ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

BACKGROUND:Exercises can reduce blood lipids and slow down the development of atherosclerosis.Atherosclerosis begins with mitochondrial dysfunction,and prohibitin 2 is involved in mitophagy by endurance training. OBJECTIVE:To explore the role of endurance training in the intervention of prohibitin 2 protein in the mitophagy autophagy pathway in atherosclerosis. METHODS:A total of 40 Wistar rats were randomly divided into control group,exercise group,atherosclerosis group and atherosclerosis combined with exercise group,with 10 rats in each group.A rat model of atherosclerosis was constructed by combining a high-fat diet(9 weeks)with vitamin D injections(weeks 1,3,and 6)in the latter two groups,while the two exercise groups were subjected to progressing intensity endurance training for 9 weeks.After the intervention,lipid and pathological detections were conducted to observe the modeling and interventional effects.Mitochondrial membrane potential and mitophagy proteins were detected by microplate reader and western blot.Immunofluorescence staining was used to observe the co-localization of mitophagy proteins in aortic tissue. RESULTS AND CONCLUSION:Lipid and pathological sections showed that compared with the atherosclerosis group,the serum low-density lipoprotein cholesterol and total cholesterol levels and aortic lipid deposition area were significantly reduced in the atherosclerosis combined with exercise group(P<0.001).The results of mitochondrial membrane potential showed that the significant decrease in mitochondrial membrane potential of the aorta in the atherosclerosis combined with exercise group was reversed(P<0.01).The results of western blot assay showed that compared with the control group,the mitochondrial protein expression of prohibitin 2,LC3Ⅱ/Ⅰ,PINK1 and Parkin was significantly increased(P<0.05),and the protein expression of PARL and PGAM5 decreased(P<0.05).Compared with the atherosclerosis group,the protein expression of PINK1 and Parkin in the mitchondria of rats in the atherosclerosis combined with exercise group was significantly decreased(P<0.05),and the protein expressions of prohibitin 2,LC3Ⅱ/Ⅰ,PARL and PGAM5 were significantly increased(P<0.05).Immunofluorescence results showed that compared with the control group,the co-localization of LC3 and PINK1 with TOMM20 was significantly increased in the atherosclerosis group(P<0.05),while compared with the atherosclerosis group,the co-localization of LC3 and PINK1 with TOMM20 was significantly increased in the atherosclerosis combined with exercise group(P<0.05).Co-localization of LC3 and PARL with prohibitin 2 was significantly increased in the atherosclerosis group compared with the control group(P<0.01),co-localization of LC3 with prohibitin 2 was significantly increased in the atherosclerosis combined with exercise group compared with the atherosclerosis group(P<0.01),and co-localization of PARL protein with prohibitin 2 was significantly decreased in the atherosclerosis combined with exercise group compared with the atherosclerosis group(P<0.01).To conclude,endurance training can induce the expression of prohibitin 2 in the inner mitochondrial membrane and promote the binding of prohibitin 2 to the mitophagy junction protein to complete mitophagy,restore mitochondrial function,and slow down the occurrence of atherosclerosis.

ObjectiveTo observe the effect of Yulin Hukun decoction on autophagy mediated by phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway in the mouse model of cyclophosphamide-induced diminished ovarian reserve and explore the follicular development-improving mechanism of this decoction. MethodsSixty female ICR mice with normal estrous cycle were assigned into a blank group （n=10） and a modeling group （n=50）. The model was established by intraperitoneal injection of cyclophosphamide （60 mg·kg^-1） for 5 days. The successfully modeled mice were randomly grouped as follows： model， estradiol （0.26 mg·kg^-1）， and high-， medium-， and low-dose （56.42， 28.21， 14.105 g·kg^-1， respectively） Yulin Hukun decoction， with 10 mice in each group. The blank group and the model group received normal saline （10 mL·kg^-1）. The intervention was performed once a day for 21 days. The general conditions， estrous cycle， body weight， and ovary index were observed and recorded for each group. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and anti-Müllerian hormone （AMH） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the ovarian tissue were observed by hematoxylin-eosin staining. Western blot was employed to determine the protein levels of PI3K， Akt， mTOR， autophagy-related protein 7 （Atg7）， beclin1， microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ）， ubiquitin-binding adaptor protein （p62）， forkhead box protein O1 （FoxO1）， and acetylated forkhead box protein O1 （Ac-FoxO1） in mouse ovaries. Real-time PCR was adopted to determine the mRNA levels of PI3K， Akt， mTOR， Atg7， beclin1， and LC3Ⅱ in the mouse ovarian tissue. ResultsCompared with the blank group， the model group had disturbed estrous cycle， decreased body weight （P<0.05）， loose ovarian structure with increased atretic follicles， increased serum FSH level （P<0.05）， and decreased AMH and estradiol levels （P<0.05）. Compared with the model group， the treatment groups showed recovered estrous cycles and body weight. The estradiol group and high- and medium-dose Yulin Hukun decoction groups showed declined FSH level （P<0.05） and elevated AMH levels （P<0.05）. In addition， the treatment groups showed downregulated protein levels of Atg7， LC3Ⅱ， beclin1， FoxO1， and Ac-FoxO1 （P<0.01）， upregulated protein levels of PI3K， Akt， mTOR， and p62 （P<0.01） in the ovarian tissue， gradual repair of the ovarian structure， with more intact and numerous follicles of various stages. ConclusionYulin Hukun decoction can inhibit autophagy in ovarian granulosa cells by activating the PI3K/Akt/mTOR signaling pathway and inhibiting the expression of autophagy-related proteins and transcription factors， thereby improving follicular development and ovarian reserve.

Objective: To investigate the influencing factors for kinesiophobia among elderly patients with chronic obstructive pulmonary disease (COPD), so as to provide the reference for alleviating kinesiophobia among COPD patients. Methods: From December 2023 to July 2024, COPD patients aged 60 years and above who sought medical treatment at a tertiary grade-a hospital in Guiyang City were selected. Demographic information was collected through questionnaire surveys. Kinesiophobia, exercise self-efficacy, social support, type D personality and coping styles were assessed using the Chinese version of Tampa Scale for Kinesiophobia, the Chinese version of the Self-Efficacy for Exercise Scale, Social Support Rating Scale, Type D Personality Scale and Chinese version of the Medical Coping Modes Questionnaire, respectively. Factors affecting kinesiophobia among elderly patients with COPD were analyzed using a multiple linear regression model. Results: A total of 300 COPD patients were surveyed, including 238 males (79.33%) and 62 females (20.67%). The majority of patients had a disease duration of less than 5 years, with 130 cases (43.33%). The average kinesiophobia score was (48.01±7.74) points. The average exercise self-efficacy score was (3.39±1.01) points. The average social support score was (34.42±6.76) points. There were 280 patients (93.33%) with type D personality. The average scores of the confrontation, avoidance, and resignation dimensions of coping styles were (17.42±5.00), (13.76±1.91), and (11.81±2.95) points, respectively. Multiple linear regression analysis showed that age (70-<80 years, β'=0.124; ≥80 years, β'=0.205), educational level (primary school and below, β'=0.228; junior high school, β'=0.182), household monthly income per capita (<3 000 yuan, β'=0.234; 3 000~<5 000 yuan, β'=0.165), social support (β'=0.294), type D personality (β'= 0.170), and coping styles (confrontation dimension, β'=-0.140; avoidance dimension, β'=0.154; resignation dimension, β'=0.175) statistically associated with kinesiophobia among elderly patients with COPD. Conclusion Kinesiophobia among elderly patients with COPD is associated with age, educational level, household monthly income per capita, social support, type D personality and coping styles.

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

Objective To explore the impact of sluggish cognitive tempo(SCT)on the efficacy of atomoxetine in the treatment of attention-deficit/hyperactivity disorder(ADHD).Methods A prospective study was conducted.Pediatric patients aged 6-12 years with a diagnosis of ADHD were selected from the Department of Psychiatry,Xijing Hospital,Air Force Military Medical University from May 2020 to May 2023.All the patients were treated with atomoxetine for 8 weeks.ADHD symptoms and SCT symptoms were assessed by Swanson,Nolan,and Pelham-Ⅳrating scale(SNAP-Ⅳ)and SCT rating scale at baseline(before treatment),4 weeks and 8 weeks after treatment.Pearson correlation analysis was used to analyze the correlation between SCT and SNAP-Ⅳscores.Results A total of 61 pediatric patients were enrolled,including 10 cases of inattentive type and 51 cases of mixed type.Baseline SCT score was positively correlated with baseline SNAP-Ⅳscore(r=0.490,P＜0.001)and reduction rate of SNAP-Ⅳscore at week 8(r=0.670,P＜0.001).The total SCT score at week 8 was positively correlated with total SNAP-Ⅳscore at baseline(r=0.320,P=0.012).The baseline SCT score of patients with mixed type was positively correlated with reduction rate of SNAP-Ⅳscore at week 8(r=0.578,P＜0.001).Conclusions The severity of SCT symptoms is positively correlated with the SNAP-Ⅳreduction rate 8 weeks after atomoxetine treatment,which could be a predictor of the efficacy of atomoxetine.

Aquaporin 5(AQP5),as the main water transport protein in the body,can regulate lung diseases by regulating airway mucus secretion,pulmonary inflammation,and lung function.Programmed cell death(PCD)plays a crucial role in chronic obstructive pulmonary disease(COPD).AQP5 may affect the development of COPD by regulating PCDs.This article reviews the molecular regulatory mechanism of AQP5 on apoptosis,autophagy,iron death and pyroptosis in PCDs in recent years,and further discusses its effect on COPD in order to provide theoretical support for clinical prevention and treatment of COPD.

Objectives:We aimed to compare the impact of dissection and re-entry(DR)recanalizing pattern with non-DR on the in-hospital results and prognostic outcomes of patients treated successfully by percutaneous coronary intervention(PCI)of chronic total occlusion(CTO)and examine the benefit of DR in CTO PCI. Methods:A total of 815 consecutive patients with CTO meeting the inclusion criteria in the Department of Cardiology of the First Affiliated Hospital of PLA Air Force Military Medical University from January 2018 to December 2020 were enrolled and divided into DR group(n=239)and non-DR group(n=576)according to whether DR recanalizing pattern was used in the procedure.The clinical characteristics,coronary angiographic characteristics,procedure results,and complications were collected,and the prognostic outcomes within one year after the procedure were observed.Propensity score matching by the clinical and coronary angiographic characteristics was performed and results were compared with 208 matched patients in each group.The endpoints were the major adverse cardiovascular events(MACE)consisting of all-cause death and myocardial infarction,clinically driven target vessel revascularization(TVR)one year after the procedure,and in-hospital outcomes. Results:The mean age of all patients was(60.9±10.9)years old,and 87.4%were male.As compared with the non-DR group,the proportion of blunt cap,ambiguous,calcification,angle＞45°,and diseased landing zone,as well as mean J-CTO score was higher in the DR group(all P＜0.05).The mean stent length and median procedure time were longer in the DR group,median guidewires and consumed contrast volume was also higher in the DR group(all P＜0.001).Incidence of in-hospital death,myocardial infarction,perforation,side branch loss,bleeding of BARC 3rd grade and above,and contrast-related impairment of renal function were similar between the two groups(all P＞0.05).However,peripheral vascular complications occurred more frequently in the DR group(P=0.007).One year after the procedure,the incidence of MACE(2.9%vs.2.4%,log-rank P=0.750)and clinically driven TVR(5.8%vs.3.9%,log-rank P=0.365)as well as all-cause death(2.9%vs.1.0%,log-rank P=0.154)and myocardial infarction(0.5%vs.1.9%,log-rank P=0.184)were similar between the two matched groups.Multivariate Cox regression analysis showed no significant association between DR and MACE(HR=1.129,95%CI:0.427-2.979,P=0.807)and TVR(HR=0.606,95%CI:0.213-1.722,P=0.347).LVEF≤40%(HR=2.775,95%CI:1.137-6.774,P=0.025)and elevated residual SYNTAX score(HR=1.089,95%CI:1.032-1.150,P=0.002)were risk factors for MACE,and diseased landing zone(HR=2.144,95%CI:1.019-4.513,P=0.045),rescued ADR(HR=3.479,95%CI:1.109-10.919,P=0.033),and prolonged procedure time(HR=1.007,95%CI:1.002-1.013,P=0.007)were risk factors for TVR. Conclusions:CTO lesion recanalized with PCI utilizing DR operation pattern was associated with more complex characteristics,more devices and time consumed,and longer stent length,while no significant association was observed between DR operation pattern and MACE and TVR one year after the procedure,as well as in-hospital complication..

Objective To investigate the current status of physical activity and depressive symptoms a-mong middle-aged and older adults in Chengdu,Sichuan and explore the relationship between physical activity and depressive symptoms.Methods Multi-stage proportional stratified random sampling was employed to select middle-aged and older adults aged ≥45 years as the participants,and face-to-face interviews were carried out to collect data.Logistic regression was adopted to explore the relationship between physical activity and depressive symptoms in middle-aged and older adults.The trend test was performed for the relationship between different lev-els of physical activity and depressive symptoms.The subgroup analysis and the test for multiplicative interactions were conducted for the relationship between physical activity and depressive symptoms.Results A total of 4376 middle-aged and older adults were included.Among them,14.58％(638/4376),25.98％(1137/4376),and 27.83％(1218/4376)had depressive symptoms,failed to reach the guideline-recommended standards of physical activity,and were at low levels of physical activity,respectively.There was a negative association be-tween reaching guideline-recommended physical activity standard and depressive symptoms in middle-aged and ol-der adults(OR=0.713,95％CI=0.589-0.861,P＜0.001).In addition,moderate levels(OR=0.714,95％CI=0.586-0.871,P=0.001)and high levels of physical activity(OR=0.705,95％CI=0.548-0.906,P=0.006)had negative associations with the presence of depressive symptoms.The trend test revealed that the negative association between physical activity and depressive symptoms in middle-aged and older adults enhanced as the level of physical activity increased(Pfor trend=0.001).The subgroup analysis and the test for multiplicative interactions revealed that neither reaching guideline-recommended physical activity standards or not nor the physi-cal activity level had an interaction with each of the subgroups(all Pfor interaction＞0.05).Conclusions The current status of depressive symptoms among middle-aged and older adults in Chengdu,Sichuan needs to be ameliora-ted.A negative association existed between reaching the guideline-recommended physical activity standard and pres-ence of depressive symptoms,and the negative association enhanced as the physical activity level elevated.

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.