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 compare the differences in virulence-related factor aspartate protease,biofilm formation,and gene expression among clinical isolates of Candida parapsilosis(C.parapsilosis).Methods Gene sequencing and microsatellite typing(MT)method were adopted to identify C.parapsilosis isolated from patients with clinical fungal infection.The production of secreted aspartate protease and biofilm formation ability of each strain were de-tected,and the expression of biofilm formation related-genes BCR1,EFG1,and HWP1,as well as aspartate prote-ase virulence genes SAPP1,SAPP2,SAPP3 were compared among the strains.Results A total of 8 clinically iso-lated C.parapsilosis strains were collected,all of which were identified as genotype Ⅰ.Based on microsatellite ty-ping results,8 clinical strains were divided into 4 microsatellite types.G1,G2,and G3 strains isolated from the urine,peripherally inserted central catheters(PICC),and blood of patient A were of different subtypes.J1,J2,J3,J4,and J5 strains were of the same type,and isolated from blood specimens of patient B at different periods.All 8 clinical strains could form biofilm,and their biofilm formation ability was higher than that of the standard strain of C.parapsilosis(ATCC 22019).G1,G3 and J5 strains had strong biofilm formation ability,J1,J2,J3,and J4 strains had moderate biofilm formation ability,and G2 strain had weak biofilm formation ability.All of the eight clinical isolates secreted aspartate protease,and their in vitro expression levels of the enzyme were higher than that of the standard strain(ATCC 22019).G3,G1,and G2 strains showed low,moderate,and high in vitro enzyme expression respectively,with statistical differences(all P＜0.05).Enzyme expressed moderately in J1 and J5 strains,and highly in J2,J3,and J4 strains.Difference between moderate and high expressions was statistically significant(P＜0.05).The expression levels of biofilm formation genes BCR1,EFG1,and HWP1 in various strains isolated from patients A and B increased.In strains isolated from patient A,the expression level of EFG1 gene in G1 strain was higher than that in G2 strain(P＜0.05).There was no statistically significant difference in BCR1,EFG1,and HWP1 gene expression levels among strains isolated from patient B.The expression levels of as-partate protein genes(SAPP1,SAPP2,and SAPP3)in various strains isolated from patients A and B increased.The expression levels of SAPP1 and SAPP2 in strain G1 were higher than those in G2 and G3(both P＜0.05).There was no statistically significant difference in the expression levels of SAPP1,SAPP2,and SAPP3 genes in strains from patient B.Conclusion Clinical isolates of C.parapsilosis have higher biofilm formation and aspartate protease production abilities than standard strain.The expression of virulence factors varies among strains isolated from different specimens,while there is no significant difference in the expression of virulence factors among strains isolated at different periods.Patients may have been infected with different MT types of C.parapsilosis in multiple sites during the same period.

AIM:To explore the possible mechanism of Yiqi-Huoxue formula(YQHXF)in treating cerebral ischemia-reperfusion injury.METHODS:Male SD rats were randomly divided into six groups,namely,the sham,mod-el,nimodipine,and low-,middle-and high-dose YQHXF groups.The middle cerebral artery occlusion/reperfusion(MCAO/R)model was established in all groups except the sham group.After successful modeling,the YQHXF low-,me-dium-,and high-dose groups were given 3.8,7.5,and 15 g?kg-1?d-1 of YQHXF,respectively,by gavage,while the ni-modipine group was given 12 mg?kg-1?d-1 of nimodipine tablets by gavage.The sham and model groups were given 10 mL?kg-1?d-1 of distilled water by gavage.After 14 days of drug intervention,the rats were euthanized and the neurological func-tion was evaluated.The infarct volume was assessed using 2,3,5-triphenyltetrazolium chloride(TTC)staining and brain histopathological changes were determined by hematoxylin-eosin(HE)staining.Transmission electron microscopy was used to investigate changes in autophagosomes,with immunofluorescence used to assess expression of microtubule-associ-ated protein 1 light chain 3(LC3)protein in the cerebral cortex,Western blot was used to measure protein levels of p-PI3K,PI3K,p-Akt,Akt,p-mTOR,mTOR,LC3B,p62,beclin-1,and Atg5,and RT-qPCR was used to determined LC3 and P62 mRNA expression.RESULTS:Compared with the sham group,the neural function scores of rats in the model group rats were significantly increased,and TTC staining revealed large areas of white cerebral infarction.There was severe pathological damage to the cerebral tissue in the ischemic cortical area,and large numbers of autophagosomes were seen inside the cells.Immunofluorescence staining showed significant numbers of LC3B-positive cells(P<0.01).Protein expression of beclin-1,Atg5,and LC3-Ⅱ/LC3-Ⅰ was significantly upregulated(P<0.01),while that of p62 was markedly downregulated(P<0.01).The expression of p-PI3K/PI3K,p-Akt/Akt,and p-mTOR/mTOR proteins was also significantly reduced(P<0.01).In addition,the mRNA expression of LC3 was significantly upregulated(P<0.01),with downregulation of P62 mRNA levels(P<0.01).Compared with the model group,both the YQHXF medium-and high-dose groups showed upregulated LC3-Ⅱ/LC3-Ⅰ values after 12 h of reperfusion(P<0.01),followed by downregulation of the ratios(P<0.05)after 3,7,and 14 days of reperfusion.Furthermore,after 14 days of reperfusion,compared with the model group,the middle-and high-dose YQHXF groups and the nimodipine group showed reduced neurological function scores(P<0.01),reduced cerebral infarction volumes(P<0.01),improvements in the pathological damage to cortical tis-sue,and reduced autophagosome formation to varying degrees.At the same time,the number of LC3B-positive cells was reduced(P<0.01).Protein expression of beclin-1,Atg5,and LC3-Ⅱ/LC3-Ⅰ was significantly downregulated,while that of p62 was upregulated(P<0.01).The mRNA expression of LC3 and p62 was consistent with the protein levels(P<0.01).In addition,the expression of p-PI3K/PI3K,p-Akt/Akt,and p-mTOR/mTOR proteins was upregulated(P<0.01).CONCLUSION:YQHXF can dynamically regulate autophagy in ischemic brain tissue,with inhibition of excess autophagy by activation of the PI3K/Akt/mTOR signaling pathway,thus reducing the infarct volume,alleviating brain dam-age,and promoting the recovery of neurological function.

The gastric fundus fornix and upper part of the gastric body pose challenges for endoscopic submucosal dissection (ESD), resulting in unsatisfactory resection outcomes for lesions in these areas,because of the difficulty in the endoscope reaching the lesion site. Drawing inspiration from the formation of α loop during flexible colonoscopy and double-channel multibending gastroscope, a single-channel treatment gastroscope was utilized to create a multibending state (referred to as single-channel endoscope multibending method, SCMB). This method was employed to treat 6 patients with lesions in the stomach at Digestive Endoscopy Center of Affiliated Hospital of Nanjing University of Chinese Medicine from June 2021 to December 2021. There were 3 cases in the gastric fundus fornix, 2 cases in the greater curvature on the upper part of the gastric body, and 1 case in the posterior wall of gastric fundus and subcardia. After 2-3 attempts during surgery, SCMB was successfully performed in all cases within 60-120 seconds. All 6 cases completed successful endoscopic resection within 20-80 minutes without significant complications, including 4 cases of ESD and 2 cases of endoscopic full-thickness resection (EFR). Preliminary results indicate that SCMB method during ESD and its derivative technologies are both safe and effective for lesions in challenging areas where gastric ESD is difficult to perform. During surgery, this approach facilitates the front end of endoscope access to the lesion, providing a clear visual field and a stable dissection plane.

Objective:To review the scope of research on the application of blood flow restriction training in the rehabilitation of patients undergoing anterior cruciate ligament (ACL) reconstruction.Methods:According to the research method of scoping review, computer searches were conducted on China National Knowledge Infrastructure, Wanfang Database, China Biology Medicine disc, VIP, Cochrane Library, PubMed, Embase, with the search period was from eatablishment of databases to December 31, 2022. The included literatures were screened, summarized and analyzed.Results:A total of 16 literatures were included, all of which were randomized controlled trials. The basic content of blood flow restriction training intervention included 8 aspects, such as intervention time, training intensity, training amount, training mode, frequency, interval time, training cycle and blood flow restriction pressure. The effect evaluation mainly involved two kinds of indexes, namely safety indicators and efficacy indicators.Conclusions:Blood flow restriction training can effectively enhance muscle strength and improve knee joint function in patients undergoing ACL reconstruction. Future studies should focus on exploring the best intervention strategy, formulating standardized and unified evaluation criteria and providing the best blood flow restriction training program for patients undergoing ACL reconstruction.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

OBJECTIVES: To study the association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects (CHD) in offspring, and to establish a model for predicting the probability of CHD based on the levels of heavy metals and trace elements during pregnancy. METHODS: Based on the prospective birth cohort study in Gansu Provincial Maternal and Child Health Hospital in 2010-2012, a nested case-control study was conducted for the follow-up observation of 14 359 pregnant women. Among the pregnant women, 97 pregnant women whose offspring were diagnosed with CHD during follow-up were enrolled as the CHD group, and 194 pregnant women whose offspring had no CHD were selected as the control group. Inductively coupled plasma mass spectrometry was used to measure the levels of heavy metals and trace elements in maternal blood samples and fetal umbilical cord blood samples. A multivariate logistic regression analysis was used to evaluate the association between heavy metal and trace elements and CHD in offspring. A nomogram model for predicting the probability of CHD in offspring was established based on the levels of heavy metals and trace elements during pregnancy. RESULTS: Compared with the control group, the CHD group had significantly higher levels of aluminum (Al), natrium (Na), calcium (Ca), titanium (Ti), selenium (Se), strontium (Sr), stannum (Sn), stibium (Sb), barium (Ba), and thorium (Th) in maternal blood samples (P<0.05), as well as significantly higher levels of Al, zinc (Zn), magnesium (Mg), kalium (K), Ca, Ti, chromium (Cr), copper (Cu), arsenic (As), Se, Sr, argentum (Ag), cadmium (Cd), Sn, and plumbum (Pb) in umbilical cord blood (P<0.05). The multivariate logistic regression analysis showed that the increase in the Sb level in maternal blood was associated with the increase in the risk of CHD in offspring [adjusted odds ratio (^aOR)=4.81, 95% confidence interval (CI): 1.65-14.07, P=0.004], while in umbilical cord blood, the high levels of Al (^aOR=4.22, 95%CI: 1.35-13.16, P=0.013), Mg (^aOR=8.00, 95%CI: 1.52-42.08, P=0.014), and Pb (^aOR=3.82, 95%CI: 0.96-15.23, P=0.049) were significantly associated with the risk of CHD in offspring. The levels of Al, Th, and Sb in maternal blood and levels of Al, Mg, and Pb in umbilical cord blood were included in the predictive model for CHD in offspring based on the levels of heavy metals and trace elements during pregnancy, and the calibration curve of the nomogram predictive model was close to the ideal curve. CONCLUSIONS Increases in the levels of Al, Th, Sb, Mg, and Pb during pregnancy may indicate the increase in the risk of CHD in offspring, and the nomogram predictive model based on these indices can be used to predict the probability of CHD in offspring.
Case-Control Studies ; Child ; Cohort Studies ; Female ; Heart Defects, Congenital/etiology* ; Humans ; Metals, Heavy ; Pregnancy ; Prospective Studies ; Trace Elements/analysis*

Objective:To investigate factors related to non-variceal upper gastrointestinal bleeding(NVUGIB)in hospitalized elderly patients.Methods:A retrospective study was conducted to collect the medical records of 1 085 elderly patients at the Affiliated Hospital of Qingdao University from January 1, 2018 to January 1, 2019.According to whether NVUGIB occurred during hospitalization, they were divided into the bleeding group(173 cases)and the control group(912 cases). General information(age, sex, smoking and drinking), diseases, medications and laboratory test results for the two groups were compared and analyzed, and factors related to NVUGIB were analyzed via binary Logistic regression.Results:There were significant differences in age, smoking, drinking, peptic ulcer, tumor, coronary heart disease, atrial fibrillation, stroke, helicobacter pylori(HP)infection, acute respiratory failure, use of anti-coagulant, anti-platelet drugs, nonsteroidal anti-inflammatory drugs and glucocorticoids, leukocyte counts, hemoglobin, C-reactive protein, procalcitonin, prothrombin time and international normalized ratio(INR), D-dimer, triglycerides, albumin and glycosylated hemoglobin(all P<0.05). Multivariate Logistic regression analysis showed that history of tumor( OR=1.552, 95% CI: 1.028-2.344), peptic ulcer( OR=4.797, 95% CI: 2.263-10.165), HP infection( OR=7.199, 95% CI: 1.825-28.571), acute respiratory failure( OR=2.977, 95% CI: 1.314-6.757), use of anti-coagulant and anti-platelet drugs( OR=2.715, 95% CI: 1.769-4.167), prolonged INR( OR=21.314, 95% CI: 2.321-195.727), increased leukocyte count( OR=10.370, 95% CI: 6.521-16.493)and hypoproteinemia( OR=1.970, 95% CI: 1.304-2.976)were independent risk factors for NVUGIB in hospitalized elderly patients. Conclusions:For hospitalized elderly patients, attention should be paid to their history of tumor, peptic ulcer, HP infection, acute respiratory failure, prolonged INR, elevated leukocyte counts, hypoalbuminemia and the use of anti-coagulant and anti-platelet drugs.The occurrence of NVUGIB, early evaluation and intervention should be carefully monitored or carried out to reduce its incidence in hospitalized elderly patients.

Objective    To analyze the clinical features and prognosis of coronavirus disease 2019 (COVID-19) patients. Methods    A total of 379 confirmed COVID-19 patients admitted to Public Health Clinical Center of Chengdu from January 16 to November 30, 2020 were divided into two groups including an elderly group (42 patients, ≥60 years) and a non-elderly group (337 patients, <60 years) by age. The epidemiology, clinical features, laboratory tests, treatment and prognosis of the two groups were compared. Results    Among the 379 patients, 286 (75.5%) were males and 93 (24.5%) were females, aged from 2 months to 87 years, with an average age of 41.2 years. The average age of the elderly group was 69.5 years, and 61.9% of them were females. They were imported from Wuhan or local secondary patients (73.8%), mainly common or critical type (88.1%). While, the average age of the non-elderly group was 37.8 years, and males were more common (80.1%). There were mostly from foreign input (75.7%), mainly mild or ordinary type (95.0%). A total of 179 patients (47.2%) had one or more underlying diseases. Hypertension (15 patients, 35.7%) and diabetes (11 patients, 26.2%) were more common in the elderly group, while non-alcoholic steatohepatitis (132 patients, 39.2%) was more frequent in the non-elderly group. The most common clinical manifestations were fever (138 patients, 36.4%) and cough (129 patients, 34.0%). Fever, cough, dyspnea, and fatigue were more common in the elderly group than those in the non-elderly group (P<0.05). Compared with the non-elderly group, the elderly group had lower total lymphocyte count, CD4+ and CD8+ T-cell count, higher level of myocardial injury or inflammation markers (P<0.05). Abnormal echocardiography in 139 patients (36.7%) was mainly caused by decreased left ventricular diastolic function (22.7%) and heart valve regurgitation (14.0%), and the rate in the elderly group was significantly higher than that in the non-elderly group (85.7% vs. 30.6%, P<0.05). After treatment, 3 patients in the elderly group died, and the others were cured and discharged. The hospitalization duration of the elderly group was longer than that of the non-elderly group (22.1 d vs. 18.8 d, P=0.033). Conclusions    Elderly COVID-19 patients are mainly imported from Wuhan or secondary to the local population, mainly common or critical type, often associated with basic diseases such as hypertension or diabetes. While, non-elderly COVID-19 patients are mainly imported from abroad, mainly mild or common type, often associated with non-alcoholic steatohepatitis. After treatment, most of the patients have a good prognosis.

Objective:To investigate the expression of microRNA (miR) -26a in human skin fibroblasts during photoaging induced by ultraviolet A (UVA) , and to evaluate the effect of up-or down-regulation of miR-26a expression on the methylation level of the whole genome, the target gene enhancer of zeste homolog 2 (EZH2) and cell aging.Methods:Some human skin fibroblasts were irradiated with 10 J/cm 2 UVA once a day for 7 consecutive days, RNA was extracted on days 0, 3 and 7, and real-time quantitative reverse PCR (RT-PCR) was performed to determine the expression of miR-26a; miR-26a mimics and inhibitors were transfected into fibroblasts to up-or down-regulate the expression of miR-26a respectively, and fluorescence microscopy and RT-PCR were performed to determine the expression of miR-26a and evaluate the transfection efficiency. Some human skin fibroblasts were divided into 6 groups: blank control group receiving no treatment, UVA group treated with UVA irradiation according to the above method, miR-26a mimic group transfected with miR-26a-mimics, UVA+miR-26a mimic group transfected with miR-26a-mimics followed by UVA irradiation, miR-26a inhibitor group transfected with miR-26a inhibitors, UVA+miR-26a inhibitor group transfected with miR-26a inhibitors followed by UVA irradiation. On day 7, cells in each group were collected after the end of UVA irradiation. Then, flow cytometry was performed to detect cell cycle, DNA methylation quantitative detection kit was used to detect the methylation level of whole genome, RT-PCR was conducted to determine the mRNA expression of EZH2 (a histone-lysine N-methyltransferase enzyme) , DNA methyltransferase 1 (DNMT1) and miR-26a, and Western blot analysis was performed to determine the protein expression of EZH2 and DNMT1. Statistical analysis was carried out by using one-way analysis of variance and least significant difference- t test. Results:Compared with the unirradiated control group, the expression of miR-26a gradually increased in the UVA irradiation group over time during the culture, and there was a significant difference in the expression of miR-26a between the two groups after 7 days of UVA irradiation ( t=5.295, P < 0.05) . Strong fluorescence signals were observed in the miR-26a mimic-or miR-26a inhibitor-transfected fibroblasts, suggesting a high transfection efficiency. Flow cytometry showed that the proportion of cells at G1 phase significantly differed among the blank control group, UVA group, miR-26a mimic group, UVA+miR-26a mimic group, miR-26a inhibitor group, and UVA+miR-26a inhibitor group (52.82% ± 2.56%, 78.56% ± 4.34%, 53.63% ± 3.13%, 89.52% ± 4.17%, 54.39% ± 3.86%, 65.34% ± 4.78%, respectively; F=46.728, P < 0.01) , and significantly higher in the UVA group than in the blank control group ( t=8.848, P < 0.01) , higher in the UVA+miR-26a mimic group than in the miR-26a mimic group and UVA group ( t=11.922, 3.154, P < 0.01, < 0.05, respectively) , and higher in the UVA+miR-26a inhibitor group than in the miR-26a-inhibitor group ( t=3.087, P < 0.05) , but significantly lower in the UVA+miR-26a inhibitor group than in the UVA group ( t=3.547, P < 0.05) . Detection of the genome-wide methylation level showed that the methylation level ( A450 value) significantly differed among the above groups (0.676 ± 0.024, 0.323 ± 0.043, 0.506 ± 0.035, 0.169 ± 0.024, 0.602 ± 0.036, 0.422 ± 0.029, respectively, F=97.402, P < 0.01) , and significantly lower in the UVA group than in the blank control group ( P < 0.01) , lower in the UVA+miR-26a mimic group than in the miR-26a mimic group and UVA group (both P < 0.01) , and lower in the UVA+miR-26a inhibitor group than in the miR-26a inhibitor group ( P < 0.01) , but significantly higher in the UVA+miR-26a inhibitor group than in the UVA group ( P < 0.05) . RT-PCR and Western blot analysis showed significant differences in the mRNA and protein expression of EZH2 and DNMT1 respectively among the 6 groups (both P < 0.05) , which were significantly lower in the UVA group than in the blank control group ( P < 0.05) , lower in the UVA+miR-26a mimic group than in the miR-26a mimic group and UVA group (both P < 0.05) , and lower in the UVA+miR-26a inhibitor group than in the miR-26a inhibitor group ( P < 0.05) , but significantly higher in the UVA+miR-26a inhibitor group than in the UVA group ( P < 0.05) . Conclusion:In the UVA irradiation-induced photoaging of skin fibroblasts, miR-26a expression was up-regulated, cellular proliferative activity and genome-wide methylation level decreased; up-regulation of miR-26a expression could down-regulate the expression of its target gene EZH2 and methylation-related gene DNM1, and promote cell photoaging, while down-regulation of miR-26a expression could up-regulate the expression of EZH2 and DNMT1, and inhibit cell photoaging.