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.

Objective:To evaluate the effect of inhibition of interleukin-6 (IL-6) trans-signaling on sepsis-associated encephalopathy (SAE) in mice.Methods:Eighty healthy male C57BL/6J mice, aged 8-10 weeks, weighing 22-24 g, were divided into 4 groups using a random number table method: sham operation group (Sham group, n=10), SAE group ( n=35), SAE plus sgp130Fc group ( n=25) and sgp130Fc group ( n=10). Sepsis was induced by cecal ligation and puncture (CLP) in anesthetized animals.Sham and sgp130Fc groups received no CLP.In group sgp130Fc and group SAE+ sgp130Fc, sgp130Fc 0.5 mg/kg was intraperitoneally injected at 1 h after sham operation or CLP.The survival rates, body weight and neurological function scores were recorded within 1-10 days after sham operation or CLP.Four mice in each group were selected at 24 h after sham operation or CLP to detect the expression of occlusin in hippocampus by Western blot.Five mice in each group were selected to measure cognitive function using Morris water maze test at day 4 after sham operation or CLP. Results:Compared with group Sham, the survival mice, body weight and neurological function scores on days 2-10 after CLP were significantly decreased, the expression of occludin was down-regulated, the frequency of crossing the original platform was decreased, and the time spent in target quadrant was shortened in group SAE ( P<0.05), and no significant change was found in the indexes mentioned above in group sgp130Fc ( P>0.05). Compared with group SAE, the survival rate and neurological function scores on days 3-10 after CLP were significantly increased, the expression of occludin was up-regulated, the frequency of crossing the original platform was increased, and the time spent in target quadrant was prolonged ( P<0.05), and no significant change was found in body weight in group SAE+ sgp130Fc ( P>0.05). Conclusions:Inhibition of IL-6 trans-signaling can reduce the damage to the blood brain barrier and SAE in mice.

Objective:To define more information for familial hematuria by genetic screening in a pedigree with familial hematuria.Methods:This was a 4 generation pedigree included 20 family members. The clinical data and laboratory manifestations of the family members were reviewed and collected from medical records. Meanwhile, the peripheral blood samples of 11 family members of the pedigree were collected, and then DNA samples were extracted by salting out method for genetic analysis. For genetic analysis, firstly, three family members including the proband were selected for whole exome sequencing, and the genetic variations were screened according to the sequence variation interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) for diagnostic sequence interpretation. Then PCR and Sanger sequencing were used to verify the identified pathogenic variants in all family members in the pedigree.Results:In the pedigree, 6 female members had persistent hematuria. Among them, 2 died due to end-stage renal disease, 2 died due to non-renal diseases, and 2 maintained stable renal function. One of the two members with stable renal function was diagnosed as IgA nephropathy by renal biopsy. Moreover, diffuse basement membrane lesions were identified in her renal biopsy sample after the electron microscope examination, which resulted in the suspected diagnosis of Alport syndrome. Genetic testing in this pedigree revealed two novel mutations in COL4A4 gene (NM_000092), c.G446T:p.G149V in exon 7 and c.G1249A:p.G417R in exon 20. Conclusion:Two novel mutations of COL4A4 gene (c.G446T:p.G149V in exon 7 and c.G1249A:p.G417R in exon 20) in a hematuria pedigree are related with phenotype of familial hematuria.

In this retrospective cohort study, we aim to evaluate the effect of endocapillary hypercellularity (E) lesions on the renal prognosis and response to immunosuppressive therapy, especially diffuse endocapillary hypercellularity lesion in IgA nephropathy (IgAN). A total of 365 patients with IgAN and E lesions and 31 patients with diffuse E lesions and over 12-month follow-up period were included in this study. We performed an 1∶1 propensity score to identify controls with matched clinical and pathological features from 769 IgAN patients without E lesions. The end-point was defined as a 30% decrease in estimated glomerular filtration rate (eGFR) or end-stage kidney disease. The kidney survival of the two groups was compared by Kaplan-Meier analysis. During median follow-up period of 41 months, kidney survival rates in patients with E lesions were 96.0% at 1 year, 83.6% at 3 years, 67.7% at 5 years; while they were 96.9% at 1 year, 83.6% at 3 years, and 68.7% at 5 years in patients without E lesions ( P=0.265).The HRof immunosuppressive therapy was 1.038 (95% CI 0.749-1.440) and 1.113 (95% CI 0.770-1.609) in patients not receiving immunosuppressive therapy ( P=0.781). (2) During median follow-up period of 52.5 months, the kidney survival rates in patients with diffuse E-lesion were 100.0% at 1 year, 96.2% at 3 years, 74.5% at 5 years; while they were 96.2% at 1 year, 82.3% at 3 years, and 63.7% at 5 years in patients without E-lesion ( P=0.158). The HR of immunosuppressive therapy was 0.625 (95% CI 0.213-1.839) and 0.447 (95% CI 0.028-7.191) in patients not receiving immunosuppressive therapy ( P=0.825). E lesion or diffuse E lesion may not be associated with prognosis or response to immunosuppressive therapy.

Objective:To evaluate the clinicopathological characteristics and prognosis of IgA nephropathy (IgAN) patients with microangiopathy lesions and with no hypertension.Methods:Adult IgAN patients without hypertension were selected from Peking University First Hospital. All kidney biopsies were independently reviewed by 2 investigators. Patients were divided into three groups (microangiopathy group, simple arterio/arteriolosclerosis group and normal vascular group) by renal arteriolar lesions. Composite kidney end point event defined as a ≥30% reduction in estimated glomerular filtration rate (eGFR) and end-stage kidney disease. Cox regression analysis was used to test the association between microangiopathy lesions and the outcomes.Results:A total of 420 patients were included in this study, of which 37(8.8%) patients had renal arteriolar microangiopathy lesions, 134 (31.9%) patients had simple arterio/ arteriolosclerosis, and the others had no vascular lesion. Compared with simple arterio/arteriolosclerosis group or non-vascular lesion group, patients with renal arteriolar microangiopathy lesions had more severe urine protein ( P=0.002), worse renal function ( P<0.001), higher proportion of segmental glomerulosclerosis and/or balloon adhesion (S1), tubular atrophy/interstitial fibrosis (T1/2), cellular/fibrocellular crescents (C1/2) (all P<0.05). During the follow-up, 20(54.1%) patients with microangiopathy lesions, 45(33.6%) patients with simple arterio/arteriolosclerosis and 82(32.9%) patients without vascular lesion reached the composite kidney end points ( χ2=6.491, P=0.039). In a multivariable Cox regression model, the presence of microangiopathy lesions was an independent risk factor for kidney disease progression in IgAN patients ( HR=1.872, 95% CI 1.044-3.357, P=0.035), and simple arterio/arteriolosclerosis was not a risk factor for kidney disease progression. Conclusion:It is not uncommon for non-hypertensive patients with IgAN having microangiopathy lesions, which suggests that hypertension is not the sole risk factor for microangiopathy lesions.

Background: In China, secondary cytoreductive surgery (SCR) has been widely used in ovarian cancer (OC) over the past two decades. Although Gynecologic Oncology Group-0213 trial did not show its overall survival benefit in first relapsed patients, the questions on patient selection and effect of subsequent targeting therapy are still open. The preliminary data from our pre-SOC1 phase II study showed that selected patients with second relapse who never received SCR at recurrence may still benefit from surgery. Moreover, poly(ADP-ribose) polymerase inhibitors (PARPi) maintenance now has been a standard care for platinum sensitive relapsed OC. To our knowledge, no published or ongoing trial is trying to answer the question if patient can benefit from a potentially complete resection combined with PARPi maintenance in OC patients with secondary recurrence. Methods SOC-3 is a multi-center, open, randomized, controlled, phase II trial of SCR followed by chemotherapy and niraparib maintenance vs chemotherapy and niraparib maintenance in patients with platinum-sensitive second relapsed OC who never received SCR at recurrence. To guarantee surgical quality, if the sites had no experience of participating in any OC-related surgical trials, the number of recurrent lesions evaluated by central-reviewed positron emission tomography–computed tomography image shouldn't be more than 3. Eligible patients are randomly assigned in a 1:1 ratio to receive either SCR followed by 6 cyclesof platinum-based chemotherapy and niraparib maintenance or 6 cycles of platinum-based chemotherapy and niraparib maintenance alone. Patients who undergo at least 4 cycles of chemotherapy and must be, in the opinion of the investigator, without disease progression, will be assigned niraparib maintenance. Major inclusion criteria are secondary relapsed OC with a platinum-free interval of no less than 6 months and a possibly complete resection. Major exclusion criteria are borderline tumors and non-epithelial ovarian malignancies, received debulking surgery at recurrence and impossible to complete resection. The sample size is 96 patients. Primary endpoint is 12-month non-progression rate.

Objective To establish the measurement of IgA1 O-glycan-specific antiglycan autoantibodies in patients with IgA nephropathy (IgAN),and evaluate their role in the development and progression of IgAN.Methods In the IgAN regular follow-up cohort of Peking University Institute of Nephrology from January 2006 to December 2015,170 patients drawn by stratified randomization were enrolled in this study.Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of plasma galactose-deficient IgA1 (Gd-IgA1) and antiglycan autoantibody (IgG and IgA1).The correlation between antiglycan autoantibodies and clinicopathological parameters was analyzed by linear correlation and multiple linear regression analysis.The receiver operating characteristic curve (ROC) was used to evaluate the value of plasma anti glycide antibodies in the diagnosis of IgAN.Results IgG and IgA1 antiglycan antoantibodies that specifically recognized Fab-hinge region (Fab-HR) antigens could be detected in both IgAN and healthy control group.Agglutinin inhibition test showed that the specific antigen epitope was N-acetylgalactosamine (GalNAc) residue exposed to galactose deficiency in IgA1 hinged region.There was no significant difference in the absolute levels of plasma IgG antiglycan autoantibodies between IgAN and healthy controls (P=0.963).After adjustment of the plasma level of IgG,the normalized antiglycan autoantibody (ln[IgG antiglycan antibody/IgG]) in patients with IgANwas significantly higher than that in healthy controls (0.58±0.31 vs 0.37±0.11,P ＜ 0.01).The normalized level of IgG antiglycan autoantibody in IgAN patients was positively correlated with 24 h urine protein level during renal biopsy (Spearman r=0.183,P ＜ 0.05),and was also significantly correlated with 24 h urinary protein level after adjusting for baseline clinical and pathological factors (β=0.713,95％CI 0.323-1.102,P ＜ 0.01).The area under ROC curve (AUC) of normalized IgG antiglycan autoantibody in the diagnosis of IgAN was 0.764 (95％ CI 0.682-0.845,P ＜ 0.05).Using the cut-off value of 0.396,the sensitivity and specificity of normalized IgG antiglycan autoantibody for IgAN were 0.729 and 0.700 respectively.There was no significant difference in the absolute or normalized levels of IgA1 antiglycan autoantibodies between IgAN patients and healthy controls.Conclusions Gd-IgA1-specific antiglycan autoantibodies can be detected both in IgAN patients and healthy controls.They are elevated in some patients with IgAN and possibly involved in the development of IgAN.

Objective To evaluate the clinicopathological characteristics and outcomes of IgA nephropathy (IgAN) with acute tubulointerstitial nephropathy (ATIN).Methods Patients who were diagnosed as IgAN with ATIN and IgAN without ATIN by renal biopsy in Peking University First Hospital were enrolled.There were 74 cases of IgAN with ATIN,and seventy-four cases of IgAN without ATIN were enrolled based on stratified sampling (chosen by 1∶ 1).The two groups were well matched with age,gender,follow-up time,mesangial hypercellularity(M),endocapillaryhypercellularity (E),segmental glomerulosclerosis(S),tubular atrophy/interstitial fibrosis(T) and cellular/fibrocellular crescent(C).The clinicopathological characteristics and outcomes of two groups were retrospectively analyzed.A composite end point,defined as 30％ or 50％ estimated glomerular filtration rate (eGFR)decline and end stage renal disease (ESRD) was used.Renal function and proteinuria during follow-up were observed.Renal survival was calculated by Kaplan-Meier survival analysis and risk factors of progression were analyzed by using univariate and multivariate Cox regression models.Results Seventy-four cases of IgAN with ATIN and seventy-four cases of IgAN without ATIN were enrolled.Serum creatinine [(185.6±83.2) μmol/L vs (146.3 ±69.2) μmol/L,P=0.010] and incidence of acute kidney disease (AKD) (31.1％ vs 5.4％,P ＜ 0.001) were higher in IgAN with ATIN group than those in IgAN without ATIN group.Patients in ATIN group received more immunosuppressive treatment (86.5％vs 58.1％,P＜ 0.001).During 1 year after biopsy,mean eGFR increased significantly in IgAN with ATIN group [(39.7+ 14.6) ml· min-1· (1.73 m2)-1 vs (47.2+ 19.9) ml· min-1· (1.73 m2)-1,P=0.017],but mean eGFR was not statistic different in IgAN without ATIN group [(60.0±30.5) ml· min-1· (1.73 m2)-1 vs (59.0±31.7) ml· min-1· (1.73 m2)-1,P=0.567].Median follow-up was 23.0 months in IgAN with ATIN group,and Median follow-up was 30.0 months in IgAN without ATIN group.Incidence of composite end point had no significant differences between two groups.IgAN with ATIN was not the independent risk factor for end point.IgAN patients with ATIN were divided into two groups (with AKD and without AKD),then renal survival rate was higher (Log-rank test,x2=5.293,P=0.021) and the risk for composite end point decreased by 79.2％ (HR=0.208,95％CI 0.046-0.939,P=0.041) in the group with AKD.Conclusions In IgAN,there is a subgroup of patients with the specific pathological phenotype combined with ATIN.Compared with those without AKD,the risk for composite end point of IgAN patients with ATIN and AKD showed a 79.2％ decrease.

Objective To explore the inhibitory effects of lobaplatin and cisplatin and their regulation of apoptosis-related genes in ovarian cancer cells in nude mice.Methods SKOV3 cells were implanted into nude mice.In monotherapy treatment study,the nude mice bearing human SKOV3 cells were randomly divided into control,lobaplatin,and cisplatin groups,with 7 mice in each group.The mice in each group were received corresponding treatment.The volume of tumor and the weight of nude mice were measured three times per week,respectively.Tumor inhibitory rate was calculated.The protein expressions of bax and bcl-2 were detected by flow cytometry.Results The growth inhibitory rate was 47.2％ in lobaplatin group and 42.8％ in cisplatin group,without significant difference between two groups (P ＞ 0.05).The expression of bcl-2 was decreased but the bax was increased in lobaplatin and ciaplatin groups compared to the control group.Conclusions Lobaplatin can significantly inhibit the growth of ovarian cancer cells,induce apoptosis by down-regulation of bcl-2 and up-regulation of bax.