Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

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.

Laboratory animals are increasingly utilized as in vivo models for life sciences, medical research, and drug development, and the associated ethical and welfare issues have attracted increasing attention. The "3R" principle (replacement, reduction, refinement) is a globally recognized guideline for conducting animal experiments, providing direction for balancing scientific research with animal welfare. New approach methodologies refer to technologies that mimic human physiological systems and can replace or reduce traditional animal experiments, mainly including in vitro (e.g., organoids, organ-on-a-chip,3D bioprinting models), in chemico , and in silico tools. This review systematically examines the technical characteristics, development history, and applications of new approach methodologies in disease modeling, drug development, toxicological evaluation, etc., and focuses on the implementation path of the "3R" principle. New approach methodologies can replace some animal experiments through in vitro biomimetic models, reduce the number of experimental animals used through high-throughput screening and computational simulation, optimize experimental design and alleviate animal suffering through accurate dose prediction and early biomarker monitoring. New approach methodologies still face challenges such as the inability to fully recapitulate the complex human physiological system, insufficient standardization and reproducibility, and underdeveloped validation and acceptance pathways. With continuous technological innovation, rigorous scientific validation, proactive international cooperation, and sound policy support, new approach methodologies are expected to gradually reduce the use of traditional animal experiments and advance biomedical research toward the coordinated pursuit of scientific rigor, animal welfare, and cost-effectiveness.

Dietary therapy represents a promising approach to modulate gut microbiota in patients with inflammatory bowel disease (IBD) and may ameliorate certain neurological conditions through the gut-brain axis. The dietary therapy rich in fatty acids has been demonstrated therapeutic efficacy in both IBD and central nervous system (CNS) disorders, mainly manifested as controlling intestinal and neural inflammation through fatty acids. However, robust clinical evidence regarding the efficacy of dietary therapy against neurological manifestations in IBD remains limited. Therefore, this review summarizes the effects of fatty acid-rich dietary therapy in patients with IBD or CNS disorders, as well as the underlying mechanisms of fatty acids, with the aim of providing a reference for the application of such dietary therapy in IBD patients presenting with concurrent CNS manifestations and the development of treatment protocols.

The wrist joint is a highly mobile functional joint. Wrist conditions including traumatic and degenerative arthritis, rheumatoid arthritis, and giant cell tumors of the distal radius, cause significant pain and mobility impairment. In joint surgery, the decision to use joint prostheses to reconstruct joint function is greatly influenced by the characteristics of the prosthesis (Mok et al., 2016). However, traditional implants have limitations such as shape mismatch, inadequate implant-bone interface strength which causes loosening, and poor bone ingrowth (Zhang et al., 2014).
Humans ; Joint Prosthesis ; Wrist Joint/surgery* ; Prosthesis Design ; Arthroplasty, Replacement ; Arthritis, Rheumatoid/surgery*

Primary splenic lymphoma is a rare malignant neoplasm， with similar clinical manifestations to Sjogren’s syndrome and liver cirrhosis， which often leads to misdiagnosis. This article reports a case of primary splenic lymphoma misdiagnosed as Sjogren’s syndrome with liver cirrhosis， in order to improve the understanding of primary splenic lymphoma， Sjogren’s syndrome， and liver cirrhosis and avoid misdiagnosis and treatment delay.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Objective To explore the efficacy and mechanism of the aqueous extract of Sauropus spatulifolius in treating constipation based on network pharmacology analysis and experiments.Meth-ods Network pharmacology analysis was conducted using an online platform to investigate the molec-ular mechanism of Sauropus spatulifolius in treating constipation.Loperamide-induced mouse consti-pation models and intestinal epithelial cell(IEC)injury models were constructed.Therapeutic effects were evaluated using indicators such as the time to the first black stool,fecal water content,and gas-trointestinal transit rate.Annexin V-FITC staining was used to assess apoptosis,JC-1 staining was used to detect mitochondrial membrane potential,chemiluminescence was used to measure adenosine triphosphate(ATP)levels,and western blotting was used to detect the expression of relevant proteins.Results Network pharmacology analysis revealed that 29 active components in Sauropus spatulifolius targeted 19 genes associated with constipation,with AKT1 identified as one of the key genes.Exper-imental results demonstrated that the aqueous extract of Sauropus spatulifolius effectively alleviated loperamide-induced constipation symptoms in mice,including weight loss,reduced intestinal motili-ty,prolonged defecation time,and decreased fecal water content.Additionally,the aqueous extract of Sauropus spatulifolius inhibited IEC-6 cell apoptosis,restored mitochondrial membrane potential,and maintained intracellular ATP levels.The therapeutic mechanism involved downregulating the ex-pression of Bel-2-associated X protein(Bax),cytochrome C,Cleaved-Caspase3,and aquaporin 3(AQP3),as well as enhancing protein kinase B(Akt)phosphorylation.Conclusion The aque-ous extract of Sauropus spatulifolius effectively ameliorates constipation symptoms in mouse models,and its mechanism may be related to improving intestinal cell energy metabolism,inhibiting IEC ap-optosis,and reducing AQP3 expression,suggesting that Sauropus spatulifolius could serve as a po-tential drug for the clinical treatment of constipation.

Objective: To investigate the ferroptosis induced by sesamin in triple-negative breast cancer ( TNBC) 4T1 cells and its underlying mechanism . Methods: The binding energy of sesamin with glutathione peroxidase 4 (GPX4) , solute carrier family 7 member 11 ( SLC7A11) , and P53 was analyzed by molecular docking. Mouse TNBC cell line 4T1 was used as a model . Different concentrations of sesamin were administered to 4T1 cells . The effect of sesamin on cell viability was assessed using the cell counting kit 8 (CCK-8) . Transwell assay was used to evaluate the effect of sesamin on cell migration and invasion . The contents of Fe2 + , malondialdehyde (MDA) , and reduced glutathione (GSH) in the cells were measured using kits . 2 ′,7 ′-dichlorofluorescein diacetate (DCFH-DA) probe was employed to detect the content of reactive oxygen species (ROS) in cells . Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot were performed to evaluate the expression of GPX4 , SLC7A11 , and P53 at mRNA and protein levels . Results: The binding energies of sesamin with GPX4 , SLC7A11 and P53 were - 21 . 46 , - 21 . 67 , and - 27 . 03 kJ/mol , respectively . Compared with the control group , the viability of 4T1 cells in different concentrations of sesamin groups decreased gradually ( P < 0. 001) , and the migration and invasion ability of 4T1 cells in 20 , 40 , and 80 μmol/L sesamin groups decreased gradually (all P < 0. 001) . Compared with the control group , the contents of Fe2 + , MDA , and ROS in 4T1 cells of 20 , 40 , and 80 μmol/L sesamin groups increased , and the content of GSH decreased . Compared with the control group , the mRNA and protein expression of GPX4 and SLC7A11 in 4T1 cells in the sesamin treatment group decreased , and the mRNA and protein expression of P53 increased ( all P < 0. 001) . Conclusion Sesamin may induce the ferroptosis in 4T1 cells through P53/SLC7A11 /GPX4 pathway .