1.Role of the portal system in liver regeneration:From molecular mechanisms to clinical management
Xu HANZHI ; Qiu XUN ; Wang ZHOUCHENG ; Wang KAI ; Tan YAWEN ; Gao FENGQIANG ; Perini Vinicius MARCOS ; Xu XIAO
Liver Research 2024;8(1):1-10
The liver has a strong regenerative capacity that ensures patient recovery after hepatectomy and liver transplantation.The portal system plays a crucial role in the dual blood supply to the liver,making it a significant factor in hepatic function.Several surgical strategies,such as portal vein ligation,associating liver partition and portal vein ligation for staged hepatectomy,and dual vein embolization,have high-lighted the portal system's importance in liver regeneration.Following hepatectomy or liver trans-plantation,the hemodynamic properties of the portal system change dramatically,triggering regeneration via shear stress and the induction of hypoxia.However,excessive portal hyperperfusion can harm the liver and negatively affect patient outcomes.Furthermore,as the importance of the gut-liver axis has gradually been revealed,the effect of metabolites and cytokines from gut microbes carried by portal blood on liver regeneration has been acknowledged.From these perspectives,this review outlines the molecular mechanisms of the portal system's role in liver regeneration and summarizes therapeutic strategies based on the portal system intervention to promote liver regeneration.
2.Evaluating clinical significance of ductular reaction in liver transplantation
Xinhao HU ; Tianchen LAN ; Jian CHEN ; Zhetuo QI ; Fengqiang GAO ; Hao CHEN ; Libin DONG ; Xinyu YANG ; Shusen ZHENG ; Xiao XU
Chinese Journal of Organ Transplantation 2024;45(8):550-557
Objective:To explore the role of ductular reaction in assessing the efficacy of liver transplantation.Method:From January 2015 to December 2020, he relevant clinical data were retrospectively reviewed for 100 recipients and their corresponding donors at Shulan (Hangzhou) Hospital. They were assigned into two groups of hepatic steatosis (HS group, 65 cases) and non-hepatic steatosis (non-HS group, 35 cases) according to whether or not receiving steatosis donated liver. Furthermore, based upon the occurrence of early allograft dysfunction (EAD), the participants were categorized into two groups of EAD (33 cases) and non-EAD (67 cases). The degree of bile duct reaction ductular reaction was defined by the percentage of staining area occupied by cytokeratin 19 (CK19) -positive bile duct cells in immunohistochemical-stained specimens. Donor of ductular reaction were compared between HS/non-HS and EAD/non-EAD groups. The risk factors for EAD were identified by univariate and multivariate Logistic regression analysis. Subgroup analysis was conducted based upon the level of ductular reaction (DR number) in donors (DR=0.4 as a threshold) and whether or not donors exhibited steatosis. The impact of DR was examined on the incidence of EAD and survival post-liver transplantation in steatosis donors.Result:The level of DR was higher in steatosis donor than that in non-steatosis donor [ (0.59%±0.385%) vs. (0.32%±0.194%), P<0.01]. And it was higher in EAD group than that in non-EAD group [ (0.72%±0.449%) vs. (0.38%±0.226%), P<0.01]. Multivariate logistic regression analysis showed that a high level of ductular reaction was an independent risk factor for EAD post-liver transplantation in donor. Subgroup analysis revealed that receiving a steatosis donor with low ductular reaction (DR<0.4%) had comparable levels of EAD occurrence and overall survival rate to receiving a non-steatosis donor. Conclusion:Steatosis with low ductular reaction donor may be safely applied for liver transplantation. And assessing donor injury based upon ductular reaction can effectively expand the clinical application of steatosis donors.
3.Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs.
Yushang WANG ; Lihua WANG ; Tianyong SUN ; Song SHEN ; Zixuan LI ; Xiaomei MA ; Xiufeng GU ; Xiumei ZHANG ; Ai PENG ; Xin XU ; Qiang FENG
International Journal of Oral Science 2023;15(1):8-8
Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.
Humans
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Fusobacterium nucleatum/metabolism*
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NF-kappa B/metabolism*
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Periodontal Ligament/metabolism*
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Signal Transduction
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Fusobacterium Infections/pathology*
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Stem Cells/metabolism*
4.Prognostic analysis of steatosis donor liver transplantation: a multicenter clinical trial
Fengqiang GAO ; Kai WANG ; Libin DONG ; Zhisheng ZHOU ; Xuyong WEI ; Li ZHUANG ; Wan LI ; Guoyue LYU ; Shusen ZHENG ; Xiao XU
Chinese Journal of Organ Transplantation 2023;44(1):23-30
Objective:To explore the early and medium-long term outcomes of steatosis donor liver transplantation(LT)for an optimal clinical application.Methods:From January 2015 to December 2020, this retrospective cohort study was conducted jointly at Shulan (Hangzhou) Hospital, First Affiliated Hospital of Zhejiang University and First Hospital of Jilin University. The relevant clinicopathological and follow-up data were collected from 1535 LT recipients. For comparison, propensity score was utilized for case-control matching of steatosis and non-steatosis donor livers. According to presence or absence of liver steatosis, the recipients were divided into two groups of steatosis donor liver (n=243) and non-steatosis donor liver (n=1292). And 1∶1 propensity score matching was made for two groups. Then early and medium-long term outcomes of two groups were examined. Counts were described as absolute numbers. Kaplan-Meier method was employed for calculating survival time and plotting survival curve and Log-rank test for survival analysis. COX regression model was utilized for univariate and multivariate analyses. Based on basic metabolic disease pre-LT, steatosis donor liver recipients were divided into three subgroups: BMI ≥25 kg/m 2 with hypertension or diabetes (n=21), BMI<25 kg/m 2 and no hypertension or diabetes (n=130) and other recipients (n=92). A comparative study was performed for determining the prognosis of subgroups according to the different characteristics of recipient and donor liver. Results:No significant inter-group difference existed in 2-year survival post-LT ( P=0.174). However, significant inter-group difference in survival existed after 2 years post-LT ( P=0.004). And 3/5-year survival rate of steatosis donor liver was 66.4% and 44.2% respectively. Both were significantly lower than those of non-steatosis donor liver. Multivariate Cox regression analysis indicated that steatosis donor liver and male recipients were independent risk factors for prognosis >2 years survival post-LT( P=0.008, P=0.004). Subgroup analysis of steatosis liver donors showed that the prognosis of patients with BMI ≥25 kg/m 2 with hypertension or diabetes was significantly worse than other subgroups (BMI <25 kg/m 2 with no hypertension or diabetes and other recipients) <2 years survival post-LT ( P=0.029, P=0.043). Conclusions:Steatosis donor liver does not affect early survival of recipients, yet reduces medium-long term survival rate of recipients notably. In steatosis donor liver recipients, early survival rate declines markedly in recipients with preoperative BMI ≥25 kg/m 2 with hypertension or diabetes as compared with BMI <25 kg/m 2 with no hypertension or diabetes group.
5.The clinical practice and consideration for donor liver expansion
Kai WANG ; Fengqiang GAO ; Xiao XU
Chinese Journal of Surgery 2023;61(10):826-832
Liver transplantation is the most effective method to address end-stage liver disease. However, there is a huge imbalance between organ supply and demand in China. Recently,effective expansion of the donor liver has become a hot research direction in academia. Authors′ group comprehensively integrates domestic and foreign evidence-based medical evidence, the latest academic outcomes and clinical experience. Based on the innovative viewshed of crossfusion between biomedical engineering and medicine, author group systematically elaborate in the main strategies for expanding the liver donor pool, including the multichannel expansion of marginal donor liver,multidimensional innovation of technologies in transplant surgery and diversified exploration of alternative resources of organs. The author group aims to promote the construction of a large cohort,the integration of big data,and the output of high quality research,achieving innovative theory and clinical translation in organ transplantation,thus promoting the higher quality development of liver transplantation in China.
6.The clinical practice and consideration for donor liver expansion
Kai WANG ; Fengqiang GAO ; Xiao XU
Chinese Journal of Surgery 2023;61(10):826-832
Liver transplantation is the most effective method to address end-stage liver disease. However, there is a huge imbalance between organ supply and demand in China. Recently,effective expansion of the donor liver has become a hot research direction in academia. Authors′ group comprehensively integrates domestic and foreign evidence-based medical evidence, the latest academic outcomes and clinical experience. Based on the innovative viewshed of crossfusion between biomedical engineering and medicine, author group systematically elaborate in the main strategies for expanding the liver donor pool, including the multichannel expansion of marginal donor liver,multidimensional innovation of technologies in transplant surgery and diversified exploration of alternative resources of organs. The author group aims to promote the construction of a large cohort,the integration of big data,and the output of high quality research,achieving innovative theory and clinical translation in organ transplantation,thus promoting the higher quality development of liver transplantation in China.
7.Therapeutic effect and safety of tirofiban combined large dose statin in patients with acute myocardial infarction
Fengqiang XU ; Junjie GUO ; Peilin LIN ; Yi AN ; Xia LI
Chinese Journal of cardiovascular Rehabilitation Medicine 2014;23(4):455-458
Objective:To observe and analyze the therapeutic effect and safety of tirofiban combined large dose statin in patients with acute myocardial infarction (AMI),and evaluate its influence on myocardial perfusion and cardiac function.Methods:A total of 97 consecutive AMI patients visited to our hospital from May 2011 to January 2013, who were beyond the emergency PCI time window (≥12h),their chest pain was remissive or not further aggravated were studied.All patients were pumped with tirofiban for 48h continuously;according to combined rosuvastatin dose,they were divided into large dose group (n = 52,20mg,once/d,until one month after infarction,then changed to routine dose of 10mg,once/d)and routine dose group (n=45,10mg,once/d).All patients received se-lective PCI after 7 ~ 10d conservative treatment.Myocardial perfusion level,left ventricular ejection fraction (LVEF)on one week after PCI and 30d after AMI,enzymology changes [creatine (CK),lactate dehydrogenase (LDH)]and major adverse cardiovascular events (MACE)during hospitalization were compared between two groups.Results:Compared with routine dose group,there were significant reductions in thrombus scores in infarct related artery (IRA)[(1.32±1.01)scores vs.(0.81±0.78)scores]and corrected TIMI frame [(32.4±4.73)vs. (26.8±2.34)]in large dose group (P =0.021,P <0.001);after selective PCI,TIMI flow of large dose group was significantly better than that of routine dose group (P =0.024).On one week after PCI,LVEF:(51.4±8.9)% of large dose group was significantly higher than that of routine dose group (47.7±8.7)%,P =0.021;there were no significant difference in levels of CK and LDH between two groups on 7d and 30d after PCI (P >0.05).There was no MACE in both groups during hospitalization and 30d after PCI.Conclusion:Tirofiban combined large dose statin is safe and effective in patients with acute myocardial infarction,it can reduce intra-coronary thrombus burden,im-prove myocardial tissue perfusion and cardiac function without increasing MACE.
8.Coronary heart disease: incidence, risk factors and interventions in Jiaozhou of Shandong province.
Hua YU ; Dan LI ; Xianming CHU ; Yi AN ; Tongxun SONG ; Huixin FENG ; Peilin LIN ; Tao WANG ; Shaoyan JIANG ; Linlin GUO ; Fengqiang XU ; Zhengke LIU ; Bin YANG
Chinese Medical Journal 2014;127(12):2275-2278
BACKGROUNDCoronary heart disease (CHD) is the most common type of heart disease and cause of heart attacks. This study investigated the epidemiological characteristics of CHD and its risk factors in Jiaozhou, Shandong province, to ultimately find a way of reducing the prevalence of cardiovascular disease, and to provide a theoretical basis for establishing a cardiovascular disease management path under the regional medical collaborative mechanism.
METHODSA questionnaire survey was performed including 1 952 people aged 35 years or older who were questioned by means of stratified, cluster, proportional sampling to investigate the prevalence of CHD and its risk factors. The data were inputted into SPSS11.0 statistical software for processing and analysis. We advised the local medical institutions to establish health files for the residents with CHD and risk factors. They were followed up regularly. Their risk factors and life-style were monitored, and advice was given as to proper medications. Green channels were established, and the patients were transmitted in a timely manner to superior hospitals for better treatment if the necessary treatments were not available in the local hospitals. The control of risk factors was observed after the follow-up for half a year.
RESULTSIn Jiaozhou, the rates of coronary artery disease, hypertension, diabetes, hyperlipidemia and overweight were 8.15%, 28.54%, 11.43%, 35.46%, and 18.70% respectively. The rates of hypertension, diabetes, hyperlipidemia and overweight were higher than the data published in "The report of Chinese cardiovascular disease 2012"; which are 24%, 9.7%, 18.6%, and 9.7%, respectively. The control of risk factors improved significantly after the guidance of the residents lifestyle and medication for six months.
CONCLUSIONSThe high prevalence of coronary artery disease in Jiaozhou is closely related to age, gender, diet structure, family history of cardiovascular disease, hypertension, diabetes, hyperlipidemia, overweight, and unhealthy lifestyle. Under the regional medical coordination mechanism, the collaborative management of cardiovascular disease can provide new management concepts for the areas short of medical resources, so as to reduce the prevalence of cardiovascular disease.
Adult ; Aged ; China ; epidemiology ; Coronary Disease ; epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Risk Factors
9.EpCam and Wnt / β-catenin pathway expression in colon cancer
Fengqiang ZHOU ; Yanmei QI ; Xinjun LI ; Huiguang GUO ; Hong XU
Journal of Chinese Physician 2012;(z1):14-17
Objective EpCam and Wnt/ β-catenin pathway in colon carcinoma and its clinic-pathological significance of the distribution,studying the relationship between EpCam and Wnt / β-catenin.Methods Retrospective analysis detected by immunohistochemistry 60 cases of colon cancer,20 cases of adjacent atypical hyperplasia,60 normal colon tissue EpCam and Wnt / β-catenin protein expression.Results (1)normal colon tissue,cancer tissue and cancer tissue showed positive expression EpCam clear upward trend,were 23.5%,62.3%,96.5% ; with normal colonic mucosa to cancer transformation,β-catenin in the membrane expression of the positive rate decreased,while the cytoplasm is followed by increased expression rate in poorly differentiated carcinoma or even nuclear expression,EpCam strong positive expression of Wnt / β-catenin cytoplasmic-positive rate of histological type,depth of invasion,lymph node metastasis; (2)the EpCam with the Wnt / β-catenin expression showed a positive correlation (r =0.653,P <0.05) ;(3)high expression EpCam and Wnt / β-catenin in patients with colon significant increase in cancer recurrence rate and 5-year survival rate was significantly reduced.Conclusion EpCam and Wnt / β-catenin pathway in colon cancer positively is correlated,EpCam and Wnt / β-catenin is connected with high expression and tumor invasion,metastasis and prognosis.
10.Influence of neo-adjuvant chemotherapy on progrsssive gastric cancer operation withi multi-disciplinary team
Fengqiang ZHOU ; Yanmei QI ; Huiguang GUO ; Hong XU ; Shilu JIN
Chinese Journal of Primary Medicine and Pharmacy 2012;19(3):373-375
Objective To discuss the influence of the progress and result in gastic cancer operation through application of neo-adjuvant chemotherapy in multi-disciplinary team (MDT).Methods Clinical data of the patients treated in MDT model 45 cases and non-MDT model(78 cases) were respectively analyzed,and the index about pathologic change,histologic transform and operative result between the two groups were compared.Results In the index of pathologic change,the incidence of abdominal adherence and ascites and pyloric obstruction in MDT model group were obviously less than non-MDT model group( P <0.05 ).In the index of histologic transform,texture of mesentery in MDT model group was more fragile than non-MDT model group( P <0.05).In the index of operative results,the operative duration and intra-operative bleeding in MDT model group were less than non-MDT model group (P <0.05).Conclusion Neo-adjuvant chemotherapy has certain influence in gastric caneer operation,but the successful operations were performed by standard and correct procedures.Therefore,optimizing combined therapy in MDT model and constructing preoperative evaluation system with neo-adjuvant chemotherapy.

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