1.Glycyrrhizic acid alleviates cisplatin-induced ototoxicity by inhibiting in-flammation of cochlear in C57BL/6J mice
Yuqian ZHANG ; Wenjun JIANG ; Hao LÜ ; Zixuan SHENG ; Ziyun HUANG ; Wenmin CHAI ; Jing XIAO ; Yang LI ; Li LI ; Xiansi ZENG
Chinese Journal of Pathophysiology 2024;40(2):291-300
		                        		
		                        			
		                        			AIM:To study whether glycyrrhizic acid(GL)can resist the ototoxicity of cisplatin(CDDP)in mice and its molecular mechanism.METHODS:Male C57BL/6J mice were divided into 5 groups:control group,DMSO(5%)group,CDDP(4 mg/kg)group,CDDP+low-dose(50 mg/kg)GL group,and CDDP+high-dose(100 mg/kg)GL group(n=14).Auditory brainstem response(ABR)was used to detect hearing changes of mice.HE staining was used to observe the morphological change of cochlear stria vascular in mice.Evans blue(EB)staining was used to observe the per-meability change of the blood-labyrinth barrier(BLB).Immunohistochemical technique was used to detect the expression and distribution of adhesion protein VE-cadherin and tight junction protein ZO-1 on the cochlear stria.ELISA assay and immunofluorescence technology were employed to detect the expression of tumor necrosis factor-α(TNF-α)and interleu-kin-1β(1L-1β).RESULTS:In CDDP group,ABR waveforms of all frequencies were disturbed,the hearing threshold was significantly increased,and I wave latency was prolonged(P<0.05).In CDDP+GL group,ABR waveforms of various frequencies were well differentiated,the hearing threshold was significantly decreased,and the latency of I-wave was shortened(P<0.01).The disordered morphology and more vacuoles in the stria vascularis were observed by HE staining in CDDP group.The GL alleviated CDDP-induced damage in the stria vascularis.In EB staining,CDDP caused an increase in per-meability of BLB(P<0.01),which was improved by GL treatment(P<0.01).Immunohistochemical results showed that the expression of VE-cadherin and ZO-1 in CDDP group were decreased(P<0.01),which was restored in CDDP+GL group(P<0.01).The ELISA and immunofluorescence results showed that the expression of IL-1β and TNF-α was in-creased after CDDP treatment(P<0.01),which was restored in CDDP+GL group(P<0.01).CONCLUSION:The GL alleviates CDDP-induced hearing loss in mice by inhibiting CDDP-induced inflammation and reducing the permeability of BLB.
		                        		
		                        		
		                        		
		                        	
2.Tubeimoside II inhibits proliferation of non-small-cell lung cancer cells by inducing ferritinophagy
Qiaoyi YANG ; Chunyun ZHANG ; Shuo SUN ; Wenmin LI ; Xin HUANG ; Yan LIANG ; Weiwei ZHANG ; Huaiyong LI ; Qingzhu YANG
Chinese Journal of Pathophysiology 2024;40(10):1834-1843
		                        		
		                        			
		                        			AIM:This study aimed to explore the induction of ferroptosis in non-small-cell lung cancer(NSCLC)cells by tubeimoside II(TBMS II)and to elucidate the underlying molecular mechanisms.METHODS:H460 NSCLC cells were cultured in vitro.Cell survival rates were assessed by using MTT assays,and doses of TBMS II resulting in below 50%survival were selected for further experimentation.Cell migration was evaluated using Transwell assays and the effects of TBMS II on H460 cell proliferation were assessed by colony formation assays.Flow cytometry and fluores-cence microscopy were used to assess changes in lipid peroxidation(lipid ROS),and the levels of GSH,T-AOC,MDA,and Fe2+were measured using commercial kits.Protein levels of GPX4,SLC7A11,FTH1,NCOA4,P62,and LC3 were examined using Western blot.Changes in mitochondrial structure were detected by transmission electron microscopy,and immunofluorescence was used to assess LC3 co-localization of FTH1 and NCOA4,as well as co-localization of LC3 and NCOA4 with lysosomes.RESULTS:Compared with the control group,TBMS II dose-dependently reduced H460 cell via-bility,migration,and clone formation,accompanied by the appearance of vacuoles within the cells.TBMS II treatment al-so led to decreased GSH and T-AOC levels,while increasing the cellular contents of MDA,indicating oxidative stress.Ad-ditionally,there was a decrease in the expression of the antioxidant proteins SLC7A11 and GPX4 in the cells,while lipid ROS and Fe2+levels were increased in proportion to the TBMS II concentration.The ferroptosis inhibitor ferrostatin-1 re-versed cell death caused by TBMS II,suggesting ferroptosis induction.Furthermore,increasing the TBMS II concentra-tion resulted in an upregulation of the autophagy marker proteins LC3 II/LC3 I and P62,indicative of increased autopha-gy.TBMS II also affected mitochondrial morphology in the cells,as seen in reduced mitochondrial fluorescence intensity.Protein expression of NCOA4 increased with higher TBMS II concentrations,while that of FTH1 decreased.Co-localiza-tion of LC3 II with FTH1 and NCOA4,as well as the lysosomal association of LC3 II and FTH1,also increased in a dose-dependent manner.CONCLUSION:TBMS II induces ferritinophagy in H460 cells,leading to decreased cell viability and increased ferroptosis.
		                        		
		                        		
		                        		
		                        	
3.Evaluation of accessibility and quality of diagnosis and treatment services of Internet hospitals in China
Wenmin LI ; Yangyujuan WU ; Zimu HU ; Zhao TAN ; Weihui ZHANG ; Huimin ZHU ; Zhiwei HUANG ; Yao CHEN ; Tingting LI ; Zilong WANG ; Yunke BU
Chinese Journal of Hospital Administration 2024;40(4):286-291
		                        		
		                        			
		                        			Objective:To evaluate the healthcare accessibility and quality of diagnosis and treatment services of Internet hospitals in China.Methods:One hundred and eighty Internet hospitals in 60 cities were seleted based on the sampling of development levels in the eastern, central and western regions of China. From April to May 2023, standardized patients methodology was applied to evaluate the accessibility(including the number of Internet hospitals, functional settings, online doctor status, the doctor′s attending rate and consultation fees) and diagnosis and treatment service quality(including the diagnosis and treatment services quality, response speed and patient′s evaluation) of Internet hospitals.Results:The average opening rate of Internet hospitals in China was 52.9% (560/1 058), the average online rate of doctors was 64.2% (1 099/1 713), the average doctor′s attending rate was 33.6% (112/333), the average consultation fee was 4.85 yuan, the average score of consultation was 1.92 out of 9, the average score of diagnosis and treatment was 1.12 out of 4, the average score of the response speed was 1.70 out of 3, and patient satisfaction was 2.73 out of 3.Conclusions:The Internet hospital accessibility in China is unevenly developed, and the overall quality of diagnosis and treatment is low. It is recommended to accurately position and optimize the function of Internet hospital, establish the incentive mechanism for online consultation doctors, construct and improve the regulatory system of Internet hospital diagnosis and treatment, so as to improve the accessibility and quality of diagnosis and treatment of Internet hospitals.
		                        		
		                        		
		                        		
		                        	
4.Mechanism of Huangqisan Regulating Autophagy by AMPK/mTOR Signaling Pathway Against Hepatic Steatosis
Wenmin FENG ; Anyu SU ; Xiaoling HUANG ; Chunyi WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(10):21-30
		                        		
		                        			
		                        			ObjectiveTo explore the mechanism of Huangqisan (HQS) in regulating autophagy to alleviate hepatic steatosis and improve non-alcoholic fatty liver disease (NAFLD) based on adenosine 5'-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. MethodThe main chemical components and targets of HQS and NAFLD-related targets were collected from database and the intersection targets were used for Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed, and in vivo experimental verification was conducted. Sixty C57BL/6J male mice were randomly divided into normal control group (NCD), model group high-fat diet (HFD), metformin group (MET, 0.25 g·kg-1), low-dose Huangqisan group (HQS-L, 0.5 g·kg-1), and the high-dose Huangqisan group (HQS-H, 1 g·kg-1), with 12 mice in each group after a one-week acclimatization period. NAFLD model was induced by HFD, and intragastric administration was performed at the same time, once a day for 13 weeks. Random blood glucose, serum total cholesterol (TC), triglyceride (TG), non-esterified fatty acid (NEFA), low density lipoprotein-chdesterol (LDL-C) levels, and liver TG content were determined. The liver weight was weighed, and liver index was calculated. Hematoxylin-eosin (HE) staining, oil red O staining, transmission electron microscope (TEM), real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and Western blot were used to verify the effect and reveal the potential mechanism of C57BL/6J mice in vivo. ResultThrough network pharmacology analysis, combined with previous studies, it was predicted that HQS may improve NAFLD by regulating autophagy via the AMPK/mTOR signaling pathway. The result of in vivo experiment showed that, as compared with NCD group, random blood glucose, body weight, serum TC, LDL-C, NEFA, liver weight, liver index, and liver TG content of mice in the HFD groups were significantly increased (P<0.01). HE staining showed massive lipid droplets (LDs) vacuolated, oil red O staining showed lipid accumulation in liver cells, and no obvious autophagosomes and autolysosome were observed under TEM. The relative mRNA expression of LC3A、LC3B、AMPKα1 and protein expression of AMPK, phosphory phosphorylated(p)-AMPK, and p-AMPK/AMPK were significantly down-regulated (P<0.01), while the protein expression of microtubule-associated protein 1 light chain 3 (LC3)Ⅱ/Ⅰ and p-mTOR was significantly up-regulated (P<0.01). As compared with HFD groups, liver weight, serum TG, and NEFA levels in HQS-L and HQS-H groups were significantly deceased (P<0.05, P<0.01). HE staining and oil red O staining showed the improvement of liver pathological changes after HQS administration. Under TEM, a small amount of autophagosome and autolysosome were observed. Besides, liver index was significantly decreased in the HQS-L group (P<0.01), and random blood glucose, serum TC level and liver TG content were significantly decreased in the HQS-H group (P<0.05). The results of Western blot and Real-time PCR showed that the mRNA expression of LC3A and LC3B and the protein expression of LC3Ⅱ/Ⅰ, p-AMPK, and p-AMPK/AMPK were significantly up-regulated (P<0.01), while the mRNA expressions of p62 and protein expression of p62 and p-mTOR were significantly down-regulated (P<0.05, P<0.01). ConclusionHQS may promote autophagy and restore autophagy flux via the AMPK/mTOR signaling pathway to alleviate hepatic steatosis improving NAFLD. 
		                        		
		                        		
		                        		
		                        	
5.Association of smartphone addiction with daily behaviors and mental health during the COVID-19 pandemic among medical college students
Chinese Journal of School Health 2021;42(5):713-718
		                        		
		                        			Objective:
		                        			To investigate the smartphone addiction among college students during the Coronavirus Disease 2019 (COVID-19) pandemic and its association with daily behaviors and mental health,and to provide reference for heath education and psychological counseling for college students.
		                        		
		                        			Methods:
		                        			An observational study using online quyestionnaire was conducted among 10 357 college students of two provincial medical schools in Guangdong and Shanxi Province from February 24th to March 4th in 2020. Participants were investigated on demographic information, smartphone addiction, daily routine, physical activity, weight status, anxiety, and other health information. Logistic regression with inverse probability treatment weighting (IPTW) based on propensity score was used to analyze the association between smartphone addiction with daily behavior and mental health.
		                        		
		                        			Results:
		                        			The prevalence of smartphone addiction was 59.42%. The prevalence of phone addiction was higher in postgraduates, senior undergraduates, students with non-medical major, students living in GuangDong and those without regular exercise habit before vacation(χ 2=47.91,17.78,42.75,138.58,P<0.05). With IPTW, there were significant associations between smartphone addiction and late bedtimes (OR=1.82, 95%CI=1.66-1.98) and wake-up times (OR=1.55, 95%CI=1.44-1.68), more sedentary behaviors (OR=1.21, 95%CI=1.12-1.31), less moderate to vigorous physical activity (OR=1.33, 95%CI=1.22-1.44), anxiety (OR=2.98, 95%CI=2.52-3.40), weight gain(OR=1.27,95%CI=1.17-1.37) and other detrimental daily behavior and feelings.
		                        		
		                        			Conclusion
		                        			High prevalence of smartphone addiction has been observed during the COVID-19 pandemic, with impaired daily behavior and mental health.
		                        		
		                        		
		                        		
		                        	
6.Influence on physical development of children aged 18 months from HIV-positive mothers for prevention mother to child transmission of HIV
Xianmin GE ; Wenmin YANG ; Zhiyong SHEN ; Huanhuan CHEN ; Bin LI ; Qin MENG ; Liuhong LUO ; Huaxiang LU ; Jinhui ZHU ; Guanghua LAN ; Qiuying ZHU ; Xiuling WU ; Guanghua HUANG ; Botao FU ; Zhuoxin HUANG ; Jiawei LI ; Jinmei CHEN ; Zhenqiang CHEN ; Jin YANG ; Yu YAN
Chinese Journal of Epidemiology 2020;41(3):354-357
		                        		
		                        			
		                        			Objective:To explore influence on physical development of children aged 18 months from HIV-positive mothers for prevention mother to child transmission of HIV (PMTCT) in Guangxi Zhuang autonomous region, and provide evidence for the improvement PMTCT program.Methods:This retrospective case control study was conducted in 554 HIV negative infants aged 18 months whose HIV positive mothers had received PMTCT services reported through PMTCT system database from January 1, 2010 to December 31, 2017 and 1 109 healthy infants born in 2017, whose mothers were healthy, in Lingshan, Luzhai, and Hengxian counties, ranking top three counties with high HIV infection prevalence, in Guangxi. PMTCT data and physical development data such as height, weight and head circumference of children aged 18 months were collected. The physical dysplasia in the infants was defined as at least one of the three main indicators of height, weight and head circumference below the normal range.Results:The number of HIV-positive mother and their infants in the case group were 667 and 554 respectively, and the PMTCT rates were 91.15 % (608/667) and 96.57 % (535/554) respectively. HIV positive rate, mortality rate and mother to child transmission rate of the infants aged 18 months were 1.44 % (8/554), 3.07 % (17/554) and 1.91 % (8/418) respectively, and the physical examination results of the infants aged 18 months showed that the physical dysplasia rate was 30.51 % (169/554). Among the 1 109 infants in the control group, the physical dysplasia rate was 9.83 % (109/1 109). The difference between the case group and the control group was significant ( P<0.01). Conclusion:The PMTCT rates of HIV positive mother and their children were more than 90.00 %, respectively. However, poor physical development rate of infants aged 18 months were more than 30.00 %. The possible influence of PMTCT on physical development of the infants aged 18 months of HIV positive mother’s needs to be further studied.
		                        		
		                        		
		                        		
		                        	
7.Characteristics of newly reported HIV/AIDS cases with non-marital or non-commercial heterosexual transmission in Guangxi Zhuang Autonomous Region, 2015-2018
Xuanhua LIU ; Qiuying ZHU ; Qin MENG ; Zhiyong SHEN ; Yuhua RUAN ; Xiuling WU ; Xinjuan ZHOU ; Jinghua HUANG ; Shuai TANG ; Wenmin YANG
Chinese Journal of Epidemiology 2020;41(4):537-541
		                        		
		                        			
		                        			Objective:To understand the characteristics and associated factors of newly reported HIV/AIDS cases with non-marital or non-commercial heterosexual transmission, in Guangxi Zhuang Autonomous Region (Guangxi), 2015-2018.Methods:Information of newly reported HIV/AIDS cases aged ≥18 years in Guangxi between 2015 and 2018 was collected from the National Comprehensive HIV/AIDS Information System. Unconditional logistic regression model was used to access those factors that were associated with HIV infections through non-marital or non-commercial heterosexual contact.Results:Between 2015 and 2018, a total number of 35 497 HIV/AIDS cases, aged ≥18 years were newly reported in Guangxi. Among them, 32 648 (92.0 %) were infected heterosexually while 10 500 were infected through non-marital or non-commercial heterosexual behavior. Non-marital or non-commercial heterosexual transmission accounted for 29.6 % (10 500/35 497) of the newly reported HIV/AIDS cases, and 32.2 % (10 500/32 648) of those with heterosexual transmission. Males counted for 53.5 % (5 617/10 500) of non-marital or non-commercial heterosexual transmission and males to females ratio was 1.2∶1 (5 617∶4 883). Those married or had regular sexual partners counted for 55.9 % (5 873/10 500). Commercial heterosexual transmission appeared the main mode of HIV transmission for males (64.4 %,16 516/25 633) while main mode for females was non-marital or non-commercial heterosexual transmission and counted for 49.5 % (4 883/9 864). Results from the multivariate logistic regression analysis showed that adjusted OR of female HIV/AIDS infected HIV via non-marital or non-commercial heterosexual transmission, was 3.98 times (95 %CI: 3.78-4.20) hight than that of males. Among the group aged<50 years and the aged 50-59 years, the adjusted ORs were 1.35 times (95 %CI: 1.27-1.44) and 1.13 times (95 %CI: 1.05-1.21) hight than that of aged ≥60 years. Those who were single/divorced/widowed, the adjusted OR was 1.53 times (95 %CI: 1.45-1.61) hight than that of those married/regular partners. Those with junior high school education, high school education and above the adjusted ORs were 1.22 times (95 %CI: 1.16-1.29) and 1.18 times (95 %CI: 1.10-1.27), compared to those only with education levels of primary school or below. Conclusions:The number of HIV/AIDS cases via non-marital or non-commercial heterosexual transmission accounted for nearly 30.0 % of all the routes of HIV transmission in Guangxi, 2015-2018. Female, aged<60 years old, single/divorced/widowed and having had junior and above high school education etc., appeared as risk factors on non-marital or non-commercial heterosexual transmission, among newly reported HIV/AIDS in Guangxi.
		                        		
		                        		
		                        		
		                        	
8. An interlaboratory comparison study on the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels
Yazhen QIN ; Liwen ZHU ; Shuang LIN ; Suxia GENG ; Shengwei LIU ; Hui CHENG ; Chengye WU ; Min XIAO ; Xiaoqing LI ; Ruiping HU ; Lili WANG ; Haiyan LIU ; Daoxin MA ; Tao GUAN ; Yuanxin YE ; Ting NIU ; Jiannong CEN ; Lisha LU ; Li SUN ; Tonghua YANG ; Yungui WANG ; Tao LI ; Yue WANG ; Qinghua LI ; Xiaosu ZHAO ; Lingdi LI ; Wenmin CHEN ; Lingyu LONG ; Xiaojun HUANG
Chinese Journal of Hematology 2019;40(11):889-894
		                        		
		                        			 Objective:
		                        			To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison.
		                        		
		                        			Methods:
		                        			Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated.
		                        		
		                        			Results:
		                        			①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH.
		                        		
		                        			Conclusion
		                        			The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same. 
		                        		
		                        		
		                        		
		                        	
9. Epidemiological characteristics of HIV/AIDS in Guangxi Zhuang Autonomous Region, 2010-2017
Xianmin GE ; Wenmin YANG ; Qiuying ZHU ; Xiuling WU ; Zhiyong SHEN ; Jinhui ZHU ; Guanghua LAN ; Huanhuan CHEN ; Qin MENG ; Xinjuan ZHOU ; Dongni DING ; Xuanhua LIU ; Shuai TANG ; Jinghua HUANG ; Yueqin DENG
Chinese Journal of Epidemiology 2019;40(3):315-321
		                        		
		                        			 Objective:
		                        			To understand the characteristics of HIV/AIDS epidemic in Guangxi Zhuang Autonomous Region (Guangxi) with a purpose to accurately provide scientific basis for prevention and control measures, 2010-2017.
		                        		
		                        			Methods:
		                        			Data were retrieved from case reporting cards of Guangxi during 2010 to 2017 through National HIV/AIDS Comprehensive Response Information Management System. Data was analyzed using epidemiological methods such number of cases, proportion and rate. 
		                        		
		                        	
            
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