Objective To investigate the effects of Zhongfengting granule on plasma metabolites in acute cerebral ischemia MCAO model rats by non-targeted metabolomics techniques,and to elucidate the neuroprotective mechanism of Zhongfengting granule.Methods 24 male SD rats were randomly divided into blank group,model group and Chinese medicine group,with 8 rats in each group.Model group and Chinese medicine group were treated with middle cerebral artery thrombus method to establish the MCAO rat model,and the medicine was administered on the same day after the successful modeling.The Chinese medicine group was given(22.68 g·kg-1)Zhongfengting granule solution by gavage,and the blank group and model group were given equal volume normal saline for 7 days.After administration,blood was collected intravenously.Plasma samples from blank group,model group and Chinese medicine group were analyzed by ultra-high performance liquid chromatogre-quadrupole tandem time-of-flight mass spectrometer,and differential metabolites were screened by multivariate statistical analysis.The metabolic pathways of the differentiated metabolites were analyzed based on KEGG database.Results Multivariate statistical analysis showed that the content of 22 potential biomarkers in the rat model of acute cerebral ischemia had significant changes,and the above-mentioned 22 potential biomarkers were significantly reversed by Zhongfengting granule(P<0.05).The enrichment results of metabolic pathways showed that Zhongfengting granule mainly affected phenylalanine metabolism,tyrosine metabolism,ascorbic acid metabolism and arachidonic acid metabolism.Conclusion Metabolites and metabolic pathways in MCAO model rats with acute cerebral ischemia are changed,and the different metabolites and metabolic pathways can be reversed by Zhongfengting granule,which mainly involve phenylalanine metabolism and regulate energy metabolism.

Objective To investigate the effects of Zhongfengting granule on plasma metabolites in acute cerebral ischemia MCAO model rats by non-targeted metabolomics techniques,and to elucidate the neuroprotective mechanism of Zhongfengting granule.Methods 24 male SD rats were randomly divided into blank group,model group and Chinese medicine group,with 8 rats in each group.Model group and Chinese medicine group were treated with middle cerebral artery thrombus method to establish the MCAO rat model,and the medicine was administered on the same day after the successful modeling.The Chinese medicine group was given(22.68 g·kg-1)Zhongfengting granule solution by gavage,and the blank group and model group were given equal volume normal saline for 7 days.After administration,blood was collected intravenously.Plasma samples from blank group,model group and Chinese medicine group were analyzed by ultra-high performance liquid chromatogre-quadrupole tandem time-of-flight mass spectrometer,and differential metabolites were screened by multivariate statistical analysis.The metabolic pathways of the differentiated metabolites were analyzed based on KEGG database.Results Multivariate statistical analysis showed that the content of 22 potential biomarkers in the rat model of acute cerebral ischemia had significant changes,and the above-mentioned 22 potential biomarkers were significantly reversed by Zhongfengting granule(P<0.05).The enrichment results of metabolic pathways showed that Zhongfengting granule mainly affected phenylalanine metabolism,tyrosine metabolism,ascorbic acid metabolism and arachidonic acid metabolism.Conclusion Metabolites and metabolic pathways in MCAO model rats with acute cerebral ischemia are changed,and the different metabolites and metabolic pathways can be reversed by Zhongfengting granule,which mainly involve phenylalanine metabolism and regulate energy metabolism.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

AIM:To evaluate and analyze the post-marketing adverse drug reaction(ADR)signals of polatuzumab vedotin,so as to provide reference for clinical safety management.METHODS:Using the FDA adverse drug event reporting system(FAERS)database and OpenVigil data platform,the ADR reports of polatuzumab vedotin were collect-ed from June 10,2019(FDA approval for market-ing)to the March 31,2023.The ADR signals were detected by using the reporting odds ratio(ROR)and proportional reporting ratio(PRR)in the pro-portional imbalance method.To increase the threshold and obtain stronger and more frequently occurring ADRs,a second screening of signals was performed.RESULTS:A total of 2 408 ADR reports related to polatuzumab vedotin were collected,and 83 ADR signals were detected after secondary screening.26 ADR signals were not mentioned in the drug instructions such as abnormal spinal mag-netic resonance imaging,increased bone resorp-tion,osteolysis,decreased aspartate aminotransfer-ase,decreased alanine aminotransferase,hypofibri-nogenemia,and pulmonary embolism.The system organ classes with a high signal counts or cumula-tive number of cases included infections and inva-sive diseases(24 signals,632 cases),various exami-nations(17 signals,675 cases),blood and lymphat-ic system diseases(11 signals,734 cases),various nervous system diseases(7 signals,153 cases),im-mune system diseases(3 signals,95 cases),system-ic diseases and various reactions at the site of ad-ministration(2 signals,145 cases),and systemic dis-eases and various reactions at the site of adminis-tration(2 signals,87 cases),etc.CONCLUSION:In addition to the common ADRs suggested by the in-structions,this study identified new ADR risk sig-nals for polatuzumab vedotin.In the clinical appli-cation of polatuzumab vedotin,in addition to the ADR mentioned in the instructions such as infec-tions,myelosuppression,peripheral neuropathies,infusion-related reactions,and abnormal liver func-tion,attention should also be paid to the risk sig-nals not mentioned such as abnormal spinal mag-netic resonance imaging,and increased bone re-sorption.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.
Pregnancy ; Female ; Humans ; Male ; Vas Deferens/abnormalities* ; Azoospermia/surgery* ; Epididymis/surgery* ; Retrospective Studies ; Tertiary Care Centers ; China ; Semen

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ² Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic ; Antiviral Agents/therapeutic use* ; DNA, Viral/therapeutic use* ; Retrospective Studies ; Mutation ; Drug Resistance, Viral/genetics* ; Lamivudine/therapeutic use*

Aim To investigate the eorrelation between angiotensin II (Ang II ) level and clinical indicators in patients with rheumatoid arthritis ( HA) , and to determine the therapeutic effect of angiotensin receptor blockers ( ARBs).Methods Plasma samples and personal information were collected from HA patients admitted to our hospital from 2019 to 2021.The level of Ang II in plasma was determined by ELISA to elucidate the correlation between plasma Ang II level and the severity of HA.The pathological changes of synovi-al tissues and T eells subtype in different groups of HA patients were determined by pathological examination and flow cytometry.A rat model of collagen-induced arthritis (CIA) was established and the pathological examination was used to confirm that valsartan could alleviate the disease course in the CIA animal model.Results Compared with control group, the plasma level of Ang II in HA patients significantly increased.After therapy with oral ARBs plasma Ang H levels and anti - cyclic citrullinated peptide antibody ( CCP) titre were significantly lower than those untreated HA patients.The level of Ang II in plasma was positively correlated with CCP and the number of monocytes, but negatively with number of RBC and hemoglobin content.Staining of synovial tissue with HE and Masson found that patients with HA had significant synovial proliferation, pannus formation , and numerous inflammatory cell infiltrates compared with control patients.Immunohistochemical results showed significant infiltration of CD4 4 T cells in synovial tissues of HA patients.Western blot and immunofluorescence analysis showed that the expression of angiotensin type 1 receptor ( ATI R ) was significantly up-regulated in CD4 + T cells and synovial tissues of HA patients.The results of animal experiments showed that valsartan harl therapeutic effect on CIA rats and could delay the disease process of CIA.Conclusions Plasma Ang II level is positively correlated with CCP level and HA severity.ARBs can down-regualte CCP level and delay disease progression in HA patients.Animal experiments showed that valsartan blocks the combination of Ang H and ATI R and has therapeutic effect on a CIA rat model.This study provides the theoretical and experimental basis for ARBs to become the preferred antihypertensive drugs for HA patients with hypertension.