ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Real-time, noninvasive programmed death-ligand 1 (PD-L1) testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy. However, the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography (PET/CT) remains limited. This investigation involved the synthesis of [¹⁸F]AlF-NOTA-PCP2, which is a novel peptide-based radiolabeled tracer that targets PD-L1, and evaluated its imaging capabilities in orthotopic glioblastoma (GBM) models. Using this tracer, we could noninvasively monitor radiation-induced PD-L1 changes in GBM. [¹⁸F]AlF-NOTA-PCP2 exhibited high radiochemical purity (>95%) and stability up to 4 h after synthesis. It demonstrated specific, high-affinity binding to PD-L1 in vitro and in vivo, with a dissociation constant of 0.24 nM. PET/CT imaging, integrated with contrast-enhanced magnetic resonance imaging, revealed significant accumulation of [¹⁸F]AlF-NOTA-PCP2 in orthotopic tumors, correlating with blood-brain barrier disruption. After radiotherapy (15 Gy), [¹⁸F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51% ± 0.73% to 12.04% ± 1.43%, indicating enhanced PD-L1 expression consistent with immunohistochemistry findings. Fractionated radiation (5 Gy × 3) further amplified PD-L1 upregulation (13.9% ± 1.54% ID/cc) compared with a single dose (11.48% ± 1.05% ID/cc). Taken together, [¹⁸F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.

Objective Comparative analysis of rule categories,key audit behaviors,and the degree of correspon-dence between rules and behaviors through intelligent auditing of key audit violations and monitoring of the rule base.To provide reference for the improvement of intelligent audit and monitoring rule library for key audit violations under DRG payment in medical insurance fund.Methods Searching and collecting policy documents such as DRG payment management methods issued by local health insurance bureaus from May 20,2019 to December 31,2023 and the literature related to DRG payment smart audit monitoring rules in the database,and targeting the rules therein that are related to the focus on auditing irregularities under the DRG payment.Literature analysis and comparative analysis were used to summarize and analyze the rules related to key audit violations under DRG payment.Results The intelli-gent audit rules for key audit violations under DRG payment can be divided into two major categories:logical judg-ment and parameter index,and the degree of correspondence between audit rules and key audit behaviors varies.Conclusion(1)Unify the key audit rules nationwide to ensure the universality and comprehensiveness of the rules;(2)Deepen the current situation of regional illegal activities and strengthen local characteristics;(3)Improve the quality of logical judgment rules and increase the quantity of parameter indicator rules;(4)Strengthen scientific re-search on new types of violations,and establish more targeted regulatory rules.

In the field of healthcare service, it is crucial to optimize medical innovation services by combining the preferences of health service providers and demanders (i.e., stakeholders). The best-worst scaling (BWS) method is a recently developed stated preference method for assessing preferences with distinctive advantages. Nevertheless, there is a lack of a comprehensive introduction to stakeholder preference assessment using BWS, thus constraining its applications and promotion. This paper introduces the process of using BWS to assess service providers' preferences for the Shared Medical Appointment for diabetes (SMART), an integrated healthcare service of medicine and health management, in the hope of providing reference for researchers for promoting the use of BWS in implementation research.

ObjectiveTo observe the inhibitory effect of sinomenine on human glioblastoma and its pharmacokinetic characteristics in glioblastoma. MethodA human glioblastoma U87 cell line stably expressing luciferase was constructed， and a mouse glioma model was established for use in both pharmacodynamic and pharmacokinetic studies. Pharmacodynamics： Model mice were randomly divided into model group and sinomenine low-， medium-， and high-dose groups （50， 100， 150 mg·kg^-1）. Sinomenine was administered intraperitoneally for 14 days. The fluorescence value of brain tumors was observed to analyze its inhibitory effect on glioblastoma proliferation. Brain tumors and the surrounding brain tissue were collected， and the expression levels of vascular endothelial growth factor A （VEGFA）， P-glycoprotein （P-gp）， breast cancer resistance protein （BCRP）， and Occludin were detected by Western blot. Pharmacokinetics： Mice were divided into a normal group （50 mg·kg^-1） and model groups （50， 100， 150 mg·kg^-1）. After a single intraperitoneal injection of sinomenine， extracellular fluid from brain tumors was collected in vivo by microdialysis every 15 min for 6 h. Sinomenine concentrations in the dialysate were detected by HPLC-MS/MS， and pharmacokinetic parameters were calculated to analyze pharmacokinetic characteristics of sinomenine in the brain and glioblastoma. ResultCompared with model group， after 14 days of sinomenine administration， the fluorescence value of brain tumors significantly decreased （P<0.05） in a dose-dependent manner. Sinomenine inhibited the increase in VEGF and the degradation of Occludin in the tissue surrounding the tumor and inhibited the expression of VEGF， P-gp， and BCRP in glioblastoma. After a single administration， sinomenine was detected in brain and tumor tissues within 7.5 min. Compared with normal group， the C_max and AUC in the tumor significantly increased， T_max shortened （from 1.63 h to 0.71 h）， and CLz/F decreased. In the dose range of 50-150 mg·kg^-1， sinomenine exhibited a linear pharmacokinetic process in glioblastoma. ConclusionSinomenine has a significant inhibitory effect on glioblastoma， which can inhibit VEGF elevation and drug transporter efflux， reduce tumor invasion， and maintain the integrity of the blood-brain barrier. Sinomenine can rapidly cross the blood-tumor barrier， reach peak concentration， and exhibit linear pharmacokinetic characteristics in the tumor.

Objective The performance characteristics of statistical quality control procedures in Westgard sigma rule are analyzed by using the power function graph.Methods According to the drawing principle of power function graph,the internal quality control program design software of clinical laboratory quantitative measurement was developed.and the Westgard sigma rule quality control procedures were simulated with power function graph.The performance of the quality control procedures recommended by Westgard sigma was analyzed by combining different sigma quality levels.Results The rules recommended by Westgard sigma were relatively simple rules that can meet the requirements of error detection probability and false rejection probability.Conclusion The internal quality control procedure design software for quantitative clinical testing has verified the performance of Westgard sigma recommendation rules.The Westgard sigma rule diagram is intuitive and convenient,the laboratory can use the Westgard sigma recommendation rules for internal quality control.

BACKGROUND:The research of dental stem cells in the fields of regenerative medicine and tissue engineering has been deepening,bringing hope for the repair of tooth-related tissues and the treatment of systemic diseases.However,there is a lack of systematic research and analysis on the biological characteristics of dental stem cells in different age groups. OBJECTIVE:To explore the biological characteristics of the human deciduous tooth and permanent tooth pulp stem cells cultured in umbilical cord blood platelet lysate to provide a reliable basis for human platelet lysates to replace fetal bovine serum. METHODS:The pulp tissues of deciduous teeth,juvenile permanent teeth and adult permanent teeth were taken out and cultured in DMEM/F-12 medium supplemented with 10%fetal bovine serum or different concentrations(5%,10%and 15%)of human platelet lysates.Cell proliferation in the four groups was detected by cytometry.The optimal concentration of human platelet lysates was selected for subsequent experiments.Under the optimal concentration of human platelet lysates,human deciduous tooth and juvenile and adult permanent tooth pulp stem cells were cultured in vitro.The cell growth status was observed under the microscope.The specific antigen on the cell surface was detected by flow cytometry.The cell proliferation ability was tested by the cell counting method and CCK-8 assay.The cell differentiation ability in vitro was observed by a three-line differentiation assay. RESULTS AND CONCLUSION:(1)The cell proliferation rate of the 10%human platelet lysate group was the highest.(2)In all three groups,fusiform fibrous cells grew and expanded from around the tissue block.There was no significant difference between deciduous teeth and juvenile permanent tooth cells,but the adult permanent tooth cells were larger than the deciduous and juvenile permanent tooth cells of the same generation.(3)The results of flow cytometry showed that deciduous teeth,juvenile permanent teeth and adult permanent teeth conformed to the phenotypic characteristics of mesenchymal stem cells.(4)The proliferative capacity of adult permanent dental pulp stem cells was significantly lower than those of deciduous teeth and juvenile permanent dental pulp stem cells(P<0.01).(5)mRNA expressions of osteoblast-related genes alkaline phosphatase and bone morphogenetic protein 2,lipoprotein lipase and peroxisome proliferator-activated receptor γ2,mRNA expressions of chondroblast related gene type II collagen α1 and cartilage oligomeric matrix protein in adult pulp stem cells of permanent teeth were significantly lower than those of deciduous teeth and juvenile permanent teeth pulp stem cells(P<0.01).(6)Compared with adult dental pulp stem cells,human deciduous teeth and juvenile permanent teeth dental pulp stem cells have the stronger proliferative capacity and multidirectional differentiation potential,and are more suitable for clinical research and disease treatment.

BACKGROUND:In vitro fertilization-embryo transfer is commonly used to solve infertility,but its success rate is not high,the more common reasons are poor endometrial receptivity,poor egg quality,etc.The follicular fluid melatonin can inhibit the aging of the ovary,to a certain extent,can promote the development of embryos,improve the probability of conception,but whether there is a correlation between the two is not known. OBJECTIVE:To explore the correlation between follicular fluid melatonin level and pregnancy rate of single-cycle in vitro fertilization-embryo transfer women. METHODS:A total of 112 female patients who received in vitro fertilization-embryo transfer treatment in the First Affiliated Hospital of Anhui Medical University from December 2020 to April 2021 were selected as the study subjects.They were divided into quartile array(Q1-Q5)according to the follicular fluid melatonin level from low to high.Among them,the melatonin level of group Q1 was<6.99 ng/L(n=18),that of group Q2 was 7.00-9.99 ng/L(n=26),that of group Q3 was 10.00-11.99 ng/L(n=27),and that of group Q4 was 12.00-13.99 ng/L(n=18);and melatonin levels in group Q5 were 14.00-19.99 ng/L(n=23).Clinical data characteristics of the five groups were compared.Multi-factor Logistic regression was used to analyze the correlation between follicular fluid melatonin level and pregnancy rate of women with single-cycle in vitro fertilization-embryo transfer and embryo transfer.A restricted cubic spline Logistic regression model was established to analyze the dose-response relationship,and the model was evaluated by clinical decision curve. RESULTS AND CONCLUSION:(1)Compared with the study population with the lowest melatonin quintile(Q1),with the increase of melatonin level(Q2-Q5),the levels of egg harvest and pregnancy success were gradually increased,and the body mass index was gradually decreased,and the differences were significant(P<0.05).(2)Multivariate Logistic regression analysis showed that after adjusting for confounding factors such as global mass index,number of eggs retrieved,luteinizing hormone,estradiol,progesterone and other confounding factors,follicular fluid melatonin level was still independently correlated with pregnancy rate of single-cycle in vitro fertilization-embryo transfer women(OR=1.538,95%CI:1.032-1.837,P<0.05),and there was significant difference in trend test of follicular fluid melatonin level from low to high quintile array(Ptrend<0.05).(3)The sensitivity test analysis showed that E value was 2.117.Subgroup analysis showed that the study population with higher levels of luteinizing hormone in follicular fluid had a more significant association between follicular fluid melatonin and pregnancy rate in single-cycle in vitro fertilization-embryo transfer women(P interaction=0.008).(4)The results of restricted cubic spline model analysis showed that there was a nonlinear dose-response relationship between follicular fluid melatonin level and pregnancy rate of single-cycle in vitro fertilization-embryo transfer women(P<0.05),and there was an overall positive correlation between follicular fluid melatonin level and pregnancy rate of single-cycle in vitro fertilization-embryo transfer women.(5)The results of clinical decision curve analysis showed that the follicular fluid melatonin level had important clinical value in predicting the pregnancy rate of single-cycle in vitro fertilization-embryo transfer women.(6)Follicular fluid melatonin level is closely related to the pregnancy rate of single-cycle in vitro fertilization-embryo transfer women,and with the decrease of follicular fluid melatonin level,the pregnancy rate of single-cycle in vitro fertilization-embryo transfer women also decreases.

Background: Clinical chemistry tests are most widely used in clinical laboratories, and diverse measurement systems for these analyses are available in China. We evaluated the imprecision of clinical chemistry measurement systems based on internal QC (IQC) data. Methods: IQC data for 27 general chemistry analytes were collected in February each year from 2013 to 2022. Four performance specifications were used to calculate pass rates for CVs of IQC data in 2022. Boxplots were drawn to analyze trends of CVs, and differences in CVs among different groups were assessed using the Mann–Whitney U-test or Kruskal– Wallis test. Results: The number of participating laboratories increased significantly from 1,777 in 2013 to 5,425 in 2022. CVs significantly decreased for all 27 analytes, except creatine kinase and lipase. Triglycerides, total bilirubin, direct bilirubin, iron, and γ-glutamyl transferase achieved pass rates > 80% for all goals. Nine analytes with pass rates < 80% based on 1/3 allowable total error were further analyzed; the results indicated that closed systems exhibited lower CVs than open systems for all analytes, except total protein. For all nine analytes, differences were significant between tertiary hospitals and non-tertiary hospitals and between accredited and non-accredited laboratories. Conclusions The CVs of IQC data for clinical chemistry have seen a continuous overall improvement in China. However, there is ample room for imprecision improvement for several analytes, with stricter performance specifications.