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Involvement of interstitial cells of Cajal in experimental severe acute pancreatitis in rats

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World Journal of Gastroenterology 2013年第14期19卷 2179-2186页

作者： Liang-Liang Shi Ming-Dong Liu Min Chen Xiao-Ping Zou department of Gastroenterology Medical Schoolthe Affiliated Drum Tower Hospital of Nanjing University

AIM:To observe the changes in interstitial cells of Cajal(ICC) in rats with experimental severe acute pancreatitis(SAP).METHODS:A total of twenty-four SD rats were randomly divided into two groups(n = 12),namely the sham(S) group and the SAP group;the SAP rat model was established by retrograde injection of 5% sodium taurocholate(1.0 mL/kg) into the pancreatic ***-four hours later intestinal motility was assessed by testing small intestinal propulsion rate,and then the rats were *** pancreas and jejunum were resected and underwent routine pathologic *** staining was used to detect c-kit-positive cells in the *** of c-kit mRNA was detected by real-time polymerase chain reaction,and the expression of c-kit protein was evaluated by Western *** of ICC was evaluated by transmission electron ***:There was bleeding,necrosis and a largeamount of inflammatory cell infiltration in pancreatic tissue in the SAP group,while in jejunal tissue we observed a markedly denuded mucosal layer,loss of villous tissue and a slightly dilated muscular *** small intestinal propulsion rate was 68.66% ± 2.66% in the S group and 41.55% ± 3.85% in the SAP *** with the S group,the rate of the SAP group decreased *** density of c-kit-positive cells in the SAP group was significantly lower than in the S group;the respective mean densities were 88.47 ± 10.49 in the S group and 56.11 ± 7.09 in the SAP *** levels of c-kit protein and mRNA were 0.36 ± 0.04 and 1.29 ± 0.91 in the SAP group,respectively,which were significantly lower than those in the S group(0.53 ± 0.06,0.64 ± 0.33,respectively).In the SAP group,ICC profiles showed the same change tendency,such as vacuolation of mitochondria,irregular vacuoles and loosened desmosome-like ***:Decreased c-kit-positive cells and ultrastructural changes in ICC resulting from blockade of the c-kit signaling pathway

关键词： Severe acute pancreatitis c-kit Interstitial cells of Cajal Real-time polymerase chain reaction Ultrastructure

Mixed serous-neuroendocrine neoplasm of the pancreas: A case report and review of the literature

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World Journal of Clinical Cases 2019年第23期7卷 4119-4129页

作者： Yue-Mei Xu Zhi-Wen Li Hong-Yan Wu Xiang-Shan Fan Qi Sun department of Pathology Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School

BACKGROUND Pancreatic mixed serous-neuroendocrine neoplasms(MSNNs)are mixed tumors containing two components with different pathologies,namely,pancreatic serous cystic neoplasm(PSCN)and pancreatic neuroendocrine tumor(PanNET).For MSNNs,diffuse PSCN involving the whole pancreas is extremely rare,with only eight previous case *** SUMMARY A 45-year-old Chinese woman,with a free previous medical history and no obvious symptoms,was found to have a pancreatic neoplasm and admitted to our hospital for further diagnosis in March *** palpation revealed a painless,mobile mass in the epigastrium,and no abnormalities were observed in an examination of the nervous system and ocular system.A computed tomography scan showed multiple cystic lesions involving the whole pancreas ranging in diameter from 0.4 to 2 cm and also revealed an enhanced mass,2.2 cm in diameter,in the head of the ***,multiple cysts were found in the kidneys bilaterally,and the right lobe of the liver contained a small cyst.A Whipple operation with total pancreatectomy and splenectomy was performed.A diagnosis of pancreatic MSNN was established,consisting of diffuse serous microcystic cystadenoma with a concomitant grade 2 *** note,the patient had no personal or family history of Von Hippel-Lindau syndrome or other *** We report the first case of MSNN with a diffuse PSCN component involving the entire pancreas in a Chinese *** is important to be aware of its relationship with VHL syndrome,and close clinical follow-up is recommended.

关键词： Mixed serous-neuroendocrine neoplasm Pancreatic serous cystic neoplasm Pancreatic neuroendocrine tumor Von Hippel-Lindau syndrome Case report

Characteristics of SARS-CoV-2-specific cytotoxic T cells revealed by single-cell immune profiling of longitudinal COVID-19 blood samples

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Signal Transduction and Targeted Therapy 2021年第1期6卷 5-7页

作者： Qing Xiong Cheng Peng Xiaomin Yan Xueqi Yan Lin Chen Beicheng Sun Shiping Jiao department of Hepatobiliary Surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210093China drum tower Research Institute of Clinical Medicine Nanjing UniversityNanjing 210093China department of Infectious Disease Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210093China

Dear Editor,The SARS-CoV-2 virus outbreak that started in December 2019 is now a global pandemic with over 42.7 million confirmed cases and 1.15 million deaths as of October 25,*** has been predicted that resurgence in contagion may be possible as late as 2024.1 A persistent anti-SARS-CoV-2 adaptive immune surveillance post infection is critical to lower the risk of resurgence and transmission.T cells are the primary effectors of cellular adaptive immunity that not only clear virus-infected cells during infection but also provide long-term protection post infection as memory cells in some pathogen ***,little is known regarding the longitudinal T cell response during and after SARSCoV-2 ***-cell T cell receptor(TCR)sequencing allows rapid identification of expanded T cell clones that are potentially the antigen-specific clonotypes.

关键词： immunity infection cytotoxic

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Resveratrol, an activator of SIRT1, restores erectile function in streptozotocin-induced diabetic rats

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Asian Journal of Andrology 2013年第5期15卷 646-651页

作者： Wen Yu Zan Wan Xue-Feng Qiu Yun Chen Yu-Tian Dai department of Urology Affiliated Drum Tower Hospital School of Medicine Nanjing University Nanjing 210008 China

The high incidence of erectile dysfunction （ED） in diabetes highlights a need for effective treatment strategies. Resveratrol, an activator of silent information regulator 2-related enzymes 1 （sirtuinl, SIRT1）, has received attention for its valuable effects in cancer, neurodegenerative diseases, longevity and cardiovascular disease. To explore the effects of resveratrol in diabetes-induced ED, resveratrol was administered to rats with streptozocin （65 mg kg-1）-induced diabetes. Erectile function, cavernous structure, tissue protein expression of silent information regulator 2-related enzymes 1 （sirtuinl, SIRT1）, p53 and forkhead transcription factor 0 3a （FOXO3a）, superoxide dismutase （SOD） activity and malondialdehyde （MDA） levels in the corpora cavernosa were studied. We found that SIRT1 was expressed in cavernosal tissue, and it was downregulated in the corpora of diabetic rats. The administration of resveratrol upregulated the expression of SI RT1 and restored erectile function. In contrast, resveratrol downregulated the expression of p53 and FOXO3a, which regulate apoptosis and oxidative stress. Furthermore, the resveratrol-treated group showed an improvement in smooth muscle content, SOD activity and MDA levels when compared with the diabetic group. Therefore, the ability of resveratrol to improve diabetes-induced ED is likely related to its activation of SIRT1 expression, thus causing the suppression of apoptosis and resistance towards oxidative stress.

关键词： apoptosis erectile dysfunction oxidative stress resveratrol

Neuronal NR4A1 deficiency drives complement-coordinated synaptic stripping by microglia in a mouse model of lupus

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Signal Transduction and Targeted Therapy 2022年第3期7卷 840-855页

作者： Xiaojuan Han Tianshu Xu Congzhu Ding Dandan Wang Genhong Yao Hongwei Chen Qijun Fang Gang Hu Lingyun Sun department of Rheumatology and Immunology Department of Traditional Chinese MedicineNanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjingChina department of Traditional Chinese Medicine Nanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjingChina department of Rheumatology and Immunology Nanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjingChina department of Pharmacology Nanjing University of Chinese MedicineNanjingJiangsuChina

Neuropsychiatric lupus(NPSLE)is a frequent manifestation of systemic lupus erythematosus(SLE)that occurs in 40-90%of SLE patients;however,the underlying mechanisms remain elusive,causing a severe lack of therapeutic targets for this ***,we show that complement-coordinated elimination of synapses participated in NPSLE in MRL/lpr mice,a lupus-prone murine *** demonstrated that lupus mice developed increased anxiety-like behaviors and persistent phagocytic microglial reactivation before overt peripheral lupus pathology.

关键词： lupus coordinated pathology

Identification of a novel splice site mutation in the DNAAF4 gene of a Chinese patient with primary ciliary dyskinesia

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Asian Journal of Andrology 2023年第6期25卷 713-718页

作者： Yang Xu Jing Wang Ji-Hai Liu Qing-Qiang Gao Bing Wang Zhi-Peng Xu department of Andrology Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Primary ciliary dyskinesia(PCD)is a rare hereditary orphan condition that results in variable phenotypes,including *** 50 gene variants are reported in the scientific literature to cause PCD,and among them,dynein axonemal assembly factor 4(DNAAF4)has been recently ***4 has been implicated in the preassembly of a multiunit dynein protein essential for the normal function of locomotory cilia as well as *** the current study,a single patient belonging to a Chinese family was recruited,having been diagnosed with PCD and *** affected individual was a 32-year-old male from a nonconsanguineous *** also had abnormal spine structure and spinal cord bends at angles diagnosed with *** reports,laboratory results,and imaging data were ***-exome sequencing,Sanger sequencing,immunofluorescence analysis,hematoxylin-eosin staining,and in silico functional analysis,including protein modeling and docking studies,were *** results identified DNAAF4 disease-related variants and confirmed their *** analysis through whole-exome sequencing identified two pathogenic biallelic variants in the affected *** identified variants were a hemizygous splice site c.784-1G>A and heterozygous 20.1 Kb deletion at the DNAAF4 locus,resulting in a truncated and functionless DNAAF4 *** analysis indicated that the inner dynein arm was not present in the sperm flagellum,and sperm morphological analysis revealed small sperm with twisted and curved flagella or lacking *** current study found novel biallelic variants causing PCD and asthenoteratozoospermia,extending the range of DNAAF4 pathogenic variants in PCD and associated with the etiology of *** findings will improve our understanding of the etiology of PCD.

关键词： DNAAF primary ciliary dyskinesia scoliosis splice site

The regulation of the Treg/Th 17 balance by mesenchyma stem cells in human systemic lupus erythematosus

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Cellular & Molecular Immunology 2017年第5期14卷 423-431页

作者： Dandan Wang Saisai Huang Xinran Yuan Jun Liang Renju Xu Genhong Yao Xuebing Feng Lingyun Sun department of Rheumatology and Immunology The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing China

Background and objective： Umbilical cord （UC）-derived mesenchymal stem cells （MSCs） have shown immunoregulation of various immune cells. The aim of this study was to investigate the mechanism of UC MSCs in the regulation of peripheral regulatory T cells （Treg） and T helper 17 （Th17） cells in patients with systemic lupus erythematosus （SLE）. Methods： Thirty patients with active SLE, refractory to conventional therapies, were given UC MSCs infusions. The percentages of peripheral blood CD4＋CD25＋Foxp3＋ regulatory T cells （Treg） and CD3＋CD8-1L17A＋ Th17 cells and the mean fluorescence intensities （MFI） of Foxp3 and IL- 17 were measured at I week, I month, 3 months, 6 months, and 12 months after MSCs transplantation （MSCT）. Serum cytokines, including transforming growth factor beta （TGF-β）, tumor necrosis factor alpha （TNF-α）, interleukin 6 （IL-6）, and IL-17A were detected using ELISA. Peripheral blood mononuclear cells from patients were collected and co-cultured with UC MSCs at ratios of 1：1, 10：1, and 50：1, respectively, for 72 h to detect the proportions of Treg and Th17 cells and the MFIs of Foxp3 and IL-17 were determined by flow cytometry. The cytokines in the supernatant solution were detected using ELISA. Inhibitors targeting TGF-β, IL-6, indoleamine 2,3-dioxygenase （IDO）, and prostaglandin E2 were added to the co-culture system, and the percentages of Treg and Th17 cells were observed. Results： The percentage of peripheral Treg and Foxp3 MFI increased 1 week, 1 month, and 3 months after UC MSCs transplantation, while the Th17 proportion and MFI of IL-17 decreased 3 months, 6 months, and 12 months after the treatment, along with an increase in serum TGF-β at I week, 3 months, and 12 months and a decrease in serum TNF-a beginning at I week. There were no alterations in serums IL-6 and IL-17A before or after MSCT. In vitro studies showed that the UC MSCs dose-dependently up-regulated peripheral Treg proportion in SLE patients, which was not depended on cell-cell co

关键词： mesenchymal stem cells regulatory T cells systemic lupus erythematosus T helper 17 cells umbilical cord

Combined mesenchymal stem cell transplantation and interleukin-1 receptor antagonism after partial hepatectomy

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World Journal of Gastroenterology 2016年第16期22卷 4120-4135页

作者： Jian-Feng Sang Xiao-Lei Shi Bing Han Xu Huang Tao Huang Hao-Zhen Ren Yi-Tao Ding department of General Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical School

AIM: To study the therapeutic effects of mesenchymal stem cells (MSCs) and an interleukin-1 receptor antagonist (IL-1Ra) in acute liver ***: Chinese experimental miniature swine (15 ± 3 kg, 5-8 mo) were obtained from the Laboratory Animal Centre of the Affiliated drum tower hospital of Nanjing University Medical School. Acute liver failure was induced via 85% hepatectomy, and animals were treated by MSC transplantation combined with IL-1Ra injection. Blood samples were collected for hepatic function analysis, and the living conditions and survival time were recorded. Liver injury was histologically analyzed. Hepatic cell regeneration and apoptosis were studied by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. The levels of protein kinase B and nuclear factor-κB expression were analyzed by Western ***: MSCs were infected with a lentivirus for expression of green fluorescent protein (GFP) for subsequent identification; 97.3% of the MSCs were positive for GFP as assessed by flow cytometry. Additional flow cytometric analysis of cell surface marker expression demonstrated that > 90% of GFP-expressing MSCs were also positive for CD29, CD44, and CD90, indicating that most of these cells expressed typical markers of MSCs, and the population of MSCs was almost pure. Transplantation of MSCs in combination with 2 mg/kg IL-1Ra therapy significantly improved survival time compared to the acute liver failure model group (35.3 ± 6.7 d vs 17.3 ± 5.5 d, P < 0.05). Combined therapy also promoted improvement in serum inflammatory cytokines and biochemical conditions. The observed hepatic histopathologic score was significantly lower in the group with combined therapy than in the model group (3.50 ± 0.87 vs 8.17 ± 1.26, P < 0.01). In addition, liver cell apoptosis in the combined therapy group was significantly inhibited (18.1 �

关键词： Mesenchymal stem cells Interleukin-1 receptor antagonist Stem cell transplantation Acute liver failure Hepatoectomy

Comparison of surgical effect and postoperative patient experience between laparoendoscopic single-site and conventional laparoscopic varicocelectomy, a *** and meta-analysis

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Asian Journal of Andrology 2017年第2期19卷 248-255页

作者： Zheng Zhang Shu-Juan Zheng Wen Yu You-Feng Han Hai Chen Yun Chen Yu-Tian Dai department of Andrology Affiliated Drum Tower Hospital School of Medicine Nanjing University Nanjing 210008 China

The present meta-analysis was conducted to compare the clinical effect and patient experience of laparoendoscopic single-site varicocelectomy （LESSV） and conventional laparoscopic varicocelectomy. The candidate studies were included after literature search of database Cochrane Library, PubMed, EMBASE, and MEDLINE. Related information on essential data and outcome measures was extracted from the eligible studies by two independent authors, and a meta-analysis was conducted using STATA 12.0 software. Subgroup analyses were conducted by study design （RCT and non-RCT）. The odds ratio （OR） or standardized mean difference （SMD） and their 95% confidence intervals （95% CIs） were used to estimate the outcome measures. Seven articles were included in our meta-analysis. The results indicated that patient who had undergone LESSV had a shorter duration of back to work （overall： SMD = -1.454, 95% Ch -2.502m0.405, P= 0.007; non-RCT： SMD = -2.906, 95% Ch -3.796-2.017, P= 0.000; and RCT： SMD = -0.841, 95% Ch -1.393-0.289, P = 0.003） and less pain experience at 3 h or 6 h （SMD = -0.447, 95% Ch -0.754-0.139, P = 0.004）, day 1 （SMD = -0.477, 95% Ch -0.905-0.05, P = 0.029）, and day 2 （SMD = -0.612, 95% Ch -1.099-0.125, P= 0.014） postoperatively based on RCT studies. However, the meta-analyses based on operation time, clinical effect （improvement of semen quality and scrotal pain relief）, and complications （hydrocele and recurrence） yielded nonsignificant results. In conclusion, LESSV had a rapid recovery and less pain experience over conventional laparoscopic varicocelectomy. However, there was no statistically significant difference between the two varicocelectomy techniques in terms of the clinical effect and the incidence of hydrocele and varicocele recurrence. More high-quality studies are warranted for a comprehensive conclusion.

关键词： complications conventional laparoscopic varicocelectomy laparoendoscopic single-site varicocelectomy meta-analysis pain score semen quality