NAFLD） based on network pharmacology and molecular docking and verify the results on the liver cell model induced by PM2.5 exposure. MethodThe targets of resveratrol were screened out from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform （TCMSP）， PubChem， DrugBank， and SwissTargetPrediction， and the potential targets of NAFLD were retrieved from Comparative Toxicogenomics Database （CTD）， DisGeNET， GeneCards， and Online Mendelian Inheritance in Man （OMIM）. Then the common targets were obtained. STRING 11.5 was used to construct the protein-protein interaction （PPI） network of the common targets. Cytoscape 3.8.2 was used to plot the “target-pathway” network， and the core modules and key targets were selected. Metascape was adopted for Gene Ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of common targets. SYBYL-X 2.0 was used for molecular docking of resveratrol to key targets. Finally，cell apoptosis and the expression of apoptosis-related proteins were detected by flow cytometry and Western blot in the PM2.5-exposed human liver cell line （HepG2）. ResultA total of 115 common targets of resveratrol and NAFLD were obtained. The key targets included tumor necrosis factor （TNF）， B-cell lymphoma-2 （Bcl-2）， and cysteinyl aspartate-specific protease-3（Caspase-3）. As revealed by KEGG enrichment analysis， 174 signaling pathways， represented by the apoptosis and TNF signaling pathways， were obtained. Molecular docking results showed that resveratrol had strong binding activities to Bcl-2 and Caspase-3. Furthermore，the results of flow cytometry and Western blot demonstrated that resveratrol inhibited cell apoptosis of PM2.5-exposed HepG2 cells by regulating the protein expression of Bcl-2 and Caspase-3. ConclusionResveratrol can treat NAFLD in a multi-pathway and multi-target way. It mainly inhibits liver cell apoptosis by affecting the expression of Bcl-2 and Caspase-3， which provides a theoretical basis for the follow-up research on the anti-NAFLD mechanism of resveratrol.

Kinetic Characteristics of Neutralizing Antibody Responses Vary among Patients with COVID-19 / 生物医学与环境科学（英文）

Objective@#The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).@*Methods@#In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2.@*Results@#NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective.@*Conclusion@#We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.

Discovery of a small-molecule activator of beclin-1 that induces autophagy-associated cell death and apoptosis in triple negative breast cancer / 药学学报

Autophagy is a lysosomal degradation pathway, and plays a crucial role in cellular homeostasis, development, immunity, tumor suppression, metabolism, prevention of neurodegeneration, and lifespan extension. Thus, pharmacological stimulation of autophagy may be an effective approach for preventing or treating certain human diseases and/or aging. Here, combined with allosteric site identification methods, high-throughput virtual screening, and in vitro activity evaluation, we found that compound 10 can activate autophagy and has good anti-MDA-MB-231 cell proliferation activity (the half maximal inhibitory concentration IC50 = 8.25 ± 1.53 μmol·L-1). Subsequently, molecular docking, molecular dynamics simulation, and immunoblotting assay demonstrate that compound 10 can target and activate beclin-1. In vitro studies have shown that compound 10 can induce autophagy-associated cell death in MDA-MB-231 cells. In addition, it was found that compound 10 can induce apoptosis in MDA-MB-231 cells. Taken together, we identified the candidate compound 10 as an effective and selective targeting beclin-1 to activate autophagy as a lead compound, which provide a reference for further development and optimization of small molecule drugs targeting beclin-1 to activate autophagy for clinical treatment.

Systematic review of efficacy and safety of Compound Danshen Injection combined with Western medicine in treatment of vascular dementia / 中国中药杂志

To evaluate the efficacy and safety of Compound Danshen Injection combined with Western medicine in the treatment of vascular dementia. Databases of Cochrane Library, PubMed, EMbase, CNKI, SinoMed, VIP, Wanfang Data were electronically retrieved for collecting randomized controlled trial(RCT)about vascular dementia treated with Western medicine alone or combined with Compound Danshen Injection from the year of database establishment to January 2020. Two researchers independently screened out li-teratures, extracted data, and evaluated the risk of bias for inclusion in the study. Meta-analysis was conducted using RevMan 5.3 software. A total of 5 RCTs were included, involving 588 patients, with 299 in treatment group and 289 in control group. Meta-analysis results showed that compared with Western medicine alone, Compound Danshen Injection combined with Western medicine was better in the effective rate(RR=1.23,95%CI[1.14,1.33],P<0.000 01), MMSE score(MD=3.54,95%CI[3.01,4.06],P<0.000 01), ADL score(MD=11.49,95%CI[8.05,14.93],P<0.000 01), the level of CRP(MD=-0.72,95%CI[-1.25,-0.20],P=0.007) and the level of IL-6(MD=-7.64,95%CI[-9.65,-5.63],P<0.000 01). Adverse reactions mainly included rash and skin prick, which did not affect the treatment effect. Based on the findings, the combination of Compound Danshen Injection in the treatment of vascular dementia could improve the effective rates, relieve the mental state damage and improve the daily living ability, with mild adverse reactions and a low incidence. However, due to the low quality of the included literatures, high-quality and large-scale randomized controlled trials are needed for further verification.

Differential analysis of different study types in clinical safety evaluation of Xuebijing Injection / 中国中药杂志

This study aimed to comprehensively analyze and compare the differences of different clinical study types currently published in the safety evaluation of Xuebijing Injection. Six databases, namely the Cochrane Library, PubMed, EMbase, CNKI, VIP and Wanfang database, were electronically retrieved to collect all types of studies on the safety of Xuebijing Injection, including randomized controlled trials, case-controlled studies, cohort studies, systematic reviews, and centralized monitoring studies of clinical safety(hospital), in order to comprehensively and objectively evaluate the safety of Xuebijing Injection, and analyze the differences of different research results. A total of 211 literatures were included, involving a total of 46 384 patients treated with Xuebijing Injection, and 423 adverse reactions(ADRs) occurred. They included 191 randomized controlled trials, 3 cohort studies, 15 systematic reviews, and 2 centralized monitoring studies of clinical safety(hospital), and the incidence of adverse reactions was 2.54%(common), 2.31%(common), 0.95%(occasionally), and 0.50%(occasionally). More than half of the 423 cases of ADRs occurred in skin and adnexal system(151 cases) and gastrointestinal system(65 cases), including such manifestations as rash, skin itching, nausea and vomiting, diarrhea. The degree of ADRs was mild. Randomized controlled trials showed that the incidence of ADR was the highest when Xuebijing Injection was used for malignant tumor and multiple organ failure. And the systematic evaluation showed that the incidence of ADR was the highest when Xuebijing Injection was used for spontaneous peritonitis of liver cirrhosis. In conclusion, different study types could lead to significant differences in the results of drug safety evaluation. Sample size, study type, and quality control are the main factors for biased results. Due to large sample size and high-quality, centralized monitoring studies become the better clinical safety evaluation model of drugs at present, and full life cycle management could more objectively reflect drug safety and guide clinical rational drug use.

Evaluating continence recovery time after robot-assisted radical prostatectomy / 北京大学学报(医学版)

OBJECTIVE@#To evaluate urinary continence recovery time and risk factors of urinary continence recovery after robot-assisted laparoscopic radical prostatectomy (RARP).@*METHODS@#From January 2019 to January 2021, a consecutive series of patients with localized prostate cancer (cT1-T3, cN0, cM0) were prospectively collected. RARP with total anatomical reconstruction was performed in all the cases by an experienced surgeon. Lymph node dissection was performed if the patient was in high-risk group according to the D'Amico risk classification. The primary endpoint was urinary continence recovery time after catheter removal. Postoperative and pathological variables were analyzed. Continence was rigo-rously analyzed 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after catheter removal. Continence was evaluated by recording diaper pads used per day, and all the patients were instructed to perform the 24-hour pad weight test until full recovery of urinary continence. The patient was defined as continent if no more than one safety pad were needed per day, or no more than 20-gram urine leakage on the 24-hour pad weight test. Time from catheter removal to full recovery of urinary continence was recorded, and risk factors influencing continence recovery time evaluated.@*RESULTS@#In total, 166 patients were analyzed. The mean age of the enrolled patients was 66.2 years, and the median prostate specific antigen (PSA) was 8.51 μg/L. A total of 59 patients (35.5%) had bilateral lymphatic dissection, and 28 (16.9%) underwent neurovascular bundle (NVB) preservation surgery. Postoperative pathology results showed that stage pT1 in 1 case (0.6%), stage pT2 in 77 cases (46.4%), stage pT3 in 86 cases (51.8%), and positive margins in 28 patients (16.9%). Among patients who underwent lymph node dissection, lymph node metastasis was found in 7 cases (11.9%). Median continence recovery time was one week. The number of the continent patients at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 65 (39.2%), 32 (19.3%), 34 (20.5%), 24 (14.5%), and 9 (5.4%). Two patients remained incontinent 24 weeks after catheter removal. The continence rates after catheter removal at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 39.2%, 58.4%, 78.9%, 93.4%, and 98.8%, respectively. Univariate COX analysis revealed that diabetes appeared to influence continence recovery time (OR=1.589, 95%CI: 1.025-2.462, P=0.038). At the end of 48 hours, 4 weeks, 12 weeks, and 24 weeks after catheter removal, the mean OABSS score of the continent group was significantly lower than that of the incontinent group.@*CONCLUSION@#RARP showed promising results in the recovery of urinary continence. Diabetes was a risk factor influencing continence recovery time. Bladder overactive symptoms play an important role in the recovery of continence after RARP.

Sodium tanshinone IIA sulfonate prevents radiation-induced damage in primary rat cardiac fibroblasts / 中国天然药物

This study investigated the effects of X-ray irradiation on primary rat cardiac fibroblasts (CFs) and its potential mechanism, as well as whether sodium tanshinone IIA sulfonate (STS) has protective effect on CFs and its possible mechanism. Our data demonstrated that X-rays inhibited cell growth and increased oxidative stress in CFs, and STS mitigated X-ray-induced injury. Enzyme-linked immuno-sorbent assay showed that X-rays increased the levels of secreted angiotensin II (Ang II) and brain natriuretic peptide (BNP). STS inhibited the X-ray-induced increases in Ang II and BNP release. Apoptosis and cell cycle of CFs were analyzed using flow cytometry. X-rays induced apoptosis in CFs, whereas STS inhibited apoptosis in CFs after X-ray irradiation. X-rays induced S-phase cell cycle arrest in CFs, which could be reversed by STS. X-rays increased the expression of phosphorylated-P38/P38, cleaved caspase-3 and caspase-3 as well as decreased the expression of phosphorylated extracellular signal-regulated kinase 1/2 (ERK 1/2)/ERK 1/2 and B cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein (BAX) in CFs, as shown by Western blotting. STS mitigated the X-ray radiation-induced expression changes of these proteins. In conclusion, our results demonstrated that STS may potentially be developed as a medical countermeasure to mitigate radiation-induced cardiac damage.

Urgency of clinical evaluation of traditional Chinese medicine decoction pieces / 中国中药杂志

Decoction piece is the basic unit of traditional Chinese medicine(TCM) prescriptions, and it is also the main material basis for clinical efficacy of TCM. The clinical efficacy of TCM decoction pieces is very important for the overall efficacy of TCM prescriptions. However, the current quality evaluation of TCM decoction pieces mainly focuses on the amount of intrinsic substances and compositions. The basic researches such as toxicology and pharmacology are deeply, but lacking with the evidences from clinical evaluation. Therefore, the current decoction pieces quality evaluation system is difficult to objectively reflect the clinical effect of traditional Chinese medicine, forming the only componential theory or blindly pursuing the large volume and heavy weight of medicine materials. The quality standard of Chinese decoction pieces is biased,with concerns that "TCM will die from Chinese medicine". Therefore, this paper proposes that it is urgent to clinically evaluate the TCM decoction pieces,and regard the clinical evaluation as a starting point and a foothold for the quality evaluation of TCM decoction pieces, based on the origin identification, origin evaluation, product evaluation, content evaluation, and harmful substance detection as an auxiliary support. Finally a new quality evaluation system for TCM decoction pieces with a clinical evaluation as the core is formed, which is composed of six steps, aiming to promote the quality improvement of TCM decoction pieces. Of course, because there is no mature experience in the clinical evaluation of TCM decoction pieces, the quality evaluation system has some challenges such as complex processes and high cost, but it is essential for maintaining the quality of medicinal materials and life safety. Therefore, it is of importance and urgency to construct and implement the quality evaluation system.

Taxus chinensis ameliorates diabetic nephropathy through down-regulating TGF-β1/Smad pathway / 中国天然药物

Diabetic nephropathy (DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg·kg body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L were selected for experiments. The DN rats were treated with Taxus chinensis orally (0.32, 0.64, and 1.28 g·kg) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-β1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-β1/Smad signaling pathway.

Taxus chinensis ameliorates diabetic nephropathy through down-regulating TGF-β1/Smad pathway / 中国天然药物

Diabetic nephropathy (DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg·kg body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L were selected for experiments. The DN rats were treated with Taxus chinensis orally (0.32, 0.64, and 1.28 g·kg) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-β1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-β1/Smad signaling pathway.

Changes of refractive status after strabismus surgery / 国际眼科杂志(Guoji Yanke Zazhi)

@#Strabismus refers to the clinical phenomenon of any deviation from the optic axis, which can be caused by the abnormality of the binocular vision or the neuromuscular abnormalities that control the movement of the eyes. Operation is the important way to strabismus, firstly people focus only on the eye position, but with the gradual observation and follow-up of surgical patients, some researches had found that may change the original refractive status, so the article made a summarize from refractive status, anterior segment parameters,its possible mechanism, and influencing factors. We hope that there will be a more comprehensive understanding of strabismus surgery, and to provide the basis for determining the ideal time for optometry.

miRNA-99b inhibits the invasion ability of glioma cells by targeting mTOR / 中国药理学通报

Aim To detect the expression of miRNA-99b and mTOR in glioma tissues and to investigate the effect of miRNA-99b on the cell invasion ability of hu-man glioma cell line U251. Methods The expres-sions of miRNA-99b and mTOR mRNA in glioma tis-sues and normal brain tissues were detected by real-time PCR. After co-transfection with miRNA-99b mim-ics and wild or mutation type mTOR 3′UTR recombina-tion vector,the specific binding ability of miRNA-99b to 3′-UTR in mTOR gene was examined by luciferase gene reporter system. The expression levels of miRNA-99b,mTOR mRNA and mTOR protein in glioma cell line U251 after transfected with miRNA-99b mimics were measured by real-time PCR and Western blot,re-spectively. The cell invasion was measured by Tran-swell assay. The changes of mTOR and miRNA-99b expression levels in U251 cells after transfection with mTOR PsiCHECK were detected by real-time PCR. The correlation between the expression of miRNA-99b and prognosis was analyzed statistically. Results The expressed level of miRNA-99b was lower, and the ex-pression level of mTOR was higher in the glioma tissues than that in the normal brain tissues. The expression of miRNA-99b was up-regulated, and the expressions of mTOR mRNA and protein were down-regulated in U251 cells after transfection with miRNA-99b mimics. However, the abilities of invasion of U251 cells after transfection with miRNA-99b mimics were inhibited. The relative protein expression levels of mTOR in mTOR PsiCHECK group were significantly different from those in negative control group, but the relative expression levels of miRNA-99b had no signifi-cant difference compared with those in negative control group. Over-expression of mTOR restored the abilities of cell invasion in U251 cells, which was reduced by miRNA-99b. The Kaplan—Meier analysis and Log-Rank Test showed that there were significant differ-ences in overall survival (OS) between the miRNA-99b high-expression and low-expression group. Con-clusions The expression level of miRNA-99b is low in human glioma tissue. miRNA-99b may inhibit the cell invasion activity of glioma cell line U251 in vitro via inhibiting mTOR expression.

Clinical study on conjoint fascial sheath suspension in the treatment of moderate and severe ptosis / 局解手术学杂志

Objective To investigate whether the conjoint combined with fascial sheath( CFS) suspension can be used as an effective method for correction of moderate and severe ptosis. Methods Thirty-five patients (39 eyes) with moderate or severe ptosis were treated in our hospital from January 2014 to March 2017 by means of CFS suspension,frontalis suspension and shortening of levator palpebrae superior-is,and all the patients were followed up for 3～12 months. Results The CFS suspension and the other two operations appeared effective;and compared with the other two methods,the difference was statistically significant(P<0. 05). The CFS suspension for the treatment of moderate and severe ptosis with a higher positive rate(95％) and the positive rate of the other two methods was 67％. In terms of complications,the CFS suspension showed eyelid dysraphism incidence rate was exposure keratitis occurred in 85. 7％ and entropion occurrence rate of 4. 7％;with the other two methods,the surgical eyelid dysraphism occurred in 100％ and the conjunctival prolapse occurred in 5. 6％. Conclusion The CFS suspension in correction of moderate and severe ptosis has the advantages of less trauma,less complications and good correction effect.

Effect of epidural labor analgesia on the prolactin levels of parturient / 新乡医学院学报

Objective To explore the effect of epidural labor analgesia on the prolactin (PRL) levels of parturient.Methods Sixty primipara who delivered in the First Affiliated Hospital of Xinxiang Medical University from October 2016 to May 2017 were selected as research object.The parturient were divided into observation group and control group,with 30 cases in each group.The parturient in observation group were given ropivacaine combined with sufentanil for epidural block labor analgesia;the parturient in control group took natural production method without any analgesia method.The pain score,duration of labor,milk yield,serum PRL level before analgesia and 24,48 h postpartum and the number of initial lactation at 30 rmin,24 h,48 h postpartum of maternal were compared between the two groups.Results The active period of the first stage of labor of parturient in the observation group was significantly shorter than that in the control group (P ＜ 0.05);there was no statistic difference in the latent period of the first stage of labor,the second stage of labor and the third stage of labor of parturient between the observation group and the control group(P ＜ 0.05).There was no statistic difference in the pain score of parturient between the two groups before analgesia(P ＜ 0.05);the pain score of parturient in observation group was significantly lower than that in the control group at the time point of uterine orifice open 3 cm,uterine orifice full dilatation and fetal disengagement(P＜ 0.05).There was no statistic difference in the PRL levels of parturient between the two groups before analgesia (P ＜ 0.05);the PRL level of parturient in observation group was significantly higher than that in the control group at 24,48 h postpartum(P ＜0.05).The condition of initial lactation of maternal in the observation group was significantly better than that in the control group(P ＜ 0.05).The milk yield of parturient in observation group was significantly more than that in the control group at 24,48 h postpartum (P ＜ 0.05).Conclusion Epidural analgesia can reduce the pain of parturient,shorten the active stage of the first stage of labor,increase the level of PRL and increase the milk yield of the postpartum.