Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.

Objective: To investigate the reciprocal causal relationships between periodontitis and hepatobiliary diseases through Mendelian randomization (MR) analyses, to provide evidence for joint prevention and clinical decision-making in patients with concurrent periodontitis and hepatobiliary diseases. Methods: Single nucleotide polymorphisms (SNPs) were extracted from the largest genome-wide association study on periodontitis (17 353 cases, 28 210 controls) and hepatobiliary diseases within the European ancestry and used as instrumental variables (IVs). The strength of the associations was examined by calculating the F-statistic. The SNPs significantly associated with the outcome were removed by scanning on Phenoscanner platform. Bidirectional causal associations between periodontitis and hepatobiliary diseases were estimated using inverse variance weighted (IVW), MR-Egger, and Weighted Median methods. The robustness of the findings was further verified through additional sensitive MR approaches, including Cochran’s Q statistic （IVW）, Rucker’s Q statistic （MR-Egger）, MR-PRESSO and Leave-one-out analysis. Further MR analyses, utilizing other available genome-wide association studies (GWAS) on hepatobiliary diseases, were conducted to validate the results. Results: The IVW method found that periodontitis had a causal impact on acalculous cholecystitis (odds ratio = 1.277, 95% CI 1.097-1.485, P=0.002), implying an increased risk of acalculous cholecystitis associated with periodontitis, while the MR-Egger regression and Weighted Median failed to observe significant causal effects of periodontitis on acalculous cholecystitis. However, no bidirectional causal associations between periodontitis and nonalcoholic fatty liver disease, cirrhosis or liver cancer were observed using IVW, MR-Egger regression and Weighted Median. The bidirectional causal relationships were deemed unlikely to be influenced by horizontal pleiotropy. Further, the validation analysis based on alternative GWAS data suggested parallel results. Conclusions The MR analyses suggest that periodontitis may elevate the risk of acalculous cholecystitis. Further investigations, including clinical studies and mechanistic explorations, are warranted to validate these findings. However, the MR analyses do not support bidirectional causal associations between periodontitis and nonalcoholic fatty liver disease, cirrhosis or liver cancer.

Aim To explore anti-inflammatory mecha-nism of urolithin A(Uro A)based on the miRNA155-5p-regulated MAPK/NF-κB pathway in a lipopolysac-charide(LPS)-stimulated RAW264.7 inflammatory cell model.Methods The mRNA expression of miR-15-5p,p38 MAPK,JNK and ERK was detected by transfection of overexpression of miR-155-5p-mimics and miR-NC into LPS-induced RAW264.7 cells,and the miR-15-5p,p38 MAPK,JNK,and ERK mRNA expressions in the cells were detected by RT-qPCR.The effect of Uro A on cell viability was detected by MTT assay.The NO content in cell supernatant was detected by Griess assay.The cell supernatant PGE2,IL-6,IL-1 β and TNF-α expression levels were detec-ted by ELISA.The iNOS,COX-2,TLR4,and the MAPK/NF-κB pathway-related protein expression lev-els were detected by Western blot.Results The p38 MAPK,JNK and ERK mRNA expression levels were significantly higher in the miRNA155-5p overexpres-sion group than those in the miR-NC group(P＜0.01).Compared with the model group,Uro A signif-icantly inhibited miRNA155-5p,NO,PGE2,TNF-α,IL-1β,and IL-6 levels(P＜0.01)as well as de-creased the expression levels of iNOS and COX-2 pro-teins(P＜0.01)in a concentration-dependent man-ner.Moreover,Uro A could significantly inhibit the expression levels of TLR4 protein and the expression levels of phosphorylation levels of p38 MAPK,JNK,NF-κB p65,and IκBα proteins in LPS irritated RAW264.7 cells(P＜0.05).However,Uro A did not show a significant inhibitory effect on ERK1/2 pro-tein phosphorylation.Conclusion Uro A could signif-icantly inhibit LPS-induced inflammatory response,and its mechanism may be related to miRNA155-5p-mediated TLR4/MAPK/NF-κB signaling pathway.

Aim To investigate the mechanisms of Chaijin JieYu Anshen formula modulating the depres-sive behaviors and the synaptic plasticity of hippocam-pal neurons in insomnia-concomitant depression rats based on the histone deacetylase 5(HDAC5)/myocyte enhancer factor 2C(MEF2C)pathway.Methods A rat model of insomnia-concomitant depression was es-tablished by PCPA injection combined with chronic un-predictable mild stress(CUMS),and the experiment was divided into the control group,the model group,the high,medium and low dose group of Chaijin JieYu Anshen formula,and the positive drug group.The de-pression of rats was evaluated by sugar-water prefer-ence test,open field test and morris water maze.The levels of 5-hydroxytryptamine(5-HT)and dopamine(DA)in serum were measured by enzyme linked im-munosorbent assay(ELISA).The pathological damage of hippocampal neurons was observed by HE staining and Nissl staining.The damage of dendritic spines of hippocampal neurons was observed by Golgi staining,and the levels of HDAC5,MEF2C,postsynaptic densi-ty-95(PSD-95)and synaptophysin 1(SYN1)in hip-pocampus were measured by Western blot,immunohis-tochemistry and immunofluorescence.Results Com-pared with the model group,the Chaijin JieYu Anshen formula could increase the sugar-water preference rate of the model rats,reduce the immobility time in the open field experiment,increase the total activity dis-tance,shorten the evasion latency in the localization navigation experiment,and prolong the residence time in the quadrant where the platform was located in the space exploration experiment(P＜0.05,P＜0.01).Moreover,the Chaijin JieYu Anshen formula improved the hippocampal neuron and dendritic spine damage and increase the dendritic branch length and dendritic spine density of hippocampal neurons(P＜0.01,P＜0.01),restore the serum levels of 5-HT and DA in insomnia-concomitant depression rats(P＜0.05,P＜0.01),down-regulate the HDAC5 protein,and up-regulate the expression of MEF2C,PSD-95,and SYN1 protein(P＜0.05,P＜0.01 or P＜0.001).Conclusions Chaijin JieYu Anshen formula may alle-viate the depression-like behavior of model rats by re-ducing the expression of HDAC5 protein,thus deregu-lating the inhibition of transcription factor MEF2C,promoting the expression of PSD-95 and SNY1 protein,and exerting a protective effect on hippocampal neurons and synapses.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Aim To investigate the effect of discoidin domain receptor 1(DDR1)on high glucose induced endothelial cell dysfunction and the underlying mecha-nism.Methods Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and divided in-to the control group and high glucose induction group(HG).HUVECs were treated with 33 mmol·L-1 D-glucose for 48 hours to construct endothelial dysfunc-tion.Pyroptosis was detected using propidium iodide staining(PI);lactate dehydrogenase(LDH)and IL-1β,IL-18 levels were determined using enzyme linked immunosorbent assay(ELISA);the expression of DDR1 and NF-κB/NLRP3 signaling pathway proteins and pyroptosis related proteinses were detected using Western blot.Subsequently,the experiment was divid-ed into the control group,HG group,HG+DDR1 NC group,and HG+DDR1 siRNA group.The effect of high glucose on the proliferation and migration of HU-VECs was observed after transfection with DDR1 siR-NA for 24 hours;ELISA was used to detect the endo-thelial nitric oxide synthase(eNOS),vascular cell ad-hesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1),as well as LDH,IL-1β,IL-18 levels;PI was employed to detect pyroptosis;Western blot was applied to detect DDR1 and NF-κB/NLRP3 signaling pathway proteins and pyroptosis related pro-teins.Results Compared with the control group,HG group decreased eNOS content,increased VCAM-1 and ICAM-1 contents,decreased cell viability and migration ability,and significantly increased the expressions of DDR1,p-NF-κB,NLRP3 and pyroptosis related pro-teins.The levels of LDH,IL-1β,IL-18 and the rate of pyroptosis significantly increased(P＜0.05).Com-pared with HG group,DDR1 siRNA could promote the secretion of eNOS,decrease the levels of VCAM-1,ICAM-1,LDH,IL-1β and IL-1 8,increase cell viability and migration ability,reduce the expression of p-NF-κB,NLRP3 and pyroptosis related proteins,and inhibit high glucose-induced pyroptosis of HUVECs(P＜0.05).Conclusions Gene silencing DDR1 can im-prove vascular endothelial cell dysfunction induced by high glucose,and the mechanism is related to the inhi-bition of NF-κB/NLRP3 signaling pathway mediated pyroptosis.

Objective:To investigate the status of nursing practice and organizational management for reperfusion therapy in ischemic stroke across medical institutions in Beijing.Methods:In June 2023, a survey was conducted among nursing managers from 62 medical institutions under the jurisdiction of the Beijing Stroke Treatment Quality Control and Improvement Center. The survey aimed to assess the current nursing practices and organizational management for reperfusion therapy in ischemic stroke.Results:Among the 62 medical institutions, 16.13% (10/62) had dedicated reperfusion therapy nurses for stroke, and 87.10% (54/62) had established specific nursing protocols and procedures for stroke reperfusion therapy within their departments. However, 27.42% (17/62) of these institutions based the development and updates of their protocols on experiential summaries rather than standardized guidelines. In terms of nursing practice, there was room for improvement in emergency identification and triage of suspected stroke patients, assistance with intravenous thrombolysis, patient condition monitoring, early rehabilitation, and related health education. Regarding nursing quality control, significant differences were observed between institutions that regularly conducted quality control of stroke reperfusion therapy nursing and those that organized regular training sessions for nurses in this area ( P<0.05) . Conclusions:While nursing practices and quality for stroke reperfusion therapy in Beijing are progressing, there are disparities in regional development. There is a high demand for specialized stroke nursing and targeted technical training.

Objective:To investigate the related factors of pleasure loss in patients with human immunodefi-ciency virus(HIV)/acquired immune deficiency syndrome(AIDS).Methods:Totally 237 patients with HIV/AIDS from a certain infectious disease hospital were selected and surveyed with a self-designed general information ques-tionnaire,the Temporal Pleasure Experience Scale(TEPS),Self Acceptance Scale(SAQ),Discrimination Percep-tion Scale(SIS),and Perceived Social Support Scale(PSSS).Results:The patient's TEPS score was(73.4±16.1).Stepwise linear regression analysis showed that the PSSS total scores,education level,and personal monthly income were positively correlated with the TEPS total scores(β=0.41,5.17,4.63),and age was negatively corre-lated with the TEPS total scores(β=-0.30).Conclusion:It suggests that more attention should be paid to the lack of pleasure in patients with HIV/AIDS,and the lack of pleasure is related to personal monthly income,educa-tion level,age and perceived social support.

Objective:To investigate the effect of sertraline hydrochloride combined with compound chamomile lidocaine gel in the treatment of premature ejaculation(PE).Methods:We selected 80 cases of PE treated in our hospital from June 2021 to May 2023 and equally randomized them into a control and an observation group,the former medicated with compound chamomile lidocaine gel while the latter with sertraline hydrochloride in addition,both for 6 weeks.We recorded and compared the intravaginal ejaculation latency time(IELT),the number of successful sexual intercourses per week,the Premature Ejaculation Diagnostic Tool(PEDT)scores,and the incidence of adverse reactions between the two groups of patients.Results:After the treatment,the IELT was signif-icantly longer([5.39±1.17]vs[2.49±0.73]min,P＜0.05),the weekly number of successful sexual intercourses remarkably higher(1.82±0.45 vs 0.93±0.19,P＜0.05)and the PEDT scores markedly lower(7.42±2.04 vs 9.85±2.36,P＜0.05)in the observation than in the control group,but no statistically significant differences were observed in the baseline PEDT scores or the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Sertraline hydrochloride combined with com-pound chamomile lidocaine gel is definitely effective in the treatment of PE,which can significantly improve the patients'quality of sexual life,with a high safety and low incidence of adverse reactions.

Objective:To analyze the intrauterine ultrasound manifestations and postnatal follow-up outcomes of fetuses with 2q13 microdeletion.Methods:This retrospective study involved 23 cases of 2q13 microdeletion, diagnosed via amniotic fluid chromosome karyotyping and single nucleotide polymorphism-array (SNP-array) following amniocentesis, between January 1, 2018, and September 1, 2022, at Wuxi Maternity and Child Health Care Hospital. Descriptive statistical analysis was applied to prenatal diagnostic indications, intrauterine ultrasound findings, prenatal diagnosis results, and postnatal follow-up outcomes.Results:(1) The prenatal diagnostic indications for the 23 cases of 2q13 microdeletion included seven cases (30.4%) of high-risk serological screening, six cases (26.1%) of increased nuchal translucency (NT), two cases (8.7%) of fetal heart defects, two cases (8.7%) of advanced maternal age, two cases (8.7%) of fetal choroid plexus cysts (one of which was also associated with high-risk serological screening), one case (4.3%) of suboptimal fetal nasal bone fusion, one case (4.3%) of non-invasive prenatal testing suggesting chromosomal abnormalities, one case (4.3%) of fetal obstructive polycystic kidneys, one case (4.3%) of fetal subependymal cysts, and one case (4.3%) of fetal growth restriction. (2) Intrauterine ultrasound findings included six cases (26.1%) of NT thickening, four cases (17.4%) of intrauterine growth restriction, two cases (8.7%) of fetal heart defects, two cases (8.7%) of choroid plexus cysts, one case (4.3%) of oligohydramnios, one case (4.3%) of suboptimal fetal nasal bone fusion, one case (4.3%) of short long bones in the fetus, one case (4.3%) of polyhydramnios with large fetal abdominal circumference, one case (4.3%) of large fetal abdominal circumference, short long bones, and subependymal cysts of the brain ventricles, and one case (4.3%) of fetal obstructive polycystic kidneys; the remaining six cases (26.1%) showed no abnormal ultrasound findings. (3) Chromosome karyotyping revealed three cases of chromosomal structural abnormalities, one case of sex chromosome numerical abnormalities, and the remaining 19 cases showed no abnormalities. Amniotic fluid SNP-array results indicated deletions ranging from 104 to 1 745 kb. Parental verification was performed in ten cases, showing maternal inheritance in four cases, paternal inheritance in five, and one case of a de novo mutation. (4) Four cases (17.4%) opted for pregnancy termination, while 19 cases (82.6%) resulted in live births. The 19 live-born children underwent telephone and child health follow-up, with ages at follow-up being 3 years (ranging from 9 to 58.8 months). Apart from two cases that did not undergo newborn congenital heart disease screening, the remaining 17 surviving infants were screened without any abnormalities. Five cases had abnormal growth and development during follow-up: one 18-month-old with mild language developmental delay, one 3-year-old plus 26 days with mild language developmental delay, one 18-month-old with language developmental delay, one 3-year-old with astigmatism, and one 30-month-old with refractive error in both eyes during a physical examination; the other 14 children showed no significant abnormalities in growth and development. Conclusions:The intrauterine ultrasound manifestations of fetuses with 2q13 microdeletion are non-specific, and most of them are inherited from their parents. Postnatal follow-up should pay attention to the development of the nervous system of children.