Objective: To analyze the epidemiological characteristics of varicella among nursery children in Shenzhen from 2015 to 2024, and to evaluate the impact of optimizing varicella vaccine (VarV) immunization strategies on varicella incidence. Methods: Varicella incidence data for nursery children in Shenzhen from 2015 to 2024 were obtained from the China Disease Prevention and Control Information System. The study period was divided into three phases:one dose self pay VarV (January 2015 to October 2017), two dose self pay VarV (November 2017 to October 2019), and two dose free VarV (November 2019 to December 2024). Interrupted time series (ITS) analysis was conducted to assess changes in the level and trend of varicella incidence associated with each phase of policy implementation. Results: A total of 27 517 varicella cases was reported among nursery children from 2015 to 2024, with an average annual incidence of 514.01/100 000. During the same period, 136 clustered outbreaks were reported in nursery institutions, involving a cumulative total of 1 091 cases. ITS analysis showed that during the self pay 1 dose stage, the varicella incidence among nursery children showed an upward trend, with an average monthly increase of 2.58/100 000 (95% CI =2.21/ 100 000 -2.95/100 000, P <0.01). After the implementation of the self pay 2 dose strategy, the incidence decreased, with a change in incidence of -26.12/100 000 (95% CI =-37.30/100 000 to -14.94/100 000) and a change in slope of -2.65/100 000 (95% CI = -3.38/100 000 to -1.93/100 000)(all P <0.01). After the implementation of the free 2 dose strategy, the incidence decreased further, with a change in incidence of -40.03/100 000 (95% CI =-50.39/100 000 to -29.66/100 000, P <0.01) and a change in slope of -0.56/100 000 (95% CI =-1.20/100 000-0.08/100 000, P =0.09). Conclusion The gradual optimization of the VarV vaccination strategy in Shenzhen from self pay 1 dose to free 2 dose has significantly reduced the varicella incidence among nursery children, demonstrating good short term control and long term intervention effectiveness.

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.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Objective To establish models for real-time dynamic monitoring of intracellular cytoplasmic adenosine triphosphate(ATP)and mitochondrial ATP levels in cells in order to study the changes in metabolic processes.Methods The lentiviral plasmids of the cytoplasmic chemogenetic green fluorescent protein(GFP)ATP probe(Chemo-G)and those of the mitochondrial-localized chemogenetic GFP ATP probe(mito-Chemo-G)were constructed before being transfected into HEK293T together with the helper plasmids,respectively.Chemo-G and mito-Chemo-G lentiviruses were obtained.HeLa cells were infected with the lentivirus.Puromycin resistance selection and flow cytometry cell sorting were employed to identify and isolate the infected HeLa cells.The growth and GFP expressions of HeLa cells were observed.A live-cell imaging system was used for continuous imaging of the cells,with stimuli added at specific time points to alter intracellular ATP levels to observe changes in the fluorescence intensity of the ATP probe.Results Lentiviral plasmids containing Chemo-G and mito-Chemo-G sequences were constructed.Two cell lines which could stably express Chemo-G and mito-Chemo-G were established that exhibited strong growth and accurate intracellular fluorescence localization.Live-cell imaging revealed that after the addition of 2-deoxy-D-glucose(2-DG)into HeLa-Chemo-G,the fluorescence resonance energy transfer(FRET)/GFP ratio showed a decrease that was partially reversed by the addition of glucose.The FRET/GFP ratio increased after histamine stimulation,but rapidly decreased after the addition of oligomycin.Conclusion The Chemo-G and mito-Chemo-G lentiviral vectors and stably transfected cell lines HeLa-Chemo-G and HeLa-mito-Chemo-G are constructed,which provides reliable experimental models for studying cellular metabolism and changes in intracellular ATP levels.

Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas with distinct clinical and pathological features. In recent years, advancements in molecular biology techniques have led to a deeper understanding of the molecular mechanisms underlying PACC. Progress in imaging, endoscopic, and molecular diagnostic technologies has improved the early detection rate of PACC. The primary treatment modalities for PACC include surgical resection, chemotherapy, targeted therapy and immunotherapy; however, the therapeutic efficacy still requires further improvement. This article reviews the current research status of PACC, covering its epidemiology, pathological characteristics, molecular alterations, diagnostic methods, and treatment strategies, and discusses the controversies and future directions in PACC research.

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.

Background Grassroots medical and health personnel are an important component of China's public health system, and guaranteeing their physical and mental health will have a profound impact on the development of China's health service. Objective To identify potential influencing factors of occupational stress, anxiety, depression, and insomnia as well as their interactions. Methods In August 2021, a cross-sectional survey was conducted among all the staff (2675 medical and health personnel) at 7 secondary public hospitals and 8 health institutions in Xiong’an New Area of Hebei Province by cluster sampling. Occupational stress, anxiety, depression, and insomnia were evaluated by the Effort-Reward Imbalance Questionnaire (ERI), the Generalized Anxiety Disorder-7 (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), and the Athens Insomnia Scale (AIS). The bnlearn and gmodels packages of R4.2.1 software were used to construct Bayesian networks on work and personal factors-occupational stress- health effects. The Bayesian network model was visualized by Netica32.0. Results Among the 3018 questionnaires distributed, a total of 2675 valid questionnaires were recovered, with an effective recovery rate of 88.63%. The positive rates of occupational stress, anxiety, depression, and insomnia were 51.48%, 62.13%, 62.50%, and 56.37%, respectively in the grassroots medical and health personnel. The positive rate of occupational stress among the medical and health workers varied by age, educational level, and organization type (P<0.05); the positive rate of anxiety varied by age, marital status, and daily working hours (P<0.05); and the positive rates of depression and insomnia varied by gender, educational level, and overcommitment (P<0.05). The final Bayesian network contained 14 nodes and 18 directed edges, and its prediction accuracy was 85.4%. .Job title, daily working hours, overcommitment and exercise directly associated with occupational stress, and other work and personal factors associated with occupational stress indirectly. Occupational stress associated with insomnia directly or indirectly via anxiety. Anxiety and insomnia associated with reporting depression. Conclusion Grassroots medical and health personnel of Xiong'an New Area, Hebei Province report high levels of occupational stress, anxiety, depression, and insomnia. Occupational stress directly or indirectly associates with anxiety, depression, and insomnia. Work and personal factors associate with occupational stress, and associate with anxiety, depression, and insomnia via occupational stress. Occupational stress may be an early warning factor of general work and personal factors affecting anxiety, depression, insomnia, and other mental health problems. Attention should be paid to the assessment and intervention of occupational stress in medical and health personnel to prevent mental health problems.

Objective:To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021.Methods:The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis.Results:A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 +T lymphocyte (CD4) counts <200 cells/μl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m 2 and baseline CD4 counts ≥200 cells/μl were more likely to have complete immune reconstitution. Conclusions:In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.