Objective To explore the association between single nucleotide polymorphism(SNP)of Rab37 gene and the age at menarche(AAM).Methods A case-control study design was used to conduct an epidemiologic survey on 2 060 women in a community in Jurong City,Jiangsu Province,and their venous blood samples were collected.ASA chip was used to explore the Rab37 gene genotyping of blood sample DNA to obtain the genotyping results for Rab37 SNPs rs62084865,rs10512597,rs35489971,rs1037170,rs6501732,rs77822106,and rs3178300.Based on menarche time of＜16 years old or≥16 years old,the participants were divided into 2 groups.Linear and logistic regression analyses were used to explore the association between the SNP of Rab37 gene and the age at menarche based on dominant,recessive and allelic models.Results Among the 2 060 healthy women,944 women had normal menstrual periods,while 1 116 women experienced delayed menarche.Linear regression analysis showed that the gene polymorphism of rs3178300 was negatively correlated with the age at menarche in females[recessive model:CC/CT+TT,β=-0.915,95%CI(-1.692,-0.137),P=0.021;allelic model:T/C,β=-0.221,95%CI(-0.410,-0.032),P=0.022].Logistic regression analysis indicated that the gene polymorphism of rs3178300 was significantly associated with the risk of delayed menarche in females[recessive model:CC/CT+TT,OR=0.295,95%CI(0.116,0.751),P=0.010;allelic model:T/C,OR=0.796,95%CI(0.652,0.972),P=0.025].The remaining 6 SNPs showed no significant association with age at menarche.Conclusion The rs3178300 polymorphism of Rab37 gene is significantly associated with delayed menarche in Chinese women.

Objective:To examine the near-complete genomic analysis of norovirus (NoV) subtype GⅡ.17 [P17] outbreaks in Beijing Chaoyang District from 2014 to 2024.Methods:Data and specimens related to outbreaks of the NoV aggregation in Beijing′s Chaoyang District from 2014 to 2024 were collected. The NoV was identified using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). Specimens with positive nucleic acid were amplified by standard PCR, whole genome sequencing and evolutionary analysis. Amino acid site variations were compared.Results:In Chaoyang District, from 2014 to 2024, a total of 637 aggregated outbreaks caused by the NoV infection were reported, of which 584 were successfully typed. The epidemic caused by the GⅡ.17 [P17] subtype accounted for 8.79% (56/637), which was the dominant epidemic gene subtype in 2014-2015, sporadic in 2016-2019, reappeared in 2022, and significantly increased in 2024 (27.27%, 24/88). Outbreaks caused by the GⅡ.17 [P17] subtype occurred mainly from October to December, with the main sites of occurrence in primary schools and kindergartens. This study yielded 53 near-complete genome sequences of the GⅡ.17 [P17] subtype from 46 incidents in Chaoyang District. The GⅡ.17 [P17] subtype sequences of Chaoyang District from 2014 to 2024 were segmented into three subgroups on the evolutionary tree, with sequences from 2014 to 2019, 2022 to April 2024, and May to December 2024 clustered into the d, e, and b subgroups, respectively. In the VP1 region′s P2 area, particularly at the HBGA binding site, subgroups b and e exhibited mutations in 22 and two sites, while subgroups b and e showed mutations in four and one sites, predominantly in the RdRp region.Conclusion:The outbreak caused by the NoV GⅡ.17 [P17] subtype in Chaoyang District from 2014 to 2024 continues, with a significant increase in 2024, and it becomes the dominant gene subtype from October to December. The sequence formation of the NoV GⅡ.17 [P17] subtype in Chaoyang District from January to April 2022 and from May to December 2024 shows two different evolutions, with specific mutation sites, requiring continuous monitoring of the NoV GⅡ.17 [P17] subtype.

Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Objective:To examine the near-complete genomic analysis of norovirus (NoV) subtype GⅡ.17 [P17] outbreaks in Beijing Chaoyang District from 2014 to 2024.Methods:Data and specimens related to outbreaks of the NoV aggregation in Beijing′s Chaoyang District from 2014 to 2024 were collected. The NoV was identified using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). Specimens with positive nucleic acid were amplified by standard PCR, whole genome sequencing and evolutionary analysis. Amino acid site variations were compared.Results:In Chaoyang District, from 2014 to 2024, a total of 637 aggregated outbreaks caused by the NoV infection were reported, of which 584 were successfully typed. The epidemic caused by the GⅡ.17 [P17] subtype accounted for 8.79% (56/637), which was the dominant epidemic gene subtype in 2014-2015, sporadic in 2016-2019, reappeared in 2022, and significantly increased in 2024 (27.27%, 24/88). Outbreaks caused by the GⅡ.17 [P17] subtype occurred mainly from October to December, with the main sites of occurrence in primary schools and kindergartens. This study yielded 53 near-complete genome sequences of the GⅡ.17 [P17] subtype from 46 incidents in Chaoyang District. The GⅡ.17 [P17] subtype sequences of Chaoyang District from 2014 to 2024 were segmented into three subgroups on the evolutionary tree, with sequences from 2014 to 2019, 2022 to April 2024, and May to December 2024 clustered into the d, e, and b subgroups, respectively. In the VP1 region′s P2 area, particularly at the HBGA binding site, subgroups b and e exhibited mutations in 22 and two sites, while subgroups b and e showed mutations in four and one sites, predominantly in the RdRp region.Conclusion:The outbreak caused by the NoV GⅡ.17 [P17] subtype in Chaoyang District from 2014 to 2024 continues, with a significant increase in 2024, and it becomes the dominant gene subtype from October to December. The sequence formation of the NoV GⅡ.17 [P17] subtype in Chaoyang District from January to April 2022 and from May to December 2024 shows two different evolutions, with specific mutation sites, requiring continuous monitoring of the NoV GⅡ.17 [P17] subtype.

BACKGROUND:High-methionine diet can cause liver injury in Cbs+/-mice,and hyperhomocystinemia is related to the occurrence and progression of various liver-related diseases,such as hepatic steatosis,autoimmune hepatitis,and alcoholic fatty liver disease.MicroRNAs(miRNAs)are involved in various cellular processes including cell survival,differentiation and autophagy,which are of great significance. OBJECTIVE:To investigate the critical role of miR-144-3p on Cbs+/-mouse hepatocyte autophagy induced by high methionine die. METHODS:(1)Ten male cystathione-β-synthase normal(Cbs+/+)mice and another 10 male mice with single gene knockout(Cbs+/-)of similar body mass,4 weeks of age,were fed a high-methionine diet and executed after 12 weeks to take liver tissue.(2)Human hepatocytes(HL-7702)were cultured in vitro and divided into control[0 μmol/L homocysteine(Hcy)],Hcy(100 μmol/L Hcy),mimic-NC(transfected with mimic-NC),mimic-NC + Hcy(mimic-NC transfecton+100 μmol/L Hcy),miR-144-3p mimic(transfected with miR-144-3p mimic),and miR-144-3p mimic + Hcy(miR-144-3p mimic transfection+100 μ mol/L Hcy),inhibitor-NC(transfected with inhibitor-NC),inhibitor-NC + Hcy(inhibitor-NC transfection + 100 μmol/L Hcy),miR-144-3p inhibitor(transfected with miR-144-3p inhibitor),and miR-144-3p inhibitor + Hcy(miR-144-3p inhibitor transfection + 100 μmol/L Hcy).Quantitative real-time PCR was used to detect the expression of miR-144-3p in liver tissue and hepatocytes.After transfection of miR-144-3p mimic or inhibitor,quantitative real-time PCR and western blot were used to detect the transfection efficiency of miR-144-3p and its effect on the expression of autophagy-related proteins LC3B and p62.The levels of alanine transferase and aspartate aminotransferase in hepatocyte supernatants were determined by enzyme linked immunosorbent assay.The correlation between the expression of miR-144-3 in hepatocyte and the levels of alanine transferase and aspartate aminotransferase in hepatocyte supernatants were analyzed by Pearson correlation analysis. RESULTS AND CONCLUSION:Compared with the Cbs+/+ group and control group,the expression of miR-144-3p in the liver tissue of the Cbs+/-group and in hepatocytes of the Hcy group was decreased(P<0.01).The expression of LC3B-Ⅱ/Ⅰ was decreased in hepatocyte after transfection of miR-144-3p mimic,while the protein expression of p62 was increased(P<0.01).The opposite results were obtained after transfection of miR-144-3p inhibitor(P<0.01).Compared with the mimic-NC group,the levels of alanine transferase and aspartate aminotransferase were decreased in the miR-144-3p mimic group(P<0.01),while the opposite results were obtained in the inhibitor-NC group(P<0.01).The expression of miR-144-3p in hepatocytes was negatively correlated with the levels of alanine transferase(P<0.01,r=-0.887 6)and aspartate aminotransferase(P<0.01,r=-0.829 9)in the supernatant of hepatocytes.To conclude,Hcy promotes hepatocyte autophagy by inhibiting the expression of miR-144-3p,which subsequently aggravates liver injury.

Objective Analyze the surveillance results of foodborne illness from a level A tertiary general hospital in Shandong Province from 2019 to 2021,to provide a realistic basis for the continuous development and improvement of foodborne disease surveillance.Methods The data were collected from a level A tertiary general hospital in Shandong Province from 2019 to 2021 in the food safety risk assessment business application platform of national health insurance information project of National Health Security Disease Control Information System,and stool/anal swab samples were collected as required for pathogen detec-tion.Results From 2019 to 2021,a total of 2 323 cases of foodborne diseases were reported and 682 samples were collected,with a sampling rate of 29.36％,and 134 positive cases were detected,with a detection rate of 19.65％.The difference between the detection rates of different years was statistically significant(P＜0.05).The detection rate of norovirus was the highest(9.53％),followed by Vibrio parahaemolyticus(8.94％)and Salmonella(1.91％).The difference between the detection rates of different pathogens was statistically significant(P＜0.05).The sex ratio of 2 323 cases was 1:1.28.Among the different age distributions,20-29 years old accounted for the highest proportion(29.19％),followed by 30-39 years old(27.21％)and＜20 years old(11.71％).The highest number of cases was reported from June to September,the peak was reached from July to Au-gust,and the number of cases was gradually reduced in October and later.Among different occupational groups,housework and unemployed people accounted for the highest proportion(30.18％),followed by farmers(15.93％),students(13.65％)and commercial service workers(11.80％).The main symptoms of the digestive system were diarrhea in 2 093 cases(90.10％),abdominal pain in 1 741 cases(74.95％),nausea in 1 575 cases(67.8％)and vomiting in 1 401 cases(60.31％).The main diarrhea was watery stool in 1 954 cases(84.12％).The main systemic symptoms were fatigue in 454 cases(19.54％)and dehydration in 212 cases(9.13％).The main clinical diagnosis was acute gastroenteritis in 1 980 cases(85.23％)and infec-tious diarrhea in 199 cases(8.57％).The suspected exposed foods were mainly aquatic animals and their products(25.10％)and meat and meat products(19.37％).The main eating places of suspected exposed foods were families(57.34％),followed by restaurants(21.91％),other places(5.94％)and street food stalls(5.21％).Conclusion From 2019 to 2021,the pathogens of foodborne diseases detected were mainly norovirus and Vibrio parahaemolyticus,mainly in the age group of 20 to 39 years old,and the occupation distribution was mainly household and unemployed people,farmers,students and commercial serv-ice personnel,with digestive system symptoms such as nausea,vomiting,abdominal pain and diarrhea.The suspected exposed foods are mainly aquatic animals and their products and meat and meat products,and the main eating places are families,restau-rants and street food stalls.The surveillance and reporting of foodborne diseases should continue to be strengthened in the future.

Objective To analyze the characteristics of platelet changes and their influencing factors during postoperative hospitalization in patients who underwent transcatheter aortic valve implantation (TAVI). Methods The patients who underwent TAVI at Beijing Anzhen Hospital Valve Surgery Center between March 2017 and October 2021 were retrospectively selected. The patients were divided into a self-limiting group and a non-self-limiting group according to the characteristics of postoperative platelet decline. In addition, the general preoperative data, preoperative and postoperative ultrasound data, intraoperative data, and the use of anticoagulant drugs during the postoperative stay in the hospital were compared between the two groups. Results A total of 249 patients were enrolled in this study. There were 175 (70.3%) patients in the self-limiting group, including 100 males and 75 females, and there were 74 (29.7%) patients in the non-self-limiting group, including 43 males and 31 females, with no statistical difference between the two groups (P=0.863). The mean age of patients was 73.11±8.88 years in the self-limiting group and 71.54±10.39 years in the non-self-limiting group (P=0.231). The decline of platelets in the self-limiting group generally occurred on the postoperative day 2 and reached the lowest count on the postoperative day 4, and returned to the baseline level on the postoperative day 5-7, while the platelets in the non-self-limiting group changed by simple rise, fall or irregular fluctuation. Patients in the self-limiting group had severer preoperative aortic stenosis (P<0.001) and used more extracorporeal circulation assistance during surgery (P<0.001). Postoperatively, patients in the self-limiting group were more likely to have periaortic valve leakage than those in the non-self-limiting group (P=0.013). Conclusion Platelet changes in most patients after TAVI show a self-limiting decline, which may be related to the severity of patients’ preoperative aortic stenosis, intraoperative extracorporeal circulation device use, and postoperative perivalvular leakage.

Objective:To construct the clinical training content system for master of nursing specialist (MNS) in China.Methods:The first draft of clinical training content system for MNS was constructed through literature review, national status survey and semi-structured interview. Delphi expert consultation was used to form the final draft, and analytic hierarchy process was used to determine the weight of indicators at all levels.Results:Two rounds of consultation were conducted among 20 experts. The questionnaire recovery rate was 100% and the expert authority coefficient was 0.93. The Kendall concordance coefficients of the two rounds were 0.499 and 0.387, respectively, with a statistically significant difference ( P<0.001) . The average assigned value of importance of indicators at all levels was 4.60 to 5.00. The final version of the clinical training content system for MNS included 6 first-level items, 17 second-level items and 24 third-level items. Conclusions:The clinical training content system for MNS has good practicability, scientificity and reliability, which can provide reference and guidance for MNS clinical training.

Objective:To construct a clinical training target system for masters of nursing specialist (MNS) , so as to provides references for clinical training of masters of nursing specialist in China.Methods:The index system was preliminarily constructed by literature review, semi-structured interview and preliminary investigation. The convenient sampling method was used to select 20 experts from Beijing, Shanghai, Jiangsu and other regions from August to October 2020 to conduct two rounds of expert letter consultation, revise and improve the indicators and establish the clinical training target system for masters of nursing specialist.Results:The valid recovery rates of the two rounds of expert letter consultation questionnaire were both 100.00% (20/20) , and the expert authority coefficient was 0.93. The Kendall's coordination coefficient of total index of the first and second rounds of expert letter consultation questionnaire was 0.461 and 0.317, respectively ( P<0.01) . Finally, the clinical training objective system for masters of nursing specialist included 3 first-level indicators (quality objectives, knowledge objectives and skills objectives) , 6 second-level indicators and 27 third-level indicators. Conclusions:The clinical training target system for master of nursing specialist established in this study is scientific, credible, comprehensive and practical, which can provide a reference for the clinical training of masters of nursing specialist in China.