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.

The Compilation Instructions for Expert Consensus on Clinical Application of Dieda Huoxue capsules systematically expound the development methods and evidence-based basis of this consensus. In view of the weak clinical application evidence and ambiguous indications of Dieda Huoxue capsules， the Institute of Basic Research in Clinical Medicine of the China Academy of Chinese Medical Sciences and Wangjing Hospital took the lead and collaborated with 33 experts from 28 medical institutions nationwide. They strictly followed the World Health Organization （WHO） guideline-making norms and the Grading of Recommendations Assessment， Development and Evaluations （GRADE） evidence-grading system and completed the compilation through multidisciplinary cooperation. The workflow included constructing clinical questions （19 items were screened by the nominal group technique）， retrieving evidence （from Chinese and English databases and grey literature）， assessing safety （integrating drug monitoring data and clinical investigations）， and forming recommendations and consensus suggestions （3 recommendations were reached via the GRADE grid method， and 16 consensus suggestions were reached by the majority vote rule）. The results indicate that the consensus clearly states that this medicine （Dieda Huoxue capsules） is applicable to conditions like traumatic injury， blood stasis-induced pain， and sudden lumbar sprains. The recommended dose is 6 capsules each time， twice a day. Combining oral administration with external application can enhance the efficacy， and elderly patients should take the medicine at intervals. Safety monitoring suggests that it should be used with caution in people with a bleeding tendency and those with an allergic constitution. The compilation process involved three rounds of reviews by internal and external experts. Literature analysis， the Delphi method， and clinical applicability tests were employed to ensure methodological rigor. The compilation instructions comprehensively present key aspects such as project approval and registration， conflict-of-interest statements， and evidence evaluation through 12 appendices， providing methodological support for the clinical translation of the consensus. In the future， it will be continuously improved through a dynamic revision mechanism.

Objective To explore whether the cognitive function of central obese mice is decreased by affecting the expression of brain-derived neurotrophic factor(BDNF)in hippocampus.Methods Healthy mice at the neonatal stage were divided into normal group and model group at random.To obtain the obese models,model group mice were injected at cervical subcutaneous with 10％L-monosodium glutamate(MSG;3 mg·g-1·d-1)for 5 days.The normal group was injected with the same dose of 0.9％NaCl.In addition,mice were removed according to the requirements.Finally,we got 8 mice in each group.The following parameters were compared:body weight,Lee's index and levels of the serum lipid.The BDNF expression levels in hippocampal tissue were measured using western blotting.Results At the 8th weekend,the body weight of the model and normal groups was(49.01±2.47)and(41.27±3.28)g;the Lee's indexes were(357.14±9.24)and(330.15±7.37)g1/3·cm-1;triglyceride levels were(1.37±0.52)and(0.73±0.31)mmol·L-1;total cholesterol levels were(2.98±0.18)and(1.98±0.30)mmol·L-1;low-density lipoprotein levels were(0.31±0.03)and(0.24±0.02)mmol·L-1;high-density lipoprotein levels were(2.70±0.15)and(1.98±0.40)mmol·L-1;the differences were statistically significant(P＜0.05,P＜0.01),which were consistent with the characteristics of the central obesity model.The BDNF protein expression levels in the hippocampus of the model and normal groups were 6.02 x 104±626.53 and 7.04 x 104±1 440.81,which has statistically significant(P＜0.01).Conclusion The cognitive function of central obese mice may be decreased by down-regulating the expression of BDNF in hippocampus.

Biological toxins are toxic molecules produced by specific microorganisms,plants or animals.Due to their wide range of sources and high toxicity,the availability of protein and non-protein toxins is becoming increasingly important,some of which are used for military purposes and developed as biotoxin warfare agents.In this paper,the classification and mechanism of action of biological toxins are discussed.In addition,the strategies for prevention and control of biological toxins as well as their therapeutic applications are reviewed.

Osteoarthritis (OA) is a chronic degenerative joint disease and the most common type of arthritis. It involves almost any joint and can lead to chronic pain and disability. In the late 19th century, Roentgen discovered X-rays, and then began to use radiotherapy to treat tumors. In the 1980s, Luckey thought that low-level radiation (LDRT) might be beneficial to biology, and it was gradually applied to the treatment of some diseases. This paper introduces the epidemiology, risk factors, clinical manifestations and treatment methods of OA, points out that the cartilage injury and the important effect of synovial inflammation in the pathogenesis of OA, namely when the homeostasis of articular cartilage are destroyed, synthetic metabolism and catabolism imbalances, cartilage cells damaged their breakdown products consumed by synovial cells. Synovial cells and synovial macrophages secrete proinflammatory cytokines, metalloproteinases and proteolytic enzymes, leading to cartilage matrix degradation and chondrocyte damage, which aggravates synovial inflammation and cartilage damage, forming a vicious cycle. The possible mechanism and clinical research progress of LDRT in alleviating OA are discussed. LDRT can regulate inflammatory response, inhibit the production of pro-inflammatory cytokines, and promote the production of anti-inflammatory cytokines, thereby achieving anti-inflammatory effect. Studies have shown that after irradiation, the expression of inducible nitric oxide synthase (iNOS) was decreased, the release of reactive oxygen species (ROS) and the production of superoxide were inhibited, the anti-inflammatory phenotype of macrophages was differentiated from M1 to M2, the inflammatory CD8⁺ T cells were transformed into CD4⁺ T cells, and the number of dendritic cells (DC) was significantly reduced. LDRT inhibit the production of proinflammatory factors in leukocytes, reduce their recruitment and adhesion, and down-regulate the expression levels of cell adhesion molecules such as selectin, intercellular adhesion molecule (ICAM) and vascular endothelial cell adhesion molecule (VCAM). LDRT can regulate endothelial cells, stimulate endothelial cells to produce a large amount of TGF-β1, reduce the adhesion of endothelial cells to peripheral blood mononuclear cells (PBMC), and contribute to the anti-inflammatory effect of LDRT. It also exerted anti-inflammatory effects by regulating mitochondrial growth differentiation factor 15 (GDF15). After low-level radiation, the MMP-13 (matrix metalloproteinases-13) and the ADAMTS5 (recombinant a disintegrin and metalloproteinase with thrombospondin-5) decreased, the Col2a1 (collagen type 2) increased in chondrocytes. In the existing clinical studies, most patients can achieve relief of joint pain and recovery of joint mobility after irradiation, and the patients have good feedback on the efficacy. The adverse reactions (acute reactions and carcinogenic risks) caused by LDRT in the treatment of OA are also discussed. During the treatment of OA, a few patients have symptoms such as redness, dryness or itching at the joint skin, and the symptoms are mild and do not require further treatment. Patients are thus able to tolerate more frequent and longer doses of radiotherapy. In general, LDRT itself has the advantages of non-invasive, less adverse reactions, and shows the effect of pain relief and movement improvement in the treatment of OA. Therefore, LDRT has a broad application prospect in the treatment of OA.

Intestinal organoids are constructed by crypts or stem cells from the intestine under the 3D support of the culture matrix. They contain all mature cells of the intestine, and have become a new and efficient platform for studying the mechanism of intestinal diseases. Compared with 2D cell culture, organoids can not only more effectively simulate the physiological structure and function of the intestine, but also better restore the true ecology of the intestine in different external environments. Therefore, it is more widely used in the study of pathogenesis of different intestinal diseases. This article reviewed the new progress of intestinal organoids culture, and the application and progress of intestinal organoids in the pathogenesis of inflammatory bowel diseases, colorectal cancer and celiac disease in recent years, and also discussed the application of intestinal organoids in drug research and development and screening.

Objective:To investigate the expression and clinical significance of microRNA-124(miR-124)and microRNA-1976(miR-1976)in the serum of patients with Parkinson's disease(PD).Methods:A total of 58 patients with PD were selected from September 2020 to June 2022 and categorized as the PD group.The Unified Parkinson's Disease Rating Scale(UPDRS)score was used to divide the PD patients into two groups: those with a UPDRS score≤60(25 patients)and those with a UPDRS score >60(33 patients). The Hoehn-Yahr grading scale was used to grade the PD patients.Additionally, 30 healthy individuals who had undergone a physical examination during the same period were selected as the control group.After collecting the subjects' serum, we performed real-time fluorescent quantitative PCR(qRT-PCR)to detect the expressions of miR-124 and miR-1976 in the serum.Logistic regression analysis was employed to analyze the influencing factors, and the diagnostic significance of serum miR-124 and miR-1976 in PD patients was evaluated using the receiver operating characteristic(ROC)curve.To predict the target genes of miR-1976, we utilized several software including TargetScan and Mirtarbase.Results:Compared to the control group, the PD group showed a significant down-regulation of serum miR-124 expression[(1.49±0.36) vs.(1.02±0.32)]( t=8.85, P<0.001), while miR-1976 expression was sharply up-regulated[(0.98±0.30) vs.(1.33±0.37)]( t=6.92, P<0.001). The low expression of serum miR-124 and the overexpression of miR-1976 were identified as independent risk factors for PD( OR>1, P<0.05). The Hoehn-Yahr rating of PD patients with a UPDRS score above 60 was higher than that of patients with a UPDRS score below 60[(3.42 ± 0.73) vs.(2.16 ± 0.42)]( t=3.05, P<0.05). However, there was no significant difference in serum miR-124 and miR-1976 expression between groups with different UPDRS scores[miR-124: (1.09±0.26) vs.(0.98±0.38)( t=0.89, P>0.05); miR-1976: (1.42±0.43) vs.(1.23±0.68)( t=0.62, P>0.05)]. The ROC analysis results demonstrated that miR-124 and miR-1976 had area under the curve(AUC)values of 0.832 and 0.797, respectively, in diagnosing PD.The corresponding cutoff values were 1.205 and 1.196, respectively.The sensitivity for miR-124 was 74.1%, while for miR-1976 it was 51.8%.The specificity for miR-124 was 77.8%, and for miR-1976 it was 90.1%.When both miR-124 and miR-1976 were combined in the diagnosis of PD, the AUC was 0.912, with a sensitivity of 76.4% and a specificity of 93.2%.Furthermore, it was found that miR-1976 targeted the PINK1 gene, suggesting its potential as a target gene in PD. Conclusions:The expression of miR-124 was found to be decreased in PD patients, while the expression of miR-1976 was increased.Both miR-124 and miR-1976 showed some reference value in PD diagnosis, and their combined diagnostic value was higher.This suggests that further study on their significance is warranted.However, it should be noted that the expressions of miR-124 and miR-1976 were not found to be correlated with the UPDRS score of PD patients.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.