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Single-cell transcriptomic dissection of the cellular and molecular events underlying the triclosan-induced liver fibrosis in mice

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Military Medical Research 2023年第5期10卷 599-619页

作者： Yun-Meng Bai Fan Yang Piao Luo Lu-Lin Xie jun-hui chen Yu-Dong Guan Hong-Chao Zhou Teng-Fei Xu hui-Wen Hao Bing chen Jia-hui Zhao Cai-Ling Liang Ling-Yun Dai Qing-Shan Geng Ji-Gang Wang Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People’s Hospitalthe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China Department of Urology Shenzhen People’s Hospitalthe First Affiliated HospitalSouthern University Science and Technologythe Second Clinical Medical CollegeJinan UniversityShenzhen 518020China Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou 510632China Artemisinin Research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Center for Reproductive Medicine Dongguan Maternal and Child Health Care HospitalSouthern Medical UniversityDongguan 523125GuangdongChina

Background: Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS], a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation stage.Methods: C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing(scRNA-seq) was then carried out on TCS-or mock-treated mice livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor(TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the cellular and molecular events after TCS exposure. To verify the TCS-induced liver fibrosis,the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson’s trichrome and Sirius red stainings. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic technologies.Results: We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control groups profiled the gene expressions of > 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells(HSCs)were significantly increased in TCS-treated group. We found that TCS promoted fibros

关键词： Triclosan Single cell RNA sequencing Liver fibrogenesis Hepatic stellate cell

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The mechanism and relevant mediators associated with neuronal apoptosis and potential therapeutic targets in subarachnoid hemorrhage

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Neural Regeneration Research 2023年第2期18卷 244-252页

作者： Qi Tian Sheng Liu Shou-Meng Han Wei Zhang Xian-Yao Qin jun-hui chen cheng-Li Liu Yu-Jia Guo Ming-Chang Li Department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.

关键词： blood-brain barrier mechanism mediators neuronal apoptosis pathways subarachnoid hemorrhage targets treatment

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An early neuroprotective effect of atorvastatin against subarachnoid hemorrhage

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Neural Regeneration Research 2020年第10期15卷 1947-1954页

作者： jun-hui chen Ting Wu Wen-Yuan Xia Zhong-Hua Shi Chun-Lei Zhang Lei chen Qian-Xue chen Yu-Hai Wang Department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina Department of Neurosurgery Wuxi Clinical College of Anhui Medical University904 Hospital of Joint Logistic Support Force of PLAWuxiJiangsu ProvinceChina Department of Cardiology Wuxi Clinical College of Anhui Medical University904 Hospital of Joint Logistic Support Force of PLAWuxiJiangsu ProvinceChina Department of Science and Education Wuxi Clinical College of Anhui Medical University904 Hospital of Joint Logistic Support Force of PLAWuxiJiangsu ProvinceChina

Atorvastatin has been shown to reduce early brain edema and neuronal death after subarachnoid hemorrhage,but its mechanism is not clear.In this study,rat models of subarachnoid hemorrhage were established by autologous blood injection in the cisterna magna.Rat models were intragastrically administered 20 mg/kg atorvastatin 24 hours before subarachnoid hemorrhage,12 and 36 hours after subarachnoid hemorrhage.Compared with the controls,atorvastatin treatment demonstrated that at 72 hours after subarachnoid hemorrhage,neurological function had clearly improved;brain edema was remarkably relieved;cell apoptosis was markedly reduced in the cerebral cortex of rats;the number of autophagy-related protein Beclin-1-positive cells and the expression levels of Beclin-1 and LC3 were increased compared with subarachnoid hemorrhage only.The ultrastructural damage of neurons in the temporal lobe was also noticeably alleviated.The similarities between the effects of atorvastatin and rapamycin were seen in all the measured outcomes of subarachnoid hemorrhage.However,these were contrary to the results of 3-methyladenine injection,which inhibits the signaling pathway of autophagy.These findings indicate that atorvastatin plays an early neuroprotective role in subarachnoid hemorrhage by activating autophagy.The experimental protocol was approved by the Animal Ethics Committee of Anhui Medical University,China(904 Hospital of Joint Logistic Support Force of PLA;approval No.YXLL-2017-09)on February 22,2017.

关键词： 3-methyladenine apoptosis atorvastatin autophagy early brain injury LC3 neuroprotection rapamycin subarachnoid hemorrhage

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Expression signatures of long non-coding RNA and mRNA in human traumatic brain injury

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Neural Regeneration Research 2019年第4期14卷 632-641页

作者： Li-Xiang Yang Li-Kun Yang Jie Zhu jun-hui chen Yu-Hai Wang Kun Xiong Department of Neurosurgery 101st Hospital of People's Liberation Army Department of Anatomy and Neurobiology School of Basic Medical Sciences Central South University

Long non-coding RNAs(lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101 st Hospital of the People's Liberation Army, China(specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue. Volcano plot filtering identified 99 lncRNAs and 63 mRNAs differentially expressed in frontotemporal tissue of the two groups(P 1.2). Microarray analysis showed that 43 lncRNAs were up-regulated and 56 lncRNAs were down-regulated. Meanwhile, 59 mRNAs were up-regulated and 4 mRNAs were down-regulated. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses revealed 27 signaling pathways associated with target genes and, in particular, legionellosis and influenza A signaling pathways. Subsequently, a lncRNA-gene network was generated, which showed an absolute correlation coefficient value > 0.99 for 12 lncRNA-mRNA pairs. Finally, quantitative real-time polymerase chain reaction confirmed different expression of the five most up-regulated mRNAs within the two groups, which was consistent with the microarray results. In summary, our results show that expression profiles of mRNAs and lncRNAs are significantly different between human traumatic brain injury tissue and surrounding tissue, providing novel insight regarding lncRNAs' involvement in human traumatic brain injury. All participants provided informed consent. This research was registered in the Chinese Clinical Trial Registry(registration number: ChiCTR-TCC-13004002) and the protocol version number is 1.0.

关键词： nerve regeneration human traumatic brain injuries long noncoding RNA messenger RNA GO analysis real-time quantitative polymerase chain reaction biomarkers microarray analysis biological processes medical informatics neural regeneration

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Relationship between genotypes and clinical manifestation, pathology, and cccDNA in Chinese children with hepatitis B virus-associated glomerulonephritis

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世界儿科杂志:英文版 2016年第3期12卷 347-352页

作者： Yong-Hong Sun Xiao-Yan Lei Yi-Pa Sai jun-hui chen Yuan-Chun Sun Xia Gao Department of Pediatrics People's Hospital of Gansu ProvinceLanzhouGansuChina

Background:Hepatitis B virus-associated glomerulonephritis(HBV-GN)is one of the extrahepatic manifestations after HBV infection,which would cause great clinical harm to people.The present study was undertaken to investigate the HBV-GN genotypes and its clinical relevance in Chinese children.Methods:A total of 41 HBV-infected children diagnosed with HBV-GN were enrolled in the study.All patients underwent liver and kidney biopsy.The genotypes and cccDNA were detected in their serum samples to analyze the relationship between HBV genotypes and clinical characteristics,cccDNA,and pathology.Results:Among the 41 children with HBV-GN,29(70.7%)had genotype C,10(24.4%)had genotype B,2(4.9%)had genotype B/C,and none of them had genotype non-B/C.Most children had genotypes B or C;moreover,the genotype C was the most frequent one.The incidence of hematuria and albuminuria,reduction in complement C3,increase in serum alanine aminotransferase levels and renal insufficiency in the children with genotype C were signifi cantly higher than those in the children with genotype B(P0.05).The frequency of HBV cccDNA positive in the genotype C group was significantly higher than that in the genotype B group(72.4%vs.30.0%,P0.05).Conclusion:Genotype C was the most frequent genotype in the described group of patients with HBV-GN,and the liver and kidney damage indicators were more likely to occur in patients with genotype C.

关键词： cccDNA genotypes glomerulonephritis hepatitis B virus pathology

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Research on focal nodular hyperplasia with MSCT and postprocessing

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World Journal of Gastroenterology 2009年第38期15卷 4838-4843页

作者： Yuan-Jian Liu Wei-jun Fan Zhi-Dong Yuan Peng-cheng Liu Chun-Rong Wang Wei-Qiang Yan Su-Mei Wang jun-hui chen Zheng Liu Imaging Center Peking University Shenzhen HospitalShenzhen 518036 Guangdong Province China State Key Laboratory of Oncology in Southem China Imaging and Interventional Center Cancer Center Sun Yat-sen University Guangzhou 510060 Guangdong Province China

AIM:To investigate and evaluate the pathological features and diagnostic value of focal nodular hyperplasia (FNH) with multi-section spiral computed tomography (MSCT) and postprocessing.METHODS: A total of 25 patients with FNH who had undergone MSCT and postprocessing were included in the investigation. All patients had been pathologically or clinically confi rmed with FNH. A number of 75 cases of hepatic carcinomas, hemangiomas and adenomas were randomly selected at a same period for a comparative study.RESULTS: There was a single focus in 22 cases and multiple foci in 3 cases. On the plain scan, 17 lesions showed hypodensity, 7 isodensity and 4 hyperdensity (the case with fatty liver). With contrast, 28 lesions were enhanced evenly or in the nodules in the arterial phase; 13 lesions still showed hyperdensity, 11 lesions isodensity and 4 lesions hypodensity in the parenchymatous phase; in the delayed phase only 5 lesions showed hyperdensity but 9 lesions showed isodensity or slight hypodensity and 14 lesions showed hypodensity. Twelve lesions of 28 had central asteroid scars. Thickened feeding arteries in postprocessing were seen in 24 lesions, and were integrated into the parenchymatous lesions with a gradual and smooth course. On the contrary, there were no artery penetrated into the lesion found in any of comparative hepatic tumors.CONCLUSION: Doctors could make a correct diagnosis and differentiation of FNH on evaluation of the characteristic appearance on MSCT with postprocessing.

关键词：螺旋CT 后处理增生结节多层诊断价值病理特点低密度

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Imaging presentation and postoperative recurrence of peliosis hepatis: A case report

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World Journal of Clinical Cases 2021年第19期9卷 5197-5202页

作者： Si-Xie Ren Pan-Pan Li Hai-Peng Shi jun-hui chen Zhen-Ping Deng Xi-E Zhang Department of Radiology Chengdu Second People’s HospitalChengdu 610000Sichuan ProvinceChina Pathology Center Chengdu Second People’s HospitalChengdu 610000Sichuan ProvinceChina

BACKGROUND Peliosis hepatis(PH)is a rare benign lesion of vascular origin with a pathological characteristic of multiple blood-filled cavities in the liver parenchyma.It is commonly misdiagnosed due to its lack of specificity in clinical presentation and laboratory test results.Herein,a case of a patient with PH who was misdiagnosed with hepatic echinococcosis before operation to remove the lesions was analyzed,with an emphasis on the computed tomography and magnetic resonance imaging characteristics of PH.CASE SUMMARY We outline the case of a 40-year-old Chinese female who was admitted with aggravated abdominal pain with fever for 1 wk.Ultrasound examination at the local hospital indicated hepatic echinococcosis.However,discordance between imaging diagnosis,clinical history and laboratory examinations in our hospital.Subsequently,the patient was pathologically confirmed as having PH-like changes,which recurred 1 year after operation removal of the lesion.CONCLUSION Our objective is to highlight the imaging diagnostic value of PH.

关键词： Peliosis hepatis Computer tomography Magnetic resonance imaging Recurrence Misdiagnosis Case report

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Role of polarization evolution in the hysteresis effect of Pb-based antiferroelecrtics

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Chinese Chemical Letters 2024年第4期35卷 516-519页

作者： Botao Gao He Qi hui Liu jun chen Beijing Advanced Innovation Center for Materials Genome Engineering Department of Physical ChemistryUniversity of Science and Technology BeijingBeijing 100083China Shanghai Institute of Ceramics Chinese Academy of SciencesShanghai 201899China Hainan University Haikou 570228China

The electric field-induced irreversible domain wall motion results in a ferroelectric(FE) hysteresis. In antiferroelectrics(AFEs), the irreversible phase transition is the main reason for the hysteresis effects, which plays an important role in energy storage performance. Compared to the well-demonstrated FE hysteresis,the structural mechanism of the hysteresis in AFE is not well understood. In this work, the underlying correlation between structure and the hysteresis effect is unveiled in Pb(Zr,Sn,Ti)O_(3) AFE system by using in-situ electrical biasing synchrotron X-ray diffraction. It is found that the AFE with a canting dipole configuration, which shows a continuous polarization rotation under the electric field, tends to have a small hysteresis effect. It presents a negligible phase transition, a small axis ratio, and electric field-induced lattice changing, small domain switching. All these features together lead to a slim hysteresis loop and a high energy storage efficiency. These results offer a deep insight into the structure-hysteresis relationship of AFEs and are helpful for the design of energy storage material.

关键词： Antiferroelectric Hysteresis effect Structure refinement Perovskite In situ synchrotron radiation

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Remarkable Wear Resistance in a Complex Concentrated Alloy with Nanohierarchical Architecture and Composition Undulation

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Research 2024年第1期2023卷 403-416页

作者： Yushan Geng Wenyuan chen hui Tan jun cheng Shengyu Zhu jun Yang Weimin Liu State Key Laboratory of Solid Lubrication Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou 730000PR China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049PR China Shandong Laboratory of Yantai Advanced Materials and Green Manufacturing Yantai 264000PR China

Sustained wear damages on the sliding surfaces of alloys are generally the culprit responsible for the failure of various mechanical systems.Inspired by high-entropy effects,here we deliberately deploy nanohierarchical architecture with composition undulation in a Ni50(AlNbTiV)_(50) complex concentrated alloy,which yields ultralow wear rate within the order of 10^(−7) to 10^(−6) mm^(3)/Nm between room temperature and 800℃.Such remarkable wear resistance heretofore represents one of the highest wear resistance reported for the bulk alloys or composites,and originates from the multi-type adaptive friction interface protection governed by intrinsically nano-coupled grains and nanoprecipitates.This cooperative heterostructure releases gradient frictional stress in stages upon wear at room temperature through the coexistence of multiple deformation pathways while activating a dense nanocrystalline glaze layer upon wear at 800℃ to minimize adhesive and oxidative wear.Our work uncovers a practical avenue for tailoring wear properties with multicomponent heterostructures over a wide temperature range.

关键词： wear alloys friction

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Pancreatic giant malignancy simulating a gastrointestinal stromal tumor

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 431-433页

作者： Ben-Jie Liu chen-hui Jin Yan-Lun Guo Zhi-Gang Ke jun-jun Huang Lin-Ping Cao Department of Hepatobiliary Surgery Department of General SurgeryPujiang Branch of the First Affiliated HospitalZhejiang University School of MedicineJinhua 322200China Department of Pathology Pujiang Branch of the First Affiliated HospitalZhejiang University School of MedicineJinhua 322200China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Pancreatic acinar cell carcinoma(PACC)is a rare malignant tumor of pancreatic epithelial cells,which produces pancreatic exocrine enzymes.PACC originates from acinar cells and terminal branches of the pancreatic ducts in the exocrine tissue of the pancreas.PACC accounts for 1%−2%of pancreatic exocrine tumors[1].Herein,we present an elderly woman with PACC who recovered after effective laparoscopic surgery.The tumor was located on the left side of the abdomen;imaging suggested that it was a gastrointestinal stromal tumor of the gastric wall origin,infiltrating the tail of the pancreas and omentum,while postoperative pathology suggested PACC.

关键词： Pancreatic gastrointestinal pancreas

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