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.

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

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Aim To investigate the effect of linarin on improving cognitive behavior of APP/PS1 mice,and to explore the therapeutic effect of linarin on A β deposi-tion and neuroinflammation and its correlation.Meth-ods APP/PS1 transgenic mice were randomly divid-ed into the model group,high-dose group,medium-dose group,low-dose group and positive control group.C57BL/6J mice were set as the normal group.Morris water maze was used to evaluate the learning and mem-ory abilities of mice.TUNEL staining was used to de-tect the apoptosis of neurons in the CA1 region of mice.IHC was used to detect the expression levels of Aβ42 and GFAP.Western blot was used to detect the expression levels of BACE1 and PS-1.Results Com-pared with the normal group,mice of the model group showed lower NCP,shorter target quadrant travel,less target quadrant residence time percentage(all P＜0.01),higher apoptosis rate of neurons in the CA1 re-gion(P＜0.01),significantly higher protein expres-sion levels of A β42 and GFAP(all P＜0.01),and significantly higher protein expression levels of BACE1 and PS-1(all P＜0.01).Compared with the model group,the medium-dose group,high-dose group and positive control group showed higher NCP,longer tar-get quadrant travel,more target quadrant residence time percentage(all P＜0.05),lower apoptosis rate of neurons in the CA1 region(P＜0.01),significantly lower protein expression levels of A β42 and GFAP(all P＜0.01),and significantly lower protein expression levels of BACE1 and PS-1(all P＜0.01).Conclu-sions Linarin can inhibit two key enzymes to reduce the decomposition of APP and the generation of A β42,thereby inhibiting the activation of astrocytes,allevia-ting neuroinflammation,improving the core pathologi-cal features of AD,and thus significantly improving learning and memory impairment in APP/PS1 mice.

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

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

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 explore the construction of an evaluation model for aortic root anatomy and calcium burden in patients with bicuspid aortic valve (BAV) stenosis before transcatheter aortic valve replacement (TAVR) based on deep learning (DL) algorithms.Methods:A retrospective collection of 362 BAV stenosis patients who underwent TAVR from September 2023 to May 2024 was performed. All patients underwent cardiac CT angiography. The patients were divided into training group ( n=104), internal validation group ( n=206), and external validation group ( n=52). A DL model was trained on the training dataset to assess aortic root anatomy and calcification burden. The evaluation included the segmentation accuracy of the algorithm, the measurement performance of key anatomical structures (i.e., valve leaflets and type-1 and type-2 fusion raphe), and calcification burden, as well as the measurement efficiency. Overall segmentation performance was assessed using the average Dice coefficient (ADC). The fine-scale segmentation quality was validated by the 95th-percentile Hausdorff distance (HD-95) and the average symmetric surface distance (ASSD). The consistency of the measurement results was assessed using the Pearson correlation coefficient and the intraclass correlation coefficient ( ICC) with a two-way mixed model for absolute agreement. In addition, the total time and total mouse movement distance required for manual assessment versus the DL model on the validation datasets were recorded and compared. Results:The algorithm demonstrated excellent segmentation performance on aortic root anatomical targets, achieving outstanding consistency within both internal and external validation datasets (0.955