Objective To investigate the mechanism and molecular structural basis of the tension-regulated interaction between ICAP1 and β1 integrin.Methods Based on the crystal structure data of the ICAP1/β1 integrin cytoplasmic tail complex(PDB ID:4DX9),tensile molecular dynamics simulations were conducted to observe and analyze the effects of tension loading on β1 integrin on the structure and binding affinity of the ICAP1/β1 integrin complex.Results The tension modulated the dissociation of the ICAP1/β1 integrin complex bidirectionally by inducing local conformational variations at the binding interface.It initially increased and then decreased the binding affinity of β1 integrin for ICAP1.The threshold point occurred at 10 pN.The main tension-sensitive residue interactions were primarily located among ARG140-THR789,MET141-THR789,and ASP145-SER785.Conclusions As the tension applied to the cytoplasmic tail of β1 integrin increased,the conformational variations at the binding interface resulted in an initial enhancement followed by a reduction in the inhibitory effect of ICAP1 on β1 integrin activation.A tension threshold of 10 pN was observed.This indicated that force-induced integrin activation requires sufficient mechanical stimulus strength.This study has provided a new approach for the development of antibody drugs targeting β1 integrins.

Objective To investigate the mechanism and molecular structural basis of the tension-regulated interaction between ICAP1 and β1 integrin.Methods Based on the crystal structure data of the ICAP1/β1 integrin cytoplasmic tail complex(PDB ID:4DX9),tensile molecular dynamics simulations were conducted to observe and analyze the effects of tension loading on β1 integrin on the structure and binding affinity of the ICAP1/β1 integrin complex.Results The tension modulated the dissociation of the ICAP1/β1 integrin complex bidirectionally by inducing local conformational variations at the binding interface.It initially increased and then decreased the binding affinity of β1 integrin for ICAP1.The threshold point occurred at 10 pN.The main tension-sensitive residue interactions were primarily located among ARG140-THR789,MET141-THR789,and ASP145-SER785.Conclusions As the tension applied to the cytoplasmic tail of β1 integrin increased,the conformational variations at the binding interface resulted in an initial enhancement followed by a reduction in the inhibitory effect of ICAP1 on β1 integrin activation.A tension threshold of 10 pN was observed.This indicated that force-induced integrin activation requires sufficient mechanical stimulus strength.This study has provided a new approach for the development of antibody drugs targeting β1 integrins.

Objective:To clarify the key genes and biological processes in spermatogenesis, integrate and analyze the differentially expressed genes (DEGs) and key signaling pathways in the differentiation process of human spermatogonia (SPG), and to explore the early molecular mechanism of spermatogenesis, increase the molecular biology understanding of SPG differentiation process.Methods:The transcriptome data of human undifferentiated spermatogonia and differentiated spermatogonia (dSPG) were downloaded from the public database. Hisat2 and StingTie were used to screen DEGs. DEGs were analyzed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment analysis. MACS2 software was used to analyze the open chromatin regions (OCRs) in ATAC-seq data.Results:A total of 8 532 DEGs were screened, including 4 127 up-regulated genes and 4 405 down-regulated genes. They regulate the differentiation of SPG through some important biological processes, such as cell cycle, cytokine-mediated signaling pathways, organic matter metabolism, cell movement, and methylation. KEGG enrichment analysis showed that some important signaling pathways including FoxO signaling pathway and JAK-STAT signaling pathway played an important role in SPG differentiation. GO enrichment analysis showed that methylation played an important role in the differentiation of SPG, and the expression of methylation-related genes was significantly different. The TDRDs family was significantly enriched, and 9 TDRDs genes were found to be more active in dSPG. Conclusion:In this study, the differentially expressed genes during SPG differentiation were identified by bioinformatics analysis, and the differences in transcription and chromatin levels of key genes were clarified, which laid an important theoretical foundation for the study of SPG differentiation mechanism.

Objective:To clarify the key genes and biological processes in spermatogenesis, integrate and analyze the differentially expressed genes (DEGs) and key signaling pathways in the differentiation process of human spermatogonia (SPG), and to explore the early molecular mechanism of spermatogenesis, increase the molecular biology understanding of SPG differentiation process.Methods:The transcriptome data of human undifferentiated spermatogonia and differentiated spermatogonia (dSPG) were downloaded from the public database. Hisat2 and StingTie were used to screen DEGs. DEGs were analyzed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment analysis. MACS2 software was used to analyze the open chromatin regions (OCRs) in ATAC-seq data.Results:A total of 8 532 DEGs were screened, including 4 127 up-regulated genes and 4 405 down-regulated genes. They regulate the differentiation of SPG through some important biological processes, such as cell cycle, cytokine-mediated signaling pathways, organic matter metabolism, cell movement, and methylation. KEGG enrichment analysis showed that some important signaling pathways including FoxO signaling pathway and JAK-STAT signaling pathway played an important role in SPG differentiation. GO enrichment analysis showed that methylation played an important role in the differentiation of SPG, and the expression of methylation-related genes was significantly different. The TDRDs family was significantly enriched, and 9 TDRDs genes were found to be more active in dSPG. Conclusion:In this study, the differentially expressed genes during SPG differentiation were identified by bioinformatics analysis, and the differences in transcription and chromatin levels of key genes were clarified, which laid an important theoretical foundation for the study of SPG differentiation mechanism.

Objective:To investigate the current status of prevention and treatment of esophagogastric variceal bleeding (EVB) in cirrhotic portal hypertension patients in Ningxia region.Methods:The retrospective and descriptive study was conducted. The clinical data of 820 cirrhotic portal hypertension patients who were admitted to 21 medical centers in Niangxia region from January 2018 to December 2020 were collected, including 85 cases in Ningxia Hui Autonomous Region People′s Hospital, 73 cases in the Fifth People′s Hospital of Ningxia Hui Autonomous Region, 59 cases in the Wuzhong People′s Hospital, 52 cases in the Qingtongxia People′s Hospital, 50 cases in the Guyuan People′s Hospital, 47 cases in the Yuanzhou District People′s Hospital of Guyuan City, 47 cases in the Yinchuan Second People′s Hospital, 40 cases in the General Hospital of Ningxia Medical University, 40 cases in the Tongxin People′s Hospital, 35 cases in the Yinchuan First People′s Hospital, 34 cases in the Third People′s Hospital of Ningxia Hui Autonomous Region, 32 cases in the Zhongwei People′s Hospital, 30 cases in the Lingwu People′s Hospital, 30 cases in the Wuzhong New District Hospital, 30 cases in the Yanchi People′s Hospital, 29 cases in the Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, 28 cases in the Shizuishan Second People′s Hospital, 25 cases in the Shizuishan First People′s Hospital, 21 cases in the Haiyuan People′s Hospital, 20 cases in the Pengyang People′s Hospital, 13 cases in the Longde People′s Hospital. There were 538 males and 282 females, aged (56±13)years. Observation indicators: (1) clinical charac-teristics of cirrhotic portal hypertension patients; (2) overall prevention and treatment of EVB in cirrhotic portal hypertension patients; (3) prevention and treatment of EVB in cirrhotic portal hypertension patients from different grade hospitals. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Results:(1) Clinical characteristics of cirrhotic portal hypertension patients: of 820 cirrhotic portal hypertension patients, 271 cases were in compensated stage and 549 cases were in decompensated stage. Of the 271 cases in compensated stage, there were 183 maels and 88 females, aged (53±12)years. There were 185 Han people, 85 Hui people and 1 case of other ethic group. The etiological data of liver cirrhosis showed 211 cases of viral hepatitis B, 4 cases of alcoholic liver disease, 8 cases of viral hepatitis C, and 48 cases of other etiology. There were 235 cases of Child-Pugh grade A and 36 cases lack of data. Of the 549 cases in decompensated stage, there were 355 males and 194 females, aged (57±14) years. There were 373 Han people, 174 Hui people and 2 cases of other ethic group. The etiological data of liver cirrhosis showed 392 cases of viral hepatitis B, 33 cases of alcoholic liver disease, 10 cases of viral hepatitis C, and 114 cases of other etiology. There were 80 cases of Child-Pugh grade A, 289 cases of grade B, 170 cases of grade C and 10 cases lack of data. (2) Overall prevention and treatment of EVB in cirrhotic portal hypertension patients: of 271 patients in compensated stage, 38 cases received non-selective β-blocker (NSBB) therapy, 16 cases received endoscopic treatment, 6 cases received interventional therapy. Of 549 patients in decompensated stage, 68 cases received NSBB therapy, 46 cases received endoscopic treatment, 28 cases received interventional therapy. (3) Prevention and treatment of EVB in cirrhotic portal hypertension patients from different grade hospitals: of 271 patients in compensated stage, 181 cases came from tertiary hospitals, of which 28 cases received NSBB therapy, 15 cases received endoscopic treatment, 6 cases received interventional therapy. Ninety cases came from secondary hospitals, of which 10 cases received NSBB therapy, 1 cases received endoscopic treatment. There was no significant difference in NSBB for prevention of EVB between tertiary and secondary hospitals ( χ2=0.947, P>0.05), while there was a significant difference in endoscopic treatment for prevention of EVB between tertiary and secondary hospitals ( χ2=5.572, P<0.05). Of 549 patients in decompensated stage, 309 cases came from tertiary hospitals, of which 22 cases received NSBB therapy, 29 cases received endoscopic treatment, 22 cases received interventional therapy. Two hundreds and fourty cases came from secondary hospitals, of which 46 cases received NSBB therapy, 17 cases received endoscopic treatment, 6 cases received interven-tional therapy. There were significant differences in NSBB and interventional therapy for prevention of EVB between tertiary and secondary hospitals ( χ2=18.065, 5.956, P<0.05). Conclusions:The proportion of receiving EUB prevention in cirrhotic portal hypertension in Ningxia is relatively low. For patients with compensated liver cirrhosis, the proportion of NSBB therapy and endoscopic treatment in the secondary hospitals was lower than that in tertiary hospitals. For patients with decompensated liver cirrhosis, the proportion of interventional treatment in secondary hospitals is lower than that of tertiary hospitals, but the proportion of NSBB in secondary hospitals taking is higher than that of tertiary hospitals.

Objective: To understand the awareness of sexual knowledge among primary and secondary school students, as well as their attitudes towards school sex education and to provide a reference for school-based sex education. Methods: A total of 5 531 primary and secondary school students were selected from Beijing, Chongqing, Heilongjiang (Harbin and Jiamusi) and Hubei (Wuhan and Xiaogan) by stratified cluster sampling and were investigated with self-reported questionnaire. Results: Sex-related knowledge scored 62.33±19.35, with a pass rate of 61.9%, and the excellent rate 17.5%. Sexual knowledge of junior high school students scored 64.30±19.07, with the pass rate of 64.7%, and the excellent rate 22.0%. A large proportion of primary students reported unaware of pubertal growth and HIV/AIDS-related knowledge, and a large proportion of junior high students unaware of reproductive physiology. Multivariate Logistic regression analysis showed region, grade, gender, and suburban areas were related to the level of sexual knowledge(P<0.05). More than 76.0% primary students and 85.9% middle school students agreed on the importance of school sexuality education. 59.7% of primary school students and 73.3% of junior high school students hoped to include school sexuality education in compulsory education courses; 59.8% of primary school students and 68.3% of junior high school students felt that school sexuality education should be equipped with specialized teachers. Conclusion Chinese primary and secondary school students are lack of sexual knowledge. As students have strong wills to get more information on sexual knowledge, schools should provide them with more comprehensive and effective sex education through appropriate courses and activities.

Objective: To understand the needs of primary and secondary school students, parents and teachers for comprehensive sexuality education content, and to explore the applicability of comprehensive sexuality education content in China. Methods: By using the method of stratified cluster sampling, 5 571 primary and middle school students and 4 835 parents from Beijing, Chongqing, Heilongjiang (Harbin and Jiamusi) and Hubei (Wuhan and Xiaogan) were selected for questionnaire survey. Depending on the physical health monitoring points of various provinces and cities, 176 sexuality education related teachers in nine regions were surveyed. The development of the questionnaire was based on the content framework of comprehensive sexuality education proposed in the International Technical Guidelines for Sexuality Education. Results: Students had a higher demand for knowledge on the concepts of "relationship" (53.4% for primary school students, 57.6% for junior high school students) and "health and well-being skills" (71.1% for primary school students, 55.9% for junior high school students). Parents had higher demand for most comprehensive sexuality education content with the exception of lower need for "sex and sexual behavior (74.7% of primary school parents, 80.8% of junior high school parents)" and "sexual and reproductive health (primary parents 74.3%, junior high school parents 75.8%)". Teachers had a high demand for most comprehensive sexuality education content, but primary school teachers had a lower need for "values, rights, culture and sex(65.9%)", "sex and sexuality(60.1%)" and "sexual and reproductive health(66.8%)". The results of correspondence analysis showed that junior middle school teachers had the highest demand for comprehensive education content, followed by primary school parents, junior middle school parents, primary school teachers, junior middle school students and primary school students. Conclusion Teachers and parents have a higher demand for most comprehensive sexuality education content, while lower demand for some relatively sensitive content. Students have a relatively low demand for comprehensive sexuality education content. It is recommended to further improve the content of school sexuality education based on the actual needs of China.

Objective To evaluate the feasibility and efficacy of twin grasper combined with endoloops on closing acute stomach perforation.Methods Two experimental porcines of stomach perforation underwent endoscopic closure by twin grasper combined with endoloops.Survival conditions and closure of perforating were observed.Results Mild infection and abdominal adhesions were observed in one week after operation.The nylon rope fell off and an ulcer-like lesion was presented in the closed position.The methylene blue leak test was negative.Histologic examination revealed chronic inflammatory cells infiltration,granulation,fibroplasias,and regenerative mucous membrane crawling toward the center of perforation.Conclusion The technique of twin grasper combined with nylon ropes in closing the acute stomach perforation is feasible and effective.

OBJECTIVETo investigate the distribution patterns of mosquito and mosquito-borne viruses in Dehong prefecture, Yunnan province, China.

METHODSMosquito samples were collected using the mosquito traps from five counties of Dehong prefecture on July, 2007 and 2010. Mosquito were cell cultured for viral isolation, and positive isolates were identified using RT-PCR and sequence analysis.

RESULTSA total of 43 634 mosquito comprised of 29 species representing six genera were collected. Culex tritaeniorhynchus and Anopheles sinensis comprised 78.69% and 14.77% of the total. Six strains of viruses were isolated from the mosquito pools. RT-PCR and phylogenetic analysis revealed three strains from Cx. tritaeniorhynchus, identified as genotype I Japanese encephalitis virus (JEV). One strain was identified from Cx. tritaeniorhynchus, as Getah virus (GETV). Two strains isolated from Cx. tritaeniorhynchus and Anopheles vagus were identified as Culex pipiens pallens Densovirus (CppDNV).

CONCLUSIONCx. tritaeniorhynchus had been the major species of mosquito and mainly transmitting vector of mosquito-borne viruses in Dehong prefecture. Genotype I JEV, GETV and CppDNV were the vectors causing transmission of mosquito-borne diseases in this area. Data from phylogenetic analysis showed that these newly discovered isolates seemed to have had close relationship with those viruses previously circulating in Yunnan and other provinces of China.

Alphavirus ; isolation & purification ; Animals ; Arboviruses ; classification ; isolation & purification ; China ; Culicidae ; virology ; Disease Vectors ; classification ; Encephalitis Virus, Japanese ; isolation & purification

ABSTRACT:In recent years ,there has been high prevalence of murine typhus in Yunnan Province ,People's Republic of China .A large outbreak of murine typhus occurred in Xishuangbanna Prefecture ,Yunnan Province in 2010 .However ,not all cases were confirmed by laboratory assays ;therefore ,field epidemiologic and laboratory investigations of murine typhus in Xishuangbanna Prefecture were conducted in 2011 .Blood samples were collected from clinical diagnostic cases at the acute and convalescence stages of murine typhus in Xishuangbanna Prefecture ,Yunnan Province ,from June to September of 2011 ,and blood and spleen samples were collected from mice sharing the same habitats as the patients .Immunofluorescence assays were used to test for the presence of IgM and IgG antibodies against Rickettsia typhi in sera from patients and mice .Real‐time PCR was used to detect the groEL gene of R .typhi in blood clots from patients at the acute stage and in spleen tissue from mice .A total of 1 157 clinically diagnosed murine typhus cases occurred in Xishuangbanna Prefecture ,Yunnan Province in 2011 ,with an incidence of 102 .10/100 000 .Of these cases ,80 were investigated by laboratory assays and 74 of 80 patients were confirmed to have murine typhus .The coincidence rate between the clinical diagnosis and laboratory detection was 92 .50% .The positivi‐ty rate for IgG antibodies against R .typhi was 14 .0% (14/100) for Rattus f lavipectus ,while the rate by PCR was 9 .0%(9/100) .That laboratory diagnoses confirmed that the severity of the murine typhus outbreak in Xishuangbanna cannot be ig‐nored .The distribution of host animals transmitting R .typhi underscores this conclusion .