Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.

The histological assessment has been considered as a detailed and accurate method for measuring the disease activity in inflammatory bowel disease(IBD).In ulcerative colitis(UC),histological activity has been demon-strated to be associated with a higher rate of relapse,prolonged corticosteroid use and long-term complications,even in patients who have achieved endoscopic remission.Therefore,histological remission may be regarded as a potential ther-apeutic target.This article introduces the clinical significance of disease activity assessment in IBD,focusing on the re-view of validated and newly proposed histological scoring systems for IBD,and explores the priorities for future research needs.

Objective To investigate the impact of gaseous pollutants (SO2,NO2,CO,O3) on hospital admissions,hospitalization costs,and length of stay for cardiovascular diseases in seven cities of Guangdong Province. Methods A total of 2,010,905 patients with cardiovascular diseases from seven cities in Guangdong Province between January 2017 and December 2019 were included. Demographic characteristics and hospitalization data for cardiovascular disease inpatients were obtained from the Guangdong Province Electronic Healthcare Information System. Daily exposure concentrations of SO2,NO2,CO and O3 were extracted from the China High-Air-Pollution Dataset. The impact of air pollutants on cardiovascular diseases in the seven cities of Guangdong Province was estimated using a multi-step time-series analysis. Results SO2,NO2,and CO concentrations on the day of admission (lag0) were positively associated with the risk of cardiovascular admissions,hospitalization costs,and length of stay,with NO2 exhibiting the strongest effect. Additionally,there was a lagged negative impact of NO2 and CO,while O3 concentrations were inversely correlated with the number of cardiovascular admissions,hospitalization costs,and length of stay over the lag0-7 period. Conclusions Short-term exposures to SO2,NO2,and CO are likely positively associated with the disease burden in CVD patients. Furthermore,given the more substantial adverse effects of NO2,enhanced monitoring of NO2 remains essential. However,as this study is retrospective,additional research is warranted.

The histological assessment has been considered as a detailed and accurate method for measuring the disease activity in inflammatory bowel disease(IBD).In ulcerative colitis(UC),histological activity has been demon-strated to be associated with a higher rate of relapse,prolonged corticosteroid use and long-term complications,even in patients who have achieved endoscopic remission.Therefore,histological remission may be regarded as a potential ther-apeutic target.This article introduces the clinical significance of disease activity assessment in IBD,focusing on the re-view of validated and newly proposed histological scoring systems for IBD,and explores the priorities for future research needs.

Objective To investigate the impact of gaseous pollutants (SO2,NO2,CO,O3) on hospital admissions,hospitalization costs,and length of stay for cardiovascular diseases in seven cities of Guangdong Province. Methods A total of 2,010,905 patients with cardiovascular diseases from seven cities in Guangdong Province between January 2017 and December 2019 were included. Demographic characteristics and hospitalization data for cardiovascular disease inpatients were obtained from the Guangdong Province Electronic Healthcare Information System. Daily exposure concentrations of SO2,NO2,CO and O3 were extracted from the China High-Air-Pollution Dataset. The impact of air pollutants on cardiovascular diseases in the seven cities of Guangdong Province was estimated using a multi-step time-series analysis. Results SO2,NO2,and CO concentrations on the day of admission (lag0) were positively associated with the risk of cardiovascular admissions,hospitalization costs,and length of stay,with NO2 exhibiting the strongest effect. Additionally,there was a lagged negative impact of NO2 and CO,while O3 concentrations were inversely correlated with the number of cardiovascular admissions,hospitalization costs,and length of stay over the lag0-7 period. Conclusions Short-term exposures to SO2,NO2,and CO are likely positively associated with the disease burden in CVD patients. Furthermore,given the more substantial adverse effects of NO2,enhanced monitoring of NO2 remains essential. However,as this study is retrospective,additional research is warranted.

Objective:To investigate the pathogen distribution, temporal trends in the rates of antimicrobial resistance, and susceptibility of bloodstream isolates and comparatively explore the epidemiological characteristics of bloodstream infections in hematology departments across 56 healthcare facilities in Guangdong Province from 2020 to 2024.Methods:A multicenter analysis was conducted to evaluate the constituent ratio of different pathogens isolated from clinical isolate data from bloodstream specimens in hematology, respiratory, and intensive care unit (ICU) departments across 56 healthcare facilities in Guangdong Province (2020-2024), and antimicrobial resistance trends in pathogens with high-detection rate over 5 years were assessed. Carbapenem-resistant Gram-negative organisms (CRO) were randomly sampled for carbapenemase gene detection and in vitro antimicrobial susceptibility tests with novel antimicrobial agents.Results:From 2020 to 2024, a total of 8 968, 6 440, and 25 511 bloodstream isolates were identified in the hematology, respiratory, and ICU departments, respectively, across 56 participating facilities in Guangdong Province, with significant differences in the pathogen constituent ratio among departments ( P<0.001). Notably, the hematology department demonstrated a predominance of Escherichia coli (24.1%), Klebsiella pneumoniae (17.5%), Pseudomonas aeruginosa (11.7%), coagulase-negative Staphylococci (15.2%), and Staphylococcus aureus (5.1%). In the resistance analysis, the rates of meropenem resistance of Escherichia coli and Klebsiella pneumonia increased from 6.7% and 5.8% (2020) to 14.0% and 15.8% (2024), respectively. Conversely, Pseudomonas aeruginosa exhibited a declining trend in the rate of meropenem resistance (6.2% to 1.9%) and imipenem (10.2% to 6.1%) during the same period. Acinetobacter baumannii demonstrated a biphasic resistance pattern to common antimicrobial agents, characterized by an initial decline, followed by a rebound. In this study, the susceptibility rates to conventional antimicrobial agents were significantly higher in Staphylococcus aureus versus coagulase-negative Staphylococci, with no glycopeptide- or linezolid-resistant strains detected. Notably, the prevalence of vancomycin-resistant Enterococcus faecium increased from 0 in 2020 to 23.1% in 2024. CRO carbapenemase phenotypes through active surveillance revealed that 80% Escherichia coli isolates were carrying blaNDM, 90% Klebsiella pneumoniae isolates were carrying blaKPC, 10% Pseudomonas aeruginosa isolates were carrying blaVIM, and 100% Acinetobacter baumannii were carrying blaOXA-23. The results of the antimicrobial susceptibility test in CRO revealed that carbapenem-resistant Escherichia coli (CRECO) demonstrated a 0 resistance rate to tigecycline, polymyxin B, and aztreonam/avibactam, whereas carbapenem-resistant Klebsiella pneumoniae exhibited a 0 resistance rate to aztreonam/avibactam, ceftazidime/avibactam, and imipenem/relebactam. Carbapenem-resistant Pseudomonas aeruginosa exhibited a 95.0% susceptibility rate to amikacin and polymyxin B, with a 45.0% resistance rate to ceftazidime/avibactam. In contrast, carbapenem-resistant Acinetobacter baumannii demonstrated complete susceptibility (100.0%) to sulbactam/durlobactam (MIC90=2 μg/ml), whereas eravacycline showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Conclusion:The pathogen constituent ratio of bloodstream isolates differed significantly among hematology, respiratory, and ICU departments. Notably, although CRO exhibited an escalating prevalence, it sustained high susceptibility to novel antimicrobial agents.

The incidence of diarrhea-predominant irritable bowel syndrome(IBS-D)remains high,with microRNA(miRNA)-mediated intestinal barrier dysfunction,visceral hypersensitivity,low-grade inflammation,and dysbiosis playing significant roles in its pathogenesis.Traditional Chinese medicines can treat IBS-D by directly or indirectly targeting miRNAs to regulate multiple pathways and targets in a coordinated manner.This article systematically reviews the involvement of miRNAs in the pathogenesis of IBS-D and the progress of traditional Chinese medicine interventions.It explores the relationship between traditional genetics,epigenetics,and the Chinese medicine concepts of'kidney'and'spleen'in terms of congenital and acquired interactions from a molecular biology perspective.This review thus provides a reference for exploring the micro-material basis of the'Zang-Xiang'theory of traditional Chinese medicine,and offers new ideas and method for the effective treatment of IaBS-D using traditional Chinese medicine.

The incidence of diarrhea-predominant irritable bowel syndrome(IBS-D)remains high,with microRNA(miRNA)-mediated intestinal barrier dysfunction,visceral hypersensitivity,low-grade inflammation,and dysbiosis playing significant roles in its pathogenesis.Traditional Chinese medicines can treat IBS-D by directly or indirectly targeting miRNAs to regulate multiple pathways and targets in a coordinated manner.This article systematically reviews the involvement of miRNAs in the pathogenesis of IBS-D and the progress of traditional Chinese medicine interventions.It explores the relationship between traditional genetics,epigenetics,and the Chinese medicine concepts of'kidney'and'spleen'in terms of congenital and acquired interactions from a molecular biology perspective.This review thus provides a reference for exploring the micro-material basis of the'Zang-Xiang'theory of traditional Chinese medicine,and offers new ideas and method for the effective treatment of IaBS-D using traditional Chinese medicine.

Background Front-line power grid workers are required to face a variety of occupational hazards (such as aerial work), which make them susceptible to psychological problems and further reduce their performance efficiency and safety level. Objective To investigate the mental health status of front-line power grid workers and explore the influence of personality traits on mental health and the potential mediating role of work-family support between them. Methods This study was designed as a cross-sectional study. From January to June 2019, a cluster random sampling method was used to select two of the 20 power supply stations owned by a Guangdong power company. A total of 485 front-line power grid workers were included in the study. Sociodemographic characteristics were investigated, and NEO Five-Factor Inventory, Work-Family Support Scale, and Symptom Checklist 90 (SCL-90) were used in the survey. Spearman correlation analysis was conducted to analyze the correlations between measured variables. Structural equation modeling was used to analyze the relationships of personality traits, work-family support, and mental health, and Bootstrap analysis was used to test the mediating effect of work-family support on the relationship of personality traits and mental health. Results The M (P₂₅, P₇₅) of total SCL-90 score was 134.00 (110.00, 167.00）, and 139 (28.66%) front-line power grid workers showed positive mental health symptoms. The correlation analysis indicated that among the front-line power grid workers, neuroticism score was negatively correlated with work-family support total score (r_s=−0.356, P<0.001), and positively correlated with the total score of SCL-90 (r_s=0.557, P<0.001) as well as all the scores of its sub-dimensions (r_s=0.436-0.550, P<0.001). Openness score was positively correlated with work-family support total score (r_s=0.269, P<0.001), and except for paranoid ideation (P>0.05), openness score was negatively correlated with the scores of all the other sub-dimensions of SCL-90 (r_s=−0.091-−0.147, P<0.05). The scores of the other three personality traits (extroversion, agreeableness, and conscientiousness) were positively correlated with work-family support total score (r_s=0.331-0.466, P<0.001), and negatively correlated with the total score of SCL-90 as well as the scores of all its sub-dimensions (P<0.001). The modified structural equation modeling indicated that the direct effect of work-family support on mental health symptoms was −0.225 (P<0.001). The direct effects of extraversion and openness on work-family support were 0.241 (P<0.001) and 0.123 (P<0.05), respectively, while the effect on mental health symptoms was not statistically significant. The direct effects of neuroticism on work-family support and mental health symptoms were -0.152 (P<0.01) and 0.467 (P<0.001), respectively. The direct effects of conscientiousness on work-family support and mental health symptoms were not statistically significant (P>0.05). The direct effect of agreeableness on work-family support was not statistically significant (P>0.05), while the direct effect on mental health symptoms was −0.180 (P<0.001). Conclusion The front-line power grid workers show a high score of SCL-90. Workers with higher neuroticism are more vulnerable to mental health symptoms. Work-family support fully mediates the effects of extraversion and openness on mental health symptoms, and partially mediates the effects of neuroticism on mental health symptoms, while does not mediate the effects of agreeableness on mental health symptoms. Sufficient work-family support may improve mental health status.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins