Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Background/Aims: Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated. Methods: TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection. Results: TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy. Conclusions Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.

Objective:This study explored the effect of nanoparticle-encapsulated curcumin on the highly expressed multidrug resistance gene 1 （MDR1） in a human low-differentiated nasopharyngeal carcinoma cell line （CNE2）. Methods:Curcumin/chitosan deoxycholic acid nanoparticles were prepared, and the cells were subjected to different treatments: radiotherapy, empty carriers, curcumin, and curcumin-loaded nanoparticles. Cell survival was analyzed using the clonogenic assay, and assessments of apoptosis, MDR1 levels, and miR593 levels were conducted. Results:The cell survival fractions in the curcumin group and the curcumin-loaded nanoparticles group were significantly reduced. Notably, higher apoptosis rates were observed in cells treated with curcumin or curcumin-loaded nanoparticles compared to those that received only radiotherapy. Moreover, a decreased MDR1 level was noted in both the curcumin group and the curcumin-loaded nanoparticles group, with further reduction in MDR1 expression observed in the nanoparticle group （P<0.05）. Enhanced expression of miR593 was found in the curcumin group and the curcumin-loaded nanoparticles group, with a relatively higher level in the nanoparticle group （P<0.05）. Curcumin encapsulated in nanoparticles exhibited a stronger radiosensitizing effect. The combination of curcumin and radiotherapy effectively inhibited nasopharyngeal carcinoma （NPC） tumor growth, suppressed MDR1 expression, and enhanced miR593 levels. After inhibiting miR593, MDR1 expression increased. The radiosensitizing effect of curcumin-loaded nanoparticles was regulated by miR593 rather than being triggered by MDR1. Conclusion:Curcumin-loaded nanoparticles mediated enhanced expression of miR593, which in turn inhibited the transcription and translation of the MDR1 gene, thereby reducing the radioresistance of NPC and effectively restraining its growth.
Humans ; Curcumin/pharmacology* ; Nasopharyngeal Neoplasms/pathology* ; Nasopharyngeal Carcinoma ; Nanoparticles ; Cell Line, Tumor ; Apoptosis/drug effects* ; MicroRNAs ; ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism* ; Cell Survival

OBJECTIVE: To investigate hypertension (HTN) trends, key risk factors, and gender disparities in rural China, and to propose targeted strategies for improving HTN control in resource-limited settings. METHODS: This longitudinal study used data from the Henan Rural Cohort Study, including baseline (2015-2017; n = 39,224) and follow-up (2018-2022; n = 28,621) participants. HTN was defined as systolic/diastolic blood pressure ≥ 140/90 mmHg, self-reported diagnosis, or use of antihypertensive medication. Severity was classified using a 7-tier blood pressure (BP) staging system (optimal, normal, high normal, and HTN stages 1-4). A generalized linear mixed-effects model (GLMM) identified associated risk factors. RESULTS: HTN prevalence increased modestly from 32.7% (95% CI: 32.2-33.2) to 33.9% (95% CI: 33.3%-34.4%). Awareness and treatment improved from 20.1% to 25.3%, and from 18.8% to 24.4%, respectively, but control rates remained low (6.2% to 12.3%). After adjustment, women had a 1.53-fold higher HTN risk than men ( OR = 1.53, 95% CI: 1.43-1.63), revealing gender-specific trends. Key risk factors included alcohol use ( OR = 1.37, 95% CI: 1.27-1.47) and overweight status ( OR = 1.76, 95% CI: 1.66-1.86). BP staging showed an increase in optimal BP (42.3% to 45.8%), but stagnant management of advanced HTN stages. CONCLUSION Hypertension in rural China is shaped by behavioral risk factors and healthcare access gaps. Gender-sensitive, community-based interventions, including task-shifting models, are necessary to mitigate the growing burden of hypertension.
Humans ; Hypertension/etiology* ; China/epidemiology* ; Female ; Male ; Rural Population/statistics & numerical data* ; Prevalence ; Risk Factors ; Middle Aged ; Adult ; Aged ; Longitudinal Studies ; Sex Factors ; Cohort Studies ; East Asian People

Quantitative CT (QCT) is a method of measuring bone mineral density (BMD) of human based on a CT machine,calibrated by QCT body model and analyzed by professional software.Compared with dual-energy X-ray absorptiometry,QCT can not only assess the cortical and cancellous BMD but also exclude the influences of osteophytes and aortic/vascular calcification,thus being capable of accurately reflecting patients' bone mass.In recent years,increasing studies on QCT and osteoporosis (OP) have been carried out,and the application of QCT in the diagnosis of OP,evaluation of vertebral bone conditions,prediction of fracture risks,and assessment of anti-OP treatment is garnering increasing attention from researchers at home and abroad.This article reviews the research progress in this field,aiming to provide a reference for the research on QCT in the diagnosis and treatment of OP.
Humans ; Osteoporosis/diagnosis* ; Tomography, X-Ray Computed/methods* ; Bone Density

Objective The aim of this study was to evaluate the efficacy and side effects of sacubitril/valsartan in the treatment of patients with chronic kidney disease(CKD)at stage 5 with resistant hypertension,and to explore the cardiovascular benefits and security of medical in the patients.Methods Patients with CKD5 resistant hypertension diagnosed and treated in the First Affiliated Hospital of Guangxi Medical University from September 2020 to March 2022 were selected and divided into the observation group(treated with routine treatment of kidney disease at end-stage and sacubitril/valsartan)and control group(include droutine treatment of renal disease at end-stage and ACEI or ARB drugs)according to treatment strategy.The patients in both two groups were treated with adequate dialysis treatment and conventional drug treatment of renal disease at end-stage.The patients were followed up for at least 3 months,the clinical efficacy of three months after treated with sacubitril/valsartan was observed,and the efficacy indicators and security indicators and adverse cardiovascular events were observed,the occurrence of adverse effects during the period of drug use were compared with the control group.Results A total of 110 patients were included in this study and there were 55 cases in each group.There were no significant differences in gender,age,age of dialysis,etiology,dialysis mode and blood pressure between the two groups(P>0.05).The Systolic blood pressure(SBP),diastolic blood pressure(DBP),b-type urinary natriuretic peptide precursor(Pro-BNP)and cardiac function grade in the observation group after treatment was significantly decreased compared with before treatment.The left ventricular ejection fraction(LVEF)and the ratio of LVEF<50%in the observation group was significantly reduced after treatment(P<0.05).SBP,DBP and Pro-BNP decreased 3 months after treatment compared with the baseline before treatment,and improved significantly in the first month after treatment(P<0.05).The decrease of DBP and BNP before and after treatment was significantly different between the two groups,and the decrease of DBP and BNP was more significant in the observation group(P<0.05).The difference of LVEF and left ventricular end diastolic diameter(LVEDD)between the two groups before and after treatment was statistically significant,and the improvement was more obvious in the observation group(P<0.05).There were no significant differences in the safety indicators of serum potassium,estimated glomerular filtration rate(eGFR)and liver function between two groups before and after treatment(P>0.05).In terms of adverse reactions,only 1 case in the control group developed hyperkalemia within 3 months of follow-up,and no hypotension or other adverse reactions occurred in the two groups.Conclusions The treatment of patients with CKD stage 5 hypertension with sacubitril/valsartan has obvious cardiovascular benefits.Sacubitril/Valsartan has efficacy in lowering blood pressure,improving cardiac function and reducing volume load,with less adverse events and higher safety than control group.

Objective To investigate the effectiveness and safety of volumetric modulated arc therapy (VMAT) hypofractionated radiotherapy and intensity modulated conformal radiotherapy technique (IMRT) conventional fractionated radiotherapy after breast cancer radical operation.Methods Eighty-five patients with breast cancer modified radical operation admitted and treated in this hospital from March 1,2021 to De-cember 30,2021 were selected as the research subjects and divided into the VMAT group (n=41) and the IM-RT group (n=42) according to the random number table method.The VMAT group adopted the hypofrac-tionated radiotherapy,with the single fractionated dose of 2.9 Gy/frequency and radiotherapeutic total dose of 43.5 Gy/15 frequencies;the IMRT group adopted the IMRT conventional fractionated radiotherapy,with the single fractionated dose of 2.0 Gy/frequency and radiotherapeutic total dose of 50.0 Gy/25 frequencies.The planning target region V95,V110,conformity index,homogeneity index,treatment time,V5,V20,V30,average dose (Dmean) in the affected side lung,humeral head Dmean and heart V30,Dmean were compared between the two groups.Meanwhile,local recurrence,distant metastasis,disease-free survival and acute and chronic radiation injury were compared between the two groups.Results Compared with the IMRT group,V95 in the VMAT was higher,V110 and homogeneity index were lower,the treatment time was shorter,V5 in the affected lung,Dmean and Dmean in the affected humeral head were lower,V30 in the affected lung was higher,heart V30 in the left side breast cancer was lower,heart Dmean in the right side breast cancer was lower,and the differences were statistically significant (P<0.05).All patients survived without local relapse.The distant metastasis rate and disease free survival rate had no statistical difference between the two groups (P>0.05).Follow up lasted for 12 months,the incidence rates of grade Ⅰ-Ⅱ acute radiodermatitis,radiation esophagitis,chronic radioder-matitis and radiation pneumonia had no statistical differences between the two groups (P>0.05).The inci-dence rate of grade Ⅰ-Ⅱ shoulder dysfunction in the VMAT group was lower than that in the IMRT group with statistical difference (P<0.05).No grade Ⅱ and above acute and chronic radiation injury in the two groups occurred.Conclusion VMAT hypofractionated radiotherapy after breast cancer radical operation is safe and effective.

Objective To investigate the impact and mechanism of efaproxiral (RSR13),a hemoglobin allosteric agent,on lung injury in rats caused by explosion-induced shock waves in plateau areas. Methods Eighty-two healthy male SD rats (8-week-old,transferred from an altitude of 2 880 m to 4700 m within 6 h)were randomly divided into blast injury group and RSR13+blast injury group (intraperitoneal injection of 150 mg/kg RSR132 h before explosion).Sixty rats were positioned at 5 m from the explosion source and divided into 5-m blast injury group (n=30)and 5-m RSR13+blast injury group (n=30). Additionally,16 rats were positioned at 6 m from the explosion source and then assigned into 6-m blast injury group (n=8)and 6-m RSR13+blast injury group (n=8).The left 6 rats served as control (n=6).Survival outcomes of each rat group positioned 5 m from the explosion source were observed over a 24-hour period.HE staining was used to evaluate the pathological score of the surviving rats positioned at 6 m from the explosion source in 24 h after explosion,along with arterial blood gas analysis.The contents of glutathione (GSH),malondialdehyde (MDA ) and superoxide dismutase (SOD ) in the lung tissues were determined by colorimetry.Western blotting was conducted to measure the expression levels of cleaved caspase-3 and occludin in the lung tissue.Results RSR13 pretreatment increased the survival rate immediately after explosion (93.3％ vs 46.7％,P<0.01 )and at 1 h after explosion (86.7％ vs 46.7％,P<0.01 )in plateau areas of 5 m from the explosion source.At high altitude,RSR13 pretreatment reduced the pathological score of lung injury in rats 6 m away from the explosion source (8.27±0.93 vs 13.70±0.78,P<0.01 ),but had no significant effect on the results of arterial blood gas analysis in rats with lung blast injury (P>0.05 ).In addition,RSR13 pretreatment also increased GSH content (40.27±12.47 vs 22.62±10.88 μg/g,P<0.05),but showed no obvious effect on MDA content and SOD activity (P>0.05 ),decreased the protein level of cleaved caspase-3 (P<0.01 )and increased that of occludin (P<0.05 )in the lung tissues.Conclusion RSR13 exerts significant protective effect on lung injury in rats caused by explosion-induced shock waves in high-altitude environment,which may be related to its increasing antioxidant capacity,reducing cell apoptosis and decreasing barrier permeability of lung ventilation.