Effects of EW-7197 on the proliferation and migration of TGF-β1 induced human Tenon fibroblasts and its mechanism / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of ALK5 inhibitor EW-7197 on the proliferation and migration of human Tenon fibroblasts(HTFs)induced by transforming growth factor-β1(TGF-β1)and its mechanism.METHODS: The cell proliferation rate was detected by MTS assay, and the optimal concentration and time of EW-7197 were explored. Then HTFs were divided into three groups: normal control group, TGF-β1 induced group and TGF-β1+EW-7197 group. Cell migration was observed by Transwell assay. The protein expression levels of Fibronectin, α-SMA, as well as the phosphorylated Smad2, Smad3(p-Smad2, p-Smad3)were measured by Western blot.RESULTS: MTS assay showed that the proliferation rate of cells treated with 6.0 μmol/L EW-7197 for 24h was the lowest(all P<0.01). Transwell assay showed that the migrated number of HTFs in TGF-β1 induced group was 228.0±17.0/field, which was significantly more than that in normal control group(149.0±15.0/field)and TGF-β1+EW-7197 group(46.0±8.0/field; all P<0.01). Western blot showed that the protein relative expression levels of Fibronectin, α-SMA and p-Smad2, p-Smad3 of HTFs in TGF-β1 induced group were significantly higher than that in normal control group and TGF-β1+EW-7197 group(all P<0.001).CONCLUSION:EW-7197 can suppress the proliferation and migration of TGF-β1-induced HTFs through TGF-β/Smad signaling pathways.

The qualitative study of effectiveness of expressive writing intervention on patients with laryngeal cancer post total laryngectomy / 中国实用护理杂志

Objective:The aim of this study was to explore the perception and cognition of patients with laryngeal cancer post total laryngectomy accepted expressive writing intervention, analyze the intervention effect from the perspective of patients, and provide a basis for psychological intervention of these patients.Methods:From July to August 2021, the descriptive research method was applied to 13 patients with laryngeal cancer post total laryngectomy who had participated in the expressive writing intervention hosted in the General Hospital of Ningxia Medical University, in order to understand the patients′ perception and cognition of the intervention, and the data were analyzed by using content analysis method.Results:A total of 2 themes and 9 sub themes were extracted. Theme 1: the positive feedback of expressive writing intervention: relieve related physical symptoms and improve sleep; reduce anxiety and regulate emotions effectively; reduce psychological stress and promote positive coping; reduce stigma and improve social withdrawal; make up for lost pronunciation and clear mind. Theme 2: Difficulties and challenges in the application of expressive writing intervention: physical discomfort affects the compliance of patients, poor economic status affects the enthusiasm of patients to participate, poor social and family support affects the willingness of patients to participate, and literacy and writing habits affect the completion of participation.Conclusions:The application of expressive writing intervention promotes the psychological and social functional rehabilitation of patients with laryngeal cancer post total laryngectomy and has satisfactory effects and certain feasibility. The researchers should fully consider the influencing factors of intervention and optimize the plan in the future.

Effect of silencing E6-associated protein on level of p53 protein in human papilloma virus negative cervical cancer cells / 中国生物制品学杂志

@#Objective To investigate the effect of silencing E6-associated protein(E6AP)on the level of p53 protein in human papilloma virus(HPV)negative cervical cancer cells(C33A cells).Methods The siRNA sequence silencing E6AP(siE6AP)and silencing control disordered siRNA sequence(siControl)were transfected into C33A cells with the mediation of LipofectamineTM2000 transfection reagent respectively.The silencing effect of siRNA on E6AP and the expression of p53and cleaved-caspase-3 proteins were detected by Western blot.Results The levels of E6AP protein in C33A cells of siE6AP group were significantly lower(t =-4.597,P<0.05),while the levels of p53 and cleaved-caspase-3 proteins were significantly higher than those of siControl group(t = 4.533 and 7.099 respectively,each P<0.05).Conclusion Silencing of E6AP significantly increased the expression of p53 protein in C33A cells,indicating that silencing of E6AP may restore the activity and function of p53 protein in C33A cells.

Comparison of aspirin treatment strategies for primary prevention of cardiovascular diseases: A decision-analytic Markov modelling study / 北京大学学报(医学版)

OBJECTIVE@#To compare the expected population impact of benefit and risk of aspirin treatment strategies for the primary prevention of cardiovascular diseases recommended by different guidelines in the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study.@*METHODS@#A decision-analytic Markov model was used to simulate and compare different strategies of aspirin treatment, including: Strategy ①: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk, recommended by the 2020 Chinese Guideline on the Primary Prevention of Cardiovascular Diseases; Strategy ②: Aspirin treatment for Chinese adults aged 40-59 years with a high 10-year cardiovascular risk, recommended by the 2022 United States Preventive Services Task Force Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease; Strategy ③: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk and blood pressure well-controlled (< 150/90 mmHg), recommended by the 2019 Guideline on the Assessment and Management of Cardio-vascular Risk in China. The high 10-year cardiovascular risk was defined as the 10-year predicted risk over 10% based on the 2019 World Health Organization non-laboratory model. The Markov model simulated different strategies for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Quality-adjusted life year (QALY) and the number needed to treat (NNT) for each ischemic event (including myocardial infarction and ischemic stroke) were calculated to assess the effectiveness of the different strategies. The number needed to harm (NNH) for each bleeding event (including hemorrhagic stroke and gastrointestinal bleeding) was calculated to assess the safety. The NNT for each net benefit (i.e., the difference of the number of ischemic events could be prevented and the number of bleeding events would be added) was also calculated. One-way sensitivity analysis on the uncertainty of the incidence rate of cardiovascular diseases and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.@*RESULTS@#A total of 212 153 Chinese adults, were included in this study. The number of people who were recommended for aspirin treatment Strategies ①-③ was 34 235, 2 813, and 25 111, respectively. The Strategy ③ could gain the most QALY of 403 [95% uncertainty interval (UI): 222-511] years. Compared with Strategy ①, Strategy ③ had similar efficiency but better safety, with the extra NNT of 4 (95%UI: 3-4) and NNH of 39 (95%UI: 19-132). The NNT per net benefit was 131 (95%UI: 102-239) for Strategy ①, 256 (95%UI: 181-737) for Strategy ②, and 132 (95%UI: 104-232) for Strategy ③, making Strategy ③ the most favorable option with a better QALY and safety, along with similar efficiency in terms of net benefit. The results were consistent in the sensitivity analyses.@*CONCLUSION@#The aspirin treatment strategies recommended by the updated guidelines on the primary prevention of cardiovascular diseases showed a net benefit for high-risk Chinese adults from developed areas. However, to balance effectiveness and safety, aspirin is suggested to be used for primary prevention of cardiovascular diseases with consideration for blood pressure control, resulting in better intervention efficiency.

Application of discrete event simulation model in analysis on cost-effectiveness of epidemiology screening / 中华流行病学杂志

Discrete event simulation (DES) model is based on individual data, by which discrete events over time are simulated to reflect disease progression. The effects of individual characteristics on disease progression could be considered in the DES model. Moreover, unlike state-transition models, DES model without setting of fixed cycle can contribute to more accurate estimation of event time, especially in the evaluation of the long-term effectiveness of screening strategies for complex diseases in which time dimension needs to be considered. This article introduces the general principles, construction steps, analytic methods and other relevant issues of the DES model. Based on a research case of estimating the cost-effectiveness of screening for abdominal aortic aneurysms in women aged 65 years and above in the United Kingdom, key points in applications of the DES model in analysis on effectiveness of complex disease screening are discussed in detail, including model construction and analysis and interpretation of the results. DES model can predict occurring time of discrete events accurately by establishing the distribution function of their occurring time and is increasingly used to evaluate the screening strategies for complex diseases in which time dimension needs to be considered. In the construction of DES model, it is necessary to pay close attention to the clear presentation of model structure and simulation process and follow the relevant reporting specification to conduct cost-effectiveness analysis to ensure the transparency and repeatability of the research.

Effect of Circular RNA hsa_circ_0067582 on the Proliferation and Invasion Ability of Gastric Cancer Cells / 中国医学科学院学报

Objective To investigate the effects on cell proliferation and invasion of the circular RNA hsa_circ_0067582 in gastric cancer(GC). Methods After hsa_circ_0067582 overexpression (Oe-circ_0067582) plasmid was transfected into AGS and SGC-7901 cells,the cell viability,proliferation,invasion ability,and apoptosis were detected by CCK-8,colony formation and EdU assays,Transwell assay,and flow cytometry,respectively.Western blotting was employed to detect the expression levels of proteins related to the cell apoptosis and epithelial-mesenchymal transition(EMT).The effect of Oe-circ_0067582 on the growth of SGC-7901 cells in nude mice was observed.Bioinformatics tools were used to predict the binding target miRNA of hsa_circ_0067582,and the competing endogenous RNA(ceRNA)regulatory network was established.Finally,functional enrichment was performed to analyze the biological functions of the target genes of the predicted miRNA. Results Compared with the pLO-ciR(empty plasmid)group,the Oe-circ_0067582 group in AGS and SGC-7901 cells attenuated the cell viability(t=7.883,P=0.001;t=5.679,P=0.005),proliferation(t=6.709,P=0.003;t=5.857,P=0.003),and invasion ability(t=7.782,P=0.002;t=6.342,P=0.003)and induced cell apoptosis(t=7.225,P=0.002;t=11.509,P=0.001).Western blotting showed that the Oe-circ_0067582 group in AGS and SGC-7901 cells up-regulated the protein levels of cysteinyl aspartate specific proteinase (Caspase) 3(t=6.863,P=0.002;t=7.024,P=0.001),Caspase 7(t=3.295,P=0.04;t=6.008,P=0.004),Caspase 9(t=4.408,P=0.012;t=6.278,P=0.004),and E-cadherin(t=12.453,P=0.002;t=10.867,P=0.001),while down-regulated those of Vimentin(t=7.242,P=0.002;t=5.694,P=0.004)and N-cadherin(t=6.480,P=0.003;t=7.446,P=0.001).Furthermore,Oe-circ_0067582 significantly inhibited the growth of tumor in the SGC-7901 tumor-bearing nude mice(t=3.526,P=0.017).The prediction based on TargetScan and miRnada suggested that hsa_circ_0067582 can competitively bind to hsa-miR-181b-3p,hsa-miR-337-3p,hsa-miR-421,and hsa-miR-548d-3p.The functional enrichment indicated that the target genes of miRNA were involved in multiple cancer-related biological processes including negative regulation of apoptotic process,gene expression,transcriptional misregulation in cancer,transforming growth factor-β,and p53 signaling pathways. Conclusion Oe-circ_0067582 can inhibit the proliferation and attenuate EMT process to reduce the invasion ability of AGS and SGC-7901 cells,which provides a new target for the treatment of GC.

Effectiveness of different screening strategies for type 2 diabete on preventing cardiovascular diseases in a community-based Chinese population using a decision-analytic Markov model / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effectiveness of different screening strategies for type 2 diabetes to prevent cardiovascular disease in a community-based Chinese population from economically developed areas based on the Chinese electronic health records research in Yinzhou (CHERRY) study.@*METHODS@#A Markov model was used to simulate different systematic diabetes screening strategies, including: (1) screening among Chinese adults aged 40-70 years recommended by the 2020 Chinese Guideline for the prevention and Treatment of Type 2 Diabetes (Strategy 1); (2) screening among Chinese adults aged 35 to 70 years recommended by the 2022 American Diabetes Association Standard of Medical Care in Diabetes (Strategy 2); and (3) screening among Chinese adults aged 35-70 years with overweight or obesity recommended by the 2021 United States Preventive Services Task Force Recommendation Statement on Screening for Prediabetes and Type 2 Diabetes (Strategy 3). According to the guidelines, individuals who were screened positively (fasting plasma glucose ≥ 7.0 mmol/L) would be introduced to intensive glycemic targets management (glycated hemoglobin < 7.0%).The Markov model simulated different screening scenarios for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Number of cardiovascular disease events or deaths could be prevented and number needed to screen (NNS) were calculated to compare the effectiveness of the different strategies. One-way sensitivity analysis on the sensitivity of screening methods and probabilistic sensitivity analysis on uncertainties of diabetes incidence, the sensitivity of screening methods, and intensive glycemic management effects were conducted.@*RESULTS@#Totally 289 245 Chinese adults aged 35-70 years without cardiovascular diseases or diagnosed diabetes at baseline were enrolled. In terms of the number of cardiovascular disease events could be prevented, Strategy 1 for systematic diabetes screening among the adults aged 35-70 years was 222 (95%UI: 180-264), Strategy 2 for systematic diabetes screening among the adults aged 40-70 years was 227 (95%UI: 185-271), and Strategy 3 for systematic diabetes screening among the adults aged 35-70 years with obesity or overweight (body mass index ≥ 24 kg/m2) was 131 (95%UI: 98-164), compared with opportunistic screening. NNS per cardiovascular disease event for the strategies 1, 2 and 3 were 1 184 (95%UI: 994-1 456), 1 274 (95%UI: 1 067-1 564) and 814 (95%UI: 649-1 091), respectively. Compared with Strategy 1, NNS per cardiovascular disease event for Strategy 2 increased by 90 (95%UI: -197-381) with similar effectiveness of cardiovascular prevention; however, NNS per cardiovascular disease event for Strategy 3 was reduced by 460 (95%UI: 185-724) in contrast to the Strategy 2, suggesting that the Strategy 3 was more efficient. The results were consistent in multiple sensitivity analyses.@*CONCLUSION@#Systematic screening for diabetes based on the latest guidelines in economically developed areas of China can reduce cardiovascular events and deaths. However, merely lowering the starting age of screening from 40 to 35 years seems ineffective for preventing cardiovascular disease, while screening strategy for Chinese adults aged 35-70 years with overweight or obesity is recommended to improve efficiency.

Effectiveness of statin treatment strategies for primary prevention of cardiovascular diseases in a community-based Chinese population: A decision-analytic Markov model / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effectiveness of statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases by the Western guidelines in a community-based Chinese population from economically developed areas using data from the Chinese electronic health records research in Yinzhou (CHERRY) study.@*METHODS@#A Markov model was used to evaluate the effectiveness of the following statin treatment strategies, including: (1) usual care without cardiovascular risk assessment(Strategy 0); (2) using the World Health Organization (WHO) non-laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 1); (3) using the WHO laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 2); and (4) using the Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR) model with statin treatment for high-risk group (risk ≥ 10%, Strategy 3). According to the guidelines, adults in the medium-risk group received lifestyle intervention, and adults in the high-risk group received life-style intervention and statin treatment under these strategies. The Markov model simulated different strategies for ten years (cycles) using parameters from the CHERRY study, published data, meta-analyses and systematic reviews for Chinese. The number of cardiovascular events or deaths, as well as the number need to treat (NNT) with statin per cardiovascular event or death prevented, were calculated to compare the effectiveness of different strategies. One-way sensitivity analysis on the uncertainty of incidence rate of cardiovascular diseases, and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.@*RESULTS@#Totally 225 811 Chinese adults aged 40-79 years without cardiovascular diseases at baseline were enrolled. In contrast to the usual care without risk assessment-based statin treatment strategy, Strategy 1 using the WHO non-laboratory-based risk charts could prevent 3 482 [95% uncertainty interval (UI): 2 110-4 661] cardiovascular events, Strategy 2 using the WHO laboratory-based risk charts could prevent 3 685 (95%UI: 2 255-4 912) events, and Strategy 3 using the China-PAR model could prevent 3 895 (95%UI: 2 396-5 181) events. NNTs with statin per cardiovascular event prevented were 22 (95%UI: 14-54), 21 (95%UI: 14-52), and 27 (95%UI: 17-67), respectively. Strategy 3 could prevent more cardiovascular events, while Strategies 1 and 2 required fewer numbers need to treat with statin per cardiovascular event prevented. The results were consistent in the sensitivity analyses.@*CONCLUSION@#The statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases recommended by the Western guidelines could achieve substantive health benefits in adults from developed areas of China. Using the China-PAR model for cardiovascular risk assessment could prevent more cardiovascular diseases while using the WHO risk charts seems more efficient.

Research on antitumor effects of small molecule inhibitors of deubiquitinases: new progress and new ideas / 药学学报

The abnormality of ubiquitin proteasome pathway is an important factor leading to the imbalance of protein homeostasis. In this process, the deubiquitinase responsible for removing the ubiquitin chain of protein substrate is very important. Its abnormal activity or expression can cause the functional changes of key oncogenic/tumor suppressor proteins, which directly or indirectly lead to the occurrence, development and malignant evolution of tumors. Based on this, the discovery and research of small molecule inhibitors targeting deubiquitinases have become a hot field of anti-tumor candidate drugs. This review will focus on the regulatory effect and mechanism of ubiquitin proteasome pathway, especially deubiquitinase on tumor, introduce the application of deubiquitinase small molecule inhibitors in tumor treatment, and discuss the research status and latest progress of small molecule inhibitors, so as to provide ideas for the research of new anti-tumor strategies based on deubiquitinase.

Changes of heparin-binding protein in severe burn patients during shock stage and its effects on human umbilical vein endothelial cells and neutrophils / 中华烧伤杂志

Objective: To investigate the changes of heparin-binding protein (HBP) in severe burn patients during shock stage and its effects on human umbilical vein endothelial cells (HUVECs) and neutrophils in vitro. Methods: Prospective observational and experimental research methods were used. Twenty severe burn patients who met the inclusion criteria and were admitted to the Department of Burns and Plastic Surgery of Affiliated Suzhou Hospital of Nanjing Medical University from August to November 2020 were included in severe burn group (12 males and 8 females, aged 44.5 (31.0, 58.0) years). During the same period, 20 healthy volunteers with normal physical examination results in the unit's Physical Examination Center were recruited into healthy control group (13 males and 7 females, aged 39.5 (26.0, 53.0) years). Enzyme-linked immunosorbent assay (ELISA) method was used to detect the protein expression levels of HBP and tissue inhibitor of metalloproteinase 1 (TIMP-1) in plasma of patients within 48 hours after injury in severe burn group and in plasma of volunteers in healthy control group. The correlation between protein expression of HBP and that of TIMP-1 in the plasma in the two groups was analyzed by Pearson correlation analysis. The fourth passage of HUVECs in logarithmic growth phase were used for the experiment. The HUVECs were divided into normal control group with routine culture (the same treatment below) and recombinant HBP (rHBP)-treated 12 h group, rHBP-treated 24 h group, and rHBP-treated 48 h group with corresponding treatment according to the random number table (the same grouping method below), and the mRNA expression of TIMP-1 in cells was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. The HUVECs were divided into normal control group and rHBP-treated 48 h group with corresponding treatment, and the protein expression of TIMP-1 in the cells was detected by Western blotting. The HUVECs were divided into normal control group, rHBP alone group, aprotinin alone group, and rHBP+aprotinin group treated with the corresponding reagents (with the final molarity of rHBP being 200 nmol/L and the final concentration of aprotinin being 20 μg/mL, respectively), cultured for 48 h, and ELISA was used to detect the protein expression of TIMP-1 in the culture supernatant of cells. The neutrophils were isolated from the peripheral venous blood of the aforementioned 10 healthy volunteers by immunomagnetic bead sorting, and the cells were divided into normal control group, recombinant TIMP-1 (rTIMP-1) alone group, phorbol acetate (PMA) alone group, and rTIMP-1+PMA group treated with corresponding reagents (with the final concentration of rTIMP-1 being 500 ng/mL and the final molarity of PMA being 10 nmol/L, respectively). After being cultured for 1 h, the expression of CD63 protein in cells was detected by immunofluorescence method, the positive expression rate of CD63 protein in cells was detected by flow cytometry, and the protein expression levels of HBP and myeloperoxidase (MPO) in the culture supernatant of cells were detected by ELISA. The normal control group underwent the above-mentioned related tests at appropriate time points. The number of samples was 3 in each group of cell experiment. Data were statistically analyzed with chi-square test, Mann-Whitney U test, Kruskal-Wallis H test, and Tamhane's T2 test. Results: The protein expression levels of HBP and TIMP-1 in the plasma of patients in severe burn group were 404.9 (283.1, 653.2) and 262.1 (240.6, 317.4) ng/mL, respectively, which were both significantly higher than 61.6 (45.0, 68.9) and 81.0 (66.3, 90.0) ng/mL of volunteers in healthy control group (with Z values of -5.41 and -5.21, respectively, P<0.01). The correlation between the protein expression of HBP and that of TIMP-1 in the plasma of volunteers in healthy control group was not strong (P>0.05). The protein expression of HBP was significantly positively correlated with that of TIMP-1 in the plasma of patients in severe burn group (r=0.64, P<0.01). Compared with that in normal control group, the mRNA expression of TIMP-1 in HUVECs was significantly increased in rHBP-treated 12 h group, rHBP-treated 24 h group, and rHBP-treated 48 h group (with t values of -3.58, -2.25, and -1.26, respectively, P<0.05). Western blotting detection showed that compared with that in normal control group, the protein expression of TIMP-1 in HUVECs in rHBP-treated 48 h group was significantly enhanced. After 48 h of culture, compared with that in normal control group, the protein expression level of TIMP-1 in the culture supernatant of HUVECs in rHBP alone group was significantly increased (t=9.43, P<0.05), while the protein expression level of TIMP-1 in the culture supernatant of HUVECs didn't change significantly in aprotinin alone group or rHBP+aprotinin group (P>0.05); compared with that in rHBP alone group, the protein expression level of TIMP-1 in the culture supernatant of HUVECs in rHBP+aprotinin group was significantly decreased (t=4.76, P<0.01). After 1 h of culture, the trend of CD63 protein expression in neutrophils detected by immunofluorescence method and that by flow cytometry were consistent in each group. After 1 h of culture, compared with that in normal control group, the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells in rTIMP-1 alone group all had no significant changes (P>0.05), while the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells were all significantly increased in PMA alone group and rTIMP-1+PMA group (with t values of 2.41, 3.82, 5.73, 1.05, 4.16, and 1.08, respectively, P<0.05 or P<0.01); compared with that in PMA alone group, the positive expression rate of CD63 protein in the neutrophils and the protein expression levels of HBP and MPO in the culture supernatant of cells in rTIMP-1+PMA group were all significantly decreased (with t values of 5.26, 2.83, and 1.26, respectively, P<0.05 or P<0.01). Conclusions: The expression level of HBP in the plasma of severe burn patients is increased during shock stage. HBP can induce HUVECs to secrete TIMP-1 in vitro, and TIMP-1 can reduce the expression of CD63 molecule in human neutrophils.

Re-understanding the physiological and pathophysiological roles of neutrophils / 中华烧伤杂志

Neutrophils have always been considered as a short-lived and homogeneous cell type in the innate immune system, which have limited pro-inflammatory or anti-inflammatory effects. However, in recent 10 years, the understanding of neutrophils has been undergoing some kind of revival as researches progressed. The researches on the heterogeneity of neutrophils and the mechanism of their interaction with other immune cells have promoted the researchers to re-understand the physiological and pathophysiological roles of neutrophils. In the following decades, with the development of single-cell sequencing technology, spatial transcriptome sequencing technology, and multi-omics combined sequencing technology, researchers will have a better understanding of the biological behaviors of neutrophils. This paper briefly reviews the biological behaviors of neutrophils and their roles in various diseases in recent years.

Network Meta-analysis of 10 Kinds of Oral Chinese Patent Medicine Combined with Chemotherapy in Treatment of Gastric Cancer / 中国实验方剂学杂志

Objective:To compare the efficacy and safety of 10 kinds of oral Chinese patent medicines combined with chemotherapy in the treatment of gastric cancer in a network Meta-analysis. Method:PubMed，Embase，Web of Science，Cochrane Library，CNKI，China biomedical literature service system，VIP，Wanfang database were retrieved to obtain Chinese and English literatures published before March 1，2020. The randomized controlled trials（RCTs） and data were screened and extracted. The quality of the included literatures was also evaluated. The pair-work Meta-analysis was conducted by Revman 5.3 software， and the Meta-analysis were conducted by ADDIS 1.16.7 software. Result:A total of 41 randomized controlled trials were eventually involved. All of them were two-arm，including 10 oral Chinese patent medicines，Cinobufotalin，Jinlong capsule，Pingxiao capsule，Shenyi capsule，Xihuang pill （or capsule），Xiaoaiping tablet，Yangzheng Xiaoji capsule，Zhenqi Fuzheng granule combined with chemotherapy for gastric cancer. The effective rate for treating cancer was significantly higher than that of chemotherapy alone （<italic>P</italic><0.05）. Zhenqi Fuzheng+chemotherapy was the best choice； the KPS improvement rate of Cinobufacin，Shenyi capsule，Yangzheng Xiaoji capsule，Zhenqi Fuzheng granule combined with chemotherapy in the treatment of gastric cancer was significantly increased（<italic>P</italic><0.05）. Shenyi capsule combined with chemotherapy might be the best regimen. The incidence rate of leukocyte decline was significantly lower in the treatment of gastric cancer（<italic>P</italic><0.05）. The combination of Zhenqi Fuzheng granule and chemotherapy was the best choice. Traditional Chinese medicine could not reduce the incidence of neurotoxicity（<italic>P></italic>0.05）. Cinobufufacin，Yangzheng Xiaoji capsule and Zhenqi Fuzheng granule combined with chemotherapy could increase CD4⁺/CD8⁺in patients with gastric cancer， which was significantly higher than that of chemotherapy alone（<italic>P</italic><0.05）. Conclusion:All kinds of oral Chinese patent medicines can play a significantly role in the treatment of gastric cancer. Zhenqi Fuzheng granule，angzheng Xiaoji capsule and Shenyi capsule combined with chemotherapy are more effective in treating gastric cancer.

Effect of Licochalcone A on Apoptosis in Human Breast Cancer MDA-MB-231 Cells / 中国实验方剂学杂志

Objective:To investigate the effect of licochalcone A （LCA） on apoptosis in human breast cancer MDA-MB-231 cells， and to explore its possible mechanism. Method:MDA-MB-231 cells were treated with LCA of different concentrations， and<italic> </italic>cell counting kit-8 （CCK-8） assay was used to detect the cell viability. The cells were treated with LCA （10， 20， and 40 μmol·L^-1） for 24 h， and apoptosis was detected by Annexin V staining with fluorescein isothiocyanate （FITC） and propidium iodide （PI） （Annexin V-FITC/PI）. The level of intracellular reactive oxygen species （ROS） was detected by 2′，7′-dichlorodihydrofluorescein diacetate （DCFA-DA） fluorescent probe. Mitochondrial membrane potential （MMP） was detected by 5， 5′， 6， 6′-tetrachloro-1， 1′， 3， 3′-tetraethyl-imidacarbocyanine （JC-1） fluorescence probe. Western blot was used to detect the expression of cell apoptosis-related proteins， such as B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）， and endoplasmic reticulum （ER） stress-related proteins， such as C/EBP homologous protein （CHOP）， activating transcription factor 4 （ATF4）， protein kinase R-like ER kinase （PERK）， p-PERK， eukaryotic translation initiation factor 2 alpha （eIF2<italic>α</italic>）， and p-eIF2<italic>α</italic>. Result:With the increase in the drug concentration （starting from 5 μmol·L^-1）， the cell viability decreased （<italic>P<</italic>0.05） with IC₅₀of 19.05 μmol·L^-1 as compared with the normal group. Additionally， the apoptosis rates of the LCA groups （10， 20， 40 μmol·L^-1） significantly increased （<italic>P</italic><0.05）， which reached 30.2% （<italic>P</italic><0.05） at LCA concentration of 40 μmol·L^-1. LCA （10， 20， and 40 μmol·L^-1） decreased the expression of Bcl-2 （<italic>P<</italic>0.05） and increased Bax expression （<italic>P<</italic>0.05） in a dose-dependent manner. Besides， the intracellular ROS level was elevated （<italic>P<</italic>0.05） and mitochondrial MMP was reduced （<italic>P<</italic>0.05） after LCA （10， 20， and 40 μmol·L^-1） treatment in a dose-dependent manner， leading to mitochondrial dysfunction. LCA （10， 20， and 40 μmol·L^-1） induced ER stress to up-regulate the expression of CHOP， ATF4， p-PERK， and p-eIF2<italic>α</italic> （<italic>P<</italic>0.05） in a dose-dependent manner. Conclusion:LCA can induce MDA-MB-231 cell apoptosis by increasing intracellular ROS level and reducing MMP to trigger mitochondrial dysfunction and ER stress.

Influence of Yuanzhisan Containing Ginseng Radix et Rhizoma or Codonopsis Radix on Memory Disorder / 中国实验方剂学杂志

Objective:To explore the effects of Yuanzhisan （YZS） containing Ginseng Radix et Rhizoma （YZSR） or Codonopsis Radix （YZSD） on memory disorder based on network and experimental pharmacology. Method:The active components and targets of YZS were retrieved from the component database and literature， and the targets of memory disorder from the disease databases. The intersection targets revealed by Veen diagram were subjected to pathway analysis. The common active components of YZSR and YZSD were molecularly docked onto the core targets. Scopolamine hydrobromide was used to establish the memory disorder model， which was employed in the behavioral experiments for evaluating the effect of YZSR and YZSD on memory disorder. Result:There existed 33 active components for Ginseng Radix et Rhizoma and 31 for Codonopsis Radix， with four common active components and 380 common targets. YZSR contained 85 active components and 790 drug targets， and YZSD 81 active components and 781 drug targets. The mapping of 425 memory disorder targets with those of YZSD and YZSD yielded 133 and 130 intersection targets， respectively. The metabolic pathways involved calcium ion signaling pathway， hypoxia-inducible factor-1 （HIF-1） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， etc. As revealed by molecular docking， the binding energy of common active components to the targets was negative， and the binding effect of frutinone A was the best. Behavioral experiment results showed that both YZSR and YZSD alleviated the memory disorder. In the step-down test， the number of errors in the YZSD group was significant lower than that in the model group （<italic>P</italic><0.01）. In Morris water maze test， the movement distance of the YZSD group was remarkably shortened in comparison with that of the model group （<italic>P</italic><0.05）. In the open field test， the movement distances of both the YZSR and YZSD group were shortened in contrast to that in the normal group （<italic>P</italic><0.05）. Conclusion:YZS had a certain effect on memory disorder. There are similarities and differences between YZSR and YZSD in the treatment of memory disorder.

Effects of Tanreqing Capsule on the negative conversion time of nucleic acid in patients with COVID-19: A retrospective cohort study / 中西医结合学报

OBJECTIVE@#Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19.@*METHODS@#A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored.@*RESULTS@#COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3@*CONCLUSION@#Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3

San-Ao Decoction () Regulates Urine Volume on Bronchial Asthma Model Mice / 中国结合医学杂志

OBJECTIVE@#To observe the effect of San-Ao Decoction (, SAD) on water metabolism of bronchial asthra model mice.@*METHODS@#Forty-five female BALB/c mice were randomly divided into control, model and SAD groups by a random number table, 15 mice in each group. A composite method with ovalbumin (OVA) sensitization and challenge was developed to establish bronchial asthma model. Mice in the control group were intraperitoneally injected with distilled water without aerosol inhalation challenge. On day 15-22, 0.3 mL SAD was administered via gastric route in SAD group, one time per day, while an equivalent volume of normal saline was used for gastric administration in the control and model groups. Changes in airway resistance in the inspiratory phase (RI-R-Area) were detected using an AniRes2005 system, and 5-h urine output was collected by metabolic cages. Histopathological changes in lung and kidney were observed by hematoxylin-eosin staining. mRNA expressions of aquaporin (AQP) 1 and AQP2 in kidney were detected by reverse transcription-polymerase chain reaction, and the protein expressions of AQP1 and AQP2 in kidney were detected by immunohistochemistry. Enzyme-linked immune sorbent assay was used to detect the OVA-specific endothelium-1 (ET-1), antidiuretic hormone (ADH), atrial natriuretic peptide (ANP), prostaglandin E@*RESULTS@#Compared with the control group, the serum IgE level in model group increased (P<0.01). Following the pathologic changes in lung tissue, no significant change in kidney tissue was observed among 3 groups. Compared with the control group, the mice in the model group showed elevated airway resistance during inhalation phase, higher mRNA and protein expression levels on AQP1 and AQP2 in kidney tissue and higher ET-1 levels in serum, lung and kidney tissues, ADH and ANP in lung and serum, PGE@*CONCLUSION@#San-Ao Decoction can regulate the urine volume through regulating AQP1 and AQP2 expression, and the expression of these in the kidneys might be regulated by ET-1, NO and Ang II.

Role and damage mechanism of retinal pigment epithelial cells in dry ARMD / 国际眼科杂志(Guoji Yanke Zazhi)

@#Age-related macular degeneration(ARMD)is a major cause of irreversible loss of central vision in the elderly. Typical characteristics of ARMD consist of retinal pigment epithelium(RPE), degenerative changes of choroidal capillaries and vitreous warts in macular area. Clinical ARMD is divided into two subtypes: non effusive(dry or atrophic)and effusive(wet or neovascular). The occurrence of the disease is the result of the interaction of many factors, such as age, environment, heredity, smoking, oxidative stress and cardiovascular dysfunction, <i>etc</i>. In view of the important role of RPE cells in pathogenesis of ARMD, the effects and possible mechanisms of blue light, smoking, oxidative stress, lipofuscin accumulation, chronic inflammation and protein homeostasis on the onset of dry ARMD are summarized by focusing on RPE cells. This will provide new ideas to help understand and prevent the occurrence of dry ARMD.

Retrospective Analysis of Hematological Phenotypes in Patients with Gene Mutation and Deletion α-Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To explore the differences between hematological phenotypes of patients with different genotypes in gene mutations and deletion α- thalassemia.@*METHODS@#By screening the α- thalassemia gene test results in the First Affiliated Hospital, Sun Yat-Sen University from January 2015 to April 2020, the patients with mutation and deletion α- thalassemia were obtained, then the differences between hematological phenotypes of patients with different genotypes were analyzed.@*RESULTS@#There were 96 patients with mutation combined with deletion α- thalassemia from the results of 24 054 α- thalassemia patients screened out, including 79 patients with non-deletion Hb H disease (α@*CONCLUSION@#The hematological phenotype changes caused by α

Renormalization of Thalamic Sub-Regional Functional Connectivity Contributes to Improvement of Cognitive Function after Liver Transplantation in Cirrhotic Patients with Overt Hepatic Encephalopathy

Objective@#The role of preoperative overt hepatic encephalopathy (OHE) in the neurophysiological mechanism of cognitive improvement after liver transplantation (LT) remains elusive. This study aimed to explore changes in sub-regional thalamic functional connectivity (FC) after LT and their relationship with neuropsychological improvement using resting-state functional MRI (rs-fMRI) data in cirrhotic patients with and without a history of OHE. @*Materials and Methods@#A total of 51 cirrhotic patients, divided into the OHE group (n = 21) and no-OHE group (n = 30), and 30 healthy controls were enrolled in this prospective study. Each patient underwent rs-fMRI before and 1 month after LT. Using 16 bilateral thalamic subregions as seeds, we conducted a seed-to-voxel FC analysis to compare the thalamic FC alterations before and after LT between the OHE and no-OHE groups, as well as differences in FC between the two groups of cirrhotic patients and the control group. Correction for multiple comparisons was conducted using the false discovery rate (p < 0.05). @*Results@#We found abnormally increased FC between the thalamic sub-region and prefrontal cortex, as well as an abnormally decreased FC between the bilateral thalamus in both OHE and no-OHE cirrhotic patients before LT, which returned to normal levels after LT. Compared with the no-OHE group, the OHE group exhibited more extensive abnormalities prior to LT, and the increased FC between the right thalamic subregions and right inferior parietal lobe was markedly reduced to normal levels after LT. @*Conclusion@#The renormalization of FC in the cortico-thalamic loop might be a neuro-substrate for the recovery of cognitive function after LT in cirrhotic patients. In addition, hyperconnectivity between thalamic subregions and the inferior parietal lobe might be an important feature of OHE. Changes in FC in the thalamus might be used as potential biomarkers for recovery of cognitive function after LT in cirrhotic patients.

Comprehensive antioxidant and anti-inflammatory activity of alcohol extracts from Chrysanthemum indicum in different areas based on entropy weight and TOPSIS methodology / 中国中药杂志

The study is aiming at investigating the application of entropy weight TOPSIS method in the comparison of the scavenging effect of DPPH, ABTS and hydroxyl radical and the inhibition effect of xanthine oxidase(XOD) and lipoxygenase(LOX) of Chrysanthemum indicum. The DPPH, ABTS, salicylic acid and spectrophotometry were used to determine the scavenging effect of DPPH, ABTS and hydroxyl radical and the inhibition effect of xanthine oxidase(XOD) and lipoxygenase(LOX) of Ch. indicum from 31 different areas in vitro. Take the half inhibition rate of as the evaluation index, two principal components were extracted by the principal component analysis, and their cumulative contribution rate reached at 92.4%. The different areas of Ch. indicum could be divided into Dabei Mountain and Qinling-Taihang Mountain by use principal component to analysis. The entropy weight TOPSIS method was used to objectively assign weights to five indexes, calculate the weight of each index and set up the best and worst scheme of the evaluation object, and the relative proximity(C_i) was used as the measure to construct the multi-index comprehensive evaluation model of Ch. indicum. And then sort with the relative proximity value. The results showed that the relative proximity was between 0.098 and 0.983 which represents there were significant differences in the scavenging effect of DPPH, ABTS and hydroxyl radical and the inhibition effect of xanthine oxidase(XOD) and lipoxygenase(LOX) between extracts of Ch. indicum from different areas. The Ch. indicum from Dabie Mountain area have a relatively high relative degree of measurement and high-quality ranking. Taken together, the quality of Ch. indicum.from the Dabie Mountain area is better. The index weight coefficient and the classification result of producing area are basically consistent with the result of principal component analysis. The results show that the TOPSIS method based on entropy weight method can be used to evaluate the comprehensive quality of Ch. indicum.