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.

AIM: To observe related influence of eye-use behaviors on the onset and progression of myopia among primary school student in Minhang district, Shanghai under the background of “double reduction”, and evaluate the impact of eye-use habit and behavior on the myopia development in children and adolescents.METHODS:A stratified cluster sampling method was adopted to select study subjects for longitudinal observation. Random sampling was conducted among grade 1-4 students from three primary schools in Minhang District, Shanghai from September to December 2021 after the implementation of the “double reduction” policy, with a 2-year observation period. Annual vision screenings were performed to obtain uncorrected visual acuity, non-cycloplegic refraction data, and spherical equivalent(SE). Biometric measurements were taken to acquire axial length(AL)and corneal curvature(CR). Questionnaires were administered to investigate the eye-use behaviors of participants. Taking myopia ≤-0.50 D as the diagnostic criterion, myopia incidence were calculated. SE and AL changes were used to evaluate myopia progression. Logistic regression analysis was employed to identify risk factors for myopia, and analyze the relationship between eye-use behaviors and myopia development or progression.RESULTS:A total of 2 986 children complete a follow-up for 2 a. The baseline prevalence of poor vision was 32.74%, increasing to 38.92% and 43.73% at 1 and 2 a follow-up, respectively, demonstrating a yearly upward trend. Taking uncorrected visual acuity combined with non-cycloplegic refraction as clinical screening criteria for myopia, the incidence was 24.72%, 27.60%, and 29.64% at baseline, 1, and 2 a follow-ups, respectively. These showed no statistical significant difference compared to the diagnostic standard of cycloplegic refraction SE(23.98%, 27.03%, and 29.17%; all P>0.05). Logistic regression analysis found that daily outdoor and sleep duration were protective factors against myopia(OR=0.54, 0.84, all P<0.05), while age, parental myopia, duration of offline education, online education, electronic device usage, and poor visual posture were identified as risk factors(OR=2.72, 1.54, 1.72, 1.12, 1.47, 1.26, all P<0.001). Further analysis of myopia progression in baseline myopic children over 2 a revealed that age, parental myopia, baseline SE, duration of offline/online education, electronic device usage, and poor visual posture may contribute to rapid myopia progression.CONCLUSION:Under the background of “double reduction”, the eye-use behavior among primary school students in Minhang District, Shanghai has an important impact on the occurrence and development of myopia. In order to effectively prevent and control myopia, it is necessary to further strengthen the education and guidance of eye-use behavior.

Objective To investigate the effect of hemoglobin A1c variability on the incidence of malignant tumors in type 2 diabetes mellitus (T2DM) patients, and to provide a reference for the prevention and treatment of diabetes. Methods A retrospective cohort study was used to integrate Shanghai malignant tumor registration information and T2DM patient management information of Minhang Districts in Shanghai. A record linkage was carried out using ID numbers for patients who had been diagnosed through the Cancer Registry System. Average Real Variability（ARV）was used to assess the variability for hemoglobin A1c results, with no less than 3 measurements and no more than 1 follow-up visit per year. Cox proportional hazards regression models and Restricted Cubic Splines (RCS) were used for statistical analysis. ARV was grouped using quartile classification, represented by Q1, Q2, Q3, and Q4, respectively. Cox regression was performed using unadjusted model I and model II adjusted for gender, age, and group. Results A total of 2 762 research subjects were included in the present study, with 45.84% males and 54.16% females. The average age was (63.58±10.11) years, and an average follow-up time was (9.96±3.66) years. Malignant tumor incidence rate was 345.45/100 000 person years. There was statistical significance among different ARV groups (P=0.01). COX regression analysis of model I and model II showed that compared with Q1, the risk of Q4 group was significantly increased, with HRs of 2.72 (1.56-4.74) and 2.68 (1.53-4.68), respectively. The RCS graph's analysis showed that except for the ≥65-year-old group, the risk of tumor incidence gradually increased with the increase of ARV coefficient. Conclusion The variability of hemoglobin A1c is positively associated with the risk of occurrence of malignant tumors in type 2 diabetes patients. It is necessary to strengthen the monitoring of hemoglobin A1c and to reduce the health hazards caused by fluctuations in hemoglobin A1c.

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 explore serological detection and blood transfusion strategies of mimicking antibodies, so as to provide appropriate transfusion strategies. METHODS: Detailed serological tests, including ABO blood group, Rh typing, antibody specificity, etc,were performed on two patients with autoimmune hemolytic anemia(AIHA). Meanwhile, the references about blood transfusion from mimicking antibody patients published from 1977 to 2024 in China and abroad were retrospectively summarized and analyzed. RESULTS: The patient 1 blood type was AB,CCDee and the antibody is mimicking anti-e, transfusion the e-negative red blood cells (RBCs) was effective. After two transfusions of e-RBCs, hemoglobin levels significantly increased from 48 g/L to 91 g/L, with complete resolution of hemolytic symptoms. The patient 2 blood type was O,CcDee, and the antibody was mimicking anti-c, the patient was diagnosed with AIHA and treated with hormone. No blood products were transfused during hospitalization, and his hemolysis was relieved. CONCLUSION Strictly grasping the indication of blood transfusion, blood transfusion should not be performed in the unnecessary conditions, and the corresponding antigen-negative RBC should be screened for transfusion in the necessay conditions.
Humans ; Blood Transfusion ; Anemia, Hemolytic, Autoimmune/therapy* ; ABO Blood-Group System ; Retrospective Studies ; Antibodies ; Male ; Blood Grouping and Crossmatching

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

OBJECTIVE: To assess the efficacy and safety of Erzhu Jiedu Decoction (EZJDD) Granules in treating mid-advanced hepatitis B virus-associated primary liver cancer (HBV-PLC) patients with Pi (Spleen)-deficiency and dampness-heat syndrome. METHODS: From January 2021 to June 2023, a cohort of 132 patients were enrolled and randomly assigned to a control group or a EZJDD group according to the random numbers, with 66 patients in each group. The patients in the control group received conventional treatment for 3 months, followed by a 3-month follow-up. In addition to the conventional treatment, patients in the EZJDD group were administered EZJDD Granules (10.9 g/pack, 2 packs twice per day) orally for same duration. Progression-free survival (PFS) as primary outcome was evaluated by Kaplan Meier method. Karnofsky performance status (KPS) scores were used to assess the quality of life in two groups before and after treatment, and survival rates were determined as well. The efficacy of Chinese medicine syndrome was calculated with Nimodipine method. Liver function, tumor indicators and T lymphocyte subsets were measured, respectively. Safety indicators were recorded and assessed. RESULTS: Of the 116 patients who completed the study, 57 were in the control group and 59 in the EZJDD group. The median PFS was 3.53 months (106 days) in the EZJDD group compared to 2.33 months (70 days) in the control group (P=0.005). Six-month survival rate was 52.63% (30/57) in the control group and 69.49% (41/59) in the EZJDD group (P=0.039). The median KPS score in the EZJDD group [70(63, 90)] was higher than that in the control group [70(60, 80)] (P=0.013). The total effective rate of CM syndrome was 52.63% (30/57) in the control group and 77.97% (46/59) in the EZJDD group (P=0.005). The levels of alpha fetoprotein, alpha fetoprotein-L3, alpha-L-fucosidase and protein induced by Vitamin K absence or antagonist- II in the EZJDD group increased less than the control group (P>0.05). CD8⁺ levels were decreased, while CD3⁺ and CD4⁺ levels, as well as CD4⁺/CD8⁺ ratio were significantly increased in the EZZJD group (P<0.05). No treatment-related adverse reactions were observed during the study. CONCLUSION EZJDD Granules significantly prolonged the median PFS and improved 6-month survival rate in patients with mid-advanced HBV-PLC (Registration No. ChiCTR2200056922).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/complications* ; Hepatitis B virus/physiology* ; Hepatitis B/complications* ; Treatment Outcome ; Adult ; Spleen/drug effects* ; Quality of Life ; Medicine, Chinese Traditional ; Aged ; Syndrome

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.

Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α _v β ₃ because of the multivalent interactions between larger active nanoparticles and integrin α _v β ₃. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.

Aralia taibaiensi, widely distributed in western China, particularly in the Qinba Mountains, has been utilized as a folk medicine for treating diabetes, gastropathy, rheumatism, and cardiovascular diseases. Saponins from A. taibaiensis (sAT) have demonstrated protective effects against oxidative stress and mitochondrial dysfunction induced by ischemia/reperfusion (I/R). However, the underlying mechanisms remain unclear. In vivo, middle cerebral artery occlusion/reperfusion (MCAO/R) induced inflammatory infiltration, neuronal injury, cell apoptosis, mitochondrial dysfunction, and oxidative stress in the ischaemic penumbra, which were effectively mitigated by sAT. sAT increased the mRNA and protein expression levels of apelin and its receptor apelin/apelin receptors (ARs) both in vivo and in vitro. (Ala13)-Apelin-13 (F13A) and small interfering RNA (siRNA) abolished the regulatory effects of sAT on neuroprotection mediated by adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/protein kinase B (Akt). Furthermore, sAT induced apelin/AR expression by simultaneously inhibiting P38 mitogen-activated protein kinase (P38 MAPK)/activating transcription factor 4 (ATF4) and upregulating hypoxia-inducible factor-1α (HIF-1α). Our findings indicate that sAT regulates apelin/AR/AMPK by inhibiting P38 MAPK/ATF4 and upregulating HIF-1a, thereby suppressing oxidative stress and mitochondrial dysfunction.
Animals ; Reperfusion Injury/prevention & control* ; Aralia/chemistry* ; Saponins/administration & dosage* ; AMP-Activated Protein Kinases/genetics* ; Male ; Apelin/genetics* ; Signal Transduction/drug effects* ; Neuroprotective Agents/administration & dosage* ; Brain Ischemia/genetics* ; Rats, Sprague-Dawley ; Rats ; Oxidative Stress/drug effects* ; Apelin Receptors/genetics* ; Humans ; Apoptosis/drug effects* ; Mice