Heart failure(HF)is a cardiovascular disease with a high prevalence and mortality rate worldwide,and despite the widespread use of existing drugs,device intervetions and surgical procedures,the clinical outcomes are still unsatisfactory.The exploration of new methods to treat HF is still an urgent problem.Gene therapy provides a new therapeutic strategy for HF by targeting the regulation of pathogenic genes.This article systematically reviewed the delivery system optimization,key targets and clinical translational challenges of gene therapy for HF,aiming to provide a theoretical basis for the optimization of treatment strategies.

Objective:To systematically evaluate the molecular characteristics and prognostic value of ammonia death-related genes in hepatocellular carcinoma(HCC).Methods:Consensus unsupervised clustering was used to identify ammonia death-related molecular subtypes in HCC samples.Weighted gene co-expression network analysis(WGCNA)was applied to identify gene modules associated with ammonia death.Support vector machine(SVM)and LASSO algorithms were used to screen four hub genes,and a risk score system was constructed based on a LASSO-Cox regression model.The association between the risk model and patient survival,tumor microenvironment,and re-sponse to immunotherapy was further analyzed.Results:Consensus clustering identified two distinct ammonia death-related molecular subtypes(P<0.05).The constructed risk score model showed good predictive performance for overall survival in HCC patients and was closely associated with immune infiltration characteristics of the tumor microenviron-ment and immunotherapy responsiveness(P<0.05).Conclusion:The ammonia death-related risk score model may serve as a novel prognostic biomarker for HCC and provide potential guidance for immunotherapy strategies.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

OBJECTIVE: The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture. METHODS: Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve. RESULTS: Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats. CONCLUSION Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals ; Urinary Bladder, Overactive/physiopathology* ; Mast Cells/physiology* ; Rats, Sprague-Dawley ; Female ; Acupuncture Therapy ; Acupuncture Points ; Rats ; Brain/physiopathology* ; Tibial Nerve/physiopathology* ; Acetic Acid ; Urinary Bladder/physiopathology*

Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.

Objective To investigate the effects of ischemia time and storage periods on RNA quality in fresh-frozen breast cancer(BC)and esophageal cancer(EC)tissue samples in order to establish evidence-based protocols for biobank sample management.Methods The tumor(T)and paired normal(N)tissue samples from 6 cases of BC and 6 cases of EC were collected and cryopreserved in Biobank,Shantou Central Hospital.Mirror paraffin-embedded tissues were simultaneously prepared into sections for morphological analysis.The samples were divided into two groups of<15 min and 15-30 min according to ischemia time,and RNA quality was analyzed at 4 storage periods of 8-10 months(T1),14-16 months(T2),26-28 months(T3)and 38-40 months(T4).Results In 96 analyzed samples,93.8%(90/96)exhibited high quality(RIN≥6),with 89.6%(43/48)in BC and 97.9%(47/48)in EC.Significant differences in RIN were observed between BC group and EC group(8.050 vs.8.600,P=0.009).In EC group,RIN value was significantly negatively correlated with RNA yield(P<0.001).Moreover,RIN values of tumor-normal pairs exhibited markedly significant differences(7.550 vs.9.000,P<0.001).In contrast,no significant difference was detected in BC group(8.200 vs.7.700,P=0.348).Statistical analysis showed that RIN value was positively correlated with 28S/18S(P<0.001),but had no correlation with tumor content(P=0.676)and necrotic content(P=0.055).Neither ischemia time(<15 min vs.15-30 min:8.200 vs.8.300,P=0.932)nor storage periods(T1-T4:8.400,7.700,8.450,8.600,P=0.163)compromised RNA quality.Conclusion Organ origin and tissue type could influence RNA quality of fresh-frozen tissue samples.However,limited ischemia time(≤30 min)and long-term storage period(38-40 months)do not adversely affect RNA quality in fresh-frozen breast cancer and esophageal cancer tissue samples.

Aim To detect the non-coding RNA(ncRNA)expression profile of neuroglioma cells via whole transcriptome sequencing,establish the ceRNA network and reveal the molecular mechanism of ncRNA participating in the inhibition of neuroglioma cell prolif-eration by melatonin.Methods Neuroglioma cells were intervened with by 0,2,4,6 and 8 mmol·L-1 melatonin for 24,48 and 72 h,and the inhibitory effect of melatonin on cell proliferation was detected via CCK-8;after the intervention of 0 and 4 mmol·L-1 melatonin to U251 cells for 24 h,differentially ex-pressed miRNA(DEmiRNA),lncRNA(DElncRNA)and mRNA(DEmRNA)were detected through whole transcriptome sequencing,along with GO and KEGG enrichment analysis of DEmRNA;the ceRNA network was constructed,and the key gene expression of ceR-NA was verified through qRT-PCR.Results Melato-nin exerts a time-dose-dependent inhibitory effect on the proliferation of neuroglioma cells;a total of 5049 DEmRNA,635 DElncRNA and 146 DEmiRNA in 0 and 4 mmol·L-1 melatonin groups were screened out via whole transcriptome sequencing;DEmRNAs were mainly enriched in cancer-related signaling pathways,such as ferroptosis,mTOR signaling pathway,FoxO signaling pathway and cell cycle;the ceRNA network included 4 lncRNAs,3 miRNAs and 48 mRNAs.As verified through real-time PCR,the expressions of hsa-miR-129-5p,hsa-miR-362-5p,LINC00707 and SLC16A1-AS1 of U251 cells were consistent with the sequencing results,and the gene expression of U87 cells was basically consistent with the sequencing re-sults.Conclusions Melatonin affects cancer-related signaling pathways through the differential expression of ncRNA so as to inhibit the proliferation of U251 cells;the ceRNA network composed of LINC00707,SLC16A1-AS1,hsa-miR-129-5p and hsa-miR-362-5p may take a part in the molecular mechanism of melato-nin in inhibiting neuroglioma cell proliferation.

Objective:To systematically evaluate the molecular characteristics and prognostic value of ammonia death-related genes in hepatocellular carcinoma(HCC).Methods:Consensus unsupervised clustering was used to identify ammonia death-related molecular subtypes in HCC samples.Weighted gene co-expression network analysis(WGCNA)was applied to identify gene modules associated with ammonia death.Support vector machine(SVM)and LASSO algorithms were used to screen four hub genes,and a risk score system was constructed based on a LASSO-Cox regression model.The association between the risk model and patient survival,tumor microenvironment,and re-sponse to immunotherapy was further analyzed.Results:Consensus clustering identified two distinct ammonia death-related molecular subtypes(P<0.05).The constructed risk score model showed good predictive performance for overall survival in HCC patients and was closely associated with immune infiltration characteristics of the tumor microenviron-ment and immunotherapy responsiveness(P<0.05).Conclusion:The ammonia death-related risk score model may serve as a novel prognostic biomarker for HCC and provide potential guidance for immunotherapy strategies.

As a physical treatment technique, modified electro-convulsive therapy (MECT) is used to treat mental and certain neurological disorders by causing seizures with short, suitable electrical currents applied to the brain while the patient is under general anesthesia and muscle relaxants. MECT is recognized for its therapeutic efficacy and clinical safety, rendering it one of the most prevalent interventions in psychiatric care. To enhance clinical outcomes and minimize adverse effects, this consensus document delineates the indications, therapeutic parameters, therapeutic procedures, potential adverse effects, and associated management strategies for MECT. These guidelines are informed by the latest clinical research and expert consensus, integrating evidence-based medicine methodologies. The objective is to furnish clinicians with precise operational guidelines and to advance the standardization of MECT practices in clinical settings.