Objective To comprehensively investigate the levels of exposure and distribution characteristics of trihalomethanes (THMs) in drinking water in Guangzhou City, and evaluate the health risks of different groups of children, adolescents and adults, and to provide data and evidence for protecting human health and promoting risk control of drinking water. Methods According to the technical requirements of the ^"Standards for Drinking Water Quality Testing Methods^" (GB/T 5750-2023), the concentration of THMs, including trichloromethane (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and tribromomethane (TBM) in drinking water in Guangzhou City from 2023-2024 were detected. The health risk model recommended by USEPA was used for risk assessment．Results TCM, BDCM and DBCM were detected in the factory water and terminal water, with TCM contributing the most. There was a statistically significant difference (P<0.05) between the wet and dry seasons, and the concentration of TCM in the wet season was higher than that in the dry season. Among the multiple exposure factors, the amount of exposure through drinking water intake was much greater than that through skin absorption. The carcinogenic risk index of THMs for children, adolescents, and adults was 22.0×10^-6, 12.2×10^-6, and 11.4×10^-6, respectively, while the non-carcinogenic risk was less than 1. Conclusion The exposure risks of THMs in children, adolescents, and adults is within an acceptable range, but monitoring needs to be strengthened, with a particular focus on children.

Hepatocellular carcinoma (HCC) develops within a profoundly immunosuppressive tumor immune microenvironment (TIME), which limits the efficacy of immunotherapy. Polarization of tumor-associated macrophages (TAMs) toward a pro-tumorigenic M2 phenotype is a major driver of immune escape. Ferroptosis, an iron-dependent regulated cell death program, intersects with hepatic iron metabolism and immune regulation and thus offers promising points of therapeutic intervention. This review systematically elucidates the mechanistic role of TAM ferroptosis in HCC immune evasion and highlights a “bidirectional regulation” intervention strategy grounded in the Traditional Chinese medicine (TCM) principle of “fortifying healthy qi and eliminating pathogens” (Fuzheng Quxie). This strategy employs “eliminating pathogens” (Quxie) approaches to exploit the metabolic vulnerability of M2-like TAMs and precisely induce their ferroptosis. Moreover, it utilizes “fortifying healthy qi” (Fuzheng) approaches to protect M1-like TAMs and CD8⁺ T cells from oxidative damage. This parallel “induction-protection” paradigm demonstrates the unique advantages of TCM in systemically remodeling TIME through multitarget synergistic actions. Accordingly, precision regulation of TAM ferroptosis based on the Fuzheng Quxie theory represents a promising integrative Chinese-Western medicine strategy for overcoming current bottlenecks in HCC immunotherapy, although its clinical translational potential warrants further validation.

Objective To construct a dynamic prediction model for JC polyomavirus (JCV) reactivation after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 128 recipients who met the inclusion criteria and received kidney transplantation in Nanfang Hospital, Southern Medical University, from June 2021 to December 2024. Dynamic Cox regression and dynamic restricted mean survival time (RMST) regression based on the landmark method were adopted to establish the dynamic prediction models, and Monte Carlo cross-validation was used to evaluate model performance. Results The dynamic models could predict the incidence and onset time of JCV reactivation within the subsequent 3 months according to covariates at each landmark time point from the 1st to the 6th month after transplantation. Remuzzi score, body mass index and warm ischemia time were independent risk factors for JCV reactivation, while a history of urinary BK polyomavirus reactivation served as a protective factor. The median values of the area under the curve, C-index and Brier score of the dynamic Cox model were 0.873, 0.851 and 0.065 respectively, and the C-index of the dynamic RMST model was 0.829, all of which were superior to those of the static model. Conclusions The landmark-based dynamic models exhibit excellent predictive performance, which may integrate baseline data and post-transplant follow-up information to realize dynamic assessment of the risk and time window of JCV reactivation, thereby providing evidence for optimizing post-operative monitoring and individualized intervention strategies.

Cancer-related anorexia (CRA) is a common and severe complication of malignant tumors. It is characterized by persistent appetite loss, early satiety, and reduced food intake. It directly leads to malnutrition, decreased treatment tolerance, reduced quality of life, and worsened prognosis. Its pathogenesis is complex, involving a multilayered network of interactions, including the dysregulation of the hypothalamic feeding center, imbalance of peripheral appetite hormones and systemic inflammatory mediators, and actions of tumor-derived factors. It is also highly influenced by anticancer treatments, such as chemotherapy, radiotherapy, and surgery. Current clinical management is dominated by multimodal comprehensive therapy based on progestogens, glucocorticoids and prokinetic agents, combined with nutritional support, rehabilitation exercise, psychological intervention and traditional Chinese medicine. However, highly effective approaches capable of fundamentally reversing the disease course of CRA are still lacking. This article provides a systematic review of the pathophysiological mechanisms, clinical assessment tools, and comprehensive treatment strategies for CRA. It also presents a discussion on future research directions based on the latest advances to provide a theoretical basis and reference for optimizing clinical practice and developing novel intervention strategies.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

ObjectiveTo observe the clinical effectiveness of horticultural therapy involving the planting of Chinese medicinal herbs （mint and lily potted plants） combined with intradermal needling therapy for generalized anxiety disorder （GAD） of liver depression transforming into fire syndrome under transcranial magnetic stimulation and basic psychological therapy， and to explore the possible mechanisms of action. MethodsA total of 180 patients with GAD of liver depression transforming into fire syndrome were randomly divided into three groups， horticultural therapy group， intradermal needling group， and horticultural therapy+intradermal needling group， with 60 patients in each. All groups received basic treatment including basic psychological therapy and transcranial magnetic stimulation. The horticultural therapy group received horticultural therapy in addition to the basic treatment； the intradermal needling group received intradermal needling therapy once a week for 8 weeks in addition to the basic treatment； the horticultural therapy+intradermal needling group received both horticultural therapy and intradermal needling therapy， following the same procedures and duration. Hamilton Anxiety Rating Scale （HAMA）， Self-Rating Anxiety Scale （SAS）， and Pittsburgh Sleep Quality Index （PSQI） scores were assessed at baseline and after 2， 4， 6， and 8 weeks of treatment. Serum levels of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） were measured before treatment and after 8 weeks of treatment. Motor-evoked potential （MEP） baseline levels were recorded before treatment， and MEP amplitude ratios were compared after 1 week and 8 weeks of treatment. Clinical effectiveness and safety were evaluated after 8 weeks of treatment. Pearson correlation analysis was used to examine the relationships between serum ACTH and CORT levels， MEP amplitude， and anxiety. ResultsIn the horticultural therapy group and intradermal needling group， HAMA， SAS and PSQI scores after 4， 6， and 8 weeks treatment were lower than baseline scores （P＜0.05）. In the horticultural therapy+intradermal needling group， these scores showed a significant decline starting after 2 weeks treatment and continuing through 8 weeks after treatment （P＜0.05）. The HAMA， SAS， and PSQI scores in the horticultural therapy+intradermal needling group were significantly lower than those in the other two groups after 2， 4， 6， and 8 weeks treatment （P＜0.05）. After 8 weeks of treatment， serum CORT and ACTH levels in the horticultural therapy+intradermal needling group were significantly lower than baseline levels （P＜0.05） and were also lower than those in the horticultural therapy group and intradermal needling group at the same time point （P＜0.01）. When comparing the level after 8 weeks treatment to that after 1 week treatment， under PAS10 stimulation， the MEP amplitude ratio in the intradermal needling group decreased at 30 minutes， while in the horticultural therapy+intradermal needling group， the MEP amplitude ratio decreased at all time points （P＜0.05 or P＜0.001）； under PAS25 stimulation， the MEP amplitude ratio in the horticultural therapy group increased at 20 minutes， and in the intradermal needle group at 10 minutes （P＜0.05）. In the horticultural therapy+intradermal needling group， the MEP amplitude ratio increased significantly at all time points after treatment （P＜0.001）. The cure rate in the horticultural therapy+intradermal needling group （74.14%， 43/58） was significantly higher than that in the horticultural therapy group （30.00%， 18/60） and the intradermal needling group （48.28%， 28/58， P＜0.05）. Correlation analysis revealed that serum ACTH and CORT levels were positively correlated with HAMA scores （r = 0.488， P＜0.01； r = 0.428， P＜0.01）. Following PAS10 intervention， the MEP amplitude ratio was positively correlated with HAMA scores （r = 0.458， P＜0.01）， whereas after PAS25 intervention， the MEP amplitude ratio was negatively correlated with HAMA scores （r = -0.562， P＜0.01）. ConclusionHorticultural therapy combined with intradermal needling treatment， under transcranial magnetic stimulation and basic psychological therapy， demonstrates significant clinical effectiveness in patients with GAD of liver depression transforming into fire syndrome. Its mechanism of action may be related to the regulation of hyperactivation of the hypothalamic-pituitary-adrenal （HPA） axis and the reduction of cortical excitability.

Objective:To identify the pathogenic gene in a family with cone-rod dystrophy (CRD).Methods:A pedigree study was conducted.Clinical data were collected from three generations of six people from a family with CRD who visited Henan Eye Hospital in December 2019, including one patient.After detailed collection of the patient's medical history, the proband and his family members underwent best-corrected visual acuity, slit-lamp microscope+ front-lens examination, optometry, non-mydriatic fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field flash electroretinography (ff-ERG). Peripheral venous blood (5 ml) was collected from the proband, his parents and siblings, and the whole genome DNA was extracted.The proband's DNA was sequenced using whole exome sequencing.Hemizygous and potentially pathogenic mutations were verified by Sanger sequencing.Pathogenicity was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines.Tools such as SpliceAI and dbscSNV were used to predict the impact of mutations on mRNA splicing.This study strictly followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]). All subjects and guardians of minor subjects signed informed consent forms.Results:The proband (Ⅲ: 1), a 5-year-old boy, presented with recessive nystagmus in both eyes and a best corrected visual acuity of 0.2.Color vision examination revealed red-green color blindness without night blindness.SD-OCT showed the presence of neuroepithelial structures in both eyes, but the interdigitation zone was blurred in both eyes.ff-ERG showed a slight decrease in rod function and a moderate-severe decrease in cone function in the right eye, and a slight decrease in cone and rod function in the left eye.Gene sequencing results showed that the proband had the hemizygous splice site variant c. 1911-3C>A of the CACNA1F gene on the X chromosome.Sanger sequencing showed that neither his mother nor his younger sister carried the variant, suggesting it was novel.This variant site was not recorded in the normal population database (PM2). Bioinformatics tools SpliceAI and dbscSNV consistently predicted that this variation affects on splicing.According to the ACMG guidelines, this variation is pathogenic. Conclusions:A novel variant c. 1911-3C>A in the CACNA1F gene was found in a family with CRD, and this variant may be a pathogenic variant site in this CRD family.This discovery expands the spectrum of pathogenic variations in CRD.

BACKGROUND:Hepatocyte-like cells induced by mesenchymal stem cells are promising seed cells for liver regeneration or liver tissue engineering.The efficiency of traditional two-dimensional culture for hepatocyte induction is low,and more and more research is focused on three-dimensional culture for inducing hepatocyte differentiation.OBJECTIVE:To summarize three-dimensional culture models for the hepatic induction of mesenchymal stem cells,focus on research progress on the epigenetic regulation mechanisms of mesenchymal stem cell hepatogenic differentiation,providing a theoretical basis for improving the differentiation efficiency of mesenchymal stem cells.METHODS:Relevant articles in the PubMed and other databases such as CNKI were searched,using Chinese and English search terms"mesenchymal stem cell,3D culture,hepatogenic differentiation,hepatocyte-like cells,epigenetics."Additionally,the literature tracing method was employed to find some of the literature for a comprehensive review and analysis.RESULTS AND CONCLUSION:(1)Common three-dimensional culture models for the hepatogenic differentiation of mesenchymal stem cells currently include spheroids,biological scaffolds,bioprinting,and microfluidic chips.Each of these models has its own advantages and disadvantages in the process of inducing hepatogenic differentiation.(2)During the differentiation of mesenchymal stem cells into hepatocyte-like cells,epigenetic regulation plays a key role,primarily involving histone modification,DNA methylation,and the regulation of non-coding RNAs.(3)Under three-dimensional culture conditions,epigenetic modifications,especially histone acetylation,play an important role in promoting the hepatogenic differentiation of mesenchymal stem cells.

Objective Methyltransferase 3(METTL3)mediated N6-methyladenosine(m6A)methylation modifica-tion of transient receptor potential cation channel subfamily M member 7(TRPM7)regulates ferroptosis and malig-nant progression in cervical cancer(CESC).Methods Totally 40 patients with cervical cancer were collected.Cer-vical cancer tissues and adjacent normal tissues(≥3 cm from the edge of the tumor tissue)were sampled at opera-tion and then divided into experimental group and control group,respectively.RT-qPCR and Western blot were used to detect the differences in TRPM7 mRNA and protein expression between the two groups.TRPM7-interfering cell lines were constructed to investigate the effects of TRPM7 on CESC cells.Cell proliferation and apoptosis were assessed using 5-ethynyl-2'-deoxyuridine(EdU)assay and flow cytometry,respectively.Transwell chamber assays were employed to evaluate cell invasion and migration capabilities.The levels of ferroptosis in CESC cells were measured using kits for reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH),and Fe2+.Bioinformatics tools were utilized to predict methyltransferases associated with TRPM7.The interaction between METTL3 and TRPM7 was examined through RNA immunoprecipitation(RIP)and methylated RNA immunoprecip-itation quantitative PCR(Me-RIP qPCR).The effect of METTL3 on the stability of TRPM7 expression was assessed using actinomycin D assay.Results TRPM7 was highly expressed in CESC tissue and cells.Knockdown of TRPM7 significantly inhibited cell proliferation,promoted cell apoptosis,suppressed cell migration and invasion capabilities,and enhanced ferroptosis levels(P＜0.05).Bioinformatics predictions suggested that METTL3 might act as a methyltransferase for TRPM7.Interference with METTL3 gene expression significantly reduced TRPM7 pro-tein levels,decreased TRPM7 m6A modification levels,and impaired TRPM7 gene stability(P＜0.05).Conclusions METTL3 regulates CESC proliferation,apoptosis,migration,invasion,and ferroptosis by m6A meth-ylation modification of the TRPM7 gene.

Mitochondria play a pivotal role in spermatogenesis and sperm activation in Caenorhabditis elegans, serving as the primary ATP supplier for cell division and differentiation while also acting as a key regulator of zinc ion homeostasis, membrane dynamics, and apoptotic signaling. This review systematically summarizes the essential mitochondrial mechanisms at different stages of sperm development, highlighting their multifaceted contributions beyond energy metabolism. Mitochondria are crucial for maintaining the health and stability of the gonads by regulating key apoptotic execution proteins that facilitate the proper elimination of damaged or unnecessary germ cells. Additionally, mitochondria dynamically adjust their energy supply to meet the metabolic demands of different stages of germline development. During early spermatogenesis, mitochondria provide ATP to fuel mitotic and meiotic divisions, support cellular differentiation, and regulate H⁺ and Zn²⁺ exchange to maintain cytoplasmic homeostasis, thereby ensuring the proper maturation and functionality of sperm cells. As spermatogenesis progresses, mitochondria participate in processing and sorting essential sperm proteins, such as major sperm protein (MSP), and contribute to the formation of membranous organelles (MOs), which are critical for subsequent activation events. During sperm activation, mitochondria play a dual role in ensuring a successful transition from immotile spermatids to fully functional spermatozoa. First, they provide ATP to facilitate pseudopod formation, MO fusion, and ion channel regulation, all of which are essential for sperm motility and fertilization potential. Second, mitochondria regulate the quality and quantity of functional mitochondria within sperm cells through mitopherogenesis—a recently discovered process in which mitochondrial vesicles are selectively released, ensuring that only healthy mitochondria are retained. This quality-control mechanism optimizes mitochondrial function, which is crucial for sustaining sperm motility and longevity. Beyond their traditional role in energy metabolism, mitochondria may also contribute to protein synthesis during spermatogenesis and activation. Recent evidence suggests that mitochondrial ribosomes actively translate specific proteins required for sperm function, challenging the long-standing belief that spermatozoa do not engage in de novo protein synthesis after differentiation. This emerging perspective raises important questions about the role of mitochondria in regulating sperm activation at the molecular level, particularly in modulating oxidative phosphorylation (OXPHOS) protein composition to optimize ATP production. In summary, mitochondria serve as both the central energy hub and a crucial regulatory factor in sperm activation, metabolic homeostasis, and reproductive success. Their involvement extends beyond ATP generation to include apoptotic regulation, ion homeostasis, vesicle-mediated mitochondrial quality control, and potential contributions to protein synthesis. Understanding these mitochondrial functions in C. elegans not only deepens our knowledge of nematode reproductive biology, but also provides valuable insights into broader mechanisms governing mitochondrial regulation in germline cells across species. These findings open new avenues for future research into the interplay between mitochondria, energy metabolism, and sperm function, with potential implications for reproductive health and fertility studies.