This paper reported a type 1 diabetes patient who had severe diabetic nephropathy, retinopathy, hypertension, and hypothyroidism before pregnancy. The patient's blood glucose control was poor before pregnancy, and the complications were not properly treated. This was an unintended pregnancy, with a pre-pregnancy glycated hemoglobin A1c of 7.8% and early pregnancy urine protein of 3.81-4.53 g/24 h. Considering the patient's poor blood glucose control before pregnancy and the lack of proper treatment for multiple complications including nephropathy, a multidisciplinary consultation at an external hospital recommended termination of the pregnancy. However, the patient was determined to continue the pregnancy and was referred to Peking University First Hospital. Through strict blood glucose control, monitoring and evaluation of complications, and comprehensive management, the patient's blood glucose and blood pressure were well controlled during pregnancy. Regular monitoring of urine protein, renal function, and ocular fundus was conducted. At 31 weeks and 4 days of gestation, the patient's 24-hour urine protein significantly increased. After promoting fetal lung maturity, a cesarean section was performed at 34 weeks and 1 day of gestation, resulting in a successful delivery with good maternal and neonatal outcomes. At the 42-day postpartum follow-up, the patient's blood glucose and blood pressure were stable, urine protein returned to pre-pregnancy levels, and the infant was in good general condition.

This paper reported a type 1 diabetes patient who had severe diabetic nephropathy, retinopathy, hypertension, and hypothyroidism before pregnancy. The patient's blood glucose control was poor before pregnancy, and the complications were not properly treated. This was an unintended pregnancy, with a pre-pregnancy glycated hemoglobin A1c of 7.8% and early pregnancy urine protein of 3.81-4.53 g/24 h. Considering the patient's poor blood glucose control before pregnancy and the lack of proper treatment for multiple complications including nephropathy, a multidisciplinary consultation at an external hospital recommended termination of the pregnancy. However, the patient was determined to continue the pregnancy and was referred to Peking University First Hospital. Through strict blood glucose control, monitoring and evaluation of complications, and comprehensive management, the patient's blood glucose and blood pressure were well controlled during pregnancy. Regular monitoring of urine protein, renal function, and ocular fundus was conducted. At 31 weeks and 4 days of gestation, the patient's 24-hour urine protein significantly increased. After promoting fetal lung maturity, a cesarean section was performed at 34 weeks and 1 day of gestation, resulting in a successful delivery with good maternal and neonatal outcomes. At the 42-day postpartum follow-up, the patient's blood glucose and blood pressure were stable, urine protein returned to pre-pregnancy levels, and the infant was in good general condition.

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.

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 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.