Alcohol exposure, as a widespread environmental factor, is highly toxic and teratogenic. Embryonic stem cells (ESCs) are pluripotent and key to development, and their gene expression is tightly regulated, allowing the cells to differentiate without self-renewal. Numerous studies showed that alcohol is an important factor affecting the differentiation of ESCs. In this paper, we systematically summarized four major molecular mechanisms underlying alcohol associated differentiation of ESCs: (1) inhibition of the Wnt signaling pathway; (2) restriction of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway; (3) alteration of the expression of pluripotent transcription factors; and (4) activation of the nuclear transcriptional program. Through the above mechanisms, alcohol induces aberrant expression of differentiation-related genes and alters the direction of cellular differentiation towards specific lineages, thereby affecting normal embryonic development. Based on the studies on ESCs modeling and other in vitro and in vivo differentiation experiments, the molecular basis of how alcohol affects differentiation by interfering with signaling networks and transcriptional regulation was elucidated, and the results of current research in this field were also summarized, which is crucial for understanding alcohol-mediated toxic effects.

Objective: To investigate the regional differences in the incidence of urothelial carcinoma among kidney transplant recipients between northern and southern China，so as to provide reference for early diagnosis of this disease. Methods: A comprehensive search was conducted across multiple databases，including CNKI，Wanfang，CBM，and PubMed，using the keywords “kidney transplantation” and “tumor” to collect clinical data from qualified kidney transplant centers.The latest and most complete literature data published by 17 transplant centers in northern China and 14 in southern China were included.Statistical analyses were performed to compare the incidence of post-transplant urothelial carcinoma and non-urothelial malignancies. Results: A total of 37 475 kidney transplant recipients were included，among whom 837 (2.23%) developed post-transplant malignancies，including urothelial carcinoma (366/837，43.73%)，non-urothelial carcinoma (444/837，53.05%)，and malignancies with unspecified pathology (27/837，3.23%).The incidence of malignancies was significantly higher in northern China than in southern China [(2.82±1.39)% vs. (1.67±0.83)%，P=0.011]，with a particularly pronounced difference in the incidence of urothelial carcinoma [(1.68±1.12)% vs. (0.32±0.32)%，P<0.001].No significant difference was observed in the incidence of non-urothelial carcinoma between the two regions [(1.11±0.56)% vs. (1.35±0.65)%，P=0.279].Additionally，female transplant recipients exhibited a higher incidence of malignancies than males in both regions (southern China：2.38% vs. 1.80%; northern China：8.93% vs. 2.52%). Conclusion: The incidence of urothelial carcinoma following kidney transplantation is significantly higher in northern China than in southern China，underscoring the importance of implementing regular tumor screening for kidney transplant recipients，particularly for female patients in northern China，to facilitate early diagnosis and timely intervention.

Infertility is a common reproductive disorder affecting millions of couples worldwide. It is estimated that male factors account for about 30%-50% of infertility cases, and some studies have found that the concentration of male sperm gradually decreases over time, a trend that suggests the importance of male fertility. Many factors contribute to the decline of male fertility, among which environmental factors have received widespread attention. After reaching adulthood, spermatogonial stem cells will continue to produce sperm, but these cells exist outside the blood testicular barrier, which makes them highly sensitive to environmental conditions such as air pollution, tobacco smoke, radiation, and heavy metals. It is reported that exposure to these adverse environmental factors not only causes oxidative stress and DNA damage to germ cells, but also leads to abnormal epigenetic modification of sperm DNA, thereby causing a series of diseases. This article reviewed the abnormal methylation changes in DNA associated with exposure to environmental pollutants during spermatogenesis and how these changes affect the quantity, quality, and function of spermatozoa.

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.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP)is a clinically rare autosomal dominant genetic disease,and its specific pathogenesis is not yet clear.The colony-stimulating factor 1 receptor(CSF1R)is a transmembrane tyrosine kinase receptor on the cell surface and mutations in the gene encoding it have been identified as potential pathogenic factors for ALSP.However,the specific mechanisms by which CSF1R gene mutations lead to the onset of ALSP are still unclear.After reviewing the mutation sites and pathogenic mechanisms of CSF1R in the pathogenesis of ALSP,CSF1R mutations have been shown to cause microglial dysfunction through mechanisms such as dominant-negative effects,loss of function,haploinsufficiency,and gain of function,thereby leading to the onset of ALSP.A deeper understanding of the causes of ALSP will help in exploring potential treatment methods.

Objective:To analyze the biological characteristics, phylogeny and the taxonomic status of strain 7712 (=CGMCC 1.17031=NBRC 113783=KCTC 15766) isolated from a clinical blood sample.Methods:Strain 7712 was identified by the cultural properties, cellular and colonial morphology, physiological and biochemical reactions, matrix-assisted laser desorption ionization time-of-flight mass spectrometry system, and genome correlation index analysis. The genomic phylogenetic tree was construct to analyze the taxonomic position. The virulence factors and resistance genes of strain 7712 and related strains were then compared by the online virulence factor database and online comprehensive antibiotic research database respectively.Results:Strain 7712 was urease negative, gram-negative nonfermenters, which was identified as Ochrobactrum anthropi by VITEK GN card. The 16S rRNA gene analysis showed that the strain was closely related to the members of genera Ochrobactrum and Brucella. The phylogenetic tree showed that strain 7712 was clustered together with Ochrobactrum teleogrylli LCB8 T and Ochrobactrum haematophilum CCUG 38531 T, along with genus Brucella and other Ochrobactrum species. The genome relatedness indexes analysis showed that the average nucleotide identity between strain 7712 and Ochrobactrum teleogrylli LCB8 T was 98.16%, which was higher than the threshold for prokaryotic species. Genetic prediction showed that strain 7712 carried several virulence-related genes and resistance-related genes, of which the existence of OCH gene might be responsible to the resistance to cephalosporin. Conclusions:A case of human infection caused by Ochrobactrum teleogrylli is identified, which would help promote the understanding of biodiversity of genus Ochrobactrum.

Objective:To evaluate the diagnostic performances of plasma placental extracellular vesicles (pcEV) and their clearance protein (Lactadherin) in predicting adverse pregnancy outcomes in patients with severe preeclampsia (sPE).Methods:This is a retrospective case-control study. 60 patients aged 32 (29, 36) years diagnosed with sPE at 27-37 weeks of pregnancy, who underwent prenatal examinations and delivered between January 31 th, 2018 and January 31 th, 2019, were recruited. According to the occurrence of endpoint events (fetal distress and/or fetal growth restriction), sPE patients were further divided into an event group of 34 cases and a non event group of 26 cases. 33 healthy pregnant women of the same gestational age were selected as the control group, aged 31 (29, 36) years old. 25 non pregnant healthy women were selected as the healthy control group, aged 26 (25, 38) years old. Flow cytometry was used to detect placental alkaline phosphatase antibody positivity as pcEV, while membrane surface expression of phosphatidylserine, i.e. membrane associated protein V (AV) positivity as AV +pcEV. ELISA kits were used to detect the level of Lactadherin. Logistic regression was used to perform multiple correlation analysis. The performances of pcEV and Lactadherin in predicting adverse pregnancy outcomes were evaluated by the receiver operating characteristic (ROC) curve. Survival analyses were performed by the Kaplan Meier curve. The hazard ratios (HR) was calculated by the Cox proportional risk regression model. Results:The plasma AV +pcEV levels in sPE patients were 8 260 (4 991, 16 751)/μl, which were higher than 1 088 (784, 1 871)/μl of healthy pregnant women and 206 (116,256)/μl of healthy controls ( H=94.490, P<0.05). The plasma AV +pcEV levels in sPE patients with endpoint events were 11 225 (7 496, 20 599)/μl, which were higher than 5 199 (2 914, 8 347)/μl of patients without endpoint events ( U=178, P<0.05). The plasma levels of Lactadherin in sPE patients were 2 635 (1876, 3 137) pg/ml, which were higher than 1 597 (1 287, 1 818) pg/ml in healthy pregnant woman and 1 123 (749, 1 405) pg/ml in healthy controls ( H=54.307, P<0.05). ROC showed that the critical value of AV +pcEV predicting fetal distress and/or fetal growth restriction events within 77 days in sPE patients was 6 524/μl and area under the curve(AUC) was 0.799 (95% CI 0.680-0.917). The critical value of Lactadherin was 2 336.5 pg/ml and AUC was 0.702 (95% CI 0.564-0.841). Logistic regression analysis showed that there was a significant correlation between AV +pcEV levels in sPE patients and 24-hour urine protein quantification ( OR=9.288, 95% CI 1.993-43.293), as well as the need for combined antihypertensive therapy ( OR=18.690, 95% CI 1.919-182.077) ( P<0.05). Survival analysis showed that the cumulative probability of fetal distress and/or fetal growth restriction events within 77 days were significantly increased in sPE patients with AV +pcEV levels above the critical value (Log-rank χ 2=21.430, P<0.05). The Cox proportional regression model showed that the levels of AV +pcEV can independently identify fetal distress and/or fetal growth restriction events ( HR=7.983, P<0.05). Conclusions:The changes of pcEV in plasma of pregnant women in late pregnancy were related to the development of PE. High concentrations of pcEV suggested an increased risk of fetal distress and fetal growth restriction, and pcEV could serve as an effective marker for early warning of adverse pregnancy outcomes.