Mechanism and experimental verification of jiawei duhuo jisheng mixture in treatment of knee osteoarthritis based on network pharmacology / 中国药理学通报

Aim To explore and verify the possible mechanism of Jiawei Duhuo Jisheng Mixture(JDJM)in the treatment on Knee Osteoarthritis(KOA)via using network pharmacology and animal experiment. Methods The ingredients of JDJM and relevant targets were collected from TCMSP and BATMAN-TCM database. The KOA-related targets were collected from GeneCard, OMIM and GEO databases. The common targets were acquired by intersecting ingredients-related and KOA-related targets, and then the Ingredient-Disease-Target Network and PPI network were constructed by Cytoscape 3.7.2 software and STRING platform. GO and KEGG enrichment analysis were performed based on Metascape database. Finally, the key targets and relevant mechanism were validated via animal experiment. Results In the network pharmacology study, 180 active ingredients related to treatment on KOA by JDJM were collected, and 152 common targets were confirmed. PPI network analysis showed that AKT1 might be the key targets of JDJM in the treatment on KOA. GO and KEGG enrichment analysis revealed that the key target mainly concentrated on inflammatory response and apoptosis. Animal experiment confirmed that JDJM could improve lesion in KOA rabbits, and suppress the expression levels of IL-1β, TNF-α, Caspase 3 and BAX in serum and articular fluid. AKT1 expression(including mRNA and protein)in articular cartilage was also down-regulated. Conclusions Based on the results of network pharmacology and animal experiment, JDJM may relieve KOA severity by anti-inflammatory and anti-apoptotic effects through a variety of molecular signaling pathways.

Application of Microhaplotypes in Sibling Kinship Testing / 法医学杂志

OBJECTIVES@#To investigate the efficacy of different numbers of microhaplotype (MH) loci and the introduction of different reference samples on the identification of full sibling, half sibling and differentiation between full sibling and half sibling kinships, and to explore the effect of changing mutation rate on sibling testing.@*METHODS@#First, a family map involving three generations was established, and four full sibling identification models, five half sibling identification models and five models distinguishing full and half siblings were constructed for different reference samples introduced. Based on the results of the previous study, two sets of nonbinary SNP-MH containing 34 and 54 loci were selected. Based on the above MH loci, 100 000 pairs of full sibling vs. unrelated individuals, 100 000 pairs of half sibling vs. unrelated individuals and 100 000 pairs of full sibling vs. half sibling were simulated based on the corresponding sibling kinship testing models, and the efficacy of each sibling kinship testing model was analyzed by the likelihood ratio algorithm under different thresholds. The mutant rate of 54 MH loci was changed to analyze the effect of mutation rate on sibling identification.@*RESULTS@#In the same relationship testing model, the systematic efficacy of sibling testing was positively correlated with the number of MH loci detected. With the same number of MH loci, the efficacy of full sibling testing was better than that of uncle or grandfather when the reference sample introduced was a full sibling of A, but there was no significant difference in the identification efficacy of the four reference samples introduced for full sibling and half sibling differentiation testing. In addition, the mutation rate had a slight effect on the efficacy of sibling kinship testing.@*CONCLUSIONS@#Increasing the number of MH loci and introducing reference samples of known relatives can increase the efficacy of full sibling testing, half sibling testing, and differentiation between full and half sibling kinships. The level of mutation rate in sibling testing by likelihood ratio method has a slight but insignificant effect on the efficacy.

Screening of prognosis-related enhancer RNAs and their corresponding target genes in patients with hepatocellular carcinoma and its prognostic significance / 中国肿瘤生物治疗杂志

@#[摘 要] 目的： 筛选与肝细胞癌（hepatocellular carcinoma，HCC）预后相关的增强子RNA（enhancer RNA，eRNA）及其对应的靶基因，并探究其调控作用及功能。方法：通过UCSC数据库下载HCC的转录本数据和临床病例数据，提取eRNA及其预测的相应靶基因表达矩阵，用Kaplan-Meier和Spearman相关性分析方法筛选HCC预后相关的eRNA和靶基因，并采用最小化绝对收缩和选择算子回归分析及多因素Cox多元回归分析构建HCC预后风险评分模型。设计合成针对筛选所获关键eRNA AP003469.2的小干扰RNA并转染肝癌SMMC-7721细胞，采用RT-PCR方法验证敲减效率，qPCR法检测AP003469.2靶基因YWHAZ的表达水平，CCK-8法检测转染后SMMC-7721细胞的增殖情况。结果：筛选获得4个与预后相关基因，包括两个eRNA（AP003469.2和SPRY4-AS1）和两个靶基因（PPARGC1A和SLC2A1）（P<0.05），其中PPARGC1A高表达提示预后较好，AP003469.2、SPRY4-AS1和SLC2A1基因高表达则提示预后较差。基于4个基因构建的预后风险评分模型，第1、3和5年的AUC分别为0.730、0.699和0.679，提示模型具备良好的预测效能。在敲减AP003469.2后，SMMC-7721细胞中YWHAZ的表达无明显改变，且对细胞的增殖无影响。结论：基于生物信息学分析共筛选出4个关键基因，其中eRNA AP003469.2是HCC预后预测效能较高的标志物，其无促癌功能且对YWHAZ基因无调控作用。

Expert Consensus on Polymyxin Antimicrobial Susceptibility Testing and Clinical Interpretation / 中国医学科学杂志(英文版)

The polymyxins are important antimicrobial agents against antibiotic-resistant gram-negative bacilli. In 2020, the Clinical and Laboratory Standards Institute modified the clinical breakpoints for polymyxin susceptibility test by eliminating the "susceptible" interpretive category, only reporting intermediate (≤2 mg/L) and resistant (≥4 mg/L). However, the European Committee on Antimicrobial Susceptibility Testing recommended the use of clinical breakpoints of ≤2 mg/L as susceptible and >2 mg/L as resistant. The first-line laboratorians and clinicians in China have been perplexed by the inconsistence of international polymyxin clinical breakpoints and discouraged by the difficulty of conducting polymyxin susceptibility testing. Therefore, it is urgently needed to make it clear for the laboratorians in China to know how to accurately carry out polymyxin susceptibility testing and standardize the interpretation of susceptibility testing results. To this end, the experts from relevant fields were convened to formulate this consensus statement on the testing and clinical interpretation of polymyxin susceptibility. Relevant recommendations are proposed accordingly for laboratorians and clinicians to streamline their daily work.

Prognostic factors in patients undergoing early-start peritoneal dialysis within 24 h after catheter insertion

This study aimed to investigate the clinical characteristics, prognosis, and factors for survival of patients who underwent early-start peritoneal dialysis (PD) within 24 h after catheter insertion three years after PD. This study was conducted from January 1, 2013 to December 31, 2017. All adult patients who were diagnosed with end-stage renal disease (ESRD) and underwent PD for the first time within 24 h after catheter insertion in our hospital were included. All patients with PD were followed-up until they withdrew from PD, switching to hemodialysis, were transferred to other medical centers, underwent renal transplantation, died or were lost to follow-up, or continued to undergo dialysis until the end of the study period. The follow-up observation lasted three years. The number of eligible patients was 110, and switching to hemodialysis and death were the main reasons for patients to withdraw from PD. The 1-, 2-, and 3-year technical survival rates of patients were 89.1, 79.1, and 79.1% respectively, while the 1-, 2- and 3-year survival rates were 90, 81.8, and 81.8%, respectively. The Charlson comorbidity index, age, hemoglobin, serum albumin, diabetic nephropathy, chronic glomerulonephritis, and hypertensive renal damage were independent risk factors that affected the prognosis of PD patients. Under the condition of ensuring the quality of the PD catheter insertion, early-start PD within 24 h after catheter insertion is a safe treatment approach for ESRD patients.

Comparison of exosome extracting methods from human umbilical cord mesenchymal stem cells / 中国组织工程研究

BACKGROUND: Cell-free stem cell therapy has been an issue of concern, but there is no conclusion on how to extract high-quality exosomes. OBJECTIVE: To extract exosomes from human umbilical cord mesenchymal stem cells by using three different methods, and then to screen the optimal method. METHODS: Exosomes were extracted from human umbilical cord mesenchymal stem cells by using the Total Exosome Isolation test kit, Exo Quick test kit and differential ultracentrifugation method, respectively. Then, transmission electron microscopy was used for morphological observations, BCA was utilized to quantify the protein, and western blot assay was applied to detect surface markers CD9, CD81 and CD63. RESULTS AND CONCLUSION: Extraction of exosomes was completed by all the three methods, and round or oval membranous vesicles were observed under the transmission electron microscope. The protein content and purity of exosomes was highest in the differential ultracentrifugation group, followed by the Exobiology Quick kit group, and lowest in the Total Exosome Isolation kit group, and there were significant differences among the three groups (P < 0.05). Under the same protein concentration, surface specific markers, CD81, CD63 and CD9, were expressed highest in the differential ultracentrifugation group, followed by the Exobiology Quick kit group, and lowest in the Total Exosome Isolation kit group. The operating time was significantly lower in the Exobiology Quick kit group compared with the other two groups (P < 0.05). To conclude, despite a longer operating time, the differential ultracentrifugation method is a rational method to extract enough exosomes with relative high purity.

Progress on diagnosis and treatment of proximal tibiofibular joint dislocation / 中国骨伤

Dislocation of proximal tibiofibular joint(PTFJ) is relatively infrequent in clinic, it can be either isolated or associated with tibia fracture, fibular fracture and ankle injury and so on. Chronic symptomatic PTFJ instability are easily mixed with meniscal tears. It was easily neglected because of the mild clinical presentation and atypical change on radiography. Early diagnosis and treatment are crucial to prevent chronic knee pain and instability. The paper concluded the anatomy, classification, complication, diagnosis, treatment, clinical effect and insufficient of the dislocation of PTFJ, to direct the diagnosis and treatment of proximal tibiofibular joint dislocation in clinical work.

Spectrum and antimicrobial resistance of common pathogenic bacteria isolated from patients with acute exacerbation of chronic obstructive pulmonary disease in mainland of China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bacteria-induced respiratory infection has been long considered to be the major cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, a clear picture about the distribution and drug-resistance of pathogenic bacteria in the lower airways should be helpful for treatment of the disease. So far, data on this topic among Chinese are lacking.</p><p><b>METHODS</b>A surveillance study was performed in consecutive patients with AECOPD at five areas in China between October 2006 and April 2008. The sputum from these patients was cultured and isolated for bacteria. Agar dilution method was used to determine the minimal inhibitory concentrations (MICs) of levofoxacin and other 15 antibiotics against these strains.</p><p><b>RESULTS</b>Three hundred and fifty-nine pathogenic bacterial strains were isolated among 884 patients with AECOPD. The predominant bacteria were Pseudomonas aeruginosa (21.7%), Klebsiella pneumoniae (12.3%), Haemophilus influenzae (14.2%) and Streptococcus pneumoniae (11.7%), followed by Haemophilus parainfluenzae (9.5%), Acinetobacter baumannii (7.8%), Moraxella catarrhalis (6.4%) and Escherichia coli (3.6%). The majority of bacterial pathogens isolated in this study were susceptible to fuoroquinolones, ceftazidime, cefepime and imipenem.</p><p><b>CONCLUSIONS</b>Gram-negative bacilli are the leading pathogens in patients with AECOPD in China. Haemophilus parainfluenzae may be one of the most important pathogens in AECOPD. This study provides evidence for local surveillance of AECOPD pathogens and appropriate choice of antimicrobials in China.</p>

An uncontrolled open-label, multicenter study to monitor the antiviral activity and safety of inhaled zanamivir (as Rotadisk via Diskhaler device) among Chinese adolescents and adults with influenza-like illness / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is the first multicenter clinical study in China to investigate zanamivir use among Chinese adolescents and adults with influenza-like illness (ILI) since 2009, when inhaled zanamivir (RELENZA(®)) was marketed in China.</p><p><b>METHODS</b>An uncontrolled open-label, multicentre study to evaluate the antiviral activity, and safety of inhaled zanamivir (as Rotadisk via Diskhaler device); 10 mg administered twice daily for 5 days in subjects ≥ 12 years old with ILI. Patients were enrolled within 48 hours of onset and followed for eight days. Patients were defined as being influenza-positive if the real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) test had positive results.</p><p><b>RESULTS</b>A total of 400 patients ≥ 12 years old were screened from 11 centers in seven provinces from March 2010 to January 2011. Three hundred and ninety-two patients who took at least one dose of zanamivir were entered into the safety analysis. The mean age was 33.8 years and 50% were male. Cardiovascular diseases and diabetes were the most common comorbidities. All the reported adverse events, such as rash, nasal ache, muscle ache, nausea, diarrhea, headache, occurred in less than 1% of subjects. Mild sinus bradycadia or arrhythmia occurred in four subjects (1%). Most of the adverse events were mild and did not require any change of treatment. No severe adverse events (SAE) or fatal cases were reported. Bronchospasm was found in a 38 years old woman whose symptoms disappeared after stopping zanamivir and without additional treatment. All the 61 influenza virus isolates (43 before enrollment, 18 during treatment) proved to be sensitive to zanamivir.</p><p><b>CONCLUSIONS</b>Zanamivir is well tolerated by Chinese adolescents and adults with ILIs. There is no evidence for the emergence of drug-resistant isolates during treatment with zanamivir.</p>

Involvement of p38 mitogen-activated protein kinase in E. coli-induced U937 apoptosis / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate whether the effect of E. coli on U937 cell lines apoptosis is mediated via p38 mitogen-activated protein kinase (MAPK) activation.</p><p><b>METHODS</b>The U937 cell lines were treated with E. coli at different time or together with SB203580, an inhibitor for p38. Cell apoptosis was analyzed by flow cytometry. p38 activities were detected by Western blotting.</p><p><b>RESULTS</b>E. coli induced apoptosis in cultured U937 cell lines in a time-dependent manner. The phosphorylation of p38 was induced after 10 minutes infection, reached the peak after 20 minutes, and started to decline after 30 minutes. In contrast, the level of total p38 protein was not changed in whole experimental period. Inhibition of p38 with SB203580 significantly inhibited E. coli induced apoptosis in U937 cells.</p><p><b>CONCLUSION</b>The activation of the p38 MAPK in U937 cell lines by E. coli is a major pathway to mediate the apoptosis.</p>

In vitro study on bacterial growth enhancement in the presence of TNF-?,IL-1? and IL-6 / 中国感染与化疗杂志

Objective To conduct an in vitro study of the growth of Pseudomonas aeruginosa,Staphylococcus aureus and Acin- etobacter spp.,and evaluate their response to various concentrations of tumor necrosis factor(TNF)-?,interleukin (IL)-1?, and IL-6.Methods To monitor the growth of bacteria incubated with the cytokines TNF?,IL-1?and IL-6 that were added to RPMI 1640 medium in various concentrations (10,50.100,500 pg,1 and 10 ng) at 2,4 to 6,8 and 16-18 h.The bacterial concentration was estimated when the mixtures of cytokines and specific neutralizing monoclonal antibodies (MoAbs) were in- cubated.Results We found that all three bacterial species showed concentration-dependent growth enhancement when incubated with one or more tested cytokines.Blockade by specific neutralizing cytokine significantly inhibited cytokine-induced growth. When compared with control,the 6 h growth response was maximal with IL-1?for Staphylococcus aureus and Acinetobacter spp.,and with IL-6 for Pseudomonas aeruginosa.Conclusions In this study we provide additional evidence for a newly de- scribed mechanism for bacterial proliferation in the presence of exaggerated and protracted inflammation.The effect that cyto kine-induced growth enhancement inhibited by specific neutralizing cytokine MoAbs may be useful for antimicrobial therapy.

Advances in studies on potential toxicity of flavonoids / 中国中药杂志

Flavonoids, including flavones, flavonols, anthocyanins, flavanones, chalcones, flavan, proanthocyanidins, isoflavonoids and biflavonoids, etc, are natural components in our diet and plants. Several beneficial properties have been attributed to these compounds, including antioxidant, anti-inflammatory and anticarcinogenic effects, etc. Flavonoid preparations are marketed as herbal medicines or dietary supplements for a variety of alleged nontoxic therapeutic effects. However, they have yet to pass controlled clinical trials for efficacy, and their potential for toxicity is an understudied field of research. This review summarizes the current studies on the toxicity induced by flavonoids and gives some advices for ingesting flavonoids.