Objective To analyze the changing prevalence and resistance profiles of multiple drug-resistant(MDR)bacteria in Minhang Hospital of Fudan University before and after the onset of COVID-19 pandemic.Methods The resistance profiles of 6 bacterial species were compared before(2017-2019)and after(2020-2022)the onset of COVID-19 pandemic.WHONET 5.6 software was used to statistically analyze the data of antimicrobial susceptibility testing.Results After the onset of COVID-19(2020-2022),the prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKP)was significantly higher than that in the pre-pandemic period(2017-2019)(40.1％vs 27.9％,P＜0.01),while the prevalence of carbapenem-resistant Escherichia coli(CREC)decreased significantly(1.9％vs 3.1％,P＜0.05).The prevalences of carbapenem-resistant Acinetobacter baumannii(CRAB),carbapenem-resistant Pseudomonas aeruginosa(CRPA),methicillin-resistant Staphylococcus aureus(MRSA),and vancomycin-resistant Enterococcus(VRE)did not show significant difference before and after the onset of COVID-19 pandemic.MDR isolates were mainly isolated from respiratory tract samples either before or after COVID-19 pandemic(78.4％vs 78.5％).The prevalence of MDR in the intensive care unit(ICU)was significantly higher during the period from 2020 to 2022 compared to the pre-pandemic period(53.1％vs 35.5％,P＜0.01).The resistance rate of MRSA to methoprim-sulfamethoxazole decreased from 15.7％during 2017-2019 to 3.5％during 2020-2022(P＜0.01).Compared to the pre-pandemic period,the E.faecalis strains showed lower resistance rates to penicillin G,ampicillin,and levofloxacin during 2020-2022.The resistance rate of E.faecium to high-level gentamicin decreased significantly from 50.1％during 2017-2019 to 39.2％during 2020-2022(P＜0.01).The resistance rate of E.coli to imipenem decreased from 2.7％to 1.2％(P＜0.01),while A.baumannii and P.aeruginosa strains showed stable resistance rates to carbapenems(P＞0.05).Conclusions After the onset of COVID-19 pandemic,the prevalence of CREC decreased significantly.The prevalences of CRAB,CRPA,MRSA,and VRE also showed a decreasing trend.However,the prevalence and resistance rates of CRKP significantly increased.It is necessary to strengthen hospital infection control measures to curb the spread of MDR bacteria.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

OBJECTIVE: To explore the effect of thoracic paravertebral anesthesia (TPVB) on prognosis of patients undergoing resection of lung cancer. METHODS: This study was conducted among the patients undergoing surgical resection of primary lung cancer under general anesthesia or TPVB combined with general anesthesia (TPVB+GA) between January, 2017 and May, 2018.The patients were enrolled in TPVB+GA group and GA group (control group) using a propensity score matching (PSM) method at the ratio of 1:2 based on their baseline characteristics.The clinical parameters, 5-year overall survival (OS), progression-free survival (PFS) and intraoperative dosage of opioids were compared between the two groups to assess the impact of TPVB on prognosis of the patients. RESULTS: Forty-seven patients were enrolled in TPVB+GA group and 94 in the control group.Kaplan-Meier survival analysis showed a significantly prolonged PFS in the patients with TPVB+GA (log-rank P=0.034), with an odds ratio (OR) of 0.45(95%CI: 0.33-0.89).Consistently, univariate and multivariate Cox regression analyses identified TPVB as an independent protective prognostic factor for patients with lung cancer resection (P=0.002, OR=0.33, 95%CI: 0.16-0.66).Cox regression analyses indicated that a lower intraoperative dose of remifentanil was significantly correlated with a longer PFS of the patients following lung cancer resection (P=0.017, OR=0.47, 95%CI: 0.25-0.87).Chi-square test confirmed that TPVB, but not general anesthesia, significantly reduced intraoperative dose of remifentanil, indicating a possible synergistic effect of TPVB with opioids to affect the survival of the patients. CONCLUSION TPVB can prolong the survival time and improve the prognosis of the patients undergoing surgical resection of lung cancer.
Humans ; Remifentanil ; Pain, Postoperative ; Nerve Block/methods* ; Analgesics, Opioid ; Prognosis ; Lung Neoplasms/surgery*

AIM: To evaluate the efficacy and safety of three doses of Conbercept intravitreal injection with panretinal photocoagulation(PRP)followed by EX-PRESS glaucoma shunt implantation on patients with neovascular glaucoma(NVG).METHODS: Prospective study. A total of 37 patients(37 eyes)with NVG from May 2018 to September 2020 were collected. All accepted intravitreal injection of Conbercept and PRP 3-5d later, and accepted EX-PRESS glaucoma shunt implantation within 1wk after surgery. They were randomly divided into the low-dose group(13 eyes), the conventional dose group(12 eyes)and the high-dose group(12 eyes)according to three doses of preoperative Conbercept intravitreal injection, and they were injected with 10mg/mL Conbercept of 0.03, 0.05 and 0.08 mL(0.3, 0.5 and 0.8 mg Conbercept contained)respectively. The regression of iris and angle neovascularization(NV)after intravitreal injection was observed in the three groups, and postoperative intraocular pressure(IOP), best corrected visual acuity(BCVA)and complications were compared among the three groups.RESULTS: All patients completed follow-up. Cases with NV regression of iris and angle in the high-dose group were significantly more than the low-dose group(χ2=0.132, P=0.003)and the conventional dose group(χ2=0.154, P=0.015)3-5d after intravitreal injection. BCVA and IOP of the three groups at 1, 3 and 6mo after surgery were improved compared with those before treatment. IOP of the low-dose group, the conventional dose group and the high-dose group at 12mo after surgery was 14.12±2.63, 13.37±2.18 and 12.15±1.43mmHg, respectively. IOP of the high-dose group was lower than that of the low-dose group and the conventional dose group(all P<0.05). The BCVA of the high-dose group at 12mo after surgery was better than that of the low-dose group and the conventional dose group(all P<0.05). There was no significantly statistical difference in the incidence of postoperative complications at 12mo after surgery among the three groups(P>0.05).CONCLUSIONS: The intravitreal injection of high-dose(0.8mg)Conbercept combined with PRP and EX-PRESS glaucoma shunt implantation has particularly significant clinical effect on the treatment of NVG.

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota.However,the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations.A well-controlled envi-ronment is thus necessary to reduce undesirable confounding effects,and recapitulate age-dependent changes in the gut microbiota of healthy primates.Herein we performed 16S rRNA gene sequenc-ing,characterized the age-associated gut microbial profiles from infant to elderly crab-eating maca-ques reared in captivity,and systemically revealed the lifelong dynamic changes of the primate gut microbiota.While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium,the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants,underlining their potential role in host development.Importantly,topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity,and its tremendous decline with age could probably be linked to healthy aging.Moreover,we identified key driver microbes responsible for such age-dependent network changes,which were further linked to altered metabolic functions of lipids,carbohydrates,and amino acids,as well as phenotypes in the microbial community.The current study thus demon-strates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota,and provides new insights into their roles in the development and healthy aging of their hosts.

Department of General practice of West China Hospital of Sichuan University has been commissioned to train general practitioner for Tibet Autonomous Region since 2015. Based on the "demand-oriented and clinical ability training", the established training framework includes four aspects: a rotation plan of general practice theory-clinical practice-community application, the closed-loop mechanism of teaching management system improvement,innovation of training assessment and teaching activities. This article summarizes the practical experience of the commissioned general practice residency training for Tibet to provide reference for the program design.

OBJECTIVES: To investigate the effect on essential hypertension of the topical application of TAT-Cu, Zn-superoxide dismutase (TAT-SOD) at left acupoint Zusanli (ST 36), and to observe whether the change of electrical potential difference (EPD) can be related to the change of blood pressure. METHODS: Sixteen patients with essential hypertension and 16 healthy subjects were included in the study. EPD between the left acupoints of Yanglingquan (GB 34) and Qiuxu (GB 40) was firstly screened out for the EPD detection. An intracellular superoxide quenching enzyme, TAT-SOD, was topically applied to the acupoint ST 36 within an area of 1 cm once a day, and the influence on EPD was investigated. The dosage applied to TAT-SOD group (n=8) was 0.2 mL of 3000 U/mL TAT-SOD cream prepared by adding purified TAT-SOD to a vehicle cream, while placebo group (n=8) used the vehicle cream instead. The left acupoints of Yanglingquan (GB 34) and Qiuxu (GB 40) were selected for EPD measurement after comparing EPD readings between 5 acupoints on each of all 12 meridians. RESULTS: EPDs between the left acupoints of GB 34 and GB 40 for 16 patients of essential hypertension and 16 healthy subjects were 44.9±6.4 and 5.6±0.9 mV, respectively. Daily application of TAT-SOD for 15 days at ST 36 of essential hypertension patients significantly decreased systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 179.6 and 81.5 mm Hg to 153.1 and 74.1 mm Hg, respectively. Responding to the change in blood pressure, EPD between the left acupoints of GB 34 and GB 40 also declined from 44.4 to 22.8 mV with the same trend. No change was observed with SBP, DBP and EPD between the left acupoints of GB 34 and GB 40 with the daily application of the placebo cream. CONCLUSION Enzymatic scavenging of the intracellular superoxide at ST 36 proved to be effective in decreasing SBP and DBP. The results reconfirm the involvement of superoxide anions and its transportation along the meridians, and demonstrate that EPD between acupoints may be an indicator to reflect its functioning status. Moreover, preliminary results suggest a close correlation between EPD and blood pressure readings, implying a possibility of using EPD as a sensitive parameter for blood pressure and to monitor the effect of antihypertensive treatment.

Objective::In this study, a network pharmacology-based method was applied to analyze the mechanism of modified Erzhiwan combined with epimedium in treatment of atherosclerosis. Method::The compounds and targets of modified Erzhiwan combined with epimedium were screened in traditional Chinese medicine(TCM) systems pharmacology database and analysis platform (TCMSP) and bioinformatics analysis tool for molecular mechanism of TCM (BATMAN-TCM). Mang related databases were applied to find the target-related to atherosclerosis.The common targets of modified Erzhiwan combined with epimedium and atherosclerosis were got by venn diagrams.Cytoscape 3.6.1 was used to construct ingredients-disease-targets networks.Then protein-protein interaction (PPI) analysis of ingredients-disease-targets was builed in STRING database, and was visualized by Cytoscape 3.6.1, then important modules were analyzed with Moleculaar complex detection(MCODE). Biological information annotation databases (DAVID) was used to carry on gene ontology (GO) analysis and enrichment analysis of gene encyclopedia kyoto encyclopedia of genes and genomes (KEGG) pathway. Result::A total of 38 active ingredients and 266 potential targets of modified Erzhiwan combined with epimedium were obtained from TCMSP and BATMAN-TCM, 254 atherosclerosis-related targets were retrieved from disease database.Then 52 common targets were obtained and 14 core genes were screened.Biological processes were related to inflammatory response, regulation of insulin secretion, positive regulation of nitric oxide biosynthetic process, etc.The biological pathways mainly included tumor necrosis factor signaling pathway, NF-kappa B(NF-κB)signaling pathway, peroxisome proliferators-activated receptors signaling pathway and so on. Conclusion::Modified Erzhiwan combined with epimedium may play the anti-atherosclerosis role by estrogen-like effect through attach estrogen receptor, inhibiting inflammation and improving insulin resistance, which may provide guidance for further experimental research.