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 explore the correlation between glycolysis related indexes of peripheral blood mononuclear cells(PBMCs)[glucose transporter 1(GLUT1),fructose-2,6-diphosphatase 3(PFKFB3)and lactate kinase M2(PKM2)]and intracranial pressure and clinical prognosis of patients with hypertensive cerebral hemorrhage(HICH)who broke into the ventricle.Methods 85 HICH patients hospitalized in our hospital from January 2021 to June 2022 were retrospectively collected as the research participants.The levels of PKM2,GLUT1 and PFKFB3 in PBMCs were analyzed by enzyme-linked immunosorbent assay kit.Six months after the onset of HICH,the short-term outcome was evaluated by modified Rankin scale(mRS),and the patients were divided into good prognosis(mRS score≤2)and poor prognosis(mRS score≥3).Results The levels of PKM2,PFKFB3 and GLUT1 in PBMCs of HICH patients with ventricular rupture were further lower than those of the patients without ventricular rupture(P<0.05).Six months after discharge,8 patients(22.9%)with HICH in non-ventricular rupture group had poor prognosis,while 28 patients(56.0%)with HICH in ventricular rupture group had poor prognosis,and the difference was statistically significant(χ2=9.263,P=0.002).Compared with the group with good prognosis,the levels of PKM2 and GLUT1 in PBMCs of HICH patients with poor prognosis were lower(P<0.05).Compared with the good prognosis group,the levels of PKM2 and GLUT1 in PBMCs of HICH patients with poor prognosis group were lower in HICH patients with ventricular rupture(P<0.05).In HICH patients who broke into the ventricle,the AUC of PKM2 and GLUT1 in predicting the poor prognosis of HICH patients were 0.879(95%CI:0.807～0.951)and 0.897(95%CI:0.831～0.963),respectively.Conclusion The levels of PKM2 and GLUT1 in PBMCs of patients with HICH breaking into ventricles decrease significantly,and are negatively correlated with intracranial pressure,which can be used to predict the short-term prognosis of the patients.

OBJECTIVES: To investigate the application of transesophageal echocar-diography assessment for mitral valve in patients with atrial septal defects undergoing repair surgery. METHODS: The study group comprised of thirty-two adult patients with atrial septal defect who underwent thoracoscopic repair surgery at the First Affiliated Hospital of the Air Force Medical University from March to September 2022. Two-dimensional and real-time three-dimensional transesophageal ultrasonography of the mitral valve were performed after anesthesia. The parameters of the mitral valve structure at the late diastolic and late systolic stages were recorded, including anteroposterior and left-right annular diameters, anterior and posterior valves lengths, the vertical distance from the coaptation point of leaflet zone 2 during systole to the annular plane (mitral valve coaptation depth) and mitral valve coaptation length. Data from 32 patients with normal intracardiac structure and no mitral valve regurgitation (control group) were also collected and compared with those of the study group. Concurrent mitral valvoplasty was performed during the atrial septal defect repair surgery for 7 patients with significant mitral valve structural abnormalities and 2 patients with significantly increased mitral regurgitation after cardiac resuscitation. The study group was followed up with transthoracic echocardiography for 2 years postoperatively. RESULTS: In the study group, 26 (81.3%) patients had varying degrees of mitral valve morphological abnormalities. Among them, 10 (31.3%) patients had short mitral valve coaptation length or depth, 12 (37.5%) patients had closure point malposition, and 4 (12.5%) patients had different bulge of anterior and posterior leaflets. Compared with the control group, the study group had significantly smaller systolic and diastolic mitral left-right annular diameter, mitral posterior valves lengths, mitral coaptation length or depth (all P<0.05), a higher pulmonary systemic flow ratio (P<0.01), and a lower maximum blood flow velocity across the mitral valve (P<0.05). After 2 years of follow-up, among the 9 patients who underwent concurrent mitral valvoplasty, the mitral valve maintained no or little regurgitation, and the average mitral valve pressure difference was less than 5 mmHg (1 mmHg=0.133 kPa). Among the 23 patients without concurrent mitral valvoplasty, 2 patients had moderate regurgitation 1 year after surgery, with a pulmonary/systemic flow ratio larger than 2.8. CONCLUSIONS Patients with large atrial septal defects often have abnormal mitral valve structure. Therefore transesophageal echocardiography is recommended for mitral valve assessment during the surgery. If significant mitral valve structural abnormalities are detected, concurrent mitral valvoplasty is recommended.
Humans ; Heart Septal Defects, Atrial/diagnostic imaging* ; Echocardiography, Transesophageal/methods* ; Mitral Valve/surgery* ; Adult ; Female ; Male ; Middle Aged ; Mitral Valve Insufficiency/diagnostic imaging*

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 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.