ObjectiveTo analyze the genomic characteristics of Streptococcus pyogenes (GAS) isolated from children with respiratory tract infections in a tertiary hospital in Jinshan District of Shanghai during 2013‒2024, to compare the changes in trend for genomic characteristics before and after 2000, and to provide scientific data for the prevention and control of GAS infections. MethodsGAS strains isolated from children with respiratory tract infections in this hospital were collected from 2013 to 2024. Antimicrobial susceptibility of the isolated strains to 12 antibiotics, including penicillin, cefotaxime, cefepime, linezolid, vancomycin, meropenem, chloramphenicol, ofloxacin, levofloxacin, erythromycin, clindamycin, and tetracycline, was determined using broth microdilution plate method. Besides, whole genome sequencing (WGS) was used to analyze multilocus sequence type (MLST), emm typing, carriage of superantigen genes, mobile genetic element (MGE), carriage of virulence gene, and genomic phylogenetic tree of the isolated strains. ResultsA total of 50 GAS strains were collected and identified from children with respiratory tract infections aged 4‒14 years old, and the resistance rates of those isolates to erythromycin, clindamycin, and tetracycline were 100.00%, 100.00%, and 86.00%, respectively. There were two emm types in the GAS isolates; the emm12 type accounted for 76.00% (38/50), corresponding to ST36 type, and the emm1 type accounted for 24.00% (12/50), corresponding to ST28, ST1274, and new-1 types. There was a statistically significant difference in the constitution of the MLST before and after 2020 (P=0.015). All the isolates carried the superantigen genes speC, speG, ssa, and smeZ. The predominant emm12 isolates belonged to the Clade Ⅱ, carrying the mobile elements ICE-emm12 (harboring erythromycin-resistance gene ermB and tetracycline-resistance gene tetM) and ΦHKU.vir (carrying virulence genes speC and ssa). The emm1 isolates carried the mobile elements ICE-HKU488 (harboring erythromycin-resistance gene ermB and tetracycline-resistance gene tetM) and ΦHKU488.vir (carrying virulence genes speC and ssa), and had close phylogenetical relationships with isolates from Hong Kong, China. No M1_UK new clone strains were found. The ST1274 isolates of emm1 were newly discovered in 2020‒2024, and belonged to a separate phylogenetic clade. ConclusionGAS strains isolated from children with respiratory tract infections in a tertiary hospital in Jinshan District of Shanghai exhibit a high resistance to erythromycin, clindamycin, and tetracycline. It is recommended that the clinical treatments change to use other antimicrobial drugs, such as penicillin, third-generation cephalosporins, and fluoroquinolones. During 2020‒2024, a new ST1274 clone strain is discovered in emm1 GAS isolates, without M1_UK new clone strains being found. It is essential to continuously concern locally prevalent GAS strains and perform early identification of MLST types to promptly monitor the internal changes of the bacterial population and potential prevalence of new clones.

Objective To explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P＜0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P＜0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.

OBJECTIVE: To construct an integrated management model for early screening and diagnosis of PCa based on the Innovative Care for Chronic Conditions Framework (ICCC) and the 1+1 contract-based tiered diagnosis and treatment system (TDTS) in China. METHODS: Based on the 1+1 contract-based TDTS platform, we conducted PCa screening for the male residents aged 60 years and above during health check-ups in Pujin Community Health Center from January 1, 2023 to December 31, 2023. For those with abnormal total prostate-specific antigen (tPSA) ≥ 4 μg/L, we promptly referred them to higher-level hospitals for further diagnosis and treatment via the two-way referral green channel platform and information sharing service using the 1+1 contract model. We further analyzed the relevant data on screening and diagnosis. RESULTS: A total of 4 080 males aged 71.39±5.059 years received PCa screening from January to December 2023. PSA screening was performed in 43.96% of the male residents, revealing 654 cases of PSA abnormality, with a PSA positivity rate of 16.03%, which was higher than that found in the previous large-scale PCa screenings in other regions of China. Among the males with PSA abnormality, 292 (44.65%) expressed their willingness for medical referral, while the others did not seek further medical attention for reasons of being asymptomatic, low awareness of the disease, no accompany for medical visits, and concerns about further costs of diagnosis and treatment. Prostate biopsy was recommended to 154 cases after further examinations, which was accepted by 92 (59.74%). Fifty-eight cases were diagnosed with Pa, and thedetection rate reached 63.04%. CONCLUSION The integrated management model for PSA examination-based early screening and diagnosis of PCa using the 1+1 contract-based TDTS platform is plays a significant role in enhancing people's awareness and knowledge of PCa and improving the early detection rate of the malignancy.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Early Detection of Cancer ; Prostate-Specific Antigen/blood* ; Aged ; China ; Mass Screening ; Middle Aged ; Chronic Disease

As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an ¹⁸F-labeled PET tracer (QTFT) that targets the P2Y₁₂, a receptor highly expressed on anti-inflammatory microglia. [¹⁸F]QTFT exhibited high binding affinity to the P2Y₁₂ (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [¹⁸F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y₁₂ antagonist. Furthermore, [¹⁸F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y₁₂ in anti-inflammatory microglia. In a pilot clinical study, [¹⁸F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [¹⁸F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y₁₂ overexpressed in anti-inflammatory microglia.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective To explore the mechanism of Xiakucao Xiaoliu Mixture against non-small cell lung cancer （NSCLC）. Methods The effective components of Xiakucao Xiaoliu Mixture were screened by TCMSP, BATMAN-TCM database and literature reviews. The targets of effective components were predicted. NSCLC related targets were collected by GeneCards, OMIM, PharmGKB, TTD and Drugbank, combined with the differential genes of Xiakucao Xiaoliu Mixture against Lewis lung cancer mice. The intersection targets of Xiakucao Xiaoliu Mixture against NSCLC were obtained. Cytoscape software was used to construct the network diagram of traditional Chinese medicine-active ingredients-core targets. STRING database was used to construct PPI network diagram. GO function enrichment analysis and KEGG pathway enrichment analysis of the intersection targets were performed by Metascape database to predict the key targets and active components of Xiakucao Xiaoliu Mixture against NSCLC, and Schrodinger software was used to perform molecular docking verification. Results The 32 active components and 24 intersection targets of Xiakucao Xiaoliu Mixture against NSCLC were obtained. 11 core targets such as ESR1, MAPK1 were found. The mechanism of action may be related to 30 signaling pathways such as cellular senescence, receptor activation, prolactin signaling pathway. Conclusion The active components of Xiakucao Xiaoliu Mixture act on multiple targets and signaling pathways to regulate complex biological processes. By regulating ESR1 agsinst NSCLC, it may play an important role in improving the survival rate and prognosis of female patients.

ObjectiveTo analyze the epidemiological characteristics of clustered vomiting and diarrhea outbreaks in Minhang District of Shanghai, to identify the influencing factors of outbreak scale and duration of epidemic, and to provide scientific evidence for further strengthening surveillance early-warning efforts in key settings and for optimizing prevention and control measures. MethodsThe data for describing epidemiological characteristics of clustered vomitting and diarrhea outbreaks in Minhang District from 2018 to 2023 were collected, multivariable logistic regression models were applied to analyze the influencing factors for epidemic scale,and Spearman rank correlation analyses were applied to analyze the factors duration. ResultsA total of 136 clustered vomiting and diarrhea outbreaks were reported in Minhang District from 2018 to 2023, all occurring in school settings, with an overall attack rate of 0.90%. The outbreaks exhibited distinct seasonality, predominantly occurring from October to December (43.38%) and March to May (32.35%). The primary settings were preschools (45.59%) and elementary schools (44.12%), with students accounted for the majority of cases (99.48%). The predominant clinical manifestation was vomiting (90.44%), with person-to-person contact being the primary transmission route (98.53%). Norovirus genogroup Ⅱ was identified as the main pathogen (71.32%). Standardized terminal disinfection of outbreak sites (OR=0.39, 95%CI=0.20‒0.74) and effective isolation of affected classes (OR=0.23, 95%CI=0.09‒0.57) were significant protective factors for reducing outbreak scale. Both response time (r=0.64, P<0.001) and the number of case generations (r=0.71, P<0.001) showed positive correlations with outbreak duration. ConclusionSchools are the key settings for the prevention and control of clustered vomiting and diarrhea outbreaks in Minhang District, with peak occurring in autumn and spring. Early detection, timely reporting, and prompt response to outbreaks are crucial. Strengthening school-based surveillance systems and standardizing outbreak management protocols are of particular importance.

ObjectiveTo develop a new mosquito trap and evaluate its effectiveness in Aedes albopictus monitoring in an urban community. MethodsThe first-round field test was conducted in a well-greened residential neighborhood with high Aedes albopictus density calculated by human landing catch in August 2022， in Minhang District， Shanghai. 65 new test containers with different designs were randomly deployed in the field. These trap containers were designed by different material， color， hole size， shape and top cover colors. The results of mosquito and its egg trapping were observed and recorded continuously for 7 days. In September 2022， the second round of experiment was conducted. After comparison， an optimized trap container was designed. 140 new trap containers were compared with 140 traditional ones to evaluate the effectiveness. SPSS 22.5 software was used for statistical analysis. ResultsThere were significant changes in the outcome of mosquito and its egg trapping on the 4th and 7th day of the pre-experiment deployment of the three kinds of containers. The 200 ml container cup with three round holes in the body had the best effect on trapping mosquitos and eggs， with a positive rate of 45.5% （5/11）， while other type of contrainer cup only had a positive rate of 12% （6/50） in trapping mosquitos and eggs. Statistical significant differences （χ²=45.443，P <0.001） existed between the two tpyes of cups within the first kind of trapping container. The second kind of trapping container showed round and oval holes had better effect on mosquito trapping， with a positive rate of 55.6% （5/9）. The third kind of hanging container can resist strong wind. The best mosquito trapping effect of three round holes was 66.7% （2/3）. The container wall should not be made of rough material， which was easy to cause the escape of adult mosquitoes. Combined with the three types of containers， the new contariner should be top transparent， and the top 1/3 of the side should paint black with 3 round holes. The effective recovery rate of the new container was higher than that of the traditional one under the exclusion of human factors， and had the advantage of preventing rain， wind and rollover， but the effect of trapping mosquito and its egg was comparable to the traditional one（χ²_D4=0.197，P=0.658； χ²_D7=0.125 ，P=0.724）. ConclusionThis new type of mosquito trap is worth further exploration and research， which can improve the trapping efficiency， overall recovery rate and the accurate confirmation of the mosquito density.

ObjectiveTo determine the epidemiological characteristics and risk factors of a norovirus GII.17 outbreak in Minhang District of Shanghai in 2018， and provide evidence for prevention and control measures of norovirus infection. MethodsDescriptive epidemiological analysis was performed. In addition， a retrospective cohort study was conducted to determine the risk factors. ResultsFrom May 30^th to June 1^st of 2018， a total of 132 cases （126 clinical cases and 6 confirmed cases） were documented，with an attack rate of 29.20%（132/452）.All cases were children in a kindergarten， with the average age of 5 years and 43.9% being male. The cases were reported in all the classes， with no clustering by class or floor．The epidemic curve was characterized by a point source exposure， which was estimated to be probably between 7 AM on May 30^thand 0：30 AM on May 31^st. The retrospective cohort study showed that the attack rate significantly differed between the children who had taken and did not take the school lunch （RR=∞） on May 30^th，and those who had taken and did not take seafood noodles （RR=4.11， 95%CI：1.09-15.55） （P<0.05）. Among a total of 73 specimens， six specimens collected in child cases and one specimen in an asymptomatic chef tested positive for GII.17 type of norovirus. In addition， one retained food specimen of seafood noodles was positive for Aeromonas hydrophila. Viral shedding in the asymptomatic chef remained over 30 days. ConclusionThe outbreak was caused by seafood noodles contaminated by norovirus. It warrants enhancement in the regulation of food safety in canteens and regular examination of norovirus infection in catering industry employees.

ObjectiveThis study aimed to understand the epidemiological characteristics of hand-foot-mouth disease （HFMD） in Minhang District， Shanghai from 2009 to 2020， and provide a scientific basis for the prevention and control of HFMD. MethodsThe case information of HFMD was collected from the National Notifiable Infectious Diseases Reporting System of Chinese Center for Disease Control and Prevention. We used descriptive epidemiological methods to analyze the population characteristics， temporal and spatial distribution of HFMD， the pathogen composition of the case and its changing trend. ResultsFrom 2009 to 2020， a total of 66，198 cases of HFMD were reported in Minhang District， Shanghai， including 377 severe cases （severe case rate 0.57%） and 3 deaths （severs case fatality rate 0.80%）. There were more cases of HFMD in boys than in girls （1.5∶1）. HFMD patients aged under 5 years predominated， accounting for 88.91% of all cases. Majority of the cases （91.42%） were in scattered children （55.80%） and children in kindergartens （35.62%）. The incidence showed a cyclical trend， with low incidence years and high incidence years appearing alternately. The peak period was from April to July， and sometimes there were small peaks during October to December. A total of 12 years time-space scanning analysis revealed 3 clusters. The cluster centers were located in Wujing Town， Huacao Town and Xinzhuang Town， respectively. The proportion of EV71 in common cases was generally decreasing， and reduced to zero in 2019. The proportion of CoxA6 had increased year by year， and reached 75.00% in 2020. CoxA6 became the dominant pathogen in recent years. The number of severe cases had decreased year by year since 2010， and the dominant pathogen was EV71 （90.03% on average） in severe cases. ConclusionThe incidence of HFMD in Minhang District of Shanghai has a downward trend from 2014. The dominant pathogen changes from EV71 to CoxA6， and the dominant pathogen in severe cases is EV71. The discovered temporal and spatial clustering pattern is helpful for in-depth understanding of the distribution and epidemic trend of HFMD in Minhang District， and provides a scientific basis for epidemic prevention and control.