1.Exploring Multi-target Effect of Erzhiwan on Improving Myocardial Injury in Ovariectomized Mice Based on Non-targeted Metabolomics
Ying YANG ; Jing HU ; Pei LI ; Ruyuan ZHU ; Zhiguo ZHANG ; Haixia LIU ; Yanjing CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):74-84
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.
2.Identification of a JAK-STAT-miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions.
Songyang LI ; Yongjie LIU ; Xiaofeng YIN ; Yao YANG ; Xinjia LIU ; Jiaxing QIU ; Qinglan YANG ; Yana LI ; Zhiguo TAN ; Hongyan PENG ; Peiwen XIONG ; Shuting WU ; Lanlan HUANG ; Xiangyu WANG ; Sulai LIU ; Yuxing GONG ; Yuan GAO ; Lingling ZHANG ; Junping WANG ; Yafei DENG ; Zhaoyang ZHONG ; Youcai DENG
Acta Pharmaceutica Sinica B 2025;15(4):1922-1937
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.
3.Peptide-based immuno-PET/CT monitoring of dynamic PD-L1 expression during glioblastoma radiotherapy.
Yong WANG ; Kewen HE ; Yang ZHANG ; Yunhao CHEN ; Shijie WANG ; Kunlong ZHAO ; Zhiguo LIU ; Man HU
Journal of Pharmaceutical Analysis 2025;15(3):101082-101082
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.
4.Research progress in online monitoring technologies for workplace dust concentration
Qiangzhi GUO ; Yuntao MU ; Jinning YU ; Chuntao GE ; Chen WANG ; Zhiguo ZHOU ; Xue JIANG ; Yazhen WANG ; Jinling LIU ; Di LIU ; Shibiao SU
China Occupational Medicine 2025;52(4):472-476
Occupational pneumoconiosis remains the most common occupational disease in China, with occupational mineral dust exposure being its primary causative factor. Although national standards for online monitoring and early warning systems of coal mine dust concentrations have been established, national occupational health standards for rapid and online monitoring of dust concentration and particle size distribution in other industries are still limited. Among dust concentration sensor technologies, the light scattering method is the preferred choice for online dust monitoring owing to its wide measurement range and low cost. The beta-ray absorption method is mature but highly sensitive to humidity. The electrostatic induction method offers high sensitivity, simple structure, and low maintenance costs but exhibits high errors in low-concentration dust monitoring. The tapered element oscillating microbalance method is highly sensitive but costly. Multi-sensor data fusion technology can improve monitoring reliability, however, mature domestic products are not yet available. For monitoring dust particle size distribution, sieving and sedimentation methods are cumbersome. The aerodynamic method shows broad prospects in the online monitoring of respirable dust but has obvious measurement errors for larger dust particles. The use of optical measurement method is limited by dust morphology and is not suitable for monitoring coal dust particle size distribution. The electrical mobility method is primarily applicable to submicron dust. Future research should focus on promoting the application of monitoring technology for respirable dust particle size distribution in online monitoring of industrial dust. By integrating Internet of Things, data mining, and artificial intelligence technologies, along with multi-sensor data fusion and numerical simulation, dust concentration prediction models can be established to achieve accurate dust concentration monitoring and early warning of exceedances. The advancements of technologies will provide scientific support for the assessment of industrial dust hazards and the prevention and control of occupational pneumoconiosis.
5.Analysis of national external quality assessment results for transfusion compatibility test, 2018 to 2023
Junhua HU ; Peng ZHANG ; Jiali LIU ; Zhiguo WANG ; Yanming LIU ; Shengchen TIAN ; Wanru MA ; Xiang LI ; Xuebin ZHAO ; Feng XUE ; Yuntian WANG ; Dong LIN ; Zheng SUN ; Jiwu GONG ; Lin ZHOU
Chinese Journal of Blood Transfusion 2025;38(12):1720-1727
Objective: To analyze the results of national external quality assessment (EQA) for transfusion compatibility test from 2018 to 2023, with the aim of providing references for improving laboratory testing quality and ensuring the safety of clinical blood transfusion. Methods: Three EQA programs were conducted annually, each distributing 22 quality assessment samples. Participating transfusion laboratories were required to complete testing within specified deadlines and to submit results along with documentation of testing methodologies, reagents, and equipment used. National Center for Clinical Laboratories (NCCL) conducted statistical analysis of laboratory results, evaluated testing outcomes and related circumstances, and provided feedback to participating laboratories. EQA data from transfusion laboratories across China from 2018 to 2023 were collected and systematically analyzed. Results: From 2018 to 2023, the qualification rates for all five items (ABO forward typing, ABO reverse typing, Rh blood group typing, antibody screening, and cross-matching) were 67.59%, 77.11%, 77.38%, 72.78%, 79.96%, and 85.16%, respectively. The mean qualification rates for ABO forward typing, ABO reverse typing, RhD blood group typing, antibody screening, and cross-matching over the past six years were 96.25%±0.59%, 90.45%±4.52%, 96.05%±0.71%, 90.88%±2.86%, and 88.34%±3.48%, respectively. The qualification rates in 2019, 2020, 2022, and 2023 all showed a stable trend of "blood stations>tertiary hospitals>secondary hospitals". The mean qualification rate of laboratories in secondary hospitals from 2018 to 2023 was significantly lower than those of laboratories in tertiary hospitals and blood stations (P<0.05), while no significant difference was observed between laboratories in tertiary hospitals and blood stations (P>0.05). The micro column agglutination method was the most widely used in all five tests. In the four test items, namely ABO forward typing, ABO reverse typing, antibody screening, and cross-matching, there was a statistically significant difference in the qualification rate of micro column agglutination method compared to other methods (P<0.05). There was a statistical difference in the qualification rate between manual and automated detection using micro column agglutination method in the cross-matching tests (P<0.05), whereas no significant difference was noted for the other test items (P>0.05). Conclusion: From 2018 to 2023, the number of laboratories participating in EQA activities has been increasing year by year, and the qualification rate has shown an overall upward trend. The type of laboratory is a key factor affecting the qualification rate, and the testing capabilities of some laboratories still need to be improved. The micro column agglutination method is widely used in transfusion compatibility tests. The established EQA program effectively monitors quality issues in laboratories, drives continuous improvement, and ensures sustained enhancement of testing standards to safeguard clinical blood safety.
6.Stakeholder Preference Assessment in Implementation Research: Application of Best-worst Scaling
Run MAO ; Yiyuan CAI ; Wei YANG ; Zhiguo LIU ; Lang LINGHU ; Jiajia CHEN ; Mengjiao LIANG ; Lieyu HUANG ; Siyuan LIU ; Dong XU
Medical Journal of Peking Union Medical College Hospital 2024;16(1):224-234
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.
7.Comparative Study on Intelligent Audit and Monitoring Repository of Focused Audit Violations under DRG Payment
Zhiguo ZHANG ; Qingqin LIU ; Chen XIANG ; Xiangping LIU
Chinese Hospital Management 2024;44(6):77-82
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.
8.Comparative Study on Intelligent Audit and Monitoring Repository of Focused Audit Violations under DRG Payment
Zhiguo ZHANG ; Qingqin LIU ; Chen XIANG ; Xiangping LIU
Chinese Hospital Management 2024;44(6):77-82
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.
9.Application of melatonin-supplemented in vitro maturation technology for human oocytes during COH cycle
Yu REN ; Xingxing HAN ; Qiqi ZHANG ; Lu LIU ; Xiaofeng XU ; Zhiguo ZHANG ; Huijuan ZOU
Acta Universitatis Medicinalis Anhui 2024;59(6):983-988
Objective To compare the early embryonic developmental potential and clinical outcomes of oocytes matured in vivo and those matured by modified in vitro maturation(LVM)technology during the same controlled ovarian hyperstimulation(COH)cycle,and to explore the clinical application of melatonin-supplemented IVM technology.Methods 159 patients were recruited into the study.920 mature oocytes were collected during their COH cycles processed for conventional IVF/ICSI protocols,while 1 283 immature oocytes from the same cycles were matured in a melatonin-supplemented IVM medium before ICSI was performed.A retrospective analysis was conducted to compare the impact of conventional assisted reproductive technology and improved IVM technology on the outcomes of assisted reproductive therapy and pregnancy outcomes.Results Compared with mature oocytes collected from COH cycles treated with conventional IVF/ICSI,oocytes promoted by improved melatonin-supple-mented IVM technology had a lower rate of high-quality blastocyst formation.However,after embryo transfer,there was no significant difference in the clinical outcomes of mature oocytes obtained through two methods,including clinical pregnancy rate,full-term birth rate,neonatal length,and neonatal Apgar score.Conclusion The applica-tion of melatonin-supplemented IVM significantly increases the utilization of immature oocytes collected from COH cycles,improving the pregnancy outcomes of patients assisted by assisted reproductive technology.
10.Evaluation of Coefficients of Variation for Clinical Chemistry Tests Based on Internal Quality Control Data Across 5,425 Laboratories in China From 2013 to 2022
Wei WANG ; Zhixin ZHANG ; Chuanbao ZHANG ; Haijian ZHAO ; Shuai YUAN ; Jiali LIU ; Na DONG ; Zhiguo WANG ; Fengfeng KANG
Annals of Laboratory Medicine 2024;44(3):245-252
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.


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