ObjectiveTo investigate the dynamic expression profiles and potential regulatory mechanisms of long non-coding RNAs （lncRNAs） in male reproductive system aging. MethodsA naturally aging C57BL/6 mouse model was used and 4 mice were selected each at 3， 15， and 21 months of age. RNA was extracted from seven regions of the male reproductive tract （testis， efferent duct， initial segment of epididymis， caput epididymis， corpus epididymis， cauda epididymis， and vas deferens）， followed by RNA sequencing and bioinformatics analysis. ResultsRegion-specific dynamic expression profiles of lncRNAs were constructed in the testis， epididymis （efferent duct， initial segment， caput， corpus， and cauda）， and vas deferens of male mice. Combined with gene functional enrichment analysis， the functional associations of lncRNAs were elucidated in reproductive system aging. The differentially expressed lncRNAs in the aging testis were primarily involved in hormone biosynthesis and extracellular matrix organization， while those in the initial segment of the epididymis were closely related to cell recognition and epithelial cell migration. A comprehensive lncRNA expression atlas associated with male reproductive aging was established. ConclusionLncRNAs may participate in male reproductive aging through the regulation of the reproductive microenvironment， which provides key molecular targets and a research foundation for understanding age-related fertility decline.

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

OBJECTIVE: To evaluate the effect of palliative care on drug use, medical service utilization and medical expenditure of patients with advanced cancer. METHODS: A cohort of patients including pal-liative care and standard care was constructed using the medical records of the patients in Peking University Cancer Hospital from 2018 to 2020, and coarsened exact matching was used to match the two groups of patients. The average monthly opioid consumption, hospitalization rate, intensive care unit (ICU) rate and operation rate, and the average monthly total cost were selected to evaluate drug use, medical service utilization and medical expenditure. Chi-square test and Wilcoxon signed rank test were used to compare the differences between the two groups before and after exposure and the change in the palliative care group. The net impact of palliative care on the patients was calculated using the difference-in-differences analysis. RESULTS: In this study, 180 patients in the palliative care group and 3 101 patients in the stan-dard care group were finally included in the matching, and the matching effect of the two groups was good (L₁ < 0.1). Before and after exposure, the average monthly opioid consumption in the palliative care group was significantly higher than that in the standard care group (Before exposure: 0.3 DDD/person-month vs. 0.1 DDD/person-month, P < 0.01; After exposure: 0.7 DDD/person-month vs. 0.1 DDD/person-month, P < 0.01; DDD refers to defined daily dose), palliative care significantly increased the average monthly opioid consumption in the patients (0.3 DDD/person-month, P < 0.01). The hospitalization rate (48.9% vs. 74.3%, P < 0.01) and operation rate (3.9% vs. 8.8%, P < 0.01) of the patients in palliative care group were significantly lower than those in standard care group, and the ICU rate became similar between the two groups (1.1% vs. 1.6%, P=0.634). Palliative care significantly reduced the patients ' hospitalization rate (-25.6%, P < 0.01), ICU rate (-4.9%, P < 0.01) and operation rate (-14.5%, P < 0.01). Before and after exposure, the average monthly total costs of pal-liative care group were slightly higher than those of standard care group (Before exposure: 20 092.3 yuan vs. 19 132.8 yuan, P=0.725; After exposure: 9 719.8 yuan vs. 8 818.8 yuan, P=0.165). Palliative care increased the average monthly total cost by 2 208.8 yuan, but it was not statistically significant (P=0.316). CONCLUSION Palliative care can increase the opioid consumption in advanced cancer patients, reduce the rates of hospitalization, ICU and surgery, but has no significant effect on medical expenditure.
Humans ; Palliative Care/economics* ; Neoplasms/drug therapy* ; Analgesics, Opioid/economics* ; Male ; Female ; Middle Aged ; Aged ; Hospitalization/economics* ; Intensive Care Units/statistics & numerical data* ; Health Expenditures/statistics & numerical data* ; Adult ; Drug Utilization/statistics & numerical data* ; Patient Acceptance of Health Care/statistics & numerical data*

Objective:To explore the clinical characteristics, audiological outcomes, and factors influencing the efficacy of pharmacological treatment in patients with sudden hearing loss associated with large vestibular aqueduct syndrome（LVAS）. Methods:A retrospective analysis was conducted on the clinical data of 77 bilateral LVAS patients（117 ears） hospitalized for sudden hearing loss from January 1, 2009, to December 31, 2023. The inclusion criteria required that patients to be diagnosed according to the Valvassori standard and had received standardized pharmacological treatment. Clinical features, audiological outcomes, and treatment efficacy were analyzed. Statistical methods were employed to identify factors associated with treatment outcomes. Results:The age of the enrolled patients ranged from 4 to 37 years. The age of onset for the initial hearing fluctuation varied between 0 and 24 years, with a mean age of 5.8 years. The male-to-female ratio was approximately balanced（37 males and 40 females）. The proportion of unilateral to bilateral sudden hearing loss was 1.0︰1.2, with unilateral right ear hearing loss being more frequently occurring（64.9%）. Triggering Factors: Triggers included no identifiable factors in 48.1% of cases, a history of head trauma（24.7%）, upper respiratory tract infections（11.7%）, onset following physical fatigue（11.7%）, and less frequently, noise exposure, alcohol consumption, or emotional stress（each 1.3%）. Clinical Symptoms: Hearing loss was the sole symptom in 35.1% of cases. Concurrent symptoms included vertigo in 44.2% and tinnitus in 46.8%. Patients with a disease duration of ≤14 days demonstrated a treatment efficacy rate of 75.0%. Among those who responded to treatment, 93.0% had profound or greater hearing loss prior to therapy, with an average improvement in hearing thresholds of 32 dB HL. In pretreatment, 68.9% of patients exhibited low-frequency air-bone gaps, increasing to 76.1% post-treatment. Additionally, 17.6% of treated ears demonstrated a ≥15 dB HL improvement in low-frequency bone conduction thresholds. In the non-responsive group, 7.3% of ears still showed some improvement in bone conduction thresholds. Statistically significant differences（P<0.05） were observed between the treatment-effective and non-effective groups concerning the age of initial hearing fluctuation, disease duration, and severity of hearing loss at onset. Conclusion:The efficacy of pharmacological treatment for sudden hearing loss in LVAS patients is influenced by the age at onset, duration of the disease, and severity of hearing impairment. Early diagnosis and timely intervention significantly enhance treatment efficacy, particularly in patients with a disease duration of ≤14 days and an initial sudden hearing loss. Patients with severe hearing loss, especially those with profound or greater impairment, exhibit greater sensitivity to treatment. Pharmacological interventions positively impact both air conduction and bone conduction thresholds, with the observed improvement in bone conduction thresholds warranting further investigation.
Humans ; Male ; Retrospective Studies ; Hearing Loss, Sudden/etiology* ; Female ; Vestibular Aqueduct/pathology* ; Adult ; Child ; Adolescent ; Child, Preschool ; Young Adult ; Treatment Outcome

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

BACKGROUND:Compared with traditional two-dimensional culture,three-dimensional microtissue culture can show greater advantages.However,more favorable cultivation methods in three-dimensional culture still need to be further explored. OBJECTIVE:To evaluate the cell behavior of microtissue and its ability to promote cartilage formation under two three-dimensional culture methods. METHODS:Cartilage-derived microcarriers were prepared by chemical decellularization and tissue crushing.DNA quantification and nuclear staining were used to verify the success of decellularization,and histological staining was used to observe the matrix retention before and after decellularization.The microcarriers were characterized by scanning electron microscopy and CCK-8 assay.Cartilage-derived microtissues were constructed by combining cartilage-derived microcarriers with human adipose mesenchymal stem cells through three-dimensional static culture and three-dimensional dynamic culture methods.The cell viability and chondrogenic ability of the two groups of microtissues were detected by scanning electron microscopy,live and dead staining,and RT-qPCR. RESULTS AND CONCLUSION:(1)Cartilage-derived microcarriers were successfully prepared.Compared with before decellularization,the DNA content significantly decreased after decellularization(P<0.001).Scanning electron microscope observation showed that the surface of the microcarrier was surrounded by collagen,maintaining the characteristics of the natural extracellular matrix of cartilage cells.CCK-8 assay indicated that microcarriers had no cytotoxicity and could promote cell proliferation.(2)Scanning electron microscopy and live and dead staining results showed that compared with the three-dimensional static group,the three-dimensional dynamic group had a more extended morphology of microtissue cells,and extensive connections between cells and cells,between cells and matrix,and between matrix.(3)The results of RT-qPCR showed that the expressions of SOX9,proteoglycan,and type Ⅱ collagen in microtissues of both groups were increased at 7 or 14 days.The relative expression levels of each gene in the three-dimensional dynamic group were significantly higher than those in the three-dimensional static group at 14 days(P<0.05).At 21 days,the three-dimensional static group had significantly higher gene expression compared with the three-diomensional dynamic group(P<0.001).(4)The results showed that compared with three-dimensional static culture microtissue,three-dimensional dynamic culture microtissue could achieve higher expression of chondrogen-related genes in a shorter time,showing better cell viability and chondrogenic ability.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.