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A benchtop brain injury model using resected donor tissue from patients with Chiari malformation

Neural Regeneration Research 2023年第5期18卷 1057-1061页

作者： Jacqueline A.Tickle Jon sen Christopher Adams David N.Furness Rupert Price Viswapathi Kandula Nikolaos Tzerakis Divya M.Chari Aston Pharmacy School College of Health and Life SciencesAston UniversityBirminghamUK School of Medicine Faculty of Medicine and Health SciencesKeele UniversityStaffordshireUK School of Life Sciences Keele UniversityStaffordshireUK department of Neurosurgery Royal Stoke University HospitalStoke-on-TrentUK

The use of live animal models for testing new therapies for brain and spinal cord repair is a controversial area. Live animal models have associated ethical issues and scientific concerns regarding the predictability of human responses. Alternative models that replicate the 3 D architecture of the central nervous system have prompted the development of organotypic neural injury models. However, the lack of reliable means to access normal human neural tissue has driven reliance on pathological or post-mortem tissue which limits their biological utility. We have established a protocol to use donor cerebellar tonsillar tissue surgically resected from patients with Chiari malformation(cerebellar herniation towards the foramen magnum, with ectopic rather than diseased tissue) to develop an in vitro organotypic model of traumatic brain injury. Viable tissue was maintained for approximately 2.weeks with all the major neural cell types detected. Traumatic injuries could be introduced into the slices with some cardinal features of post-injury pathology evident. Biomaterial placement was also feasible within the in vitro lesions. Accordingly, this ‘proof-of-concept’ study demonstrates that the model offers potential as an alternative to the use of animal tissue for preclinical testing in neural tissue engineering. To our knowledge, this is the first demonstration that donor tissue from patients with Chiari malformation can be used to develop a benchtop model of traumatic brain injury. However, significant challenges in relation to the clinical availability of tissue were encountered, and we discuss logistical issues that must be considered for model scale-up.

关键词： biomaterial Chiari malformation cerebellar slice human tissue injury model neuroregeneration organotypic traumatic brain injury

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Extensive gene flow in secondary sympatry after allopatric speciation

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National Science Review 2022年第12期9卷 24-36页

作者： Xinfeng Wang Ziwen He Zixiao Guo Ming Yang Shaohua Xu Qipian Chen Shao Shao sen Li Cairong Zhong Norman C.Duke Suhua Shi State Key Laboratory of Biocontrol Guangdong Key Laboratory of Plant Resources School of Life SciencesSouthern Marine Science and Engineering Guangdong Laboratory(Zhuhai) Sun Yat-sen University Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering School of Life Sciences Fudan University department of Laboratory Medicine& pathology University of Washington Hainan Academy of Forestry (Hainan Academy of Mangrove) Centre for Tropical Water and Aquatic Ecosystem Research James Cook University

In the conventional view,species are separate gene pools delineated by reproductive isolation(RI).In an alternative view,species may also be delineated by a small set of ’speciation genes’ without full RI,a view that has gained broad acceptance.A recent survey,however,suggested that the extensive literature on’speciation with gene flow’ is mostly(if not all) about exchanges in the early stages of *** is no definitive evidence that the observed gene flow actually happened after speciation is ***,we wish to know whether ’good species’(defined by the ’secondary sympatry’ test) do continue to exchange genes and,importantly,under what conditions such exchanges can be *** novo whole-genome assembly and re-sequencing of individuals across the range of two closely related mangrove species(Rhizophora mucronata and R. stylosa) reveal the genomes to be well delineated in *** became sympatric in northeastern Australia but remain distinct ***,their genomes harbor～4000-10 000 introgression blocks averaging only about 3-4 *** fine-grained introgressions indicate continual gene flow long after speciation as non-introgressable ’genomic islets,’～1.4 Kb in size,often harbor diverging genes of flower or gamete *** fine-grained introgression in secondary sympatry may help settle the debate about sympatric ***-allopatric *** conclusion,true’good species’ may often continue to exchange genes but the opportunity for detection is highly constrained.

关键词： mangroves population genomics speciation introgression species hybridization

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Hangzhou criteria as downstaging criteria in hepatocellular ca

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Hepatobiliary & Pancreatic Diseases International 2020年第4期19卷 349-357页

作者： Qi-Fan Zhan sun-Bin Ling Yi-Nan Deng Qiao-Nan Shan Qian-Wei Ye Sheng-Jun Xu Guang-Jiang Jiang Di Lu Xu-Yong Wei Li Zhuang Wu Zhang Tian Shen Bei-Ni Cen Hai-Yang Xie Ji-Min Liu Jian Wu Shu-sen Zheng Yang Yang Xiao Xu department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China NHC Key Laboratory of Combined Multi-organ Transplantation Key Laboratory of the Diagnosis and Treatment of Organ TransplantationCAMSHangzhou 310003China department of Hepatic Surgery and Liver Transplantation Center the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou 310000China department of pathology and Molecular Medicine Faculty of Health SciencesMcMaster UniversityHamiltonOntario L8S 4K1Canada

Background:The downstaging of hepatocellular carcinoma(HCC)has been confirmed to benefit liver transplantation(LT)patients whose tumors are beyond the transplantation *** criteria(MC),a tumor size and number-based assessment,is currently used as the endpoint in these ***,many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging ***,this study aimed to explore the feasibility of Hangzhou criteria(HC),which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number,as an endpoint of ***:We performed a multicenter and retrospective study of 2.6 patients accepted locoregional therapy(LRT)as downstaging/bridge treatment prior to LT in three centers of ***:Recipients were divided into four groups:failed downstaging to the HC(group A,n=46),successful downstaging to the HC(group B,n=30),remained within the HC all the time(group C,n=113),and tumor progressed(group D,n=17).The 3-year HCC recurrence probabilities of groups B and C were not significantly different(10.3%vs.11.6%,P=0.87).The HCC recurrent rate was significantly higher in group A(52.3%)compared with that in group B/C(P2.)whose tumor exceeded the the HC were successfully downstaged to the MC,and 39.5%(30/76)to the the *** group B,2. patients remained beyond the MC and their survivals were as well as those of patients within the ***:Compared to the MC,HC downstaging criteria can give more HCC patients access to LT and furthermore,the outcome of these patients is the same as those matching MC downstaging *** downstaging criteria therefore is applicable in clinical practice.

关键词： Hepatocellular carcinoma Liver transplantation Downstaging

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Association between ADIPOQ gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2017年第6期16卷 602-609页

作者： Chao Cen Hai-Xing Fang Song-Feng Yu Ji-Min Liu Yuan-Xing Liu Lin Zhou Jun Yu Shu-sen Zheng department of Hepatobiliary and Pancreatic Surgery Key Laboratory of Combined Multi-organ TransplantationMinistry of Public HealthCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of Medicine department of Hepatobiliary Surgery the First People's Hospital of Fuyang department of pathology and Molecular Medicine Faculty of Health SciencesMcMaster University

BACKGROUND:New-onset diabetes after transplantation(NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation(LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver ***:A total of 2.6 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom Mass ARRAY. Modified clinical models in predicting NODAT were established and ***:The GG genotype of ADIPOQ rs15012.9 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients(56% vs 39%, P=0.014). Dominant model(GG vs GT+TT, P=0.030) and recessive model(GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age(OR=1.048, P=0.004), BMI(OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT(OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs15012.9 could improve the ability of clinical model in predicting NODAT(AUROC=0.743, P2.9 gene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.

关键词： ADIPOQ gene polymorphisms diabetes mellitus liver transplantation

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Sonic Hedgehog stimulates migration of MCF-7 breast cancer cells through Rac1

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The Journal of Biomedical Research 2019年第5期33卷 297-307页

作者： Tian Shen Bo'ang Han Yan Leng sen Yan Junfeng Shi Shen Yue Steven Y Cheng Jiangsu Key Laboratory o f Xenotransplanation Department of Medical GeneticsCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China department of pathology andPathophysiology Collaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingJiangsu 211166China department of pathology Jiangsu Province HospitalNanjingJiangsu 210029China department of Oncology Nanjing First Hospital Affiliated to Nanjing Medical UniversityNanjingJiangsu 210006China.

As one of the most common tumors in women, breast cancer has drawn considerable interest from investigators and clinicians in recent years. Despite early diagnosis and best therapeutic regimens available, the prognosis of malignant or metastatic breast cancer patients is still not optimistic. Hedgehog signaling, a classical pathway indispensable to embryonic development, participates in the growth of a variety of tumors. In the present study,the effect of Sonic Hedgehog(Shh) on breast cancer cells was investigated. We identified that Shh signal stimulated the migration of MCF-7 breast cancer cells. Smo and Gli1 were involved in Shh-stimulated migration of MCF-7 cells. Activating Smo and Gli1 induced cell migration, which was blocked by their specific *** effect of Shh signaling on MCF-7 cells was independent of Wnt5 a, Dvl2.and Rab35, but directly dependent on Rac1. In conclusion, our study suggested that Shh promotes breast cancer cell migration via Rac1 independently of the non-canonical Wnt signaling pathway, which may represent a rational molecular target for combination medication in breast cancer.

关键词： Sonic Hedgehog Rac1 breast cancer MCF-7 migration

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Comparative visual analytics for assessing medical records with sequence embedding

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Visual Informatics 2020年第2期4卷 72-85页

作者： Rongchen Guo Takanori Fujiwara Yiran Li Kelly M.Lima Soman sen Nam K.Tran Kwan-Liu Ma department of Computer Science Beihang UniversityBeijingChina department of Computer Science University of CaliforniaDavisUnited States department of pathology and Laboratory Medicine University of CaliforniaDavisUnited States department of Surgery University of CaliforniaDavisUnited States

Machine learning for data-driven diagnosis has been actively studied in medicine to provide better *** analysis of a patient cohort similar to a patient under treatment is a key task for clinicians to make decisions with high ***,such analysis is not straightforward due to the characteristics of medical records:high dimensionality,irregularity in time,and *** address this challenge,we introduce a method for similarity calculation of medical *** method employs event and sequence *** we use an autoencoder for the event embedding,we apply its variant with the self-attention mechanism for the sequence ***,in order to better handle the irregularity of data,we enhance the self-attention mechanism with consideration of different time *** have developed a visual analytics system to support comparative studies of patient *** make a comparison of sequences with different lengths easier,our system incorporates a sequence alignment *** its interactive interface,the user can quickly identify patients of interest and conveniently review both the temporal and multivariate aspects of the patient *** demonstrate the effectiveness of our design and system with case studies using a real-world dataset from the neonatal intensive care unit of UC Davis.

关键词： Electronic medical records Event sequence data Autoencoder Self-attention Sequence similarity Visual analytics

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Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases

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Chinese Journal of Cancer 2017年第11期36卷 537-547页

作者： Yun Wang Yun-Fei Yuan Hao-Cheng Lin Bin-Kui Li Feng-Hua Wang Zhi-Qiang Wang Pei-Rong Ding Gong Chen Xiao-Jun Wu Zhen-Hai Lu Zhi-Zhong Pan De-sen Wan Peng sun Shu-Mei Yan Rui-Hua Xu Yu-Hong Li sun Yat-sen {2. Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangzhou 510060 Guangdong P. R. China department of Medical Oncology Sun Yat-sen University Cancer Center Guangzhou 510060 Guangdong P. R. China department of Hepatobiliary Surgery Sun Yat-sen University Cancer Center Guangzhou 510060 Guangdong P. R. China department of Colorectal Surgery sun Yat-{2. university Cancer Center Guangzhou 510060 Guangdong P. R. China department of pathology Sun Yat-sen University Cancer Center Guangzhou 510060 Guangdong P. R. China

Background: Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorecal cancer patients with liver metastases who underwent ***, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese *** and methods: In this retrospective study, we analyzed the data of 380 liver metastases in 159 *** pathologic response was evaluated according to the tumor regression grade(TRG).The prognostic role of pathologic response in recurrence-free survival(RFS) and overall survival(OS) was assessed using Kaplan-Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U ***: Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy(median RFS: 9.9 vs.6.5 months, P = 0.009; median OS: 40.7 vs. 2..1 months, P = 0.040). Multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors,and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases(all P < 0.05). A decrease in the serum carcinoembryonic antigen(CEA) level after preoperative chemotherapy predicted an increased pathologic response rate(P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemoth

关键词： Colorectal cancer Liver metastases Chemotherapy Pathologic response

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Field evaluation of Streptomyces rubrogriseus HDZ-9-47 for biocontrol of Meloidogyne incognita on tomato

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Journal of Integrative Agriculture 2017年第6期16卷 1347-1357页

作者： JIN Na XUE Hui LI Wen-jing WANG Xue-yan LIU Qian LIU Shu-sen LIU Pei ZHAO Jian-lon JIAN Heng department of Plant pathology China Agricultural University/Key Laboratory of Plant Pathology Ministry of Agriculture Beijing 100193 P.R.China

Streptomyces rubrogriseus HDZ-9-47,isolated from eggs of Meloidogyne spp.,was evaluated as a potential biocontrol agent of Meloidogyne incognita under in vitro and protective *** observations showed that HDZ-9-47 parasitized eggs of *** within 7 *** vitro,the culture filtrate of HDZ-9-47 caused 97.0%mortality of second-stage juveniles（J2.）of *** and inhibited more than 50%egg *** the field,compared with the control,the rootknot index and J2. density in the treatment of drench the broth contained 1012.HDZ-9-47 spores were respectively reduced by 51.1 and 80.7%at 90 days post transplantation,which were better than that in other application doses and *** addition,reduction rates of root-knot index and J2. density of the treatment of combined application of HDZ-9-47 with biofumigation was 87.1 and 91.0%,respectively,better than either of HDZ-9-47 or biofumigation used alone or fosthiazate *** tomato yield also increased by 16.1%.Together,our results suggest that HDZ-9-47 could be an effective biocontrol agent of ***,and that application of HDZ-9-47 combined with cabbage residue biofumigation was a promising and sustainable option for *** control.

关键词： Meloidogyne incognita Streptomyces rubrogriseus biocontrol parasitism nematicidal metabolites control efficacy

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锰和锗对CCl＿4肝损害保护作用的实验研究

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卫生毒理学杂志 1995年第2期9卷 84-87页

作者：赖玉熔周炯亮中山医科大学卫生学院劳动卫生教研室福建医学院卫生系

实验用ＳＤ大鼠。ＣＣｌ４５００ｍｇ／ｋｇ经口染毒。每周两次。连续染毒６周。于染毒的同时分别给予锰４ｍｇ／ｋｇ和锗－１３２１０ｍｇ／ｋｇ混入饲料中喂饲。ＶｉｔＥ以１０ｍｇ／ｋｇ经腹腔注射。每周两次。每两周处死一批动物。... 详细信息

实验用ＳＤ大鼠。ＣＣｌ４５００ｍｇ／ｋｇ经口染毒。每周两次。连续染毒６周。于染毒的同时分别给予锰４ｍｇ／ｋｇ和锗－１３２１０ｍｇ／ｋｇ混入饲料中喂饲。ＶｉｔＥ以１０ｍｇ／ｋｇ经腹腔注射。每周两次。每两周处死一批动物。结果显示，锰组、锗－１３２组和ＶｉｔＥ组染毒后，ＳＧＰＴ在第二周增加的幅度均低于ＣＣｌ４组，并于停止染毒后迅速下降。且锰组、锗－１３２组比ＶｉｔＥ组早两周恢复正常水平。各处理组肝匀浆中ＭＤＡ在整个观察期上升的幅度均低于ＣＣｌ４组。在染毒停止后第８周恢复正常。锰组肝匀浆中ＧＳＨ含量于整个染毒期均未见显著的下降，锗－１３２组于第４周降低显著，第８周恢复。细胞色素Ｐ４５０染毒后各组均显著降低并持续至第１０周，ｂ５值锰组和锗－１３２组分别在第四周及第六周有一最低值。均于第八周恢复。病理结果显示，锰组和锗－１３２组其纤维化、脂变的程度明显减轻。提示锰、和锗－１３２对ＣＣｌ４肝损害有一定的保护作用，其效果优于ＶｉｔＥ。

关键词：四氯化碳肝损害保护作用锰锗药理学

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Coexpression of TLR9 and VEGF-C is associated with lymphatic metastasis in prostate cancer

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Asian Journal of Andrology 2022年第4期24卷 380-385页

作者： Xian-Zi Zeng Zhan-sen Huang Hong-Peng Fang Jie-Ying Wu Qun-Xiong Huang Chu-Bin Zhuang Jing Zhou Jin-Ming Di department of Urology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China department of Infertility and Sexual Medicine The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China department of pathology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

Prostate cancer(PCa)is one of the most frequent cancers in men,and its biomolecular targets have been extensively *** study aimed to analyze the expression of toll-like receptor 9(TLR9)and vascular endothelial growth factor C(VEGF-C)and the clinical value of the coexpression of TLR9 and VEGF-C in *** retrospectively evaluated 55 patients with clinically localized,intermediate-risk,or high-risk PCa who underwent laparoscopic radical prostatectomy(LRP)and extended pelvic lymph node dissection(ePLND)without neoadjuvant hormonal therapy at a single institution from June 2.13 to December *** all 55 patients,the median number of lymph nodes(LNs)resected was 2.(range:18-31),and a total of 12.9 LNs were removed,of which 78 LNs were *** patients had positive LNs,with a positive rate of 30.9%.In addition,the immunohistochemical results in the above patients revealed that high TLR9 expression was correlated with higher Gleason score(GS)(P=0.049),increased LN metastasis(P=0.004),and more perineural invasion(PNI)(P=0.033).Moreover,VEGF-C expression was associated with GS(P=0.040),pathological stage(pT stage)(P=0.02.),LN metastasis(P=0.003),and PNI(P=0.001).Furthermore,a significant positive correlation between TLR9 and VEGF-C was found(P47).Collectively,we propose that TLR9 stimulation may promote LN metastasis in PCa cells through the upregulation of VEGF-C expression,thereby affecting the prognosis of PCa ***,these markers may serve as valuable targets for the treatment of PCa.

关键词： biochemical progression-free survival coexpression lymphatic metastasis prostate cancer toll-like receptor 9 vascular endothelial growth factor C

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