1.The effect and mechanism of Huangkui capsule pretreatment of human umbilical cord mesenchymal stem cell-derived exosomes on improving renal ischemia-reperfusion injury
Yawei YAO ; Jiahui HE ; Hao WANG ; Yutong WANG ; Ruiyan WANG ; Xingyu WAN ; Yujia LIU ; Xinghua LÜ
Organ Transplantation 2025;16(2):237-245
Objective To explore the effects and mechanisms of human umbilical cord mesenchymal stem cell (HUC-MSC)-derived exosomes (Exo) pretreated with Huangkui capsules on renal ischemia-reperfusion injury (IRI). Methods HUC-MSCs were cultured in media containing different concentrations of Huangkui capsules for 24 hours to determine cell viability and select an appropriate concentration for subsequent experiments. HUC-MSCs were pretreated with 50 μg/mL Huangkui capsules for 24 hours, and Exo were extracted using an exosome extraction kit. The morphology was observed under a transmission electron microscope, particle size was measured by nanoparticle tracking analysis, and the expression of exosomal membrane surface marker proteins was detected by Western blot. Human renal tubular epithelial cells (HK-2 cells) were randomly divided into hypoxia/reoxygenation group (M group), hypoxia/reoxygenation + Exo group (E group), and hypoxia/reoxygenation + Huangkui capsules pretreated Exo group (H group). Western blotting was used to measure the expression of endoplasmic reticulum stress (ERS)-related proteins, and real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to measure the expression of ERS-related gene messenger RNA (mRNA). Mice were randomly divided into sham operation group (Sham group), ischemia-reperfusion group (I/R group), ischemia-reperfusion + Exo group (E group), and ischemia-reperfusion + Huangkui capsules pretreated Exo group (H group). Renal histological assessment, serum creatinine (Scr), blood urea nitrogen (BUN) measurement and inflammatory factor detection were performed 24 hours later. Results Both Exo and Huangkui capsules prereated Exo had a bilayer membrane structure and a cup-shaped morphology; their average particle sizes were 116.8 nm and 81.3 nm, respectively. Both expressed CD9, CD63, TSG101. Compared with the M group, the E group had decreased relative expression of transcription factor 6 (ATF6) and protein kinase R-like endoplasmic reticulum kinase (PERK) proteins, increased mRNA relative expression, increased relative expression of C/EBP homologous protein (CHOP) protein, and decreased mRNA relative expression. Compared with the E group, the H group had decreased relative expression of ATF6, PERK, CHOP proteins, and decreased mRNA relative expression of ATF6 and PERK (all P<0.05). Animal experimental results showed that compared with the Sham group, the I/R group had increased renal tubular injury scores, Scr, BUN, interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor (TNF)-α levels. Compared with the I/R group, the E and H groups had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels. Compared with the E group, the H group had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels (all P<0.05). Conclusions Huangkui capsules pretreatment HUC-MSC-derived Exo may alleviate renal IRI by inhibiting ERS.
3.Requirements and Technical Aspects of Real world Data Governance in China's Medical Standards and Specifications
Xinmiao GUAN ; Yanzi ZHU ; Hao LIU ; Minjing LUO ; Changhao LIANG ; Feng CAO ; Zhihan LIU ; Jianguo ZHOU ; Dong ZHANG ; Yutong FEI
Medical Journal of Peking Union Medical College Hospital 2025;16(4):1008-1017
Objective To investigate the governance requirements for real world data(RWD)in China's medical standards and specifications,summarize key technical aspects of data governance,and provide refer-ences for RWD governance-related research.Methods Computerized searches were conducted in CNKI,Wan-fang Data,VIP,and SinoMed,as well as the official websites of 29 national medical societies and the National Standard Information Public Service Platform,covering all records from inception to December 12,2023.A data extraction form was developed,and the included standards and specifications were categorized according to the first six RWD governance processes outlined in the Guidelines for Real World Data Used to Generate Real-World Evidence(Trial)issued by the National Medical Products Administration:data security,data extraction,data cleaning,data transformation,data transmission and storage,and quality control.Relevant content on data governance was systematically summarized and comparatively analyzed.Results A total of 32 standards and specifications were included,comprising 15 foundational medical data standards and 17 data gov-ernance technical specifications.Among these,6 addressed data security,6 covered data extraction,5 focused on data cleaning,5 involved data transformation,6 pertained to data transmission and storage,and 4 discussed quality control.Foundational medical data standards included data description elements,terminology,and format standards,broadly covering essential data elements and meeting basic standardization needs.Data gov-ernance technical specifications primarily provided general guidelines for medical data governance,emphasizing requirements and recommendations.While requirements for data security and extraction were relatively well-de-fined,technical guidance on data transformation and quality control remained limited,and implementation pathways for data cleaning,transmission,and storage were insufficiently detailed.Conclusions As real-world evidence plays an increasingly critical role in healthcare decision-making,China's medical standards and speci-fications have established a preliminary governance framework for RWD.However,technical details and practi-cal implementation of RWD governance still require further refinement.
4.Requirements and Technical Aspects of Real world Data Governance in China's Medical Standards and Specifications
Xinmiao GUAN ; Yanzi ZHU ; Hao LIU ; Minjing LUO ; Changhao LIANG ; Feng CAO ; Zhihan LIU ; Jianguo ZHOU ; Dong ZHANG ; Yutong FEI
Medical Journal of Peking Union Medical College Hospital 2025;16(4):1008-1017
Objective To investigate the governance requirements for real world data(RWD)in China's medical standards and specifications,summarize key technical aspects of data governance,and provide refer-ences for RWD governance-related research.Methods Computerized searches were conducted in CNKI,Wan-fang Data,VIP,and SinoMed,as well as the official websites of 29 national medical societies and the National Standard Information Public Service Platform,covering all records from inception to December 12,2023.A data extraction form was developed,and the included standards and specifications were categorized according to the first six RWD governance processes outlined in the Guidelines for Real World Data Used to Generate Real-World Evidence(Trial)issued by the National Medical Products Administration:data security,data extraction,data cleaning,data transformation,data transmission and storage,and quality control.Relevant content on data governance was systematically summarized and comparatively analyzed.Results A total of 32 standards and specifications were included,comprising 15 foundational medical data standards and 17 data gov-ernance technical specifications.Among these,6 addressed data security,6 covered data extraction,5 focused on data cleaning,5 involved data transformation,6 pertained to data transmission and storage,and 4 discussed quality control.Foundational medical data standards included data description elements,terminology,and format standards,broadly covering essential data elements and meeting basic standardization needs.Data gov-ernance technical specifications primarily provided general guidelines for medical data governance,emphasizing requirements and recommendations.While requirements for data security and extraction were relatively well-de-fined,technical guidance on data transformation and quality control remained limited,and implementation pathways for data cleaning,transmission,and storage were insufficiently detailed.Conclusions As real-world evidence plays an increasingly critical role in healthcare decision-making,China's medical standards and speci-fications have established a preliminary governance framework for RWD.However,technical details and practi-cal implementation of RWD governance still require further refinement.
5.Clinical performance of fecal syndecan 2/tissue factor pathway inhibitor 2 gene methylation assay in colorectal cancer screening
Tiao ZHANG ; Yutong HAO ; Haiyan WEN ; Qijun LIU
Journal of Chongqing Medical University 2025;50(7):983-987
Objective:To investigate the clinical performance of fecal syndecan 2(SDC2)/tissue factor pathway inhibitor 2(TFPI2)gene methylation assay in prospective colorectal cancer screening.Methods:The individuals who underwent routine physical examina-tion were enrolled as subjects,and their fecal samples were collected and tested with fecal SDC2/TFPI2 gene methylation assay.In addition,enteroscopy was recommended for the subjects with positive results.Results:A total of 1215 subjects received fecal SDC2/TFPI2 gene methylation assay,among whom there were 708 male subjects and 507 female subjects,with a mean age of(44.7±13.9)years.Among all subjects,28 had positive test results,resulting in a positive rate of 2.30%,and among these 28 subjects,27(96.43%)underwent enteroscopy,among whom 16(59.26%)had abnormal findings.With enteroscopy and/or pathological examination as diag-nostic criteria,fecal SDC2/TFPI2 gene methylation assay had a positive predictive value of 7.41%for colorectal cancer,22.22%for progressive precancerous lesion,and 7.41%for non-progressive precancerous lesion.Conclusion:Fecal SDC2/TFPI2 gene methyla-tion assay shows good clinical performance in prospective colorectal cancer screening and thus provides a noninvasive method for the screening and auxiliary diagnosis of colorectal cancer.
6.Multiple synchronous pituitary neuroendocrine tumors(PitNETs):a clinicopathological analysis of thirteen cases
Shixuan DU ; Yutong FU ; Qiqi SHAO ; Wenli GUO ; Zengfang HAO ; Lei LOU ; Yuehong LI
Chinese Journal of Clinical and Experimental Pathology 2024;40(5):490-496
Purpose To investigate the cell components in different tumor lineages of multiple synchronous pituitary neuro-endocrine tumors(PitNETs)/neuroendocrine tumors(MSPs)and to carry out accurate histological typing,which provides an important basis for determining the follow-up plan and adjuvant therapy after surgery.Methods The clinical data of 855 pa-tients with PitNETs were collected and reclassified according to the new WHO standard.The clinicopathological features of 13 patients diagnosed as MSPs were analyzed retrospectively.The immunohistochemical EnVision two-step method was used to de-tect the expression of PIT-1,SF-1,T-PIT,GH,PRL,TSH,LH,FSH,ACTH,etc.,and related literatures were reviewed.Methods A total of 855 cases of pituitary neuroendocrine tumor from the second hospital of the Chinese Hebei Medical U-niversity were collected and reclassified according to the new WHO standard,and review the literature.Results(1)The age of patients were 39-68 years with median age of 55 years.7 cases were female and 6 were male;(2)Imaging findings:There was 1.2~3.8 cm(mean 2.5 cm)in maximum tumor di-ameter.13 patients were large adenomas,neither MSPs nor sin-gle lineage PitNETs could not assessed on imaging;(3)Clinical manifestations:3 cases had hyperprolactinemia which all contai-ning PitNETs components of PRL,one case was immature PIT-1 polyhormone cell tumor,one was dense granular prolactinoma,and one case was eosinophilic stem tumor.One patient had Cushing's disease and contained a Crook cell tumor component;two had elevated ACTH,and one had an adrenocorticotropic ad-enomatous component.In the two patients with no evidence of hormone excess,all contained gonadotropin cell tumor compo-nents;(4)Combination form:11 cases of the combination of the two cell lineages(5 cases of combination of SF-1 lineage and PIT-1 lineage;4 cases of combination of T-PIT lineage and PIT-1 lineage;1 case of null cell tumor and PIT-1 lineage;1 case of plurihormonal PitNETs and SF-1 lineage);Two cases of three cell combinations(null cell tumor,PIT-1 lineage,and T-PIT lineage);Among them,13 cases were PIT-1 lineage tumors,46.2%(6/13)were gonadotropin cell tumor,38.5%(5/13)were prolactinoma;(5)The presence of high-risk lineage tumors in the 10 patient combinations:3 immature PIT-1-lineage tumor,1 Crooke cell PitNETs,1 acidophil stem cells tumor,3 zero-cell PitNETs,and 4 silent-type sparse granular adrenocorti-cotropic hormone PitNETs;Two of them were combinations of two high-risk subtypes.Conclusion MSPs in our center are large adenomas,although their incidence is only 1.5%of Pit-NETs,2/3 cases have high-risk lineage tumor components,and the use of pituitary cell lineage transcription factors and adeno-hypophyseal hormones plays an important role in distinguishing and clarifying the different components of MSPs.
7.Analysis of research hotspots and trend of the clinical comprehensive evaluation of Chinese patent medicine in China
Hongguo RONG ; Jiaxin HAO ; Mei HAN ; Jianping LIU ; Yutong FEI
China Pharmacy 2023;34(16):1921-1925
OBJECTIVE To analyze the research status, hotspots, and trend of the clinical comprehensive evaluation of Chinese patent medicine in China. METHODS Based on CNKI, VIP and Wanfang database, clinical comprehensive evaluation of Chinese patent medicine was used as the subject of retrieval, and the retrieval time was from the inception to October 30th, 2022. CiteSpace 6.1.R3 and VOSviewer were used to conduct a visualization analysis of the relative literature of clinical comprehensive evaluation of Chinese patent medicine in terms of annual publication quantity, authors, institutions, keywords, etc. RESULTS & CONCLUSIONS A total of 1 460 pieces of literature related to the clinical comprehensive evaluation of Chinese patent medicine were included. The overall annual publication quantity showed a growth trend. There were 714 authors in the included literature. The institutions with a large publication quantity included the Chinese Academy of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, etc., and there was little cooperation among the authors and institutions. High-frequency keywords included Chinese patent medicine, safety, adverse drug reactions, rational drug use, etc. Research hotspots focused on the safety and effectiveness evaluation of Chinese patent medicine. It may be a research trend in this field to strengthen the prescription review of Chinese patent medicine, and build a multi-dimensional and multi-criteriaclinical comprehensive evaluation system for the rational use of Chinese patent medicine.
8.Effect of hemopurification on acute chlorfenapyr poisoning
Yutong SHI ; Zhengsheng MAO ; Feng CHEN ; Jinsong ZHANG ; Yi ZHU ; Hao SUN ; Yu XIA ; Tao DING ; Peipei HUANG
Chinese Journal of Emergency Medicine 2023;32(2):215-219
Objective:To evaluate the therapeutic effect of hemopurification on acute chlorfenapyr poisoning according to the blood concentration of chlorfenapyr and to provide experience for clinical treatment.Methods:Two patients who presented to our Emergency Department following an ingestion of chlorfenapyr and then were treated with hemopurification in 2022 were included. The concentrations of chlorfenapyr and its highly toxic metabolite tralopyril were dynamically monitored, and the clinical data of the patients were collected.Results:Case 1 was given hemoperfusion for the first time 13 hours after ingestion. During l hour hemoperfusion, the tralopyril decreased by 28.82%. The concentration increased and exceeded the pre-perfusion level after 2 hours of hemoperfusion. After three times of hemoperfusion, the concentrations of chlorfenapyr and tralopyril were still higher than those before the first time, reaching 248 ng/mL and 1 307 ng/mL respectively. The concentration of chlorfenapyr showed a downward trend after 130 h, and the tralopyril in blood reached the peak 3 164 ng/mL at 130 h and decreased to 2 707 ng/mL at 178 h. In case 2, the blood chlorfenapyr and tralopyril concentration was 392 ng/mL and 7 598 ng/mL respectively 150 hours after ingestion. The blood chlorfenapyr concentration decreased by 37.75% respectively after first hemoperfusion, and the tralopyril concentration decreased by 38.02% respectively. During 85 hours of continuous veno-venous hemodiafiltration (CVVHDF), the concentration of tralopyril was maintained at 4 234~6 410 ng/mL. Case 1 was followed up to 12 days and lost follow-up. Case 2 died and the survival time was 247 hours.Conclusions:Hemoperfusion can scavenge tralopyril, but CVVHDF has poor scavenging ability for tralopyril. And the apparent volume of distribution (Vd) of chlorfenapyr and tralopyril are large. After ingestion, chlorfenapyr spreads to various tissues quickly, and it is easy to accumulate in the adipose tissue. The chlorfenapyr in the tissue slowly is released back to the blood and stays in the blood for a long time. The peak concentration of chlorfenapyr appeared earlier than that of tralopyril. Clinicians should pay attention to the early removal of toxins from the digestive tract.
9.Analysis of clinical characteristics of 294 acute poisoning patients with gastric lavage
Yutong SHI ; Jinsong ZHANG ; Yu XIA ; Tianshi LI ; Hao SUN ; Lili JIANG ; Peipei HUANG
Chinese Journal of Emergency Medicine 2023;32(2):220-224
Objective:To describe the current situation of gastric lavage operation and put forward measures for improvement by analyzing the clinical characteristics of 294 patients with gastric lavage in Poisoning Treatment Center of The First Affiliated Hospital of Nanjing Medical University.Methods:The clinical data of 294 patients with acute poisoning and gastric lavage from 2019 to 2021 were collected and analyzed retrospectively, and the related parameters (poison type, gastric lavage volume, poisoning to gastric lavage time, etc.) of each year were compared.Results:A total of 653 poisoning patients underwent gastric lavage from 2019 to 2021, with an average age of (44.2 ±20.1) years, and 134 (45.6%) were male. The main causes of gastric lavage were pesticide poisoning (52.72%) and drug poisoning (42.86%). The volume of gastric lavage was less than 10 L for 43.8% of patients and 10-20 L for 32.7% of patients. Patients with gastric lavage within 60 min after ingestion of poison accounted for 45.3%, followed by 25.8% within 61-120 min. The in-hospital mortality rate was 17.7%. The common complications of gastric lavage were: the incidence of gastrointestinal bleeding (55/121, 45.5%), the incidence of aspiration pneumonia (54/140, 38.6%), and the incidences of electrolyte disorder (21% of low potassium, 29% low calcium, and 10.0% low sodium). Compared with the groups in different years, the proportion of gastric lavage in poisoning was 58.85% vs. 46.60% vs. 32.41%, which decreased year by year, with statistical difference ( P <0.05). And there was no difference in the period from ingestion to gastric lavage and gastric lavage fluid volume. There was an increasing trend in poison types between diquat and other insecticides, but there was no statistical difference. Conclusions:From 2019 to 2021, the most common causes of acute gastric lavage were pesticide poisoning and drug poisoning, and the proportion of diquat and other pesticides showed an overall upward trend. A majority of the patients (71.1%) had gastric lavage within 2 h, and 76.5% of the patients had less than 20 L gastric lavage fluid. In the future, we will further control the amount of gastric lavage fluid and pay attention to the gastric lavage operation of new insecticide poisoning.
10.A metabolic intervention strategy to break evolutionary adaptability of tumor for reinforced immunotherapy.
Qianhua FENG ; Yutong HAO ; Shuaiqi YANG ; Xiaomin YUAN ; Jing CHEN ; Yuying MEI ; Lanlan LIU ; Junbiao CHANG ; Zhenzhong ZHANG ; Lei WANG
Acta Pharmaceutica Sinica B 2023;13(2):775-786
The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8+ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.

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