ObjectiveTo investigate the current awareness and optimization recommendations on pneumonia with unknown etiology (PUE) surveillance among Shanghai healthcare professionals, and to provide evidence for the improvement of the surveillance system. MethodsIn December 2024, healthcare professional participants from diverse medical and health institutions were randomly selected within each stratum using a stratified cluster sampling method in all 16 districts of Shanghai for questionnaire surveys on their knowledge and suggestions for optimization of the PUE surveillance system. Descriptive statistics analyses, multivariate logistic regressions, and content analyses were used for data analyses. ResultsA total of 385 survey subjects were involved in the study, including 119 professional staffs from disease prevention and control centers and 266 from medical institutions. Those who understood the case definition for PUE correctly accounted for 67.01% (258/385). Multivariate regression model analyses showed that female gender (aOR=2.22, 95%CI: 1.36‒3.66), professionals from disease control institutions (aOR=2.02, 95%CI: 1.12‒3.72), and those who self-assessed as being familiar with the monitoring system (aOR=2.18, 95%CI:1.23‒3.89) had better understanding of the definition. Overall, 89.61% (345/385) of the survey subjects acknowledged the necessity of the surveillance system. Small number of cases meeting the case definition (54.46%, 214/379), insufficient diagnostic awareness (39.84%, 151/379), and lack of incentives for case reporting (29.29%, 111/379) were major problems for the current surveillance system, with variations observed across different types of institutions. Suggested segments for optimizing the surveillance system included monitoring purpose, case definition, form of monitoring and reporting procedure, organization mechanism, and epidemiological investigation and response. ConclusionThe necessity of PUE surveillance is commonly recognized among healthcare workers. However, the existing system falls short in terms of mastery of case definition and overall surveillance adaptability. There is an urgent need for optimization and improvement to enhance the capacity for preventing and controlling emerging and sudden respiratory infectious diseases.

BACKGROUND: Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process. METHODS: DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 - T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice. RESULTS: CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 - T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice. CONCLUSION The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
Animals ; T-Lymphocytes, Regulatory/immunology* ; Dendritic Cells/immunology* ; Mice ; Mice, Inbred BALB C ; Membrane Proteins/metabolism* ; Receptors, Notch/metabolism* ; Lymphoid Tissue/metabolism* ; Signal Transduction/physiology* ; Coculture Techniques ; Flow Cytometry

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective:To analyze the incidence trends of malignant tumors in the elderly population aged over 60 years in Qidong City from 1972 to 2021, as well as to predict the incidence rate for the next decade.Methods:Data were obtained from the Qidong Cancer Registry and Reporting System.The crude incidence rate(CR), age-standardized incidence rate using the Chinese standard population(ASRC), and age-standardized incidence rate based on Segi's world standard population(ASRW)were calculated.Joinpoint regression analysis was conducted using Joinpoint 4.9.1.0 software to determine the average annual percentage change(AAPC)in incidence.Additionally, the ARIMA model implemented in SAS 9.2 software was utilized for time series analysis to forecast incidence trends over the forthcoming 10 years.Results:In Qidong City, a total of 87, 401 malignant tumors were reported in the elderly population.The ASRW increased from 736.85 per 100, 000 in the years 1972-1976 to 1 056.33 per 100, 000 in 2017-2021.Specifically, the ASRW for males rose from 968.56 per 100, 000 to 1 332.75 per 100, 000, while the ASRW for females increased from 550.62 per 100, 000 to 825.44 per 100, 000, with AAPC values of 1.16%, 0.94%, and 1.44% over 50 years(all P<0.001).The incidence trend exhibited an upward trajectory with age, peaking in the 75-79 age group.The AAPC values for the incidence rates in the age groups of 60-64, 65-69, 70-74, 75-79, and those aged over 80 were 0.64%, 0.93%, 0.92%, 2.02%, and 2.44%, respectively(all P<0.001).Among the various cancers, lung cancer, which ranked first, saw an increase in ASRW from 100.87 per 100, 000 in 1972-1981 to 248.84 per 100, 000 in 2012-2021.In contrast, gastric cancer, ranked second, decreased from 216.23 per 100, 000 in 1972-1981 to 103.54 per 100, 000 in 2012-2021.Liver cancer, ranked third, fluctuated from 113.47 per 100, 000 in 1972-1981 to 125.13 per 100, 000 in 2012-2021.Colorectal cancer, ranked fourth, increased from 40.06 per 100, 000 in 1972-1981 to 123.47 per 100, 000 in 2012-2021, while esophageal cancer, ranked fifth, decreased from 63.42 per 100, 000 in 1972-1981 to 28.65 per 100, 000 in 2012-2021.The AAPC values over 50 years for these cancers were 2.25%, -1.89%, 0.36%, 3.13%, and -1.86%, respectively(all P<0.05).Projections indicate that by 2031, the incidence of malignant tumors among the elderly population in Qidong will reach 1 253.84 per 100, 000, with estimates of 1 566.67 per 100, 000 for males and 983.14 per 100, 000 for females. Conclusions:The incidence of malignant tumors among the elderly population in Qidong City is increasing.Common types of cancer in this demographic include lung cancer, gastric cancer, liver cancer, colorectal cancer, and esophageal cancer.Notably, lung cancer, liver cancer, and colorectal cancer are on the rise and should be prioritized in cancer prevention and control efforts.

Objective:To analyze the drug resistance and virulence characteristics of KPC-2-producing carbapenem-resistant Klebsiella pneumoniae(CRKP). Methods:A total of 26 non-repeating CRKP strains clinically isolated from a Class Ⅲ hospital in Kunming from August 2021 to March 2022 were collected. Mass spectrometry and the VITEK 2 Compact system were used to identify the bacteria and perform drug susceptibility tests. PCR was used to amplify the drug resistance and virulence genes carried by the strains. These CRKP strains were divided into a hypervirulent CRKP(CR-hvKP) group and a CR-non-hvKP group according to the characteristic virulence genes of hypervirulent Klebsiella pneumoniae. The virulence phenotypes of CRKP were investigated by wire drawing test, serum resistance test and siderophore qualitative and quantitative tests. The whole genomes of CRKP-67 (a CR-hvKP strain) and CRKP-94 (a CR-non-hvKP strain) were sequenced by the Illumina high-throughput sequencing platform, to further analyze the drug resistance genes, virulence genes, and virulence plasmidds carried by the strains. Results:The drug sensitivity results indicated that all 26 strains were resistant to carbapenem, cephalosporins, fluoroquinolones and β-lactam/β-lactam inhibitor complexes. The resistance rates to amicacin, cotrimoxazole and gentamicin were 61.54%(6/26), 57.69%(15/26) and 73.08%(9/26), respectively. Regarding the drug resistance gene amplification results, the carrying rates of blaKPC-2, blaNDM-1, blaOXA-48, blaVIM, blaIMP, blaSME, blaSHV, blaCTX-M and blaTEM were 100.00%(26/26), 0, 0, 0, 0, 100.00%(26/26), 100.00%(26/26), 15.38% (4/26) and 73.08%(19/26), respectively. In the 26 strains, the carrying rates of toxic genes entB, entC, ureA, uge, wabG, ycf, irp1, irp2, mrkD, fimH and ybtS were 100.00%(26/26), while the carrying rates of virulence genes kfuB, iroN, aero, magA and alls were 0. The positive rate of string test was 66.7%(6/9) in the CR-hvKP group and 0 in the CR-non-hvKP group. The serum killing test showed a high sensitivity rate of 77.78%(7/9), a low sensitivity rate of 11.11%(1/9), and a serum resistance rate of 11.11%(1/9) in the CR-hvKP group. In the CR-non-hvKP group, the high sensitivity rate was 29.41%(5/17); the low sensitivity rate was 17.65%(3/17), and the serum resistance rate was 52.94%(9/17). There was no statistical significance between the two groups( P>0.05). The qualitative results of siderophore showed that all strains produced yellow chelating circles with slightly different color depth and size. The quantitative results of siderophore experiment showed that the average siderophore production level of CR-hvKP group was 40.74%, and that of CR-non-hvKP group was 28.21%. The level was higher in the CR-hvKP group than in the CR-non-hvKP group, and the difference was statistically significant( P<0.05). Whole-genome sequencing results showed that CRKP-67 was ST11 type and contained 3 plasmids. Among them, plasmid pCRKP-67-A carried a series of virulence genes, including iucABCD, iutA, rmpA, rmpA2, iroB and peg344, which were highly virulent characteristic genes. Plasmid pCRKP-67-B carried blaKPC-2, blaCTX-M, blaSHV, blaTEM and other drug-resistant genes. Plasmid pCRKP-67-C carried sul2, tetR, tetA and other drug-resistant genes. The CRKP-94 was of ST340 type and contained a drug-resistant plasmid carrying blaKPC-2, blaCTX-M, blaSHV, blaTEM and other drug-resistant genes. Conclusions:CRKP strains are highly resistant, and are only sensitive to a few antibiotics, and carry a variety of drug resistance genes. The main resistance mechanism to carbapenem antibiotics is the presence of the blaKPC-2 gene, which is located on the plasmids, which results in the spread of carbapenem resistance. The types and quantity of virulence genes carried by the CR-hvKP strain are more and greater respectively than those carried by the CR-non-hvKP strain. The co-existence of drug-resistant and virulence plasmids in CR-hvKP strains may lead to the co-transmission of high drug resistance and hypervirulence, which should be highly valued by relevant departments.

Objective:To evaluate the detection rate, anatomical distribution, and influencing factors of bone marrow edema-like signal (BMELS) in the knees of amateur marathon runners.Methods:This was a cross-sectional study. This study publicly recruited amateur marathon runners through the Hangzhou Long-distance Running Association from January 2019 to December 2024. Based on knee magnetic resonance imaging (MRI) results, participants were divided into a BMELS-positive group (BMELS present in at least one knee) and a BMELS-negative group. General clinical information was collected from participants using a questionnaire. All participants underwent a knee MRI scan to screen for the presence of BMELS and to assess its severity. Logistic regression models were used to analyze the associated factors of BMELS in amateur marathon runners, while Spearman′s correlation analysis assessed the correlation between BMELS grade and these factors.Results:A total of 60 subjects (120 knee joints) were enrolled, including 39 males (65%), aged (40.0±8.4) years. Of these, 39 were in the BMELS-positive group, and 21 were in the BMELS-negative group. The BMELS detection rate for the 120 knee joints of these 60 subjects was 53.3% (64/120). BMELS were detected in 43.3%(52/120) of the femur, 34.2% (41/120) of tibia and 17.5% (21/120) of patella. Multivariate logistic regression analysis showed an independent positive correlation between monthly running volume and knee BMELS in amateur marathon runners ( OR=1.007, 95% CI: 1.000-1.013, P=0.035). Spearman′s correlation analysis showed a weak positive correlation between the BMELS grade of the knees and the monthly running volume of amateur marathon runners ( r s=0.360, P=0.005). Conclusions:The detection rate of knee BMELS is high in amateur marathon runners, and they are distributed in a way that is characteristic of the region, with a higher incidence in the medial femoral condyle. In this population, monthly running volume is independently associated with knee BMELS, with a higher grade associated with greater monthly running volume.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To observe the effects of general anesthesia with remazolam on electrophysiological monitoring indicators and cerebral oxygen saturation(ScO2)in patients undergoing carotid endarterectomy(CEA).Methods Patients who underwent elective CEA from July 2022 to June 2024 in neurosurgery department of our hospital were randomly divided into the ramazolam group(R group)and the propofol group(P group).Patients in both groups were given propofol 1.5 to 2.0 mg/kg,cisatracurium 0.1 to 0.2 mg/kg,and sufentanil 0.3 to 0.4 μg/kg for anesthesia induction.Anesthesia maintenance:patients in the R group received intravenous infusion of remifentanil 0.5 to 1.0 mg·kg-1·h-1,while patients in the P group received intravenous infusion of propofol 5.0 to 7.0 mg·kg-1·h-1.Both groups received intravenous infusion of remifentanil 0.1 to 0.2 μg·kg-1·min-1 for anesthesia maintenance.The operation time,carotid artery occlusion time,intraoperative infusion volume,remifentanil and norepinephrine dosage,and awakening time of patients in the two groups were recorded.The hemodynamic and cerebral oxygen indicators,amplitude and latency of evoked potentials before anesthesia(T0),after anesthesia(T1),5 minutes before blockade(T2),5 minutes after blockade(T3),5 minutes after unblocking(T4)and at the end of surgery(T5)of patients in the two groups were observed and compared,and the total incidence of postoperative complications was followed up and calculated.Results Compared with the P group,the dosage of intraoperative norepinephrine of patients in the R group was reduced(P<0.05),and the awakening time was shortened(P<0.05).At T2,the average arterial pressure(MAP)of patients in the R group was higher than that in the P group(P<0.05).At T3,the ScO2 of patients in the R group was significantly higher than that in the P group,and the percentages of prolonged latency and decreased amplitude of motor evoked potentials(MEP)were significantly lower than those in the P group(P<0.05),the percentage of decreased amplitude of lower limb somatosensory evoked potentials(SSEP)was lower than that in the P group(P<0.05);At T5,the MEP amplitude of patients in the R group was significantly increased compared to that at T2,while the MEP amplitude of patients in the P group was significantly decreased compared to that at T2,and the differences were statistically significant(P<0.05).There was no statistically significant difference in the total incidence of postoperative complications between the two groups(P>0.05).Conclusion As a general anesthesia maintenance drug,remazolam can achieve satisfactory anesthesia effects for CEA,with more stable intraoperative hemodynamics,and less impact on ScO2 and evoked potential monitoring during carotid artery occlusion compared to propofol,resulting in higher safety.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP