ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

BackgroundObstructive sleep apnea （OSA） represents a prevalent sleep disordered breathing condition characterized by complex pathophysiology. The arousal threshold （ArTH）， a core non-anatomical contributor to OSA pathogenesis， is intimately tied to the disease severity and clinical phenotypes. To date， research regarding factors associated with ArTH has yielded inconsistent findings， and ArTH profiles and disparities across populations with different genetic backgrounds are not fully elucidated. ObjectiveTo explore the differences of ArTH in OSA patients with different genetic backgrounds and analyze the key factors affecting ArTH， thereby providing evidence for understanding OSA pathophysiology and formulating targeted treatment regimens. MethodsA total of 285 patients who met the diagnostic criteria for OSA， as defined by the Multidisciplinary Diagnosis and Treatment Guidelines for Adult Obstructive Sleep Apnea， were retrospectively enrolled in this study. All participants underwent overnight polysomnography （PSG） at the Sleep Medicine Center of Inner Mongolia Mental Health Center from December 2022 to May 2024. Based on the study design， the cohort was stratified into two distinct genetic background subgroups （group A and group B）. Demographic and clinical characteristics， the Epworth Sleepiness Scale （ESS） score， and overnight PSG data were collected. The apnea hypopnea index （AHI）， the lowest pulse oxygen saturation （LSpO₂）， and fraction of hypopneas （F_Hypopneas） were utilized as surrogate indicators to estimate ArTH in OSA patients. The influencing factors of low ArTH were tested by binary Logistic regression analysis. ResultsAmong the 285 OSA patients， there were 227 cases （79.65%） in group A and 58 cases （20.35%） in group B. Comparisons between the two genetic background subgroups revealed no statistically significant differences in the proportion of low ArTH， ESS score， PSG parameters， and the three markers for low ArTH （AHI<30 events/h， LSpO₂>82.5%， F_Hypopneas>58.3%） （P>0.05）. Binary Logistic regression analysis identified sex （OR=2.421， 95% CI： 1.070–5.478）， BMI （OR=0.847， 95% CI： 0.770–0.932）， N1 sleep duration （OR=0.974， 95% CI： 0.963–0.985）， and hypertension （OR=0.348， 95% CI： 0.143–0.848） as independent factors associated with low ArTH in the total cohort. Stratified analysis by genetic backgrounds revealed that sex（OR=3.799， 95% CI： 1.389–10.392）， BMI（OR=0.819， 95% CI：0.723–0.929）， and N1 sleep duration（OR=0.973， 95% CI： 0.961–0.986） were independent factors of low ArTH in group A. In contrast， only N1 sleep duration （OR=0.951， 95% CI： 0.911–0.993） remained a significant factor in group B. ConclusionArthur may have conservative characteristics in patients with OSA with different genetic backgrounds， but the pathophysiological mechanism of OSA may have population heterogeneity. ［Funded by Inner Mongolia Autonomous Region Natural Science Fundation Project （number， 2024QN08050）； Intra-institutional Scientific Research Project of Inner Mongolia Mental Health Center （number， 2022QNWN0010）］

Objectives:To investigate the enhancement of tumor penetration and photodynamic therapy (PDT) efficacy in triple-negative breast cancer by hyaluronidase (HAase) using a novel pH-responsive IR780-loaded photosensitive micelle.Methods:The pH-responsive IR780-loaded photosensitive micelles were prepared using the nanoprecipitation method, and their morphology, size, and encapsulation efficiency were characterized. The in vitro stability and pH-responsive drug release of the micelles were also evaluated. The cytotoxicity of the micelles on triple-negative breast cancer cells (MDA-MB-231) was assessed using a cell counting kit. A nude mouse breast cancer model was established, and HAase was injected intratumorally 24 hours before intravenous injection of the photosensitive micelles. The effect of HAase on the biodistribution and tumor uptake of the micelles was detected using small animal in vivo imaging. CD31 and HIF-1α immunofluorescence staining were performed to investigate the mechanism of HAase-enhanced tumor penetration. The body weight and tumor volume of the mice were measured, and necrosis and apoptosis of tumor tissues were assessed using HE staining and TUNEL staining, respectively. Results:Transmission electron microscopy showed that the micelles had a uniform particle size of approximately 60-70 nm, with a hydrated particle size of (98.03±0.22) nm. The IR780 encapsulation efficiency was 74.15%, with a drug loading content of 2.07%. After 7 days at 4 ℃, there was no significant change in hydrated particle size ( P=0.062). The 24-hour release rates of the micelles in PBS at pH 7.4 and 6.5 were (2.41±0.21)% and (43.69±2.09)%, respectively, showing a significant difference ( P＜0.000 1). The cytotoxicity assay revealed that the cell viability in the micelles group without light exposure was significantly higer than that in the micelles group under light exposure [(97.00±5.38)% vs. (53.27±9.00)%, P=0.000 2]. The micelles were able to target and accumulate in the tumor tissue, and this accumulation increased significantly with HAase treatment. CD31 and HIF-1α immunofluorescence staining indicated that the CD31 signal was enhanced [(0.27±0.05)% vs. (4.57±0.27)%, P＜0.000 1] and the HIF-1α signal was reduced [(5.14±0.38)% vs. (0.08±0.04)%, P＜0.000 1] in the HAase-treated group compared to that in the micelle-only group. After 11 days of treatment with HAase combined with photosensitive micelles, there was no statistically significant difference in mouse body weight ( P＞0.05). However, the tumor volume inhibition rate in the HAase-micelle-mediated PDT group was significantly higher than that in the micelle-mediated PDT group [(87.66±6.37)% vs. (25.34±12.63)%, P=0.002]. Histological staining showed a significant increase in tumor cell necrosis and apoptosis in the HAase-micelle-mediated PDT group. Conclusion:HAase enhances the deep tumor penetration and targeted accumulation of pH-responsive IR780-loaded photosensitive micelles, significantly improves the efficacy of photodynamic therapy in triple-negative breast cancer.

BACKGROUND: Acupuncture has shown potential therapeutic benefits for individuals with simple obesity. However, some researchers argue that some of the effectiveness of acupuncture may be due to the placebo response. OBJECTIVE: To understand the placebo response of acupuncture treatment in simple obesity, a systematic review and meta-analysis was designed based on the comparison between sham acupuncture before and after treatment. SEARCH STRATEGY: Eight databases (PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Database, China Biology Medicine Database, and Chinese Scientific Journals Database) were searched from inception to August 1, 2023. The MeSH search terms comprised obesity and acupuncture. INCLUSION CRITERIA: Randomized controlled trials (RCTs) using sham or placebo acupuncture as a control in treating obesity were enrolled. DATA EXTRACTION AND ANALYSIS: Two researchers independently extracted data, and the results were cross-checked after completion. Each RCT's detailed sham/placebo acupuncture treatment protocol was assessed according to the SHam Acupuncture REporting guidelines. The revised Cochrane risk-of-bias tool for randomized trials and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system were used to determine the risk of bias and quality of evidence, respectively. Body mass index (BMI) was defined as the primary outcome. Anthropometric parameters and laboratory test parameters related to obesity were defined as secondary outcomes. We used standardized mean difference (SMD) with 95% confidence interval (CI) to calculate treatment effects of outcomes. RESULTS: Fifteen RCTs with a total of 1250 patients were included. The BMI significantly decreased after treatment in the sham acupuncture group compared to baseline (SMD 0.37, 95% CI 0.09-0.66; I² = 81%, random model; P < 0.01). Treatment duration (P = 0.02) and other interventions significantly impacted the placebo response rate (P = 0.00). CONCLUSION The placebo response of sham acupuncture was strong in the RCTs for simple obesity, and the effect sizes differed between various outcomes. The treatment duration and other interventions emerged as potential influencing factors for the placebo response of sham acupuncture. Please cite this article as: Liu KJ, Jiao RM, Ji J, Yao WW, Han CR, Zhao XY, Zhao JJ. Placebo response in sham acupuncture therapy trials for simple obesity: a systematic review and meta-analysis. J Integr Med. 2025; 23(3): 264-273.
Humans ; Acupuncture Therapy/methods* ; Obesity/therapy* ; Placebo Effect ; Placebos ; Randomized Controlled Trials as Topic

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans ; China/epidemiology* ; Hearing Loss/epidemiology* ; Prevalence ; Middle Aged ; Male ; Female ; Adult ; Aged ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Aged, 80 and over ; Cost of Illness

The morphological characteristics of hepatocellular carcinoma(HCC)tumor margins are pivotal in influencing patient's prognosis and the selection of therapeutic strategies.This paper re-viewed the classification methods of HCC tumor margins,ranging from traditional macroscopic classifi-cations to refined classification systems based on multi-omics analysis,and analyzed the role of these classification methods in guiding the formulation of personalized treatment plans.Additionally,this paper emphasized the crucial role of three-dimensional imaging techniques in assessing tumor margin morphology and outlined future research directions,including validating the effectiveness of multi-omics classification systems and developing new imaging and molecular biomarkers to achieve more precise treatment plans and prolong patient survival.

Objective To investigate the expression levels of LINC02009 and LOC107984895 in peripheral lymphocytes of patients with atrial fibrillation and their clinical significance.Methods A total of 75 hospitalized patients with atrial fibrillation(50 with persistent atrial fibrillation and 25 with paroxysmal atrial fibrillation)from Kunming First People's Hospital between January 2023 and December 2023 were selected as study subjects,along with 50 normal control patients.Real-time quantitative PCR was used to detect the expression levels of LINC02009 and LOC107984895 in peripheral blood leukocytes of patients with atrial fibrillation.Logistic regression analysis was employed to assess the relationship between expression levels and risk factors for atrial fibrillation,and ROC curves were used to predict the diagnostic cut-off values for LINC02009 and LOC107984895 in diagnosing atrial fibrillation.Results There were statistically significant differences in baseline diseases such as hypertension and coronary heart disease,biochemical indicators such as Cr and BNP,and myocardial remodeling indicators such as LAd and LVEF between the AF(paroxysmal atrial fibrillation and persistent atrial fibrillation)group and the Normal group(P＜0.05).The expression levels of LINC02009 and LOC 107984895 in the plasma of the atrial fibrillation group were significantly higher than those in the control group(P＜0.05)and were negatively correlated with LVEF(P＜0.05).The areas under the curve(AUC)of LINC02009 and LOC 107984895 in predicting atrial fibrillation were 0.967(95％CI:0.938～0.995)and 0.900(95％CI:0.838～0.963),respectively.The optimal cut-off values were 1.985 and 0.915,with sensitivities of 88％and 76％,respectively,and specificities of 94％and 90％,respectively.Conclusion LINC02009 and LOC 107984895 are independent risk factors for atrial fibrillation and have certain predictive value for the occurrence of atrial fibrillation.

As global greenhouse gases continue rising, the urgency of more ambitious action is clearer than ever before. China is the world's biggest emitter of greenhouse gases and one of the countries affected most by climate change. The evidence about the impacts of climate change on the environment and human health may encourage China to take more decisive action to mitigate greenhouse gas emissions and adapt to climate impacts. This article aimed to review the evidence of environmental damages and health risks posed by climate change and to provide a new science-based perspective for the delivery of sustainable development goals. Over recent decades, China has experienced a strong warming pattern with a growing frequency of extreme weather events, and the impacts of climate change on China's environment and human health have been consistently observed, with increasing O ₃ air pollution, decreases in water resources and availability, land degradation, and increased risks for both communicable and non-communicable diseases. Therefore, China's climate policy should target the key factors driving climate change and scale up strategic measures to curb carbon emissions and adapt to inevitable increasing climate impacts. It provides new insights for not only China but also other countries, particularly developing and emerging economies, to ensure climate and environmental sustainability whilst pursuing economic growth.
Climate Change ; China ; Humans ; Greenhouse Gases ; Air Pollution ; Sustainable Development ; Environment

P-glycoprotein(P-gp)is an ATP-dependent efflux transporter that is distributed in many tissues and organs.P-gp can selectively pump endogenous substrates and exogenous chemicals from the cell to the outside of the cell to maintain a stable endo-environment.However,it meanwhile restricts the entry of therapeutic drug into tissues and organs,and in particular,mediates the multidrug resistance of tumor cells to chemotherapeutic drugs.Therefore,understanding the localization of P-gp in different tissues and organs may be an important breakthrough point for disease treatment.In this paper,we mainly review the molecular structure,transport mechanism,localization,and regulation of P-gp in different tissues and organs,providing reference for the subsequent treatment of diseases.
Humans ; ATP Binding Cassette Transporter, Subfamily B, Member 1/chemistry* ; Animals ; Drug Resistance, Multiple

Objective:To conduct enrichment and biological behavior studies on CD44 + CD24 - triple-negative breast cancer (TNBC) stem-like cells, and to construct 68Ga-labeled CD44 peptide ( 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-CD44p) and evaluate its targeting ability towards the surface marker CD44 of TNBC stem-like cells. Methods:Suspension sphere culture method was utilized to enrich and cultivate CD44 + CD24 - cell subpopulations from TNBC cell line MDA-MB-231 and non-TNBC cell line MCF-7. Flow cytometry was used to detect the expression of stem cell markers of different groups, cell scratch assay was performed to assess the migration ability of CD44 + CD24 - cell subpopulations, and Transwell invasion assay was performed to evaluate the invasion ability of CD44 + CD24 - cell subpopulations. 68Ga-NOTA-CD44p was prepared, followed by purification and identification with high-performance liquid chromatography (HPLC). The targeting ability of 68Ga-NOTA-CD44p towards CD44 + TNBC cells was evaluated through cellular uptake and blocking experiments. Data were analyzed by independent-sample t test, one-way analysis of variance and the least significant difference t test. Results:Suspension sphere culture successfully enriched CD44 + CD24 - TNBC stem-like cell spheres. Compared to the non-TNBC cell line MCF-7, TNBC cell line MDA-MB-231 exhibited better sphere-forming ability (18.50±3.73 vs 31.83±4.92; t=5.29, P<0.001) and a higher proportion of CD44 + CD24 - cell subset ((24.97±8.12)% vs (90.93±4.46)%; F=170.10, t=14.93, both P<0.001). The wound healing rate ((71.00±11.00)% vs (28.33±4.16)%; F=42.91, t=8.02, both P<0.001) and invasion rate ((60.60±16.87)% vs (24.16±8.15)%; F=11.83, t=4.40, both P<0.01) of CD44 + CD24 - MDA-MB-231 group cells were significantly increased compared to the CD44 + CD24 - MCF-7 group. MDA-MB-231 cells showed strong uptake ability of 68Ga-NOTA-CD44p, which decreased after CD44p blocking. Conclusions:Compared to CD44 + CD24 - MCF-7 cells, CD44 + CD24 - MDA-MB-231 cells exhibit higher malignant biological behavior. 68Ga-NOTA-CD44p targets the surface marker CD44 of TNBC stem-like cells, laying the research foundation for targeted therapy against TNBC with tumor stem cells as targets.