ObjectiveTo investigate the epidemic trends, key populations, and high-risk area characteristics of hand-foot-mouth disease (HFMD) in Ningbo from 2018 to 2023, and to provide evidence-based references for optimizing prevention strategies and precise allocation of prevention and control resources. MethodsData on HFMD cases with current addresses in Ningbo from 2018 to 2023 were collected from the China Information System for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze the epidemiological characteristics of HFMD. Global spatial autocorrelation analyses were applied to detect spatial clustering of HFMD, and spatiotemporal scan analyses were conducted to identify spatiotemporal clusters. ResultsA total of 116 967 HFMD cases, were reported of which 2 were severe and none were fatal. The average annual incidence rate was 206.33 per 100 000 population, showing an overall declining trend. Seasonal patterns were observed, with bimodal distributions in 2018, 2019, 2021, and 2022 (main peak from May to July; secondary peak from September to November), and unimodal distributions in 2020 (peak from October to December) and 2023 (peak from July to October). Children aged 5 years and under accounted for the majority of cases (104 634 cases, 89.46%), with a mean age of (3.48±3.29) years. The male-to-female ratio was 1.44∶1. Children cared for at home (56.39%) and those attending kindergarten (35.97%) were the predominant populations. The highest average incidence rate was observed in Ninghai County (261.46/100 000), and the lowest in Fenghua District (152.46/100 000), while the average incidence rates in most districts/counties ranged from 188.22 to 226.53 per 100 000 population. The highest incidence rate was observed in areas classified as urban-rural fringes (240.08 per 100 000 population). Spatial analyses revealed global clustering in 2020 (Moran’s I=0.35, P<0.05), with hotspots concentrated in Ninghai county and Xiangshan county. Spatiotemporal scan analyses identified significant clusters each year from 2018 to 2023. The strongest cluster was detected in Cixi City from May to September in 2018 (LLR=27 249.53, RR=13.06, P<0.01), followed by Yinzhou District from April to October in 2019 (LLR=25 172.16, RR=10.61, P<0.01). ConclusionThe overall incidence of HFMD in Ningbo City shows a declining trend. The disease shows bimodal (spring-summer and autumn-winter) or unimodal (autumn-winter) seasonal patterns. Cases are predominantly seen in boys aged 5 years and under, and who are cared for at home or attend kindergarten、 High-risk areas are concentrated in southern counties (Ninghai and Xiangshan). It is recommended to strengthen health education and vaccination coverage for children aged 5 years and under, and to implement dynamic surveillance and targeted interventions in key areas during high-incidence seasons, so as to reduce transmission and spread.

Osteoporosis and cardiovascular calcification,two major age-related chronic diseases that China is confronting today,pose serious threats to public health.Previous studies have reported overlapping connections in the pathological processes and molecular mechanisms of these two diseases,particularly concerning inflammation,oxidative stress,and dysregulation of mineral metabolism,and that these two diseases tend to share common pathogenic factors.However,research exploring the comorbidity mechanisms of the two diseases remains limited in both depth and scope,largely due to the lack of widely accepted comorbidity animal models.Herein,we analyzed the latest research findings on the comorbidity mechanisms of vascular calcification and osteoporosis,focusing on summarizing the animal disease models currently in extensive use and the relevant evaluation criteria.We aim to provide new references for comorbidity research models and offer scientific evidence for future studies on pathological mechanisms and the development of new therapeutic strategies.

Objective:To evaluate the hemodynamic changes and short-term (one year) outcomes after superficial temporal artery(STA)-middle cerebral artery (MCA) bypass by vascular ultrasonography.Methods:Operation group included a total of 41 hemispheres of 38 patients who underwent STA-MCA bypass for severe stenosis or occlusion of MCA or severe stenosis or occlusion of internal carotid artery(ICA), or Moyamoya disease at Xuanwu Hospital between August 2017 and June 2020. The following examinations were performed in all patients: cranial MRI, CT perfusion imaging, and cerebral angiography. All of the patients were retrospectively followed up for one year postsurgery. Normal group included a total of 40 hemispheres of 20 healthy people who had been examined by vascular ultrasonography of carotid artery and intracranial artery. Inner diameter, peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV), resistance index (RI), pulsatility index (PI) and flow of STA, PSV, EDV, MV, PI, RI of external carotid artery (ECA) and PSV, EDV, MV, PI, RI of MCA at 1 week, 6 months and 12 months after STA-MCA bypass of operation group were compared with normal group.Results:①Inner diameter, PSV, MV and flow of STA were increased significantly in operation group at 1 week, 6 and 12 months than normal group (all P<0.05). The flow of STA was decreased significantly from 1 week to 12 months after operation (all P<0.05), but Inner diameter, PSV and MV were only decreased gradually from 1 week to 12 months after operation (all P>0.05). ②STA/ECA PI and RI decreased significantly after operation compared with normal group (all P<0.01). Conclusions:Vascular ultrasonography is a non-invasive examination which can objectively evaluate the extracranial and intracranial hemodynamic changes after STA-MCA bypass, and provide reference effectiveness of the operation. The flow of STA has decreased gradually from 1 week to 12 months after operation to achieve the homeostasis, but it is still higher than normal.STA/ECA PI and RI can be a steady indirect pointer to show the fluency of bypass.

A series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC values in the range of 0.0038-0.4759 μmol/L. Among those compounds, had an EC value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. anti-HIV-1 activity and resistance profile studies suggested that compounds and displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (ECs range from 4.3 to 63.6 nmol/L and 18.9-219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC values of 2.77 and 4.87 μmol/L for HIV-1A (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both and obtained sub-micromolar IC values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound has acceptable pharmacokinetic properties and bioavailability. Preliminary structure-activity relationships and molecular modeling studies were also discussed.

Objective To investigate the expression and clinical significance of transcription factor SOX5 in peripheral blood mononuclear cells (PBMCs) and serum in patients with rheumatoid arthritis (RA). Methods The relative expression of representative genes of the SOX gene family in the PBMCs from RA patients were detected by Real-Time Polymerase Chain Reaction (RT-PCR), and serum levels of SOX5 expression were measured by enzyme-linked immunosorbent assay (ELISA) in 30 RA patients, 27 osteoarthritis (OA) patients and 30 healthy controls (HC). The expression levels of SOX5 in PBMCs were detected by RT-PCR after stimulated with IL-6, TNF-α, IL-1β and IL-17 for 24 hours. The relationship between SOX5 and receptor activator of nuclear factor κB ligand (RANKL) was detected by co-Immunoprecipitation (co-IP). The formation of TRAP-positive cells after silence SOX5 in osteoclast precursor cell treated with RANKL was observed by Tartrate-resistant acid phasphate stain (TRAP). The differences were tested using one-way ANOVA followed by Student-Newman-Keuls post hoc analysis Correlations were analyzed using Pearson's analysis. Results SOX5 was predominantly expressed in the PBMCs of RA as compared with other SOX family genes in PBMC. PBMC levels of SOX5 in RA patients (21±19) were higher than the OA patients (10±8) and healthy control group (5±4)(F=8.343, P<0.01). While, Serum levels of SOX5 in RA patients [(19132±12054) pg/ml were higher than the OA patients [(9065±15172) pg/ml] and healthy control group [(3242±1251) pg/ml] (F=15.31, P<0.01). IL-6, TNF-α, IL-1β and IL-17 led to the up-regulation of SOX5 expression in PBMCs. IL-6, TNF-α, IL-1β promoted the interaction of SOX5 and RANKL in PBMCs. Silencing SOX5 reduced the formation of TRAP-positive cells in osteoclast precursor cell treated with RANKL. Conclusion Our results have proven that transcriptional factor SOX5 regulates the expression of RANKL and participates in the process of RA bone erosion. Inhibition of SOX5 expression may be a new therapy target of RA.