Objective To investigate the effect and mechanism of miglitol on regulating the energy metabolism of brown adipocytes by activating UCP1 and preventing cold injury in mice after cold exposure. Methods Primary brown adipocytes were induced into mature adipocytes, the effect of miglitol on the viability of brown adipocytes was investigated by MTT method, the lipid droplet consumption level of cells after drug administration was investigated by Oil Red O staining technology, and the level of UCP1, a key protein of thermogenesis in brown adipocytes, was detected by Western blotting. The activity of anti-frostbite was investigated in cold exposure at 4 ℃ and −20 ℃. KM mice, which were randomly divided into control group, cold exposure group, miglitol group and all-trans retinoic acid group, and after 7 days of repeated administration, the body surface temperature of mice was detected by infrared thermal imaging system, the anal temperature change was detected by anal thermometer, and the expression levels of UCP1 and PGC1-α in adipose tissue were detected by immunoblotting. Results Compared with the control group, the lipid droplet consumption and UCP1 expression levels in brown adipocytes in the miglitol group were significantly increased. The levels of body surface temperature and rectal temperature increased significantly after cold exposure, and the levels of UCP1 and PGC1α in the brown adipose tissue of mice increased significantly, which indicated that the miglitol could activate the critical proteins UCP1 and PGC1α of the thermogenesis pathway, increase the thermogenesis of mice after cold exposure, and thus improve the effect of cold injury for toe swelling. Conclusion Miglitol could play a role in improving cold injury and body temperature in mice by increasing the level of UCP1 and PGC1α, which are key targets of the thermogenesis pathway to promote the thermogenesis of brown fat.

Objective: To investigate the present situation of health education on school myopia prevention and control in primary and middle schools in Beijing, so as to provide scientific basis and suggestions for effective implementation of health education on school myopia prevention and control. Methods: From November 6-17, 2023, a total of 551 school doctors and health care teachers from public primary and secondary schools in seven districts of Beijing were investigated by using stratified random cluster sampling method. The contents included basic information, the basic situation of school health work, and the status of myopia prevention and control in schools. The data was described by frequency and proportion. Chisquare test was used to analyze the influencing factors. Results: A total of 89.8% of the respondents were found in the school of offering health education courses about myopia prevention and control. Among these respondents, 54.5% were equipped with health education course material of professional myopia prevention and control, and the teachers were primarily class teachers (57.6%), health care teachers (45.5%), and physical education teachers (45.1%), and most of the classes were conducted once a month (33.7%) and once a semester (28.1%). A total of 95.6% of the subjects had health education activities about myopia prevention and control at their schools. The frequency of activities was once a month (38.5%) and once a semester (27.9%). There were statistically significant differences of the report rate in setting up health education courses on myopia prevention and control, and the frequency of activities in different areas and different types of schools (χ2=19.53, 13.15, 34.30, 20.32, P<0.05). Conclusions Health education on school myopia prevention and control in primary and middle schools in Beijing is supportive. But health education courses taught by professional teachers should pay attention to the norms of the course material to complete a certain amount of class time, and development of health education activities should be diversified, so as to effectively implement health education of myopia prevention and control at school.

Objective:The epidemiological and host animal pathogen data of leptospirosis in the population of Zhejiang Province in 2023 were analyzed, providing scientific basis for formulating prevention and control strategies of leptospirosis.Methods:The data of human leptospirosis in the population were collected from the China Information System for Disease Control and Prevention, and analyzed using descriptive epidemiological methods. The data on isolation, culture, and nucleic acid testing of Leptospira pathogens from mouse kidneys, frog kidneys, pig kidneys, and duck kidneys as well as duck serum antibody data were collected from Zhejiang Provincial Center for Disease Control and Prevention "Leptospirosis Surveillance Project of Zhejiang Province". The carrying and changing status of Leptospira epidemic microbiota in populations and host animals were analyzed. Results:In 2023, a total of 83 cases of leptospirosis were reported in Zhejiang Province, with a incidence rate of 0.126 2/ 100 000, aged (62.66 ± 11.31) years, including 68 males and 15 females. Leptospirosis cases were reported in 11 cities, mainly concentrated in the southern cities of Wenzhou City, Lishui City and Taizhou City(a total of 68 cases), accounting for 81.93% of the total number of cases. August to October were high incidence months for leptospirosis (a total of 70 cases), accounting for 84.34% of the total number cases. The male to female ratio of patients was 4.53 ∶ 1.00, and all were adults ≥20 years old, the middle and old people aged 45 - 79 years were the high-risk population (a total of 77 cases), accounting for 92.77% of the total number of cases. The patient's occupation was mainly farmers, with a total of 54 cases, accounting for 65.06% of the total number cases. The shortest time from onset to initial diagnosis for patients with leptospirosis was 0 day, and the longest was 13 days. The shortest time from initial diagnosis to confirmed diagnosis was 0 day, and the longest was 16 days. The 72.29% of the leptospirosis cases (60 cases) had a history of field labor or suspected contact with contaminated water within one month before the onset of the disease, and 18.07% of the leptospirosis cases (15 cases) had a history of contact with animals such as mice, frogs, pigs, cows, dogs, fish or ducks, or their excreta within one month before the onset of the disease. The average nucleic acid positive rate of host animals with leptospirosis was 5.92% (31/524) in mouse kidney, 6.74% (36/534) in frog kidney, and 0.66% (1/151) in pig kidney. The isolation and culture of leptospirosis from duck kidney, nucleic acid detection, and antibody detection in duck blood were all negative. The leptospirosis bacteria detected in human population were serogroup Icterohaemorrhagiae (3 samples) and Hebdomadis (4 samples), and the bacteria group detected in host animals was serogroup Icterohaemorrhagiae (3 samples). Conclusions:The outbreak of leptospirosis in Zhejiang Province mainly occurs in the summer and autumn, with the affected areas mainly concentrated in the southern region of Zhejiang Province. The affected population is mainly middle-aged and elderly males, and the population carrying Leptospira is still mainly composed of the serogroup Icterohaemorrhagiae and the Hebdomadis, with the host animal being the serogroup Icterohaemorrhagiae.

Objective To evaluate the efficacy of Schroth PSSE combined with 3D printing braces in the treatment of adolescent idiopathic scoliosis.Method Forty patients were included and divided into a support group(3D printing support group)and a support+exercise therapy group(3D printing support+Schroth PSSE group).Excluding outliers and lost follow-up data,32 patients were ultimately included,with 16 patients in each group.Wearing time≥18 h for both groups of 3D printing supports.The intervention period of Schroth PSSE is 12 weeks,and exercise is maintained after 12 weeks until the end of follow-up.The longest follow-up time for the brace group was 25 months,with an average follow-up time of(15.00±1.29)months.The longest follow-up time for the brace+exercise therapy group was 24 months,with an average follow-up time of(16.59±1.01)months.Relevant indicators were evaluated after follow-up.Results The support and exercise therapy group showed better improvement in Cobb angle and trunk rotation angle(ATR)than the support group,with statistically significant differences(P<0.05);The distance between the midpoint of the C7 vertebral body and the midline of the sacrum(C7-CSVL)in the support and exercise therapy group showed a statistically significant difference before and after treatment(P<0.05),while there was a significant difference before and after Apical Vertebral Translation(AVT)treatment(P<0.01).There was no statistically significant difference compared to the support group(P<0.05);In terms of SRS-22 score,the brace+exercise therapy group can comprehensively improve the SRS-22 score.Conclusion The combination of Schroth PSSE and 3D printing braces has a better effect on improving Cobb angle and torso rotation angle,improving coronary imbalance,increasing patient satisfaction,and improving quality of life compared to using 3D printing braces alone.

Oral and maxillofacial organoids (OMOs), tiny tissues and organs derived from stem cells cultured through 3-d cell culture models, can fully summarize the cell tissue structure, physiological functions and biological characteristics of the source tissues in the body. OMOs are applied in areas such as disease modelling, developmental and regenerative medicine, drug screening, personalized treatment, etc. Although the construction of organoids in various parts of the oral and maxillofacial (OM) region has achieved considerable success, the existing cocktail formulae (construction strategies) are not widely applicable for tissues of various sources due to factors including the heterogeneity of the source tissues and the dependence on laboratory technology. Most of their formulae are based on growth factor niches containing expensive recombinant proteins with their efficiency remaining to be improved. In view of this, the cocktail formulae of various parts of the OM organs are reviewed with further discussion of the application and prospects for those OMOs to find some affordable cocktail formula with strong operability and high repeatability for various maxillofacial organs. The results may help improve the efficiency of organoid construction in the laboratory and accelerate the pace of the clinical use of organoid technology.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Objective:To construct the molecular transmission network of human immunodeficiency virus type 1 (HIV-1) epidemic strains in northern Zhejiang Province (Jiaxing City and Huzhou City) and to explore the HIV-1 transmission characteristics in this region.Methods:A total of 371 newly diagnosed human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Jiaxing City and Huzhou City in 2017 were included as study subjects, and the blood samples were collected and the basic demographic and epidemiological information were obtained. RNA in plasma was extracted, and the pol region gene sequence was amplified by reverse transcriptase polymerase chain reaction (RT-PCR) and nested polymerase chain reaction (PCR) to construct phylogenetic tree for identifying subtypes. The pairwise genetic distances were calculated, and the optimal threshold of genetic distance was selected, and finally the molecular transmission network was constructed. Chi-square test was used for statistical analysis. Results:The pol region gene sequences of 336 samples were successfully obtained, and 11 subtypes were detected, mainly including circulating recombinant form (CRF)07_BC (40.8%, 137/336) and CRF01_AE (31.2%, 105/336). Based on the 1.0% genetic distance threshold, the molecular transmission network of HIV-1 was plotted. A total of 38 transmission clusters (cluster sizes ranging from two to 28) including 119 patients were found, with males predominantly (82.4%, 98/119) and most of the patients aged over 40 (include 40) years old (52.9%, 63/119), mainly infected with CRF07_BC subtype (57.1%, 68/119) and CRF01_AE (24.4%, 29/119). The clustering rate of CRF07_BC (49.6%, 68/137) was significantly higher than that of CRF01_AE (27.6%, 29/105), the difference was statistically significant ( χ2=5.27, P=0.022). Two large clusters C1 (28 cases) and C2 (11 cases) were identified, the majority of which were men who have sex with men (17 cases and seven cases, respectively). High-risk cases generally sought sexual partners in local or nearby cities through mobile phone dating software, of which the infected sequences mostly had high homology with other economic developed regions (Guangdong Province, Beijing City and Hangzhou City, etc.). Conclusions:The HIV-1 subtypes are diverse in Jiaxing City and Huzhou City, mainly CRF07_BC and CRF01_AE. The HIV-1 transmission networks are complex, among which high-risk cases may be the key factor leading to the HIV-1 epidemic in the region. Therefore, it is urgent to deepen the transmission network monitoring and formulate timely precise intervention and prevention strategies.

Objective:To investigate the clinical and diagnostic value of liver stiffness measurement (LSM) for the evaluation and comparison of aspartate aminotransferas/platelet ratio index (APRI), fibrosis 4 indexes (FIB-4) and NAFLD fibrosis score (NFS) with liver fibrosis staging in relation to nonalcoholic fatty liver disease (NAFLD).Methods:103 cases with NAFLD who met the inclusion criteria confirmed by liver biopsy were selected for retrospective analysis. The results of serological tests and LSM were recorded. The APRI, FIB-4 and NFS were calculated. The accuracy and applicability of four liver fibrosis models in the diagnosis of liver fibrosis in NAFLD patients were compared with the receiver operating characteristic curve (ROC), and the diagnostic cut-off value of LSM was established.Results:Varying degrees of LSM, APRI, FIB-4 and NFS had shown positive correlations with the increasing degree of liver fibrosis. Among them, LSM was positively correlated with the degree of liver fibrosis, and the correlation coefficient was r = 0.727, P < 0.0001. Consistent with this, the area under the receiver operating characteristic curve, sensitivity, and specificity of LSM diagnosis of liver fibrosis in different stages was significantly higher than APRI, FIB-4 and NFS. Area under receiver operating characteristic curve of LSM was 0.862 and 0.928 for significant liver fibrosis ( f ≥ 2), and advanced liver fibrosis ( f ≥ 3). Conclusion:LSM has a good diagnostic exclusion value for NAFLD-induced fibrosis, and its sensitivity and specificity are better than APRI, FIB-4 and NFS.

Objective:To evaluate the applicability of limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA, LAg for short) in determining the new HIV-1 infection status of MSM population with seroconversion and make correlation analysis of other biological indicators.Methods:The 15 cases with HIV seroconversion were found in a MSM observation cohort for calculating the HIV prevalence in Zhejiang.The subjects were conducted epidemiological investigation and sampled.The interval of infection time was estimated according to the exposure history and the time of HIV-positive confirmation.LAg, immunoblotting, CD4 cell counting and viral load test were applied in the testing of the related blood samples. McNermar test was conducted for consistency of the two methods.Results:Of 15 cases, the average age was (31.5±8.0) years old, ranging from 24 to 57 years old. The interval of infection time ranged from 40 days to 366 days, and the median was 134 days, with inter-quartile range from 89 to 180 days. A total of 7 cases were classified as new HIV-1 infection by LAg, and 8 cases were classified as chronic infection.The consistent rate was high to 86.67%, and kappa value was 0.73.The samples lacking at least two bands in p31, p51, p66 and gp120 by immunoblotting were determined as recent infection, of which the new infection proportion was significantly higher than that of other samples ( P=0.029).There was no statistical difference in the distribution of CD4 counts ( P=0.533) and viral loads ( P=0.467) between the new infection and chronic infection groups that divided by LAg. Conclusion:By combining with exposure history, the limiting antigen avidity enzyme immunoassay can be used to estimate the new HIV-1 infection.The other biological indicators such as immunoblotting bands, CD4 cell counts and viral loads, can be used as accessory indicators in evaluating the status of new HIV-1 infection.

Objective:To evaluate the applicability of limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA, LAg for short) in determining the new HIV-1 infection status of MSM population with seroconversion and make correlation analysis of other biological indicators.Methods:The 15 cases with HIV seroconversion were found in a MSM observation cohort for calculating the HIV prevalence in Zhejiang.The subjects were conducted epidemiological investigation and sampled.The interval of infection time was estimated according to the exposure history and the time of HIV-positive confirmation.LAg, immunoblotting, CD4 cell counting and viral load test were applied in the testing of the related blood samples. McNermar test was conducted for consistency of the two methods.Results:Of 15 cases, the average age was (31.5±8.0) years old, ranging from 24 to 57 years old. The interval of infection time ranged from 40 days to 366 days, and the median was 134 days, with inter-quartile range from 89 to 180 days. A total of 7 cases were classified as new HIV-1 infection by LAg, and 8 cases were classified as chronic infection.The consistent rate was high to 86.67%, and kappa value was 0.73.The samples lacking at least two bands in p31, p51, p66 and gp120 by immunoblotting were determined as recent infection, of which the new infection proportion was significantly higher than that of other samples ( P=0.029).There was no statistical difference in the distribution of CD4 counts ( P=0.533) and viral loads ( P=0.467) between the new infection and chronic infection groups that divided by LAg. Conclusion:By combining with exposure history, the limiting antigen avidity enzyme immunoassay can be used to estimate the new HIV-1 infection.The other biological indicators such as immunoblotting bands, CD4 cell counts and viral loads, can be used as accessory indicators in evaluating the status of new HIV-1 infection.