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.Comparison of clinical efficacy between unilateral biportal endoscopy and percutaneous endoscopic transforaminal discectomy in treatment of lumbar disc herniation
Jing ZENG ; Yindong SONG ; Zhiguo WANG ; Aiju LOU ; Dongdong WU ; Bing XU ; Jiayi LIU ; Zili XIONG
Journal of Jilin University(Medicine Edition) 2025;51(5):1349-1357
Objective:To analyze the efficacies of unilateral biportal endoscopy(UBE)and percutaneous endoscopic transforaminal discectomy(PETD)in treatment of lumbar disc herniation(LDH),and to explore the optimal selection of minimally invasive surgical approaches for the The LDH patients.Methods:A retrospective analysis was performed on the clinical data of 64 LDH patients who underwent surgery at Liwan Central Hospital of Guangzhou City in Guangdong Province,between January 2020 and June 2024.The surgical approaches were determined through physician-patient communication,and the patients were divided into UBE group(n=30)and PETD group(n=34).The materials of patients were recorded including gender,age,body mass index(BMI),percentages of affected segments,course of disease,duration of hospitalization,operation duration,intraoperative blood loss,numbers of intraoperative fluoroscopy,total incision length,and time to full weight-bearing(WB).The therapeutic outcomes were evaluated using Oswestry disability index(ODI),Visual Analog Scale(VAS)scores for low back pain and leg pain,MacNab criteria,and spinal canal areas at the affected segment.the postoperative complications of the patients in two groups were analyzed.Results:There were no statistically significant differences in age,gender composition ratio,BMI,course of disease,and percentages of affected segments of the patients between UBE group and PETD group(P>0.05).Compared with PETD group,the intraoperative blood loss,total incision length,and time to full WB of the patients in UBE group were significantly increase(P<0.01),while the number of intraoperative fluoroscopy time was decreased(P<0.01).Compared with pre-operation,the ODI scores and VAS scores for low back and leg pain of the patients at final follow-up in both groups were decreased(P<0.01),and the spinal canal areas at the affected segments of the patients were increased(P<0.01).At final follow-up,compared with PETD group,the ODI score and VAS scores for low back and leg pain of patients in UBE group were decreased(P<0.01),while the spinal canal areas at the affected segments of the patients was increased(P<0.01).According to MacNab criteria,the percentages of excellent and good had no significant difference between two groups(P>0.05).The incidence of complication showed no statistical difference between two groups(P>0.05).Conclusion:Both UBE and PETD yield satisfactory outcomes in the treatment of single-segment LDH.PETD is less invasive and permits earlier time to full WB,whereas UBE provides more extensive decompression and superior long-term efficacy.The surgical approach selection should be individualized based on specific factors in the clinic.
7.Therapeutic Efficacy of Yiqi Wenyang Sanjie Decoction for Patients with Pulmonary Ground Glass Nodules and Yang-Deficiency Constitution and Its Effect on Serum Inflammatory Factors and Immune Function
Jinling SONG ; Hui ZHAO ; Zhiguo ZHANG ; Mingjun LIU ; Shuai CHEN ; Xiaolin LEI ; Hui JI
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(5):1091-1096
Objective To investigate the efficacy of Yiqi Wenyang Sanjie Decoction in the treatment of patients with pulmonary ground glass nodules and yang-deficiency constitution,and to observe its effect on serum inflammatory factors and immune function.Methods From January 2020 to June 2024,a total of 106 patients with pulmonary ground glass nodules and yang-deficiency constitution admitted to the Department of Respiratory Medicine and Preventive Treatment of Disease Center of Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine were selected.The patients were randomly divided into control group and Chinese medicine group by random number table method,with 53 cases in each group.The patients in the control group were only given follow-up without any intervention,and the patients in the Chinese medicine group were treated with Yiqi Wenyang Sanjie Decoction for 3 months.Before and after treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,maximum diameter of pulmonary ground glass nodules,serum levels of inflammatory factors of interleukin-6(IL-6),interleukin-17A(IL-17A),and tumor necrosis factor-α(TNF-α),and levels of immune function indicators of peripheral blood CD3+,CD4+cell percentage and CD4+/CD8+ratio.After treatment,the efficacy and safety of the two groups were evaluated.Results(1)During the trial,5 cases fell off from the control group and 3 cases fell off from the Chinese medicine group.A total of 98 cases were eventually included,and 48 cases were in the control group and 50 cases were in the Chinese medicine group.(2)After 3 months of treatment,the total effective rate of the Chinese medicine group was 46.00%(23/50),and that of the control group was 10.42%(5/48).The intergroup comparison(tested by chi-square test)showed that the efficacy of the Chinese medicine group was significantly superior to that of the control group(P<0.01).(3)After treatment,the TCM syndrome score and the maximum diameter of pulmonary ground glass nodules in the Chinese medicine group were lowered(P<0.05),while the TCM syndrome score and the maximum diameter showed no obvious changes compared with those at enrollment(P>0.05);the intergroup comparison showed that the reduction of TCM syndrome score and the maximum diameter of pulmonary ground glass nodules in the Chinese medicine group was significantly superior to that in the control group(P<0.05).(4)After treatment,the levels of serum inflammatory factors of IL-6,IL-17A and TNF-α in the Chinese medicine group were significantly lowered compared with those at enrollment(P<0.05),while there was no significant change in serum IL-6,IL-17A and TNF-α levels of the control group(P>0.05);the intergroup comparison showed that the decrease of serum IL-6,IL-17A and TNF-α levels in the Chinese medicine group was significantly superior to that in the control group(P<0.05).(5)After treatment,the percentage of T lymphocyte subset CD4+and the ratio of CD4+/CD8+in the Chinese medicine group were significantly increased compared with those at enrollment(P<0.05),while there was no significant change in the percentage of CD3+,CD4+cells and the ratio of CD4+/CD8+of the control group and in the percentage of CD3+cells of the Chinese medicine group(P>0.05).The intergroup comparison showed that the increase of CD4+percentage and CD4+/CD8+ratio in the Chinese medicine group was significantly superior to that in the control group(P<0.05).(6)There were no obvious adverse reactions occurring in the Chinese medicine group during the treatment,showing relatively high safety.Conclusion Yiqi Wenyang Sanjie Decoction exerts certain effect in the treatment of patients with pulmonary ground glass nodules and yang-deficiency constitution.It can effectively promote the reduction of nodules,relieve clinical symptoms,decrease serum levels of inflammatory factors,improve immune function,and has good safety.
8.Inhibitory Effect of Sinomenine on Human Glioblastoma and Its Pharmacokinetic Characteristics
Yue JIAO ; Yumao JIANG ; Danqiao WANG ; Jingyi WANG ; Yang LIU ; Xiaoliang ZHAO ; Zhiguo WANG ; Tao LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):179-186
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 Cmax and AUC in the tumor significantly increased, Tmax 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.
9.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.
10.Evaluate the Performance of Statistical Quality Control Procedures in Westgard Sigma Rules Based on Power Function Graphs in Clinical Laboratories
Jiali LIU ; Wei WANG ; Bingquan CHEN ; Zhiguo WANG
Journal of Modern Laboratory Medicine 2024;39(1):175-178,191
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.

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