Objective To screen ferroptosis genes related to the prognosis of cervical cancer and to construct a prognosis model. Methods Ferroptosis genes were obtained from FerrDb database, and cervical cancer related data were obtained from The Genome-Wide Association Study Catalog database and The Cancer Genome Atlas database. Transcriptome-Wide Association Study, colocalization analysis and differential expression analysis were conducted to screen out candidate ferroptosis genes; Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted on candidate genes. Univariate Cox regression analysis was used to further screen out genes related to the prognosis of cervical cancer. Kaplan-Meier method was used to analyze the relationship between genes and the overall survival of patients. The expression levels of genes in pan-cancer were analyzed through the TIMER database. Two prognostic models were conducted, Model 1 included age and tumor stage, while Model 2 incorporated age, tumor stage, and prognostic genes. The predictive capabilities of the two models were compared. Results A total of 91 candidate genes related to ferroptosis were obtained. Univariate Cox regression analysis showed that 15 genes were associated with the prognosis of cervical cancer. CA9, SCD, TFRC, QSOX1 and CDO1 were risk factors affecting the prognosis of cervical cancer patients (P＜0.05), while PTPN6, ALOXE3, HELLS, IFNG, MIOX, ALOX12B, DUOX1, ALOX15, AQP3 and IDO1 were protective factors (P＜0.05). The mRNA expression levels of the 15 genes showed significant upregulation or downregulation in at least 7 types of cancers, among which TFRC was associated with the largest number of cancer types. Kaplan-Meier analysis showed that HELLS, DUOX1 and ALOXE3 were associated with poor prognosis in cervical cancer. The AUC of the model 1 for predicting 1-year and 3-year overall survival rates of cervical cancer patients was 0.455 and 0.478, and the AUC of Model 2 was 0.854 and 0.595. Model 2 (C-index = 0.727) had better predictive ability than Model 1 (C-index = 0.502). Conclusion The prognostic model composed of 15 prognostic-related genes selected based on bioinformatics has better predictive performance for the survival outcomes of cervical cancer patients, providing important reference value for the prognostic assessment of cervical cancer patients.

Skeletal muscle atrophy is characterized by a reduction in both the size and quantity of skeletal muscle fibers, resulting in impaired muscle strength and function. It mainly includes disuse muscle atrophy, aging muscle atrophy, denervated muscle atrophy and muscle atrophy caused by disease etc. As a cost-effective way, exercise has been widely used in the prevention and treatment of skeletal muscle atrophy, but its mechanism for improving skeletal muscle atrophy remains unclear. Recent studies have indicated that insulin-like growth factor 1 (IGF-1) plays an important role in improving muscle atrophy through exercise, in addition to promoting the survival of neurons, lowering blood sugar, and anti-inflammation. This article reviews recent findings on the mechanisms by which IGF-1 mediates exercise-induced improvement in skeletal muscle atrophy, providing a theoretical basis for the prevention and treatment of this disease.
Insulin-Like Growth Factor I/physiology* ; Muscular Atrophy/therapy* ; Humans ; Exercise/physiology* ; Muscle, Skeletal ; Animals ; Insulin-Like Peptides

Gegen Qinlian Decoction(GQD) is a classic prescription for the clinical treatment of ulcerative colitis(UC). This study, based on the differences in efficacy observed in UC mice under different level of bile acids treated with GQD, aims to clarify the impact of bile acids on UC and its therapeutic effects. It further investigates the expression of bile acid receptors in the liver of UC mice, and preliminarily reveals the mechanism through which GQD affects bile acid synthesis in the treatment of UC. A UC mouse model was established using dextran sulfate sodium(DSS) induction. The efficacy of GQD was evaluated by assessing the general condition, disease activity index(DAI) score, colon length, and histopathological changes in colon tissue via hematoxylin and eosin(HE) staining. ELISA and Western blot were used to evaluate the inflammatory response in colon tissue. The total bile acid(TBA) level and liver damage were quantified using an automatic biochemistry analyzer. The expression levels of bile acid receptors and bile acid synthetases in liver tissue were detected by Western blot and RT-qPCR. The results showed that compared with the model group, GQD treatment significantly improved the DAI score, colon shortening, and histopathological damage in UC mice. The levels of pro-inflammatory factors TNF-α and IL-6 in the colon were significantly reduced. Serum TBA levels were significantly decreased, while alkaline phosphatase(ALP) levels significantly increased. After administration of cholic acid(CA), UC symptoms in the CA + GQD group were significantly aggravated compared with the GQD group. The DAI score, degree of weight loss, colon injury, serum TBA, and liver injury markers all increased significantly. However, compared with the CA group, the CA + GQD group showed a marked reduction in TBA levels and a significant improvement in UC-related symptoms, indicating that GQD can alleviate UC damage exacerbated by CA. Further investigation into the expression of bile acid receptors and synthetases in the liver showed that under GQD treatment, the expression of farnesoid X receptor(FXR) and small heterodimer partner(SHP) significantly increased, while the expression of G protein-coupled receptor 5(TGR5) and cholesterol 7α-hydroxylase(Cyp7A1) significantly decreased. These findings suggest that GQD may affect bile acid receptors and synthetases, inhibiting bile acid synthesis through the FXR/SHP pathway to treat UC.
Animals ; Colitis, Ulcerative/genetics* ; Bile Acids and Salts/biosynthesis* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Male ; Humans ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Colon/metabolism* ; Disease Models, Animal ; Liver/metabolism* ; Mice, Inbred C57BL

Osteoporosis(OP) is a metabolic bone disorder characterized by reduced bone mass and degenerative bone tissue. Osteoporotic pain(OPP) is its most common clinical symptom, significantly affecting the quality of life of patients. With the limitations of modern medical treatments and the intensification of aging, it is imperative to explore more cost-effective interventions for OPP. This paper, based on databases such as China National Knowledge Infrastructure(CNKI), VIP, Wanfang, BioMed, and Web of Science, uncovered the connection between the pathogenesis of OPP in traditional Chinese medicine(TCM) and modern medical mechanisms and retrospectively summarized the basic and clinical research methods and evidence of TCM prescriptions in the treatment of OP and related pain diseases. Studies have shown that TCM prescriptions, focusing on treatments such as nourishing the kidney, strengthening the spleen, and activating blood circulation to remove blood stasis, can significantly improve pain symptoms, increase bone mineral density(BMD), and adjust bone metabolic indicators such as C-terminal telopeptide of type Ⅰ collagen(CTX), serum bone Gla-protein(S-BGP), and alkaline phosphatase(ALP). The mechanisms of action of TCM prescriptions in treating OP and improving OPP symptoms were related to signaling pathways such as Wnt/β-catenin, nuclear factor kappa-B(NF-κB), mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), and the osteoprotegerin(OPG)/receptor activator of NF-κB(RANK)/receptor activator of NF-κB ligand(RANKL) axis. Further strengthening the accumulation and analysis of clinical data, rigorously designing and conducting randomized controlled trials of TCM treatments for OPP with large sample sizes, standardizing outcome measures in basic and clinical research by using methods such as the core outcome set(COS), and incorporating mass spectrometry and omics approaches to uncover more potential active components and mechanisms may contribute to a deeper exploration of the advantages and essence of TCM prescriptions in the treatment of OPP.
Humans ; Osteoporosis/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Retrospective Studies ; Bone Density/drug effects* ; Medicine, Chinese Traditional ; Pain/metabolism* ; Animals

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

Male factors contribute to 50% of infertility cases, with 20%-30% of cases being solely attributed to male infertility. Helicase for meiosis 1 ( HFM1 ) plays a crucial role in ensuring proper crossover formation and synapsis of homologous chromosomes during meiosis, an essential process in gametogenesis. HFM1 gene mutations are associated with male infertility, particularly in cases of non-obstructive azoospermia and severe oligozoospermia. However, the effects of intracytoplasmic sperm injection (ICSI) in HFM1 -related infertility cases remain inadequately explored. This study identified novel biallelic HFM1 variants through whole-exome sequencing (WES) in a Chinese patient with severe oligozoospermia, which was confirmed by Sanger sequencing. The pathogenicity of these variants was assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunoblotting, which revealed a significant reduction in HFM1 mRNA and protein levels in spermatozoa compared to those in a healthy control. Transmission electron microscopy revealed morphological abnormalities in sperm cells, including defects in the head and flagellum. Despite these abnormalities, ICSI treatment resulted in a favorable fertility outcome for the patient, indicating that assisted reproductive techniques (ART) can be effective in managing HFM1 -related male infertility. These findings offer valuable insights into the management of such cases.
Humans ; Male ; Sperm Injections, Intracytoplasmic ; Oligospermia/therapy* ; Adult ; Spermatozoa/ultrastructure* ; Exome Sequencing ; Mutation

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index