ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Diabetic sarcopenia (DS) is a common but often ignored skeletal muscle complication in individuals with diabetes mellitus. It is characterized by progressive loss of skeletal muscle mass, reduced muscle strength, and impaired physical performance, which may further increase the risk of falls, disabilities, metabolic disorders, and adverse clinical outcomes. Traditionally, DS has been attributed mainly to hyperglycemia, insulin resistance, aging-related muscle decline, and chronic complications of diabetes. However, increasing evidence suggests that lipid metabolic disturbance and pathological lipid metabolic reprogramming are not merely secondary consequences of diabetes, but may actively participate in the initiation and progression of DS. Under diabetic conditions, impaired fatty acid uptake, transport, oxidation, and storage disrupt skeletal muscle metabolic homeostasis, leading to ectopic lipid deposition and accumulation of lipotoxic intermediates. These lipid-derived metabolites can aggravate insulin resistance, impair mitochondrial energy production, enhance oxidative stress, activate chronic low-grade inflammation, and disturb protein synthesis and degradation balance, thereby accelerating skeletal muscle atrophy and functional decline. Lipid metabolic dysregulation may also interact with multiple pathological processes involved in DS, including mitochondrial dysfunction, inflammatory signaling, oxidative damage, impaired autophagy, and gut microbiota imbalance. These mechanisms do not occur independently; instead, they form a complex bidirectional vicious cycle with diabetes-related metabolic disorders. Specifically, mitochondrial dysfunction reduces fatty acid oxidative capacity, which further promotes lipid accumulation and lipotoxicity. Inflammatory activation can impair insulin signaling and muscle protein metabolism, while lipid overload may in turn amplify inflammatory responses. Similarly, gut microbiota dysbiosis and altered microbial metabolites may influence systemic inflammation, lipid metabolism, and skeletal muscle homeostasis. Therefore, lipid metabolic reprogramming provides an important mechanistic perspective for understanding the progression of DS from metabolic disturbance to structural and functional muscle impairment. Exercise intervention is an effective and clinically feasible non-pharmacological strategy for the prevention and management of DS. Both aerobic exercise and resistance training have been shown to improve insulin sensitivity, enhance fatty acid oxidation, increase mitochondrial biogenesis, reduce ectopic lipid deposition, and attenuate lipotoxic metabolite accumulation. These adaptations not only improved glucose and lipid metabolism, but also increased the preservation of muscle mass, muscle strength, and physical function. Moreover, combined exercise strategies may provide complementary benefits by integrating the metabolic advantages of aerobic exercise with the anabolic and functional effects of resistance training. Based on analyses of publicly available datasets and literature evidences, this review systematically summarizes the role of lipid metabolic disorders in the pathogenesis of DS, with particular attention to the molecular mechanisms linking lipid dysregulation to insulin resistance, chronic inflammation, oxidative stress, mitochondrial dysfunction, and gut microbiota disturbance. Furthermore, this review discusses the potential mechanisms by which exercise intervention improves DS through the regulation of lipid metabolic reprogramming, and outlines exercise prescription strategies in terms of modality, intensity, frequency, and duration. Understanding the interaction between lipid metabolism and skeletal muscle dysfunction may provide new theoretical evidence for early identification, mechanistic research, and precision exercise therapy in DS. Overall, targeting pathological lipid metabolic reprogramming through exercise intervention represents a promising and clinically actionable approach for improving muscle health and prognosis in individuals with DS.

ObjectiveThis study aimed to provide a scientific basis for the safety management of drinking water by assessing the contamination levels of 21 per- and polyfluoroalkyl substances (PFASs) in water samples collected from the Yangtze River Delta region. MethodsSolid-phase extraction coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed to determine 21 PFASs in 6 source water samples, 20 treated water samples, and 60 tap water samples collected from 5 administrative districts in the Yangtze River Delta region across four seasons in 2023. The Kruskal-Wallis H test was used to compare differences in PFAS concentrations among the three types of water samples, followed by post hoc pairwise comparisons with Bonferroni correction. Removal efficiencies of target compounds were also calculated. ResultsAmong the 86 samples, 14 PFASs were detected, with 7 compounds detected in 100% of samples. The total concentrations of PFASs in source water, treated water, and tap water ranged from 63.85 to 190.54 ng·L^-¹, 55.75 to 774.36 ng·L^-¹, and 40.72 to 689.80 ng·L^-¹, respectively. The compounds with the highest median concentrations were perfluorobutanoic acid (PFBA) (40.19, 15.20, and 14.05 ng·L^-¹), perfluorohexanoic acid (PFHxA) (29.69, 32.62, and 34.24 ng·L^-¹), perfluorooctanoic acid (PFOA) (17.65, 39.45, and 36.83 ng·L^-¹), and potassium perfluorobutanesulfonic acid (PFBS) (16.99, 24.38, and 23.89 ng·L^-¹). Notably, concentrations of PFOA (7.71‒71.63 ng·L^-¹) and PFOS (-¹) in tap water were below the regulatory limits specified in GB 5749‒2022 Standards for Drinking Water Quality (PFOA: 0.000 08 mg·L^-1, PFOS: 0.000 04 mg·L^-1). Significant seasonal variations in PFAS concentrations were observed, with total PFAS levels in March being higher than those in September and November (adjusted P<0.001, and P=0.006), and levels in May being higher than those in September (adjusted P=0.037). The removal efficiencies of PFASs in the water treatment plants ranged from -14% to 34%. ConclusionPFAS contamination is widespread in source water, treated water, and tap water in the Yangtze River Delta region, and concentrations of PFOA and PFOS in all tested water samples comply with the Chinese national standards for drinking water quality (GB 5749‒2022). The use of PFASs should be continuously regulated to ensure water safety.

Objective: To analyze the consumption frequency of major foods among Chinese children aged 6-17 years old, and to provide a basis for optimizing the dietary structure of children in China. Methods: Using data from the China Nutrition and Health System Survey and Application Program for Children 0-18 years old, 56 734 children aged 6-17 years old from North, Norththeast East, Central, South, Southwest and Northwest seven regions in China were selected for the study using stratified cluster random sampling from 2019 to 2021. A food frequency questionnaire was used to investigate the intake frequency of eight food groups in a month, including fresh vegetables, fresh fruits, livestock and poultry meats, aquatic products, eggs, dairy products, legumes, and cereals and potatoes. The foods were grouped according to whether they met the recommended intake criteria outlined in the Dietary Guidelines for Chinese Residents 2022. The〖KG*2〗χ2 test was used to compare the differences in the proportion of childrens intake frequency of each food group meeting the standard in different regions and age groups. Results: The proportions of Chinese children aged 6-17 years who consumed fresh vegetables and cereals and potatoes ≥3 times/d were 12.1% and 67.2%, respectively. The proportions of children who consumed fresh fruits, livestock and poultry meats, eggs and dairy products ≥1 time/d were 50.8%, 58.8%, 36.0% and 54.3%, respectively. The proportion of legumes consumed ≥4 times/week was 37.4%, and the proportion of aquatic products consumed ≥2 times/week was 39.7%. Fresh vegetables (5.5%), fresh fruits (33.1%), and dairy products (36.4%) had the lowest frequency of meeting the recommended standards in South China, and aquatic products (27.4%) and eggs (21.1%) had the lowest frequency of meeting the recommended standards in Northwest (P<0.008 3). Conclusion The overall intake frequency of fresh vegetables, fresh fruits, legumes, and dairy products are insufficient among Chinese children, with significant regional variations.

Acute kidney injury (AKI) is a common clinically critical syndrome in hospitalized patients with high morbidity and mortality. At present, the mechanism of AKI has not been fully elucidated, and no therapeutic drugs exist. As known, glycolytic product lactate is a key metabolite in physiological and pathological processes. The kidney is an important gluconeogenic organ, where lactate is the primary substrate of renal gluconeogenesis in physiological conditions. During AKI, altered glycolysis and gluconeogenesis in kidneys significantly disturb the lactate metabolic balance, which exert impacts on the severity and prognosis of AKI. Additionally, lactate-derived posttranslational modification, namely lactylation, is novel to AKI as it could regulate gene transcription of metabolic enzymes involved in glycolysis or Warburg effect. Protein lactylation widely exists in human tissues and may severely affect non-histone functions. Moreover, the strategies of intervening lactate metabolic pathways are expected to bring a new dawn for the treatment of AKI. This review focused on renal lactate metabolism, especially in proximal renal tubules after AKI, and updated recent advances of lactylation modification, which may help to explore potential therapeutic targets against AKI.
Humans ; Acute Kidney Injury/metabolism* ; Lactic Acid/metabolism* ; Animals ; Glycolysis/physiology* ; Gluconeogenesis/physiology* ; Kidney/metabolism*

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*