ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.

OBJECTIVE: Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. METHODS: HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively. A series of approaches including cell counting kit-8, flow cytometry, wound healing and transwell assays were used to evaluate tumor cell functions. Transmission electron microscopy, immunofluorescence and Western blotting were used to assess mitophagy. Mitochondrial oxygen consumption rate, reactive oxygen species and membrane potential were used to reflect mitochondrial function. After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-143-3p, and ribonucleoside reductase M2 (RRM2), the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro. Additionally, dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes. RESULTS: Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro, while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo. Interestingly, MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells, which subsequently inhibited RRM2 expression. Furthermore, in nude mice grafted with HCC tumors and treated with Res, the expression of MALAT1, miR-143-3p and RRM2 were altered significantly. In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2. Therefore, a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC; these experiments revealed that MALAT1 knockdown, miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy. CONCLUSION Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis. Please cite this article as: Feng CY, Cai CS, Shi XQ, Zhang ZJ, Su D, Qiu YQ. Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma. J Integr Med. 2025; 23(1): 79-91.
Humans ; MicroRNAs/genetics* ; Liver Neoplasms/metabolism* ; Carcinoma, Hepatocellular/metabolism* ; Mitophagy/drug effects* ; Resveratrol/pharmacology* ; Animals ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Hep G2 Cells ; Mice ; Disease Progression ; Mice, Inbred BALB C

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

The development of novel point-to-point drugs targeting resistance mechanisms is a critical and popular research field; nevertheless, success remains challenging. Therefore, given the short survival time and heightened expectations of patients with advanced NSCLC, the design of various combination therapy strategies––integrating preclinical, clinical, and real-world evidence (such as radiotherapy, chemotherapy, targeted therapy, antibody–drug conjugates, oncolytic viruses, and cell therapy)––may be a wise and practical choice to address the disease. Resistance to immunotherapy involves almost all cell types in the body, primarily cancer cells and T cells involved in immune surveillance. As a result of space limitations, this article focuses on the progress and challenges of various combined strategies for directly eliminating cancer cells. We also emphasize the realignment of treatment goals, shifting from primarily focusing on eliminating cancer cells (via chemotherapy and radiotherapy) to fully utilizing immune regulation to overcome resistance to immune checkpoint inhibitors.

Background Per- and polyfluoroalkyl substances (PFAS), a group of persistent organic pollutants associated with adverse health effects including hepatotoxicity, immunosuppression, and carcinogenicity, have undergone risk assessments by multiple international organizations, with dietary exposure being the primary pathway. Objective To characterize the exposure to PFAS from food and drinking water sources of elderly residents in Songjiang District of Shanghai and to evaluate associated health risk and health effects. Methods A cross-sectional study was conducted from May to July 2024 in Songjiang District based on the Shanghai Suburban Adult Cohort and Biobank (SSACB) cohort. Dietary surveys were administered via face-to-face interviews among older adults aged 65 years and above, yielding 4 583 valid questionnaires. The estimated daily intake (EDI) of PFAS was calculated by integrating data from the Sixth National Dietary Survey and recent literature on PFAS concentrations in food and drinking water in Shanghai. Health risk assessment was performed using health-based guideline values (HBGV) proposed by various institutions and studies. Additionally, correlation analysis and linear regression modeling of EDI and biochemical indicators in the elderly were conducted to evaluate potential adverse health effects. Results The elderly population in Songjiang District exhibited dietary characteristics consistent with the Eastern Healthy Diet Pattern. Among PFAS compounds, PFOA showed the highest level of oral exposure [mean: 1.495 ng·(kg·d⁻¹)], followed by PFOS [mean: 0.637 ng·(kg·d⁻¹)], PFHxS [mean: 0.636 ng·(kg·d⁻¹)], and PFBS [mean: 0.273 ng·(kg·d⁻¹)]. Specifically, drinking water was the primary source of PFOA [1.415 ng·(kg·d⁻¹), accounting for 94.60%], while aquatic products were the major source of PFOS [0.278 ng·(kg·d⁻¹), accounting for 43.66%]. Using the HBGV derived by China's epidemiological studies, the mean hazard index (HI) for PFAS exposure was 1.39, indicating 54.35% of the population had potential health risks (HI>1). Following the 2024 standard established by the Food Safety Commission of Japan (FSCJ), the HI value dropped to 0.11, suggesting negligible risk. PFAS exposure was negatively associated with triglyceride levels and the indicators of liver and kidney function, but positively associated with low-density lipoprotein cholesterol (LDL-C) and lung cancer markers in the elderly residents. Conclusion PFAS exposure among the elderly residents in Songjiang District is predominantly attributed to PFOA, PFOS, PFHxS, and PFBS, with drinking water and aquatic products identified as primary exposure sources. Current exposure levels demonstrate significant associations with biomarkers of lipid metabolism and lung cancer markers, suggesting potential population health risks. These findings underscore the urgent need to establish HBGV for PFAS compounds based on Chinese population-specific metabolic characteristics.

Purpose The results of EBER in situ hybridization on the external quality assessment(EQA)organ-ized by the pathology Equipment Branch of the China Association of Medical Equipment were analyzed,for providing technical support for the standardization and normalization of the technology.Methods Paraffin-embedded sections of confirmed EBV-positive diffuse large B-cell lymphoma were selected as the evaluation specimens.Additionally,EBER in situ hybridization liquid cell controls were applied to the slides as evaluation references.A questionnaire was distrib-uted to collect staining information and methodologies from participating laboratories.Finally,the stained slides were collected and independently evaluated by pathology experts from the association according to predefined scoring criteria.Results A total of 38 pathology laboratories from 7 provinces and municipalities directly under the central government participated in the EQA,including 32 hospital pathology departments and 6 independent clinical laboratories.21 par-ticipants used manual staining,and others(17)used automated staining method by immunohistochemistry(IHC)stainers.The overall qualification rate of EBER in situ hybridization staining was 94.74％(36/38),and the excellent& good rate was 26.32％(10/38).The excellent & good rate of automated staining(41.12％,7/17)was significant-ly higher than that of manual staining(14.29％,3/21)(x2=4.852,P=0.028).The positive cell line control showed good consistency with the tissue control(Kappa=0.909,r=0.944).Conclusion The EBER in situ hybrid-ization technique in most of the pathology laboratories in the external quality assessment is qualified.There is a statisti-cally significant difference in the excellent & good rate between different staining methods.EBER in situ hybridization using automated IHC stainers is recommended as the preferred method.There is no difference in the performance of positive cell line control and tissue control.Some laboratories' staining techniques need to be improved.

Atherosclerosis is a chronic inflammatory disease and the root cause of most cardiovascular diseases.Soluble guanylate cyclase(sGC)agonists play an important role in the regulation of atherosclerotic diseases by nitric oxide(NO)/sGC/cyclic guanosine phosphate(cGMP)signaling pathway.sGC plays an anti-atherosclerotic role in reducing blood lipid levels,improving endothelial dysfunction,reducing inflammatory responses,inhibiting platelet activation,in-hibiting smooth muscle cell proliferation and apoptosis via activating downstream cGMP.This article reviews the effect of sGC agonists on atherosclerosis and its mechanism,in order to provide a theoretical basis for the clinical application of sGC agonists.

Schizophrenia is a common, severe, and complex psychiatric disorder worldwide. Genetic factors account for around 80% of the etiology of schizophrenia, yet objective diagnostic biomarkers remain lacking. This article reports two cases of female monozygotic twins diagnosed with schizophrenia, exhibiting a balanced translocation between 22q11.2 and 4p15.3. Reviewing the literature, we analyze and discuss the correlation between chromosomal balanced translocation regions and the pathogenesis of mental disorders. This aims to encourage psychiatrists to consider new perspectives on the diagnosis of schizophrenia.

Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.