ObjectiveTo clarify the expression of TRIM28 in non-M3 acute myeloid leukemia （AML） and its correlation with clinical indicators and prognosis， and to further explore the effect of TRIM28 expression levels on the proliferation and apoptosis of AML cells using small interfering RNA. MethodsThe GSE34577 dataset was analyzed using R software to compare TRIM28 expression between healthy controls and non-M3 acute myeloid leukemia （AML） patients. Clinical samples from non-M3 AML patients were collected， with TRIM28 expression levels measured using real-time quantitative PCR （qPCR）. The analysis focused on correlations between TRIM28 expression and various clinical indicators， treatment efficacy， and patient prognosis. Furthermore， small interfering RNA （siRNA） technology was employed to downregulate TRIM28 expression in human primary AML cells （HL60 cell line）. The effects on cell proliferation and apoptosis were then assessed through CCK-8 assays and flow cytometry， respectively. ResultsThe results showed that TRIM28 was up-regulated in non-M3 AML of both online database GSE34577 and clinical samples （P<0.000 1）， TRIM28 expression of new diagnosis group and relapsed refractory group was higher than iron deficiency anemia group （P<0.01）， and there was no significance between different French-American-British classification systems subtype. TRIM28 expression was higher in non-M3 AML patients with a poor genetic prognosis stratified as moderate than in the good prognosis group， and TRIM28 expression was associated with NPM1 combined with the FLT3-ITD mutation， positively correlated with age， bone marrow blast， peripheral blood blast and white blood cell， negatively correlated with hemoglobin. In addition， interference TRIM28 greatly inhibited cell proliferation and promoted cell apoptosis. ConclusionThis study reveals that TRIM28 is highly expressed in non-M3 AML and associated with prognosis， and plays a key role in the proliferation and apoptosis of AML cells， suggesting that TRIM28 may serve as a novel therapeutic target for non-M3 AML.

OBJECTIVE To investigate the effect of plasma trough concentration of venetoclax and its influencing factors in patients with acute myeloid leukemia （AML）. METHODS After 5 days of venetoclax administration， venous blood samples were collected from AML patients before the next dose. Plasma trough concentrations of venetoclax were determined using high-performance liquid chromatography-tandem mass spectrometry. Spearman correlation was used to assess the correlations between venetoclax plasma trough concentration and various parameters （including patients’ general information， venetoclax-related indicators， liver function indicators， kidney function indicators， and blood routine indicators）. Multiple linear regression analysis was performed to identify independent factors influencing plasma trough concentration of venetoclax. Using efficacy as dependent variable [complete remission （CR）+partial remission （PR） vs. no remission （NR）]， univariate and multivariate binary Logistic regression analyses were conducted to identify factors affecting efficacy. The receiver operating characteristic （ROC） curve was used to evaluate the predictive value of venetoclax plasma trough concentration for clinical efficacy （assessed as CR）. RESULTS A total of 172 venetoclax plasma trough concentration measurements from 101 patients were included in this study. The median plasma trough concentration of venetoclax was 2.38 （1.18， 3.85） μg/mL； the median sampling time for plasma trough concentration of venetoclax was 10 （7， 15） d； the duration of venetoclax use was （34±12） d. Multiple linear regression analysis showed that alkaline phosphatase （ B ＝14.65， 95%CI： 5.35-23.95， P ＝0.002）， total bilirubin （ B ＝－101.71， 95%CI： －197.16 to －6.25， P ＝0.037）， and white blood cell count （ B ＝－106.84， 95%CI： －187.61 to －26.07， P ＝0.010） were independent factors influencing plasma trough concentration of venetoclax. Due to patient attrition during treatment， 114 venetoclax plasma trough concentration measurements from 69 patients were included for efficacy evaluation. The results showed that 46 patients （66.7%） achieved CR， 11 patients （15.9%） achieved PR， and 12 patients （17.4%） were NR. Multivariate binary Logistic regression analysis showed that age， hemoglobin， venetoclax plasma trough concentration， hematocrit， and mean corpuscular hemoglobin were independent factors affecting patient efficacy （ P ＜0.05）. ROC curve analysis showed that the cut-off value of plasma trough concentration of venetoclax for predicting patient efficacy （assessed as CR） was 1.68 μg/mL （AUC＝0.66， 95%CI： 0.54-0.78， P ＝0.014）. CONCLUSIONS There is considerable inter-individual variability in plasma trough concentration of venetoclax among AML patients. Plasma trough concentration of venetoclax is significantly correlated with alkaline phosphatase， total bilirubin， and white blood cell count. Plasma trough concentration of venetoclax is an independent factor affecting patient’s efficacy， and when the cut-off value for predicting CR is above 1.68 μg/mL， better effects may be achieved.

ObjectiveTo understand the epidemiological characteristics and post-exposure prophylaxis of rabies exposure cases in Suqian City of Jiangsu Province from 2021 to 2024, providing a reference for optimizing the allocation of health resources and formulating scientific prevention and control measures. MethodsData on individuals exposed to rabies and treated at Suqian’s rabies post-exposure prophylaxis (PEP) clinics from 2021 to 2024 were collected. Descriptive epidemiological methods were used to analyze patient characteristics, exposure classification, animal species responsible for injuries, wound management, and vaccination status. ResultsBetween 2021 and 2024, the number of outpatient visits for rabies PEP clinics in Suqian City totaled 333 450. The median age and the 25th and 75th percentiles of exposed individuals was 23 (9, 47) years. The highest proportion of exposed individuals was recorded in 2023 (27.09%); the majority were female (52.22%), aged 5‒9 years (17.49%), and in other occupations (37.05%). The rabies exposure rate in Suqian City from 2021 to 2024 was 16.75‰. The overall rabies exposure rate showed an upward trend (χtrend2=1 994.80, P<0.001). The exposure rate among males was lower than that among females (χ²=890.43, P<0.001). The highest exposure rate was observed in the 5‒9 age group (χ²=67 063.20, P<0.001). The number of individuals seeking medical care for rabies exposure exhibited a weak bimodal distribution, with the primary peak occurring in August and the secondary peak in January. The primary animal responsible for injuries was the cat (53.70%), and the source of these animals was predominantly domestic pets (88.90%). The proportion of exposed individuals bitten by cats showed an upward trend from 2021 to 2024 (χtrend2=548.44, P<0.001). Grade Ⅲ exposure accounted for the highest proportion (53.53%), and 301 652 cases (90.46%) presented within 24 hours of exposure. The coverage rate of rabies vaccine was 98.18% (13 625/13 877) for those with Grade Ⅰ exposure and 99.95% (319 413/319 573) for those with Grade Ⅱ and Ⅲ exposures; 64 042 individuals received rabies immunoglobulin or anti-rabies serum; 8 360 exposed individuals received tetanus vaccine, with the usage rate of tetanus vaccine among exposed individuals was only 2.51%, though the rate was on the rise (χtrend2=618.26, P<0.001). ConclusionBetween 2021 and 2024, the overall incidence of rabies exposure in Suqian City showed an upward trend, with a higher incidence among women than men. The incidence was particularly high among children and adolescents aged 14 and under, with the majority of injuries caused by cats; most injuries were inflicted by domestic animals. The overall uptake of tetanus vaccines showed an upward trend. Suqian City should step up health education on rabies exposure during January and August each year, with a particular focus on raising awareness of rabies exposure prevention among people aged 14 and under and women. It should also strengthen the management of domestic animals and ensure that they receive regular rabies vaccinations, particularly for pet cats. Preventive measures against tetanus should be strengthened for individuals exposed to rabies. Medical staff at rabies PEP clinics should receive enhanced training on the management of rabies exposures and the completion of information system reports to ensure the standardized operation of these clinics.

Objective To analyze the molecular epidemiology and colistin-resistant genes of carbapenem-resistant Klebsiella pneumoniae(CRKP)by whole-genome sequencing,and to provide reference for clinical diagnosis and treatment.Methods 57 CRKP strains isolated from clinical specimens of hospitalized patients in a tertiary general first-class hospital in Anhui Province from 2021 to 2023 were collected and antimicrobial susceptibility testing was performed.Multilocus sequence typing,capsule serotype,resistance genes,and virulence genes of CRKP strains were analyzed by whole-genome sequencing technique,and single nucleotide polymorphism analysis was conducted on sequences of all strains.Colistin resistance-related genes were amplified by polymerase chain reaction(PCR).Results 57 CRKP strains exhibited resistance to 14 antimicrobial agents,with the exception of tigecycline.The se-quencing results showed that 93.0％(53/57)of CRKP carried blaKPC-2,and the ST11 type CRKP strain had the highest detection rate(51/57,89.5％).Single nucleotide polymorphism clustering analysis showed that the 57 CRKP strains were divided into 11 clone groups,of which 4 clone groups were all ST11-KL64 type CRKP.40(70.2％)CRKP strains carried multiple virulence genes.Five strains of CRKP were colistin-resistant strains,the resistance mechanism involved the insertion of ISKpn26 element at site 70 of the mgrB gene.Conclusion The CRKP strain is primarily characterized by the production of KPC-2 ST11-KL64,with disseminated transmission in intensive care unit.The insertion of ISKpn26 element leading to mgrB gene mutation is related to resistance of CRKP to colistin in this region.

Objective:To investigate the effect and preliminary mechanism of hypervirulent Klebsiella pneumoniae (hvKP) on the immune response to sepsis induced by liver abscess in mice. Methods:C57BL/6 mice were intraperitoneally injected with hvKP strain NTUH-K2044 or classical Klebsiella pneumoniae (cKP) strain HS11286 suspension to prepare the model of sepsis. The survivals rates of mice within 24 h were recorded. HE staining was used to observed the inflammatory cell infiltration in mouse liver tissues. The levels of neutrophil marker lymphocyte antigen 6G (Ly6G) in mouse liver tissues were detected by immunohistochemistry. The activity of reactive oxygen species (ROS) in mouse liver macrophages and peripheral blood monocytes was measured by ROS assay kit. The activation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes was detected by Western blot. The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were detected by qRT-PCR and ELISA, respectively. One-way analysis of variance and t test were used for statistical analysis. Results:Compared with cKP, hvKP infection could induce C57BL/6 mice to develop obvious liver abscess with massive inflammatory cell infiltration. Moreover, the level of Ly6G in liver tissues was significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.000 1), but the survival rate of hvKP-infected mice was significantly lower than that of cKP-infected mice ( P<0.000 1). hvKP significantly promoted the ROS activity ( P<0.000 1) and enhanced the phosphorylation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes as compared with cKP ( P<0.001). The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.001). Conclusion:hvKP can promote the development of liver abscess and induce sepsis in mice.

Objective:To investigate the distribution of health needs and healthcare workforce demands among potential service users in community health service institurions (CHSIs) and establish a comprehensive health needs profile for targeted service development.Methods:This is a cross-sectional study. A questionnaire survey (55 items for adults and 39 items for minors) was conducted among 564 residents aged 3-65 in Dapuqiao Subdistrict, Shanghai from March to May 2024. A health sketch model was developed, encompassing five dimensions (intake, basal metabolism, consumption, influencing factors, and somatosensory perception). Health issues were mapped to standardized healthcare services, and annual standardized workloads (SW) were calculated to quantify human resource demands. Results:Among 534 valid responses (94.68% response rate), 355 from the adults and 179 from minors, the top health issues for adults were irregular diet, nutritional imbalance, obesity, somatic fatigue, and disordered eating; for minors, they were nutritional imbalance, medication overuse, insufficient physical activity, picky eating, and anorexia. The total annual SW required to address these needs was 3 906 807.93. Among them, the total SW for each age group was as follows: the total annual SW demand for children aged between 3 and 5 years old was 24 108.90, for children aged between 6 and 11 years old was 141 355.70, for adolescents aged between 12 and 17 years old was 29 813.74, 223 475.50 for 18-24 year olds, 476 426.53 for 25-34 year olds, 1 221 105.84 for 35-44 year olds, 812 200.22 for 45-54 year olds; and 978 321.50 for 55-65 year olds. Workforce allocation analysis revealed a total demand for 139.84 standardized personnel, with rehabilitation therapists (38.16), general practitioners (35.69), and nurses (27.34) being the top three required roles.Conclusions:Health needs and workforce demands vary significantly across age groups. This study provides a data-driven framework for optimizing community health services through stratified health needs profiling and precision resource allocation. Future strategies should prioritize tailored interventions and workforce planning to bridge service gaps and enhance health outcomes.

Objective:To investigate the descrepancy between current supply and demand based on standardiized workload for rational human resource allocation in community health service centers.Methods:A retrospective study was conducted in Dapuqiao Community Health Service Center of Shanghai Huangpu District from January 1st to December 3lst 2023. The current status of demand and supply were analyzed using the 2023 data of the institution. The standardised workload was measured according to the potential basic medical and public health service needs based on the disease profile and population groups in the community. The discrepancy between the current supply and theoretical demand was analyzed.Results:A total of 36 634 patients paid 277 262 visits in outpatient clinics of Dapuqiao Community Health Service Center in 2023. There are total 161 employees in the center, 124 of whom are female (77.02%). The actual calibrated workload of basic medical care and public health service in the center calculated on fee-based medical service items in 2023 was 2 888 425.61 and 455 898.35, respectively; while the theoretically calibrated workload was 5 416 492.42 and 711 230.94, respectively. The center employed 131 medical and health workers currently, calibrated as 90.67 employees based on current demand, while it should be 183.74 calibrated on the theoretical demand, there was a certain discrepancy between the current staffing and the standard staffing based on the standardized workload calculation.Conclusion:At present, the actual standardized workload of basic medical and public health services in Dapuqiao Community Health Service Center still has room for improvement, but there is a certain gap between the current human resource allocation and the demand.

Objective To investigate the expression of adenosine A3 receptor(ADORA3)in human glioma and its effects on prognosis and epithelial-mesenchymal transition.Methods The mRNA expression data and corresponding clinical information of ADORA3 were obtained from TCGA,CGGA,Rembrandt,Gravendeel and Gill databases,and the effects of ADORA3 expression on the prognosis of glioma patients and the process of epithelial-mesenchymal transition were analyzed.The surgically resected glioma samples of 35 cases,along with non-tumor brain tissues of 7 cases obtained from decompression surgery for severe craniocerebral injury were collected in the Department of Neurosurgery at Renmin Hospital of Wuhan University from July 2023 to April 2024,and the ADORA3 expression was detected by immunohistochemical staining.Glioblastoma multiforme(GBM)cells of U87 and U251 were transfected with NcRNA and SiRNA,respectively,as the control group and the knockdown group,and the effects of ADORA3 on cell invasion ability and epithelial-mesenchymal transition related proteins were analyzed by Transwell and Western blot.Results Bioinformatics analysis and immunohistochemical staining showed that the expression level of ADORA3 in human glioma tissues was significantly higher than that in non-tumor brain tissues(P<0.05),and the expression of ADORA3 was associated with glioma WHO grading(P<0.05).Kaplan-Meier survival curve analysis in TCGA,CGGA,Rembrandt and Gravendeel databases showed that the overall survival rate of patients with high ADORA3 expression was significantly lower than that of patients with low ADORA3 expression(P<0.001);and Cox regression analysis showed that high expression of ADORA3 was an independent risk factor for poor prognosis in patients with glioma(P<0.05);the expression level of ADORA3 in the mesenchymal type of GBM patients was significantly higher than that of the classical type and the proneural type;furthermore,ADORA3 showed significant correlations with epithelial-mesenchymal transition related markers of Vimentin,SNAI1,SNAI2,TWIST1,TWIST2,MMP2,CD44,and FN1.The knockdown of ADORA3 in vitro reduced the cell invasive ability,decreased the expression levels of MMP2,Vimentin,and SNAI1 proteins,and increased the expression of E-cadherin,with statistically significant differences(P<0.05).Conclusion ADORA3 is highly expressed in glioma,which can promote the process of epithelial-mesenchymal transition in patients,and serve as an independent risk factor for poor prognosis.

Objective To investigate the expression of adenosine A3 receptor(ADORA3)in human glioma and its effects on prognosis and epithelial-mesenchymal transition.Methods The mRNA expression data and corresponding clinical information of ADORA3 were obtained from TCGA,CGGA,Rembrandt,Gravendeel and Gill databases,and the effects of ADORA3 expression on the prognosis of glioma patients and the process of epithelial-mesenchymal transition were analyzed.The surgically resected glioma samples of 35 cases,along with non-tumor brain tissues of 7 cases obtained from decompression surgery for severe craniocerebral injury were collected in the Department of Neurosurgery at Renmin Hospital of Wuhan University from July 2023 to April 2024,and the ADORA3 expression was detected by immunohistochemical staining.Glioblastoma multiforme(GBM)cells of U87 and U251 were transfected with NcRNA and SiRNA,respectively,as the control group and the knockdown group,and the effects of ADORA3 on cell invasion ability and epithelial-mesenchymal transition related proteins were analyzed by Transwell and Western blot.Results Bioinformatics analysis and immunohistochemical staining showed that the expression level of ADORA3 in human glioma tissues was significantly higher than that in non-tumor brain tissues(P<0.05),and the expression of ADORA3 was associated with glioma WHO grading(P<0.05).Kaplan-Meier survival curve analysis in TCGA,CGGA,Rembrandt and Gravendeel databases showed that the overall survival rate of patients with high ADORA3 expression was significantly lower than that of patients with low ADORA3 expression(P<0.001);and Cox regression analysis showed that high expression of ADORA3 was an independent risk factor for poor prognosis in patients with glioma(P<0.05);the expression level of ADORA3 in the mesenchymal type of GBM patients was significantly higher than that of the classical type and the proneural type;furthermore,ADORA3 showed significant correlations with epithelial-mesenchymal transition related markers of Vimentin,SNAI1,SNAI2,TWIST1,TWIST2,MMP2,CD44,and FN1.The knockdown of ADORA3 in vitro reduced the cell invasive ability,decreased the expression levels of MMP2,Vimentin,and SNAI1 proteins,and increased the expression of E-cadherin,with statistically significant differences(P<0.05).Conclusion ADORA3 is highly expressed in glioma,which can promote the process of epithelial-mesenchymal transition in patients,and serve as an independent risk factor for poor prognosis.

Compared with matrix-assisted laser desorption ionization mass spectrometry(MALDI-MS)using organic small molecule matrix,surface-assisted laser desorption ionization mass spectrometry(SALDI-MS)based on nanomaterial matrix is more effective in analysis of small molecule compounds.Ion sputtering instruments have obvious advantages for applying inorganic nanomatrix.In this work,the carbon-platinum material was sputtered onto a glass cover slip using an ion sputtering instrument to form a carbon-platinum(C-Pt)composite nanomatrix,and an SALDI-MS analytical method was thus established based on the prefabricated C-Pt composite matrix.The experimental results showed that the C-Pt composite nanomatrix could significantly improve the signal intensity and signal-to-noise ratio of the mass spectrum peaks of the components to be measured.The ratio of carbon to platinum,the duration of ion sputtering,and the laser power in mass spectrometer were investigated to select the optimal C-Pt matrix prefabricated conditions and SALDI-MS experimental conditions.Using the prefabricated C-Pt composite matrix,the melittriose and daidzein sample solution were applied as sample to examine repeatability.The results showed that the intra-point repeatability(RSD)was≤4.8%and the inter-point repeatability(RSD)was≤6.4%.The quercetin and melitriose were applied as model samples,and a linearity between MS peak intensity and respective concentration in the range of 0.05-1.0 mg/mL was found,with linear correlation coefficients(R2)greater than 0.994,showing good potential for quantitative and imaging analysis.Then,the prefabricated C-Pt composite matrix was applied to SALDI-MS analysis of the 50%ethanol extract of soybean,and 15 kinds of compounds including oligosaccharides and triglycerides were identified from the mass spectra.Furthermore,the C-Pt matrix was employed in SALDI-MS imaging for the compositions in corn tissue section,and the results showed that diglycerides and triglycerides were mainly distributed in the corn embryo and around the embryo,and the distribution of oligosaccharides was relatively even.