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.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Objective:To discuss the effect of long-term use of chlorhexidine on the resistance of Enterococcus faecalis(E.faecalis),and to clarify its mechanism.Methods:The standard strain of E.faecalis was repeatedly exposed to chlorhexidine for 10 generations,and the minimum inhibitory concentration(MIC)was recorded at each passage.The bacteria collected from the 10th generation with increased MIC values were designated as the E.faecalis chlorhexidine-resistant strains(E.faecalis-Cs).The growth curves of two strains were drawn;the morphology of two strains were observed by transmission electron microscope;the number of biofilm formation of two strains was detected by crystal violet staining;the bacterial hydrophobicities of two strains were detected by microbial adhesion to hydrocarbons(MATH)method;the expression levels of S-ribosylhomocysteine lyase(LuxS)mRNA in the bacterial biofilms of two strains were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Results:From the 0th to the 10th generation,the MIC values of E.faecalis were gradually increased.The growth curves of E.faecalis and E.faecalis-Cs showed no significant differences.The transmission electron microscope observation results showed that both E.faecalis and E.faecalis-Cs appeared oval or diplococcal,with intact cell wall structures,smooth edges,and evenly distributed cytoplasm.There were no significant differences in the morphology,size,cell wall thickness,or integrity between two types of bacteria.The crystal violet staining results showed that compared with E.faecalis,the number of biofilm formation of E.faecalis-Cs was significantly increased(P<0.05).The MATH results showed tha the hydrophobicity of E.faecalis-Cs was significantly higher than that of E.faecalis(P<0.05).The RT-qPCR results showed that the expression level of LuxS mRNA in the biofilms of E.faecalis-Cs was significantly higher than that of E.faecalis(P<0.05).Conclusion:E.faecalis develops the resistance after repeated exposure to the chlorhexidine,and the pathogenicity of the resistant strain is enhanced.The high expressin of quorum sensing(QS)system LuxS gene and stronger biofilm forming ability of bacteria may be the potential mechanism for E.faecalis to tolerate the chlorhexidine.

Objective:To analyze the root canal diameter of the mandibular first premolar by using finite element analysis to simulate the stress distribution of dentin under three different preparation methods,and to provide the basis for clinical root canal preparation strategies of the mandibular first premolars.Methods:Twenty-one patients with complete cone beam computed tomography(CBCT)images were selected.The original DICOM format data from CBCT were imported into Mimics 21.0 software to measure the root canal diameter at 3,6,9,and 12 mm from the apex and the root canal taper was segmentally calculated.Based on this,three-dimensional finite element models of the dental and periodontal tissues were constructed.Control group,maximum diameter preparation group,uniform preparation group,and 0.06 taper instrument preparation group were designed.In ANSYS Workbench 17.0 finite element analysis software,a 200 N load was applied to the buccal,lingual,and occlusal surfaces in various groups,and the stresses on dentin in various groups were analyzed.Results:The analysis of root canal taper at 3-6 mm,6-9 mm,and 9-12 mm from the apex of mandibular first premolar teeth showed that the taper was similar in the mesial-distal direction at 3-6 mm from the apex.The average taper in the buccal-lingual direction at 6-9 mm from the apex was 0.29,which was greater than the taper in the apical 1/3 and coronal 1/3.Under the same load,the peak stress values in dentin of mandibular first premolar teech in various groups were increased sequentially:4.693 6,16.304 0,14.278 0,and 18.682 0 MPa.The stress in maximum diameter preparation group concentrated on the canal wall with the highest stress value.The stress in uniform preparation group concentrated on the root surface,and the stress values on each section were lower than those in maximum diameter preparation group.The stress in 0.06 taper instrument preparation group concentrated on the apical 1/3 of the root surface.Conclusion:The root canal of the mandibular first premolar has a unique elliptical taper shape,and there are significant differences in diameter and taper between the mesial-distal and buccal-lingual directions.Different preparation methods result in different stress distributions on the canal wall,and the uniform preparation is the best method for enlarging the canal.

ObjectiveThe absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver. On the contrary, the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly. Alcohol consumption is strongly linked to global health risk. Previous reports have analyzed the changes of metabolites in plasma, serum, urine, liver and feces after alcohol consumption. Whether alcohol consumption affects the metabolites in lymph fluid is still unknown. Therefore, it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking. MethodsIn this study, male Wistar rats were divided into high, medium, and low-dosage alcohol groups (receiving Chinese Baijiu at 56%, 28% and 5.6% ABV, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 d, 10 ml·kg^-1·d^-1. Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry (LC-MS) and bioinformatic analysis. Principal component analysis and hierarchical clustering were performed by using Biodeep. Meanwhile, KEGG enrichment analysis of the differential metabolites was also performed by Biodeep. MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases. ResultsThe metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most. Based on the KEGG enrichment analysis, the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, etc. Interestingly, in the biosynthesis of unsaturated fatty acids category, the content of arachidonic acid is increased by 7.25 times, whereas the contents of palmitic acid, oleic acid, stearic acid, arachidic acid and erucic acid all decrease, indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake. It’s worth noting that arachidonic acid is closely related to inflammatory response. Furthermore, the differential metabolites are mainly related with schizophrenia, Alzheimer’s disease and lung cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and cholesterol metabolism. The differential metabolites are mainly related to schizophrenia, Alzheimer’s disease, lung cancer and Parkinson’s disease. As the dose of alcohol increases, the contents of some metabolites in lymph fluid increase, including cholesterol, L-leucine, fumaric acid and mannitol, and the number of metabolites related to schizophrenia also tends to increase, indicatingthat some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake. ConclusionAfter alcohol intake, the metabolites transported via the intestinal-lymphatic pathway are significantly changed, especially in the high-dosage group. Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake. Most importantly, alcohol intake may cause inflammatory response and the occurrence of neurological diseases, psychiatric diseases and cancer diseases. High-dosage drinking may aggravate or accelerate the occurrence of related diseases. These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.

Acute respiratory distress syndrome (ARDS) is severe respiratory failure in clinical practice, with a mortality rate as high as 40%. Injury of pulmonary endothelial cells and alveolar epithelial cells occurs during ARDS, and pulmonary endothelial injury results in endothelial barrier disruption, which usually occurs before epithelial injury. Especially, when harmful factors enter the blood, such as sepsis and hemorrhagic shock, the pulmonary endothelial cells are affected firstly. The injured endothelial cells may loss cell-to-cell connections and even die. After the endothelial barrier is disrupted, fluid and proteins cross the endothelial barrier, causing interstitial edema. The alveolar epithelium is more resistant to injury, and when the tight barrier of the epithelium is broken, fluids, proteins, neutrophils, and red blood cells in the interstitium enter the alveolar space. From this process, it is easy to find that the endothelium is the first barrier to prevent edema, therefore, the protection of endothelium is the key to the prevention and treatment of ARDS. In addition, the injured endothelial cells express selectin and cell adhesion molecules, promoting the recruitment of immune cells, which exacerbate the inflammatory response and pulmonary endothelial cell injury. Mesenchymal stem cells (MSCs) can be derived from umbilical cord, bone marrow, adipose and so on. Because of low immunogenicity, MSCs can be used for allogeneic transplantation and have great application potential in tissue repairing. Through paracrine effect, MSCs can promote cell survival and balance inflammatory response. MSCs infused intravenously can locate in lungs rapidly and interact with endothelial cells directly, thus MSCs have advantages in protecting pulmonary microvascular endothelial cells. Animal experiments and clinical trials have found that MSC transplantation can significantly improve the symptoms of ARDS and reduce inflammatory reactions and endothelial permeability. Mechanically, MSCs acts mainly through paracrine and immunomodulatory effects. Paracrine cytokines from MSCs can not only promote pulmonary endothelial proliferation, but also reduce inflammatory response and promote cell survival to maintain endothelial integrity. In addition to paracrine cytokines, extracellular vesicles of MSCs are rich in RNAs, proteins and bioactive substances, which can protect pulmonary endothelial cells by intercellular communication and substance transport. Furthermore, MSCs may protect pulmonary endothelial cells indirectly by regulating immune cells, such as reducing the formation of extracellular trapping network of neutrophils, regulating macrophage polarization and regulating Th17/Treg cell balance. Although the beneficial effects of MSCs are verified, much work still needs to be done. MSCs from different tissues have their own characteristics and the scope of application. Different lung diseases possess different endothelial injury mechanisms. Thus, determining the indications of MSCs derived from different tissues is the direction of pulmonary disease clinical trials. From the perspective of transplantation route, intravenous injection of MSCs may have better clinical application in pulmonary endothelial injury caused by endogenous harmful factors in blood. Previous reviews mostly focused on the protective effects of MSCs on alveolar epithelium. In this article, we focused on endothelial cells and reviewed the direct protective effects and mechanisms of MSCs on endothelium through paracrine cytokines and extracellular vesicles, and summarize the mechanisms by which MSCs may indirectly protect pulmonary endothelial cells by regulating immune cells.