ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.

With the growing aging population, female stress urinary incontinence (SUI), due to its high incidence, has become a common disease that seriously affects patients' quality of life and brings heavy economic burden to families and society.Over the past century, the surgical treatments of SUI were continuously updated along with the in-depth research on the disease mechanism.However, in recent years, the concept of anti-incontinence surgery has shifted from treating the causes to reshaping the urinary control mechanism.As a result, the mid-urethral sling (MUS) procedure has gained global acceptance since its introduction, swiftly acknowledged both domestically and internationally as the gold standard due to its minimally invasive nature and proven effectiveness.MUS is also the most commonly used surgical method for SUI patients treated in our center.Based on our own surgical experience, we will analyze the main steps, technical points, and preventive strategies of surgical complications of MUS, so as to provide clinical reference.

Objective To systematically review the sex differences in efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) patients. Methods We conducted a computer search of Medline, The Cochrane Library, and EMbase from inception to November 2022 to identify randomized controlled trials (RCTs) assessing the efficacy of ICIs in patients with NSCLC. A meta-analysis was performed using RevMan 5.4 software. Results Finally 16 RCTs with a total of 9 653 patients were included, and the modified Jadad scale score was≥4 points. Meta-analysis results showed that in female NSCLC patients receiving immune therapy, the median overall survival (OS) [HR=0.72, 95%CI (0.61, 0.85), P<0.001] was longer than that in males [HR=0.73, 95%CI (0.69, 0.78), P<0.001]. Males [HR=0.64, 95%CI (0.58, 0.71), P<0.001] had an advantage over females [HR=0.76, 95%CI (0.57, 1.03), P=0.760] in median progression-free survival (PFS). Conclusion Females receiving ICIs have an advantage over males in terms of median OS. However, males tend to derive greater benefit from ICIs in terms of median PFS.

Objective The pathogenic characteristics of Escherichia coli(E.coli)in bacterial infections were analyzed using a combination of multiple molecular typing techniques in order to provide evidence for the management of clinical medication safety.Methods Samples from some bacterial infection-related cases in a district of Chongqing in 2021 were collected.A total of 30 E.coli strains were selected by a completely random method,and phoA gene PCR assay was performed for identification.Molecular typing of the strains was analyzed using pulsed-field gel electrophoresis(PFGE)and multilocus sequence typing(MLST).Antimicrobial susceptibility testing was conducted to determine the drug resistance of the strains,and four β-lactamase-encoding genes(blaCTX-M,blaTEM,blaSHV,blaZ)were selected to detect the carriage of resistance genes.Results All 30 E.coli strains displayed the phoA gene target band.Their PFGE banding patterns,with a similarity of 50%～98%,could be classified into 8 clusters.Cluster C was the dominant group,accounting for 53.3%(16/30).C1 and C2 exhibited high genetic correlation,indicating a close phylogenetic relationship.One E.coli strain could not be assigned a sequence type(ST)by MLST,while the remaining 29 E.coli isolates were classified into 16 different STs,demonstrating a polymorphic distribution.Among them,10 isolates belonged to ST131(10/30,33.33%).Evolutionary analysis of the 10 ST131 E.coli strains revealed their distribution across different branches,indicating varying degrees of genetic relatedness.Antimicrobial susceptibility testing revealed that all 30 E.coli strains exhibited varying degrees of resistance,with the highest resistance rate observed against the β-lactam antibiotic ampicillin(25/30,83.33%).Among them,60.0%were multidrug-resistant bacteria(MDRB).These MDRB strains exhibited 16 distinct resistance profiles,displaying a scattered distribution without a dominant resistance pattern.50.0%(9/18)of the MDRB strains exhibited six-drug resistance,while the most drug-resistant strain showed eight-drug resistance.Furthermore,the blaCTX-M gene carriage rate among the 30 E.coli strains was 86.67%(26/30),while no blaZ gene was detected.Conclusion E.coli related to bacterial infections from a Chongqing district exhibited diverse PFGE/MLST patterns and significant drug resistance.The application of multiple molecular typing techniques can reveal the genetic diversity,evolutionary relationships,and antimicrobial resistance characteristics of pathogenic bacteria.Countermeasures It is recommended to enhance the molecular typing and drug resistance surveillance network for pathogenic bacteria,establish an early warning mechanism,and implement hierarchical management of antibiotics,thereby improving targeted prevention and epidemic traceability capabilities for key drug-resistant bacteria such as ST131.

In this work,a rapid and label-free sensing platform was designed for visual detection of p53 gene.The rolling circle amplification(RCA)process of the assay platform was activated by p53 gene to produce long DNA-wires,which could bound with berberine hydrochloride(BBH)and further enhanced its fluorescence.This method showed high sensitivity with a low detection limit of 5.63 pmol/L,and high specificity toward p53 gene over other interference materials,even for single-base mutation gene.The method could realize the visual detection of targets under the illumination of a UV lamp.In addition,the designed fluorescence detection platform was successfully applied to p53 gene analysis in 10% fetal bovine serum samples,and the relative standard deviation and the recoveries were 0.1% -1.2% and 99.5% -104.7%,respectively.This approach had satisfactory characteristics,such as low cost,label-free,rapidity,high sensitivity,good selectivity and anti-interference ability,and reliable detection capability for complex practical samples,demonstrating a promising prospect in the diagnosis and treatment of diseases,especially for cancer.

Objective:To compare the diagnostic, staging, and prognostic performance of three AKI criteria (KDIGO, cROCK, and APKD) in patients with pre-existing kidney dysfunction (PKD).Methods:Clinical data from 570 PKD patients admitted to the ICU of the First Affiliated Hospital of Wenzhou Medical University (October 2020-October 2022) were analyzed. Patients were classified by three AKI diagnostic criteria. We compared AKI detection rates and mortality predictions using ROC analysis and logistic regression (reporting ORs with 95% CIs). Results:AKI detection rates differed significantly: APKD 80.7% (460/570), KDIGO 66.0% (376/570), and cROCK 47.0% (268/570) (both P<0.001 vs. APKD). Mortality rates were comparable across criteria (APKD 32.4%, KDIGO 33.0%, cROCK 33.6%; P>0.85). APKD showed superior predictive value for in-hospital mortality (AUC=0.736, 95% CI 0.691-0.781), with significantly higher sensitivity than KDIGO (0.738 vs. 0.663, P<0.001) and cROCK (0.738 vs. 0.613, P<0.001). KDIGO staging identified few AKI2 cases (1.1%), with mortality rates of 27.3% (AKI1), 0% (AKI2), and 37.0% (AKI3). APKD staging demonstrated graded mortality risks: 20.1% (AKI1), 28.1% (AKI2), and 40.9% (AKI3) (all P<0.05). Multivariate analysis revealed increasing mortality risk with APKD stage (AKI1: OR=2.34, 95% CI 1.09-5.31; AKI2: OR=4.50, 95% CI 2.05-10.46; AKI3: OR=7.03, 95% CI 3.59-15.01). APKD staging outperformed KDIGO in mortality prediction (AUC=0.756 vs. 0.724, P=0.02). Conclusions:The APKD criteria demonstrate superior AKI detection in PKD patients and better prognostic prediction compared to KDIGO and cROCK. APKD staging provides more clinically meaningful risk stratification than KDIGO for this population.

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count