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.

BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

Objective To explore the influencing factors of postoperative pancreatitis in elderly patients with common bile duct stones undergoing endoscopic retrograde cholangiopancreatography(ERCP).Methods 304 elderly patients with common bile duct stones treated with ERCP in our hospital from February 2021 to June 2023 were selected as the study subjects.They were divided into a group with concurrent pancreatitis(n=22)and a group without concurrent pancreatitis(n=282)based on whether postoperative pancreatitis occurred.And the levels of serum lipase,whole blood PLR,and serum CRP were measured before surgery and 3,6,and 24 hours after surgery,respectively.At the same time,the differences in other relevant clinical data between the two groups of patients were compared.Binary Logistic regression was used to analyze the risk factors of pancreatitis after ERCP.Results The serum lipase levels in the concurrent pancreatitis group at 3,6,and 24 hours after the operation were(1060.48±131.23)U/L,(1137.45±126.34)U/L,and(1152.87±135.05)U/L,respectively.The levels of PLR in whole blood were 192.24±29.26,216.45±30.24,and 243.62±38.22 respectively,all of which were higher than those in the group without concurrent pancreatitis during the same period.There was a statistically significant difference between the two groups(P＜0.05).The serum CRP level in the group with pancreatitis was significantly higher than that in the group without pancreatitis at 6 and 24 h after operation(P＜0.05).Body mass index,Oddi sphincter dysfunction,difficulty in intubation,pancreatic development,ERCP operation time＞60 min,multiple entry of the catheter into the pancreatic duct were associated with postoperative pancreatitis after ERCP in elderly patients(P＜0.05).Multivariate Logistic regression analysis showed that after adjusting for confounding factors such as gender,age,BMI,course of disease,and number of stones,Serum lipase at 3 h after surgery,whole blood PLR at 3 h after surgery,serum CRP level at 6 h after surgery,difficulty in intubation and pancreatic development were independent risk factors for pancreatitis after ERCP in elderly patients(P＜0.05).Conclusion Serum lipase,whole blood PLR levels 3 hours after surgery,and serum CRP levels 6 hours after surgery are independent risk factors for pancreatitis after ERCP in the elderly with common bile duct stones.

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.

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 evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets