The application of immunosuppressants has significantly reduced the incidence rate of rejection reaction after liver transplantation， but the clinical efficacy of immunosuppressants is greatly affected by individual differences between patients. This article systematically reviews the recent research advances in the interaction between immunosuppressants and gut microbiota， with a focus on the regulatory role and mechanism of intestinal microflora communities on the efficacy of immunosuppressants. Studies have shown that intestinal microbiome is one of the key factors influencing the efficacy of immunosuppressive therapy after liver transplantation. This review aims to provide a theoretical basis for in-depth research in this field and provide new insights for developing individualized immunosuppressive treatment regimens based on the regulation of intestinal microflora.

Objective To construct prostate cancer(PCa)prediction models based on machine learning algorithms, so as to improve the accuracy of early diagnosis of PCa. Methods A retrospective analysis was performed on the clinical data of 504 patients who underwent prostate biopsy at our hospital during Jan. 2020 and Nov. 2024. Patients' age, body mass index(BMI), history of hypertension, diabetes and smoking, total prostate-specific antigen(tPSA), free prostate-specific antigen(fPSA), f/tPSA, prostate volume(PV), neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio(NLR), Prostate Imaging Reporting and Data System(PI-RADS)score, digital rectal examination(DRE)results, and pathological findings were collected. The patients were divided into the training and testing sets at a ratio of 7:3. Ten early diagnosis prediction models of PCa were constructed using 10 supervised machine learning algorithms. Model performance was evaluated and validated using metrics including area under the receiver operating characteristic curve(AUC), accuracy, sensitivity, specificity, calibration curves, and decision curve analysis(DCA). SHAP analysis was used to interpret the models, and to clarify the importance of each feature and the basis for model decisions. Results All models showed good predictive value, with the gradient boosting machine(GBM)model performing the best(AUC=0.905, accuracy=84.1%, sensitivity=90.2%, specificity=80.0%). Calibration curves indicated good calibration and fitting of the GBM model, while DCA demonstrated favorable clinical net benefits. SHAP analysis identified the most significant features affecting PCa occurrence in descending order:tPSA, f/tPSA, PIRADS score, PV, age, and DRE. Conclusion The GBM model exhibits the optimal performance among the 10 models. The importance of features for predicting the occurrence of PCa, from the highest to the lowest, is as follows:tPSA, f/tPSA, PIRADS score, PV, age, and DRE.

Osteonecrosis of femoral head （ONFH） is a disease that causes osteocyte death due to interruption of blood supply of the femoral head， which may cause symptoms such as joint movement disorders， pain， and even femoral head collapse. Currently， the commonly used methods for treating ONFH in clinical practice are accompanied by problems such as long-term side effects， inaccurate efficacy， technical limitations， and complication risks. Traditional Chinese medicine （TCM） has shown unique advantages of holistic regulation， mild side effects， and symptom alleviation. A review of the related literature shows that Salviae Miltiorrhizae Radix et Rhizoma， as a representative Chinese herbal medicine for activating blood and resolving stasis， has the effects of activating blood， resolving stasis， dredging meridians， and relieving pain. Its active ingredients （such as salvianolic acid B， tanshinone Ⅱ_A， and tanshinone Ⅰ） interfere with bone metabolism balance， osteogenesis and differentiation， and improve bone microcirculation and bone microstructure. Salviae Miltiorrhizae Radix et Rhizoma is often combined with the herbal medicines with the effects of tonifying the liver and spleen or activing blood to form herb pairs （such as Salviae Miltiorrhizae Radix et Rhizoma-Angelicae Sinensis Radix， Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma， and Salviae Miltiorrhizae Radix et Rhizoma-Drynariae Rhizoma）， which enhances the efficacy through synergistic effects. In the application of TCM compound formulas， Bushen Huoxue prescription， Bushen Huoxue capsules， Gubi Tongxiao granules， and Shenggu Zaizao pills can regulate signaling pathways such as Wnt/β-catenin， Hedgehog， Notch， transforming growth factor（TGF）-β₁/Smads， and mitogen-activated protein kinase （MAPK） through multiple targets to significantly improve bone metabolism and hip joint function， playing an important role in preventing and treating ONFH. Through a review of available studies， this paper systematically explains the outstanding advantages of the active ingredients， herb pairs， and compound formulas of Salviae miltiorrhizae Radix et Rhizoma in the prevention and treatment of ONFH. The mechanisms may be related to factors such as promoting osteoblast generation and inhibiting osteoclast formation， increasing osteogenic differentiation， promoting angiogenesis， increasing bone density， inhibiting inflammatory response， and regulating signaling pathways. In the future， modern technology can be employed to optimize dosage forms， and high-quality clinical research should be conducted to further clarify its mechanism of action and promote the precise application of TCM. This review aims to provide more thinking directions for the application of Salviae miltiorrhizae Radix et Rhizoma in preventing and treating ONFH.

AIM:To analyze differential proteins associated with the pathogenesis of dry eye(DE)using bioinformatics methods, in order to reveal their potential molecular mechanisms.METHODS: Articles published in PubMed and EMBASE databases from the inception of the database to August 31, 2023, that used proteomic methods to detect protein expression in clinical samples of dry eye were searched. Differential proteins were selected and further analyzed using the STRING database and Cytoscape software for hub gene screening and module analysis. Protein-protein interaction(PPI)analysis, gene ontology(GO)functional annotation, and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed.RESULTS: A total of 21 articles were included, identifying 74 differentially expressed proteins. The most frequently occurring differential proteins were calgranulin A(SA1008), lipocalin-1(LCN1), lysozyme C(LYZ), mammaglobin-B(SCGB2A1), proline-rich protein 4(PRR4), transferrin(TF), and calgranulinB(S100A9). The top 10 hub genes were serum albumin(ALB), tumor necrosis factor(TNF), interleukin 6(IL6), IL1B, IL8, matrix metalloproteinase 9(MMP9), alpha-1-antitrypsin(SERPINA1), IL10, complement component 3(C3), and lactotransferrin(LTF). Module analysis suggested MMP9 and PRR4 as seed genes. KEGG analysis showed that differential proteins were mainly enriched in the IL17 signaling pathway(61.9%).CONCLUSION: The results reveal potential molecular targets and pathways for DE and confirm the association between the pathogenesis of DE and inflammation. Further in-depth research is needed to confirm the significance of these biomarkers in clinical practice.

Objective To investigate the relationship between peripheral blood receptor-interacting protein kinase 1(RIPK1),bone morphogenetic protein-7(BMP-7),glucose-regulated protein 78(GRP78),NOD-like receptor pyrin domain-containing protein 3(NLRP3)inflammasome and prognosis in children with severe Mycoplasma pneumoniae pneumonia(SMPP).Methods A total of 228 children with SMPP admitted to Guangyuan Maternal and Child Health Hospital from June 2020 to June 2024 were selected as SMPP group.Based on prognosis,they were divided into a poor prognosis group(48 cases)and a good prognosis group(180 cases).Additionally,228 healthy children who underwent physical examinations during the same period were selected as control group.Peripheral blood levels of RIPK1,BMP-7,GRP78,and NLRP3 inflammasome-relat-ed factors[NLRP3,cysteinyl aspartate specific proteinase 1(Caspase-1),and apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)]mRNA were detected and compared between two groups.Pearson method was used to analyze the correlation between peripheral blood RIPK1,BMP-7,GRP78,and the expression of NLRP3 inflammasome-related factors in children with SMPP.Multivariate Logistic re-gression analysis was performed to determine the influencing factors of poor prognosis in children with SMPP.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of pe-ripheral blood RIPK1,BMP-7,and GRP78 for poor prognosis in children with SMPP.Results The levels of RIPK1,GRP78,NLRP3 mRNA,Caspase-1 mRNA,and ASC mRNA in the SMPP group were higher than those in the control group(P＜0.05),while the level of BMP-7 was lower than that in the control group(P＜0.05).In children with SMPP,peripheral blood RIPK1 and GRP78 were positively correlated with NLRP3 mRNA,caspase-1 mRNA,and ASC mRNA(P＜0.05),whereas BMP-7 was negatively correlated with NLRP3 mRNA,caspase-1 mRNA,and ASC mRNA(P＜0.05).The body temperature upon admission,C-reactive protein,procalcitonin,NLRP3 mRNA,Caspase-1 mRNA,ASC mRNA,peripheral blood RIPK1,and GRP78 levels in the poor prognosis group were all higher than those in the good prognosis group(P＜0.05),while BMP-7 level was lower than that in the good prognosis group(P＜0.05).High peripheral blood levels of RIPK1 and GRP78,along with low BMP-7 level,were identified as independent risk factors for poor prognosis in children with SMPP(P＜0.05).The area under the curve(AUC)of the single detection of RIPK1,BMP-7,and GRP78 for predicting the poor prognosis was 0.786,0.781,and 0.767,respectively,while the combined detection yielded an AUC of 0.904.Conclusion High peripheral blood levels of RIPK1 and GRP78 and low level of BMP-7 are closely associated with NLRP3 inflammasome activation and poor prognosis in children with SMPP.The combined detection of RIPK1,BMP-7,and GRP78 in peripheral blood has high predictive val-ue for the prognosis in children with SMPP.

The incidence of chronic venous disease(CVD)is significantly higher in the elderly population compared to non-elderly individuals,with more severe disease manifestations.Additionally,elderly CVD patients often have comorbid conditions such as cardiovascular diseases,making the evaluation process more complex and increasing treatment difficulty.Currently,there are no established recommendations in China for the diagnosis and treatment of CVD in individuals aged 60 and above.Against this backdrop,the Peripheral Vascular Disease Management Branch of the Chinese Geriatric Society has developed the Chinese Expert Consensus on the Diagnosis and Treatment of Chronic Venous Disease in the Elderly based on domestic and international guidelines,relevant evidence-based medical research,and the physiological and clinical characteristics of the elderly population in China.This consensus aims to provide an important reference for improving the diagnosis and treatment of CVD in elderly patients in China.

Heat stress(HS)is a critical factor contributing to male infertility,primarily by disrupting the testicular spermatogenic microenvironment,leading to oligospermia,asthenospermia,teratospermia and other male healthcare con-cerns.Sertoli cells are the major components of spermatogenic microenvironment and the blood-testis barrier(BTB),provi-ding structural and nutritional support for spermatogenesis.HS impairs the structure and function of Sertoli cells and the BTB,disrupts the spermatogenesis,and damages other testicular cells and extracellular matrix components.Current re-search predominantly employs surgical or environmental simulation models.A large number of studies have found that natu-ral compounds and traditional Chinese medicines exhibit therapeutic potential through antioxidant,anti-apoptotic,and hor-mone synthesis-regulating mechanisms.Patent and market translation efforts focus on optimizing formulars and developing novel antioxidant molecules.This review systematically summarizes the mechanisms of HS-induced reproductive damage,advances in basic research,and translational progress,aiming to provide a theoretical foundation for clinical diagnosis,treatment,and product development,while enhancing awareness of male reproductive health protection.

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Objective To identify the taste critical quality attribute and design and optimize the flavor-correcting formulation of the traditional Chinese medicine oral preparation Qingre Jiedu Oral Liquid,in order to improve its taste and enhance patient medication adherence.Methods The taste assignment method was employed to identify the taste critical quality attribute of Qingre Jiedu Oral Liquid.Based on human sensory evaluation and the standardized Euclidean distance in electronic tongue analysis,suitable types of corrigent were determined.Subsequently,under constraints such as maximum allowable dosage,solubility,and sweetness,the optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined using Box-Behnken experimental design combined with electronic tongue and human sensory evaluation results.The study was reviewed and approved by the Ethics Committee of Beijing University of Chinese Medicine(Ethics Approval Number 2020BZYLL0609).Results The quantitative score for bitter taste of Qingre Jiedu Oral Liquid accounted for 30.36%,confirming bitterness as the taste critical quality attribute requiring attention.The optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined to be 120 mg·mL?1 erythritol,12 mg·mL?1 acesulfame potassium,and 2.4 mg·mL?1 stevioside.This formulation achieved an 11.75-point improvement in sensory evaluation scores compared to the original commercially available oral liquid.Conclusion This study successfully improved the taste of Qingre Jiedu Oral Liquid and established a comprehensive strategy for flavor-correcting formulation optimization,including a method for identifying taste critical quality attribute.This strategy provides a referential paradigm for palatability enhancement of similar traditional Chinese medicine oral preparations,laying a crucial technical foundation for elevating the clinical value of Chinese herbal medicines and promoting the high-quality development of traditional Chinese medicine(TCM).

Objective:To explore the research hotspots and trends in the literature related to hearing loss caused by organic solvents, and to provide an effective theoretical basis for further research on the impact of ototoxic organic solvents on the auditory system.Methods:In January 2024, literatures that met the inclusion/exclusion criteria from 1974 to 2023 in the PubMed database were selected. The authors, countries, journal fields and publishing institutions of the literatures were analyzed through Bicomb version 2.01. The author co-occurrence knowledge network graph and the literature publication institution graph were plotted using CiteSpace 6.3R1 Advance, and the co-occurrence clustering map of keywords was drawn using VOS viewer 1.6.19 software.Results:A total of 380 relevant literatures were retrieved, and 256 were finally included. The top three countries in terms of the number of published literature were the United States (accounting for 30.08%, 77/256), the United Kingdom (accounting for 17.97%, 46/256), and the Netherlands (accounting for 10.16%, 26/256). The published authors were represented by Pierre Campo, involving a total of 165 institutions, mainly occupational health research institutions and hearing institutions. It mainly involved related fields such as audiology, occupational medicine, environmental hygiene, toxicology, and otolaryngology. The key groups were painters, aviation industry personnel, gas station workers and agricultural workers. The key solvents included organic solvent mixtures, benzene and its derivatives, trichloroethylene, ethanol, carbon disulfide, etc.Conclusion:Research on hearing loss caused by organic solvents mainly focuses on countries such as the United States, the United Kingdom, and the Netherlands, with a particular emphasis on occupational groups such as painters, aviation industry personnel, gas station workers, and agricultural personnel, as well as the ototoxic effects of organic solvent mixtures, benzene and its derivatives, etc. This provides a basis for subsequent mechanism exploration, protection strategy formulation, and hearing health management of the target population.