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.

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.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

Objective To develop the functions and optimize the automatic monitoring module for arrhythmias of the adverse drug event active surveillance and assessment system-Ⅱ,in order to continuously improve the performance,enhance the monitoring efficiency,and explore the ways to optimize the module.Methods Expand and optimize the functions of the module,increase the customized configuration,and determine the optimal setting conditions;compare the optimized test data with the results of the evaluation studies on the automatic monitoring of drug-induced arrhythmias in large samples of medicated population previously,and verify the optimization extent as well as the accuracy of the module.Results In the new module optimized according to the characteristics of the monitoring population,the function of"mandatory medical order keywords"was added,and it was determined that the inclusion of 6 electrocardiogram examination-related medical order keywords with a frequency of not less than 2 occurrences was the optimal configuration condition for the optimization of the module;combining the results of the previous automatic monitoring and evaluation researches,the system functions were verified and compared under the conditions of using the whole drugs and 2 kinds of single drug.While there was no loss of true positive cases,the number of cases with system alarms decreased by 30.75％,80.13％and 90.82％,respectively,compared with that before the optimization of the module,and the positive predictive value was significantly improved.Conclusion After the function expansion and optimization,the automatic monitoring module of drug-induced arrhythmias significantly reduces the labor cost of case evaluation and keeps the accuracy of monitoring results constant;the new module can better adapt to the demands of different automatic monitoring modes and operates stably,which is more generalizable and flexible,and provides a new way of considering for the research and development of automatic monitoring modules.

ObjectiveTo explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3 （SCA3） and further evaluate its correlation with disease severity and disease duration. MethodsWe prospectively enrolled 81 genetically diagnosed SCA3 patients ［59 symptomatic （sym-SCA3） and 22 pre-symptomatic （pre-SCA3）］ and 35 age- and sex-matched healthy controls （HCs）. MRI structural images （3D T1 MPRAGE） and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior， middle and inferior cerebellar peduncle （SCP， MCP and ICP）， the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra- and inter-observer reliability， respectively. One-way ANOVA， rank-sum test， ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3， and the correlation between the metrics and clinical variables was analyzed. ResultsNot depending on the radiological experience， the metrics based on morphological MRI showed high intra- and inter-observer reliability， among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP， MCP， ICP， pons and spinal cord （except spinal cord at the level of the upper edge of the 5th cervical vertebra） decreased successively in HCs， pre-SCA3 and sym-SCA3 with a statistical difference （P<0.017）. ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3 （AUC=0.911）， with sensitivity， specificity and a cut-off value of 85.7%， 95.5% and 10.15 mm， respectively. In contrast， the right SCP had the highest diagnostic value for sym-SCA3 （AUC=0.999）， with sensitivity， specificity and a cut-off value of 100%， 98.3% and 2.62 mm， respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency （AUC= 0.970， specificity=93.1%）， and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia （SARA） and disease duration （P<0.05）. ConclusionNot depending on radiological experience， measurements of brain structure based on morphological MRI are reliable， which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3， respectively. Therefore， the structural MRI is recommended for assisting the clinical diagnosis of SCA3.

In recent years, laparoscopic surgery and robotic surgery have been widely used, and various intraoperative image navigation systems have also developed rapidly. However, the liver itself has a complex vessel and duct system, which increase the difficulty of liver surgery. The augmented reality image navigation system combines the three-dimensional reconstructed image of the liver with the real liver anatomy, which presents the specific relationship between the tumor location and the surrounding vessels for the surgeon. Compared with other intraoperative image navigation methods, augmented reality has its unique advantages. This paper provides an overview of current advances in registration technology in augmented reality image navigation system, and focuses on its applications in liver surgery, including laparoscopic surgery and robotic surgery. Finally, the technological problems and difficulties still faced at present are summarized, and future directions worth studying in this field are proposed.

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.
Animals ; Mice ; Rats ; Proto-Oncogene Proteins c-akt ; Network Pharmacology ; Alzheimer Disease/drug therapy* ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases/genetics* ; Tandem Mass Spectrometry ; Drugs, Chinese Herbal/pharmacology*

Objective: To evaluate the effects on short-term clinical outcomes and long-term quality of life of laparoscopic-assisted radical proximal gastrectomy with esophageal gastric tube anastomosis versus total gastrectomy with Roux-en-Y anastomosis for adenocarcinoma of the esophagogastric junction. Methods: This was a propensity score matching, retrospective, cohort study. Clinicopathological data of 184 patients with adenocarcinoma of the esophagogastric junction admitted to two medical centers in China from January 2016 to January 2021 were collected (147 in the First Affiliated Hospital of Xiamen University and 37 in the Affiliated Hospital of Qinghai University). All patients had undergone laparoscopic-assisted radical gastrectomy. They were divided into two groups based on the extent of tumor resection and technique used for digestive tract reconstruction. A proximal gastrectomy with reconstruction by esophageal gastric tube anastomosis group comprised 82 patients and a total gastrectomy with reconstruction by Roux-en-Y anastomosis group comprised 102 patients. These groups differed significantly in the following baseline characteristics: age, preoperative hemoglobin, preoperative albumin, tumor length, tumor differentiation, and tumor TNM stage (all P<0.05). To eliminate potential bias caused by unequal distribution between the two groups, 1∶1 matching was performed by the nearest neighbor matching method. The 13 matched variables comprised sex, age, height, body mass, body mass index, preoperative glucose, preoperative hemoglobin, preoperative total protein, preoperative albumin, neoadjuvant radiotherapy, tumor length, degree of differentiation, and pathological TNM stage. Postoperative complications, postoperative nutritional status, incidence of reflux esophagitis 1 year after surgery, and quality of life were compared between the two groups. Results: After propensity score matching, 60 patients each were enrolled in the proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis groups. The baseline characteristics were comparable between these groups (all P>0.05). There were no significant differences between the two groups in operative time, intraoperative bleeding, time to semifluid diet, postoperative hospital days, tumor length, and total hospital costs (P>0.05). Patients in the proximal gastrectomy with esophageal gastric tube anastomosis group had earlier postoperative gastric tube and abdominal drainage tube removal time than those in the total gastrectomy with Roux-en-Y anastomosis group (t=-2.183, P=0.023 and t=-4.073, P<0.001, respectively). In contrast, significantly fewer lymph nodes were cleared and significantly fewer lymph nodes were positive in the proximal gastrectomy with esophageal gastric tube anastomosis group than in the total gastrectomy with Roux-en-Y anastomosis group (t=-5.754, P<0.001 and t=-2.575, P=0.031, respectively). The incidence of early postoperative complications was 43.3% (26/60) in the total gastrectomy with Roux-en-Y anastomosis group; this is not significantly higher than the 26.7% (16/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ²=3.663，P=0.056). The incidences of pulmonary infection (31.7%, 19/60) and pleural effusion (30.0%, 18/60) were significantly higher in the total gastrectomy with Roux-en-Y anastomosis group than in the proximal gastrectomy with esophageal gastric tube anastomosis group (13.3%, 8/60 and 8.3%, 5/60, respectively); these differences are significant (χ²=8.711, P=0.003 and χ²=11.368, P=0.001, respectively). All early complications were successfully treated before discharge. The incidence of long-term postoperative complications was 20.0% (12/60) in the total gastrectomy with Roux-en-Y anastomosis group and 35.0% (21/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this difference is not significant (χ²=3.386，P=0.066). The incidence of reflux esophagitis was 23.3% (14/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this is significantly higher than the 1.7% (1/60) in the total gastrectomy with Roux-en-Y anastomosis group (χ²=12.876, P<0.001). Body mass index had decreased significantly in both groups 1 year after surgery compared with preoperatively; however, the difference between the two groups was not significant (P>0.05). The differences in hemoglobin and albumin concentrations between 1 year postoperatively and preoperatively were not significant (both P>0.05). Quality of life was assessed using the Visick grade. Visick grade I dominated in both groups. The percentage of patients with Visick II and III in the total gastrectomy with Roux-en-Y anastomosis group was 11.7% (7/60), which is significantly lower than the 33.3% (20/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ²=8.076, P=0.004). No patients in either group had a grade IV quality of life. Conclusions: Both proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis laparoscopic-assisted radical surgery for adenocarcinoma of the esophagogastric junction are safe and feasible. However, both procedures have their own advantages and disadvantages in terms of postoperative complications. The incidence of reflux esophagitis is higher after proximal gastrectomy with esophageal gastric tube anastomosis, whereas the long-term quality of life is lower than that of patients after total gastrectomy with Roux-en-Y anastomosis.
Humans ; Anastomosis, Roux-en-Y ; Retrospective Studies ; Cohort Studies ; Esophagitis, Peptic ; Quality of Life ; Propensity Score ; Gastrectomy/methods* ; Esophagogastric Junction/surgery* ; Anastomosis, Surgical/methods* ; Adenocarcinoma/pathology* ; Stomach Neoplasms/pathology* ; Postoperative Complications ; Treatment Outcome

Aim To investigate the mechanism of corn silk decoction on diabetic nephropathy (DN) rats using metabolomics technology. Methods DN rat model was established by feeding with high-sugar and high-fat diet, combined with intraperitoneal injection of low dose streptozotocin. Renal organ index, fasting blood glucose, albumin creatinine ratio, serum creatinine, blood urea nitrogen, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol indexes were measured, and the pathological changes of renal tissues were also observed to evaluate the intervention effect of corn silk on DN model rats. Further, UPLC/Q-TOF-MS technology was used to screen potential biomarkers in renal tissues and urine, combined with principal component analysis (PC A) and orthogonal partial least squares discriminant analysis (OPLS-DA). After identification by HM-DB and KEGG database, the biomarkers were imported into MetaboAnalyst for metabolic pathway analysis. Results All indexes and pathological damage of kidneys were improved in groups with different doses of corn silk, indicating that corn silk had a good intervention effect on DN. Metabolomic analysis showed that 18 biomarkers could be significantly called back by corn silk, and it involved 18 metabolic pathways mainly including phenylalanine, tyrosine and tryptophan biosynthesis, riboflavin metabolism, arachidonic acid metabolism, and tyrosine metabolism. Conclusions The mechanism of corn silk decoction intervention on DN may be related to amino acid metabolism, riboflavin metabolism, and arachidonic acid metabolism.