ObjectiveTo study the effect of Wulingsan on cerebral edema after intracerebral hemorrhage （ICH） in mice and explore the treatment mechanism. MethodsThe mouse model of ICH was established by injection of collagenase into the caudate nucleus. Mice were randomly assigned into the following groups： sham， ICH， intervention before modeling with low-dose and high-dose （3.69， 11.07 g·kg^-1， respectively） Wulingsan， and intervention after modeling with high-dose Wulingsan. The modified neurological severity score （mNSS） was recorded， and the small animal MRI T2 sequential scanning was performed to measure the volume of cerebral hemorrhage after the modeling of ICH in each group. The Y-maze test， open field test， and Morris water maze test were conducted to evaluate the neurological behaviors of mice in each group. Hematoxylin-eosin staining was employed to observe the pathological changes in the brain tissue. Immunohistochemistry was employed to observe the expression of aquaporin 4 （AQP4）， neuronal nuclei （NeuN）， and glial fibrillary acidic protein （GFAP） in the brain tissue. Western blot was employed to determine the protein levels of AQP4， Claudin-5， and zonula occludens-1 （ZO-1） in the hematoma area. ResultsCompared with the sham group， the ICH group showed increases in the mNSS， the cerebral hemorrhage volume， and the escape latency in the Morris water maze test （P<0.01）， decreases in the times of touching the platform and times of entering the quadrant where the platform was located in the Morris water maze test， and reductions in the spontaneous alternation rate in the Y-maze test and the ratio of distance of center travel to total travel distance in the open field test （P<0.01）. Moreover， pathological changes such as cell disarrangement， cell space enlargement， and cell swelling were observed in the ICH group. Immunohistochemistry results showed that the ICH group had higher proportions of AQP4- and GFAP-positive cells and lower proportion of NeuN-positive cells than the sham group （P<0.01）. Compared with the sham group， the ICH group showed an up-regulated protein level of AQP4 and down-regulated protein levels of Claudin-5 and ZO-1 （P<0.01）. Compared with the ICH group， the intervention with Wulingsan decreased the mNSS， the volume of cerebral hemorrhage， and the escape latency in the Morris water maze test （P<0.05， P<0.01）， while increasing the times of touching the platform and times of entering the quadrant where the platform was located in the Morris water maze test， the spontaneous alternation rate in the Y-maze test， and the ratio of distance of center travel to total travel distance in the open field test （P<0.05， P<0.01）. Furthermore， the intervention with Wulingsan alleviated the pathological changes in the brain tissue after ICH， decreased the proportion of AQP4- and GFAP-positive cells （P<0.01）， increased the proportion of NeuN-positive cells （P<0.01）， down-regulated the protein level of AQP4 （P<0.01）， and up-regulated the protein levels of Claudin-5 and ZO-1 （P<0.01）. ConclusionThe intervention with Wulingsan could reduce the neural function score and the cerebral hemorrhage volume， up-regulate the expression of Claudin-5 and ZO-1， and down-regulate the expression of AQP4 to ameliorate the neurological function defect and cerebral edema after ICH， thereby protecting the brain.

Objective:To investigate the relationship between intracerebral high-density foci and progressive stroke (PS) morbidity by using dual-energy CT, which can quantify the intracerebral high-density foci of patients with acute ischemic stroke after endovascular treatment.Methods:Ninety-two patients with acute ischemic stroke who received interventional treatment in Gaozhou People′s Hospital from May 2019 to August 2020, and underwent dual-energy CT scan immediately after intervention, were analyzed. The patients were divided into PS group ( n=35) and non-PS group ( n=57) according to the National Institutes of Health Stroke Scale (NIHSS) score, and the patients whose NIHSS score increased≥4 points within 72 hours of stroke were included in the PS group, while the patients whose NIHSS score increased<4 points were included in the non-PS group. The clinical data, volume of high-density foci and CT values were compared between the 2 groups. Logistic regression analysis was used to adjust for confounding factors and screen for risk factors. The correlations of the admission NIHSS score, presence and volume of high-density lesions, maximum CT (CTmax) value and average CT (CTave) value with the onset of PS were analyzed, and the receiver operating characteristic curve was used to screen predictive indicators of PS. Results:In the PS group, the NIHSS score (18.80±8.50 vs 14.40±9.58, t=2.229, P=0.028), proportion of high-density foci [29/35(82.9%) vs 32/57 (56.1%), χ 2=6.928, P=0.008], high-density focal volume [13.23 (39.33) cm 3vs 0.76 (9.82) cm 3, U=1 440.000, P<0.001], CTmax value [80.00 (92.00) HU vs 65.00 (87.50) HU, U=1 337.000, P=0.005] and CTave value [53.48 (23.79) HU vs 45.94 (55.11) HU, U=1 345.000, P=0.004] were higher than those in the non-PS group. The NIHSS score ( OR=1.054, 95% CI 1.004-1.106, P=0.033; rs=0.255, 95% CI 0.051-0.447, P=0.014), presence of high-density foci ( OR=3.776, 95% CI 1.358-10.503, P=0.011; rs=0.274, 95% CI 0.093-0.460, P=0.008), high-density focal volume ( OR=1.026, 95% CI 1.003-1.049, P=0.027; rs=0.381, 95% CI 0.183-0.560, P<0.001), CTmax value ( OR=1.006, 95% CI 1.001-1.011, P=0.014; rs=0.292, 95% CI 0.088-0.475, P=0.005) and CTave value ( OR=1.021, 95% CI 1.007-1.035, P=0.004; rs=0.299, 95% CI 0.092-0.484, P=0.004) were all risk factors affecting PS morbidity and were positively correlated with PS morbidity. The area under the receiver operating characteristic curve of NIHSS score, high-density lesion volume, CTmax value, and CTave value to predict the onset of PS was 0.652, 0.722, 0.670 and 0.674, respectively. The volume of high-density lesions had moderate predictive value for the onset of PS. Conclusions:For AIS patients, CT examination should be performed immediately after interventional operation. The volume, CTmax value and CTave value of high-density lesions newly appeared in the ischemic area are positively correlated with the onset of PS. Quantifying the volume of high-density lesions can help to predict the onset of PS.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective To explore whether hepatocyte Perilipin-2(Plin2)is involved in the development of fatty liver related to comparative gene identification-58(CGI-58)deficiency mice and compare the effects of Plin2 and Plin3 on lipid droplet formation and lipid accumulation.Methods Based on CGI-58Flox/Flox mice as animal model,the adeno-associated viruses targeting mouse liver,CGI-58 knockout and Plini2 knockdown were achieved by co-expression Cre protein and micro-RNA targeting Plin2(Mi-KD).Then CGI-58 deficiency mice were used as control(NC)to detect the differences in metabolic phenotype and liver pathology.AML-12 mouse hepatocytes were used as cellular model and interfered with siRNA to achieve Plin2/Plin3 knockdown in AML-12 cells.Lipid droplet formation and lipid accumulation were compared with Bodipy staining and enzyme colorimetry in basal condition or lipid-overloaded condition(OA inducement)after Plin2/Plin3 knockdown.Results Plin2 knockdown(Mi-KD)reduced PLIN2 protein level by＞99％in mouse livers.Mi-KD decreased hepatomegaly(P=0.019 5)and liver injury(P=0.000 4),while reduced the histological NAS score(P=0.000 2)and hepatic triglyceride content(P=0.016 6)in the CGI-58 deficiency female mice.Mi-KD prevented microvesicular hepatic steatosis in the CGI-58 deficient female mice.Plin3 knockdown significantly reduced the triglyceride content in basal condition of hepatocytes(P=0.001 4),and Plin2 knockdown just showed a decreased trend.Plin2 or Plin3 knockdown significantly reduced the triglyceride content separately in lipid-overloaded hepatocytes(P＜0.05).Conclusion Hepatocyte Plin2 is essential in the development of microvesicular hepatic steatosis caused by CGI-58 deficiency.Both Plin2 and Plin3 are involved in lipid droplet formation and lipid accumulation in hepatocytes,and Plin3 shows a stronger effect.

Objective:To investigate the role and mechanism of astrocyte (AS) derived exosomes in protecting brain microvascular endothelial cells (bEnd. 3) from cerebral ischemia reperfusion injury by establishing an oxygen-glucose deprivation/re-oxygenation (OGD/R) model in vitro. Methods:(1) Dual-luciferase reporter gene assay was used to confirm the regulating effect of miR-193b-3p on transient receptor potential cation channel, subfamily M, member 2 (TRPM2). OGD/R model was established by OGD 8 h followed by reoxygenation 24 h in bEnd. 3 cells after being transfected miR-193b-3p mimics/negative sequence (OGD/R+miR-193b-3p mimics group or OGD/R+miR-193b-3p negative sequence group); real-time quantitative PCR (RT-qPCR) was used to detect the miR-193b-3p expression, Western blotting (WB) was used to detect the expressions of TRPM2, cleaved caspase-3, Bax, Bcl-2, ZO-1 and Claudin-5, and flow cytometry was used to detect the apoptosis. (2) AS was extracted from the cerebral cortex of C57BL/6 suckling mice and identified; modeling time was determined by CCK-8 and AS-derived exosomes were extracted by ultracentrifugation from cell supernatant and identified by electron microscopy, particle size analysis, and WB for marker proteins. RT-qPCR was used to detect the miR-193b-3p expression in AS and AS-derived exosomes. Low-expressed miR-193b-3p exosomes were extracted from AS after being transfected miR-193b-3p inhibitory sequence and co-incubated with OGD/R bEnd. 3 cells (group of OGD/R+AS-derived inhibitory sequence exosomes); exosomes were extracted from AS transfecting with miR-193b-3p negative sequence, and co-incubated with OGD/R bEnd.3 cells (group of OGD/R+AS-derived negative sequence exosomes); and normal exosomes were co-incubated with OGD/R bEnd. 3 cells (group of OGD/R+AS-derived exosomes). The miR-193b-3p expression in these 3 groups was detected by RT-qPCR, expressions of TRPM2, cleaved-caspase-3, Bax, Bcl-2, ZO-1, and Claudin-5 were detected by WB, cell apoptosis was detected by flow cytometry, and cell migration ability was detected by scratch test.Results:(1) Dual-luciferase reporter gene assay showed that miR-193b-3p could bind to TRPM2 mRNA. The miR-193b-3p can improve the TRPM2-mediated apoptosis and tight junction reduction in bEnd.3 cells during OGD/R: compared with OGD/R group, OGD/R+miR-193b-3p mimics group had significantly decreased TRPM2, cleaved-caspase-3, and Bax protein expressions, and statistically increased Bcl-2, ZO-1 and Claudin-5 protein expressions ( P<0.05). Flow cytometry further verified the above results: compared with OGD/R group, OGD/R+miR-193b-3p mimics group had significantly decreased cell apoptosis rate (21.34% vs. 13.93%, P<0.05). (2) The extracted exosomes exhibited lipid bilayer cup-like structure with particle size of 126.5 nm (exosome marker proteins: negative Cal and positive CD81 and SG101), indicating successful exosome extraction. After modeling, miR-193b-3p expression in AS and AS-derived exosomes was significantly decreased compared with that in the Control goup ( P<0.05). Compared with the OGD/R group, the group of OGD/R+AS-derived exosomes and group of OGD/R+AS-derived negative sequence exosomes had significantly increased miR-193b-3p expression, statistically decreased TRPM2, cleaved-caspase-3 and Bax protein expressions, and significantly increased ZO-1, Claudin-5 and Bcl-2 expressions ( P<0.05); while compared with those in the OGD/R group, no significant changes in the above protein expressions in group of OGD/R+AS-derived inhibitory sequence exosomes were noted ( P>0.05). Compared with the OGD/R group (18.22%), group of OGD/R+AS-derived exosomes and group of OGD/R+AS-derived negative sequence exosomes had significantly decreased apoptosis rate (14.09% and 13.79%, P<0.05), while group of OGD/R+AS-derived inhibitory sequence exosomes had no significant change (18.41%, P>0.05). Compared with the OGD/R group (13.55%), group of OGD/R+AS-derived exosomes and group of OGD/R+AS-derived negative sequence exosomes had significantly increased migration ability (43.01% and 40.59%, P<0.05), while group of OGD/R+AS-derived inhibitory sequence exosomes had no significant change (16.26%, P>0.05). Conclusion:AS-derived exosomes can suppress TRPM2 protein expression in brain microvascular endothelial cells distantly by miR-193b-3p to improve the brain microvascular endothelial cell injury caused by OGD/R, and then improve OGD/R injury.

Objective　To analyze the survival status and influencing factors among HIV/AIDS transmitted through homosexual contact from 2004 to 2022 in Nan'an District, Chongqing, China. Methods　HIV infected/AIDS patients transmitted through homosexual contact in Nan'an District, Chongqing from 2004 to 2022 were selected for analysis. The survival rate was calculated using the life table method, the median survival time was calculated using the Kaplan-Meier method, and the survival curve was plotted. The Cox regression model was performed to identify factors influencing survival. Results　A total of 3 110 subjects were included in the study, of which 1 199 individuals (38.55%) were transmitted through homosexual contact. The majority of patients were under 30 years old (694, 57.88%), unmarried (917, 76.48%), and had a higher education level of college or above (724, 60.38%), mainly belonging to the Han ethnicity (1 160, 96.75%). Students accounted for 10.43% of occupational status. The majority of patients were initially diagnosed with HIV (1 104, 92.08%), with 71.45% having a CD4+T lymphocyte count >350 cells/μL at the time of initial testing. The primary source of samples was from testing and consultation (52.88%), and the vast majority (93.16%) underwent antiviral treatment. The median survival time for patients transmitted through homosexual contact was 191.45 months, which was higher than 158.37 months of patients transmitted through other routes, demonstrating statistical significance (P<0.001). Multivariate analysis showed that among patients transmitted through homosexual contact, those with CD4+T lymphocyte count≤200 cells/μL had a higher risk of death compared to those with CD4+ T lymphocyte count>350 cells/μL. HIV infected/AIDS patients who did not receive antiviral treatment also had a higher risk of death. Conclusions　From 2004 to 2022, the reported incidence level of HIV/AIDS in Nan'an District showed an overall upward trend, with a slight decrease influenced by respiratory infectious diseases.The risk of death for individuals infected through same-sex transmission routes had not yet been found to be significantly lower than that of other transmission routes, which may be influenced by the late diagnosis time and short follow-up time of individuals infected through same-sex transmission routes.

Objective:To analyze the comorbidity status and influencing factors of hypertension, diabetes, and dyslipidemia among middle-aged and elderly Chinese adults and to provide support for the "co-management of three diseases".Methods:Using the relevant information collected from the National Chronic Disease and Risk Factor Surveillance in China in 2018, 134 950 permanent residents aged ≥45 years were selected as the research objects. After being weighed, the prevalence and comorbidity of hypertension, diabetes, and dyslipidemia in residents with different groups were compared; a multivariate logistic regression model was used to explore the influencing factors of comorbidity of the "three diseases".Results:The prevalence of hypertension, diabetes, and dyslipidemia among middle-aged and elderly Chinese adults were 46.0% (95% CI:45.1%-47.0%), 19.5% (95% CI:18.7%-20.2%), 43.3% (95% CI:42.3%-44.4%), respectively. The comorbidity rates of hypertension and diabetes, hypertension and dyslipidemia, and diabetes and dyslipidemia were 12.3% (95% CI:11.7%-12.8%), 22.8% (95% CI:22.1%-23.4%),11.6% (95% CI:11.1%-12.0%), respectively; the comorbidity rate of hypertension, diabetes, and dyslipidemia was 7.6% (95% CI: 7.2%-8.0%). These comorbidity rates increased with age and BMI, which was more significant in the urban areas than rural areas and more outstanding in North and Northeast China ( P<0.05). The comorbidity rate of hypertension, diabetes, and higher cholesterol was 1.9% (95% CI:1.7%-2.1%). The comorbidity rate of hypertension, diabetes, and higher low-density lipoprotein was 1.6% (95% CI:1.4%-1.7%), which was higher in women than in men ( P<0.05). Multivariate logistic regression results showed that male, age, city, overweight/obesity, excessive drinking, physical inactivity, daily sedentary behavior time ≥5 hours, and sleep duration <7 hours were risk factors for the comorbidity of the "three diseases". Conclusions:The comorbidity of hypertension, diabetes, and dyslipidemia, is common among middle-aged and elderly adults in China; comprehensive prevention and control of risk factors and "co-management of three diseases" are critical measures for health promotion in middle-aged and elderly populations.

Objective:To understand the regular leisure-time physical activity status of residents aged ≥60 years in China and to explore the potential influencing factors.Methods:National Chronic Disease and Risk Factor Surveillance were conducted in 298 counties (districts) in China in 2018, which covered 31 provinces (autonomous regions, municipalities), using a multi-stage stratified cluster random sampling method to select 194 779 permanent residents aged ≥18 years, using a questionnaire containing the Global Physical Activity Questionnaire. A face-to-face survey to obtain demographic information about the survey respondents, the frequency of moderate and vigorous-intensity leisure-time physical activity in their spare time and time, and other information related to chronic diseases and risk factors. Daily temperatures of 298 monitored counties (districts) in 2018 were obtained by inversion of satellite remote sensing data information such as MODIS, OMI, and AIRS, and the number of parks in 2017 was obtained by me. In this study, 68 379 residents aged ≥60 years who completed the survey and had complete information on leisure-time physical activity-related variables, temperature, and parks were used as survey respondents, and the prevalence of regular leisure-time physical activity and average weekly exercise time was calculated by gender in groups of age, urban and rural areas, education level, and geography. Multi-factor logistic regression models were used to analyze the individual and environmental influences on the regular exercise rate. All the results were weighted according to a complex sampling scheme.Results:The prevalence of regular leisure-time physical activity of residents aged ≥60 years in China in 2018 was 13.1% (95% CI: 12.1%-14.0%). The figures were slightly higher for men [13.6% (95% CI: 12.6%-14.7%)] than for women [12.5% (95% CI: 11.5%-13.5%)]; urban [17.5% (95% CI: 15.9%-19.1%)] were significantly higher than those in rural areas [9.6% (95% CI: 8.8%-10.4%)]; the prevalence of regular leisure-time physical activity in East China [15.1% (95% CI: 13.3%-16.9%)] was higher than those in other regions; older residents in counties (districts) with ≥28 parks [17.3% (95% CI: 15.3%-19.2%)] the highest. The average weekly exercise time of elderly residents in China was 68.3 (95% CI: 63.5-73.2) minutes; among them, men [74.3 (95% CI: 68.1-80.5) minutes] was higher than women [62.5 (95% CI: 57.8-67.2) minutes]; urban [89.8 (95% CI: 82.0-97.7) minutes] were higher than rural [51.4 (95% CI: 46.8-56.1) minutes]. The results of the multi-factorial logistic analysis showed that factors such as: living in rural areas, lower annual household income for literacy, poorer self-rated health status, and lack of parks in the area of residence were associated with a lower prevalence of regular leisure-time physical activity among elderly residents. Conclusions:The prevalence of regular leisure-time physical activity among elderly residents in China is still at a low level, and exercise time needs to be improved. We should increase the publicity of "national fitness", pay attention to the disadvantaged elderly groups and provide more suitable activity places to encourage more elderly residents to participate in leisure-time physical activity.

Objective: To identity patterns of psychological abuse and neglect among male and female adolescents, and to examine the relationship between psychological abuse and neglect with mobile phone dependence. Methods: A total of 1 070 adolescents from 5 middle schools in Ganzhou and Wuhan were investigated with Child Psychological Abuse and Neglect Scale (CPANS), Mobile Phone Addiction Index Scale (MPAI) and demographic questionnaire. Latent profile analysis (LPA) was used to construct typologies of psychological abuse and neglect involvement in male and female adolescents. Results: Three latent classes were identified for boys: low level psychological abuse and neglect group (56.68%), medium level psychological abuse and neglect group ( 29.80 %), high level psychological abuse and neglect group (13.52%). For girls, four latent classes were identified including low level psychological abuse and neglect group (49.38%), medium level psychological abuse and neglect group (29.01%), high level psychological abuse and neglect group (11.12%); high level psychological abuse group (10.49%). Adolescents who suffered from psychological abuse and neglect were more likely to be dependent on mobile phones. Among them, boys dependence on mobile phones was manifested as out of control, withdrawal, escape and inefficiency[Medium level： B(95%CI )=0.28(0.12-0.44)，0.29(0.11-0.46)，0.35(0.16-0.53)，high level： B(95%CI )=0.37(0.16-0.59)，0.42(0.19-0.65)，0.33(0.07-0.59)，0.50(0.25- 0.74 )， P ＜0.05], while girls showed evasion and inefficiency in high levels of psychological abuse[ B(95%CI )=0.34(0.01-0.67)，0.46(0.14-0.78)， P ＜0.05]. Conclusion There are heterogeneous differences in psychological abuse and neglect between male and female adolescents, and the relationship between each category and mobile phone dependence varies. The results provide suggestions for adolescent mental health intervention.

Adult ; Atherosclerosis ; Cardiovascular Diseases ; China ; Habits ; Humans ; Lipids