1.Protective mechanism of rhubarb decoction against inflammatory damage of brain tissue in rats with mild hepatic encephalopathy: A study based on the PI3K/AKT/mTOR signaling pathway
Guangfa ZHANG ; Yingying CAI ; Long LIN ; Lei FU ; Fan YAO ; Meng WANG ; Rongzhen ZHANG ; Yueqiao CHEN ; Liangjiang HUANG ; Han WANG ; Yun SU ; Yanmei LAN ; Yingyu LE ; Dewen MAO ; Chun YAO
Journal of Clinical Hepatology 2024;40(2):312-318
ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction (RD) retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy (MHE). MethodsA total of 60 male Sprague-Dawley rats were divided into blank group (CON group with 6 rats) and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks, 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group (MOD group), lactulose group (LT group), low-dose RD group (RD1 group), middle-dose RD group (RD2 group), and high-dose RD group (RD3 group), with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day; the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day; the rats in the RD1, RD2, and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5, 5.0, and 7.5 g/kg, respectively, once a day. After 10 days of treatment, the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects: behavioral status; the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and the level of blood ammonia; pathological changes of liver tissue and brain tissue; the mRNA and protein expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group, the RD1, RD2, and RD3 groups had a significantly shorter escape latency (all P<0.01), significant reductions in the levels of ALT, AST, IL-1β, IL-6, TNF-α, and blood ammonia (all P<0.05), significant alleviation of the degeneration, necrosis, and inflammation of hepatocytes and brain cells, and significant reductions in the mRNA and protein expression levels of PI3K, AKT, and mTOR in brain tissue (all P<0.05), and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats, possibly by regulating the PI3K/AKT/mTOR signaling pathway.
2.Application and potential value of endogenous lipid mediators in liver failure
Gengjie YAN ; Yong LIN ; Huiji SU ; Hanxiao CHEN ; Shaoqun BAN ; Ailing WEI ; Dewen MAO ; Fuli LONG
Journal of Clinical Hepatology 2023;39(1):211-217
Liver failure is a common end-stage liver disease syndrome in clinical practice characterized by massive necrosis of hepatocytes leading to rapid liver failure, and it is currently believed that excessive inflammation and immune response are the core mechanisms of this disease. Endogenous lipid mediators are involved in the regulation of a variety of inflammatory processes, including initiation, maintenance, and regression, and eicosanoids and pro-decomposition lipid mediators, as well as their complex metabolic pathways and transduction signals, play a key role in the regulation of these processes. This article reviews the key role of endogenous lipid mediators in the pathophysiological mechanism of inflammation and immune dysfunction in liver failure and the potential significance and new therapeutic opportunities of lipid immune pathway in liver failure, in order to provide new ideas for the clinical diagnosis and treatment of liver failure.
3.Role of macrophage polarization and its crosstalk with neighboring cells in hepatocellular carcinoma
Huiji SU ; Gengjie YAN ; Hanxiao CHEN ; Shaoqun BAN ; Ailing WEI ; Dewen MAO ; Fuli LONG
Journal of Clinical Hepatology 2023;39(5):1204-1211
Inflammation is closely associated with the development of cancer. Tumor-associated macrophages (TAM) actively participate in tumor-related inflammation and promote tumor growth and metastasis, while under certain conditions, TAM also show cytotoxicity and tumor killing activity and thus inhibit the progression of cancer. Crosstalk between TAM and neighboring cells is closely associated with the progression of hepatocellular carcinoma (HCC) and drug resistance during treatment. This article summarizes the role of macrophages in HCC and the crosstalk between macrophages and other cells, so as to provide new strategies for the clinical diagnosis and treatment of HCC.
4.Association between glycolysis and mitochondrial dysfunction and its potential value in liver diseases
Gengjie YAN ; Yong LIN ; Huiji SU ; Hanxiao CHEN ; Shaoqun BAN ; Ailing WEI ; Dewen MAO ; Fuli LONG
Journal of Clinical Hepatology 2022;38(8):1931-1936
Glycolysis plays an important role in the development and progression of liver diseases and shows varying degrees of enhancement in different liver diseases, and it is closely associated with mitochondrial dysfunction (oxidative phosphorylation deficiency and reactive oxygen species production), which helps to fill energy production deficiency caused by impaired oxidative phosphorylation. Therefore, it might be possible to search for potential new therapies for liver diseases through targeted regulation of the key factors in aerobic glycolysis, such as hexokinase 2, pyruvate kinase M2, and other regulatory pathways. From the perspective of the association between glycolysis and liver diseases, this article elaborates on the therapeutic significance and potential value of glycolysis in liver diseases, in order to provide new ideas for the diagnosis and treatment of liver diseases.
5.Impact of adjuvant chemotherapy on prognosis in intrahepatic cholangiocarcinoma patients underwent radical resection.
Jing Bo SU ; Jing Wei ZHANG ; Chen CHEN ; Ying He QIU ; Hong WU ; Tian Qiang SONG ; Yu HE ; Xian Hai MAO ; Wen Long ZHAI ; Zhang Jun CHENG ; Jing Dong LI ; Shu Bin SI ; Zhi Qiang CAI ; Zhi Min GENG ; Zhao Hui TANG
Chinese Journal of Surgery 2022;60(4):356-362
Objectives: To investigate the clinical value of adjuvant chemotherapy(ACT) in patients with intrahepatic cholangiocarcinoma(ICC) who underwent radical resection and to explore the optimal population that can benefit from ACT. Methods: A retrospective cohort study method was adopted. The clinical and pathological data of 685 patients with ICC who underwent curative intent resection in 10 Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected;There were 355 males and 330 females. The age(M(IQR)) was 58(14) years (range: 22 to 83 years). Propensity score matching(PSM) was applied to balance the differences between the adjuvant and non-adjuvant chemotherapy groups. Log-rank test was used to compare the prognosis of the two groups of patients. A Bayesian network recurrence-free survival(RFS) prediction model was constructed using the median RFS time (14 months) as the target variable, and the importance of the relevant prognostic factors was ranked according to the multistate Birnbaum importance calculation. A survival prognostic prediction table was established to analyze the population benefiting from adjuvant chemotherapy. Results: Among 685 patients,214 received ACT and 471 did not receive ACT. A total of 124 pairs of patients were included after PSM, and patients in the ACT group had better overall survival (OS) and RFS than those in the non-ACT group(OS: 32.2 months vs. 18.0 months,P=0.003;RFS:18.0 months vs. 10.0 months,P=0.001). The area under the curve of the Bayesian network RFS prediction model was 0.7124. The results of the prognostic factors in order of importance were microvascular invasion (0.158 2),perineural invasion (0.158 2),N stage (0.155 8),T stage (0.120 9), hepatic envelope invasion (0.090 3),adjuvant chemotherapy (0.072 1), tumor location (0.057 5), age (0.042 3), pathological differentiation (0.034 0), sex (0.029 3), alpha-fetoprotein (0.028 9) and preoperative jaundice (0.008 5). A survival prediction table based on the variables with importance greater than 0.1 (microvascular invasion,perineural invasion,N stage,T staging) and ACT showed that all patients benefited from ACT (increase in the probability of RFS≥14 months from 2.21% to 7.68%), with a more significant increase in the probability of RFS≥14 months after ACT in early-stage patients. Conclusion: ACT after radical resection in patients with ICC significantly prolongs the OS and RFS of patients, and the benefit of ACT is greater in early patients.
Bayes Theorem
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Bile Duct Neoplasms/surgery*
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Bile Ducts, Intrahepatic/pathology*
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Chemotherapy, Adjuvant
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Cholangiocarcinoma/surgery*
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Female
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Humans
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Male
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Prognosis
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Retrospective Studies
6.Effect of Dredging Correcting Manipulation on Stunting in Children with cblC Methylmalonic Aciduria
Hong ZHENG ; Rui-xing LIANG ; Xiang-peng LU ; Jian-kui ZHANG ; Yi-zhen WANG ; Ke-gong XIE ; Hui JIN ; Su-zhen GUO ; Shu-ying ZHAO ; Chi ZHANG ; Xiao-meng LI ; Xin MAO ; Jin-long SUN ; Hua-wei LI ; Bin FENG ; Bing-xiang MA
Chinese Journal of Rehabilitation Theory and Practice 2020;26(8):964-968
Objective:To observe the effect of Dredging Correcting Manipulation on cblC methylmalonic aciduria (MMA). Methods:From October, 2017 to October, 2018, 72 children with cblC MMA combined with growth retardation were divided into control group (
7.The expression and correlation of BMI1 gene in gastrointestinal stromal tumor
Guo-Ding XU ; Hong-Mian JIANG ; Mao-Guang ZHU ; Shi-Long ZHU ; Ze SU ; Chun-Ling LI ; Hai HUANG
Journal of Medical Postgraduates 2018;31(6):631-635
Objective The role of BMI1 gene in the development of gastrointestinal stromal tumor (GIST) has not yet been clarified. This study aimed to explore the expression of BMI1 gene in gastrointestinal stromal tumor,and analyze its relationship with clinical pathological features of GIST. Methods The clinical data of 68 GIST patients treated in The First People's Hospital of Nan-ning from August 2012 to October 2015 were analyzed retrospectively. The expression of BMI1 in normal gastrointestinal tissues and GIST tissues were detected with immunohistochemistry method,and analyzed the relationship between various clinicopathological pa-rameters of GIST and BMI1. The expression of BMI1 protein was detected by Western blot. Results The positive rate of BMI1 was much higher in GIST group than in non-GIST (76.47% vs 36.84%,P<0.05). The difference in the expression of BMI1 protein between the different risk groups was statistically significant (P<0.05). The positive expression rate was the highest in the high-risk group (93.75%),but had no statistically significant difference among different genders,age,locations,histological types and whether me-tastasis (P>0.05). Expression of proliferation genes such as PCNA,CyclinD1 mRNA in BMI1 positive group were higher than those in BMI1 negative group,the expression of Pro-apoptotic genes such as Caspase-7,Smac mRNA were lower than those in BMI1 negative group,the expression of anti-apoptosis genes such as Livin,p53,Bcl-2 mRNA were higher than those in BMI1 negative group (P<0.05). Conclusion The expression of BMI1 protein was increased in GIST tissue. It is correlated with the risk classification,and is an important factor affecting the prognosis of patients.
8.The safety and effi cacy of epicardial ventricular restoration in patients with antero-septal scar and dilated ischemic cardiomyopathy
Jian WANG ; Guo-Sheng XIAO ; Bin WANG ; Zhi LIN ; Hao YOU ; Bo-Yuan HU ; Qian YANG ; Ke-Ke LAI ; Mao-Long SU ; Hong-Mei WEN ; Zhi-Wei ZHAO ; Yan WANG
Chinese Journal of Interventional Cardiology 2018;26(1):31-35
Objective To evaluate the safety and efficacy of epicardial ventricular restoration (EVR) using REVIVENT system in patients with antero-septal scar and dilated ischemic cardiomyopathy. Methods Ten ischemic heart patients with antero-septal scar underwent the operation. The scarred lateral left ventricular wall was apposed to the septal scar with serial paired anchors placed through epicardial transmural excluding the non-viable portions of the chamber. Left ventricular hemodynamic assessments as well as left ventricular ejection fraction, left ventricular end-systolic/diastolic volume (LVEDV/LVESV) and their indexes (LVEDVI/LVESVI) were measured by cardiac magnetic resonance (CMR). Results Ten ischemic heart failure patients with antero-septal scar, aged(55.2±13.9)years, received a hybrid epicardial ventricular restoration. Cardiac MR done at one a month after the procedure showed an elevation of LVEF from(27.8±4.6%)to(37.5±11.4)% (+35%, P<0.01). LVESV was significantly reduced from(149.9±61.6) ml to(109.9±58.0)ml (–26.7%, P<0.01), LVESVI was reduced from(84.8±36.7)ml/m2to(63.0±34.2) ml/m2(reduced by 25.7%, P<0.01); LVEDV was reduced from(203.0±64.0)ml to(167.9±58.2)ml (reduced by 17.3%, P<0.01), and LVESV was reduced from(114.5±37.8)ml/m2to(96.2±35.2)ml/m2(reduced by 16.0%, P<0.01). Cardiac output (CO) increased from(4.0±1.5)L/min to(4.8±1.2)L/min(increased by 20.0%, P=0.034) and cardiac index (CI) increased from(2.2±0.7)L/(min ? m2) to(2.7±0.7)L/(min ? m2) (increased by 22.4%, P=0.023). Conclusions Our preliminary experience on EVR using the REVIVENT system demonstrated signifi cant increase in LVEF, CO and CI, with decreases in LVEDV/LVESV at 1 month following the procedure. Its feasibility and safety need further evaluation in the future.
9.Preliminary experience and mid-term follow up results of patients after transcatheter aortic valve replacement
Bin WANG ; Mao-Long SU ; Ke-Ke LAI ; Feng QIU ; Guo-Sheng XIAO ; Tao YE ; Hong-Mei WEN ; Jian WANG ; Yan WANG
Chinese Journal of Interventional Cardiology 2018;26(3):138-143
Objective To evaluate the preliminary experience and mid-term outcome of transcatheter aortic valve replacement(TAVR)in patients with calcifi ed severe aortic stenosis.Methods From December 2014 to February 2016, 10 TAVR cases were admitted in the Cardiovascular Hospital, Xiamen University. The baseline characteristics, echocardiography parameters and clinical follow-up data were analyzed. Results All cases were complicated with impaired heart function(NYHAⅢ in 4 cases, NYHA Ⅳ in 6 cases). The mean age was (75.1±6.2) years and 4(4/10) of them were men. The mean logistic EuroSCORE was (27.2±23.6) % and the mean society of thoracic surgery (STS) mortality score was (9.1±4.8) %. Five cases had bicuspid aortic valve. TAVR was successfully performed in all 10 patients, and valve-in-valve implantation was done in 1 (10%) case. Immediately after procedure, the peak trans-aortic valve pressure gradient decreases from (85.9±22.7) mmHg to (23.2±5.4) mmHg. One case had marginal moderate periprosthetic leak and one case received stent implantation for femoral artery complication during the procedure. During hospitalization, 1 case had blood transfusion for gastrointestinal bleeding and permanent pacemakers were implanted in 2 (2/10) cases. The survival rate was 10/10 at 30 days after TAVR. One case with end-stage renal disease died for gastrointestinal bleeding 36 days after TAVR. For the other 9 patients, 12 months echocardiography data showed that the peak and mean trans-aortic valve gradient was (20.0±5.2) mmHg and (10.6±3.1) mmHg respectively. The lef t ventricular diastolic diameter(LVDD)decreased[(56.5±9.4)mm vs.(51.8±7.6)mm,P=0.035] and left ventricular ejection fraction(LVEF)increased significantly[(46.9±22.2)% vs.(63.7±9.4)%, P=0.029].To date,median follow-up period was(22.0±4.8)month.Clinical symptoms improved in all the 9 cases. The patient with periprosthetic leak had record of hospitalization for several times due to heart failure. Conclusions From the initial TAVR experience of our hospital, TAVR can be done safely and smoothly after strictly TAVR candidate cases selection.
10.Clinical Application of Percutaneous Balloon Aortic Valvuloplasty in Patients With Calcified Severe Aortic Stenosis Combining Heart Failure
Bin WANG ; Mao-Long SU ; Feng QIU ; Ke-Ke LAI ; Hong-Mei WEN ; Jian WANG ; Yan WANG
Chinese Circulation Journal 2018;33(2):152-156
Objective: To assess the clinical application of percutaneous balloon aortic valvuloplasty (PBAV) in patients with calcified severe aortic stenosis (AS) combining heart failure (HF). Methods: A total of 15 relevant patients treated by PBAV in our hospital from 2014-12 to 2017-05 were studied. The baseline information, echocardiography parameters, peri-operative situation and follow-up condition were summarized. Results: All 15 AS patients were combined with severe HF including 3 with NYHA III and 12 with NYHA IV; 2 cases had cardiac shock. 6/15 patients received palliative PBAV for symptom relieving and 9 for bridging step (1 case pre-operative step for non-cardiogenic surgery). PBAV was successful in all patients; the average operative dilation was (2.60±1.3) times; 2 patients suffered from complete left bundle block at immediate post-operation, 1 had ventricular tachycardia during the operation and 1 had ischemic stroke 3 days after operation, no other complications occurred. Catheter measured immediate post-operative peak trans-valvular pressure gradient was decreased from (75.0±24.0) mmHg to (39.8±14.2) mmHg, P<0.01. Echocardiography showed that before discharge, the max flow velocity was reduced from (4.98±0.76) m/s to (4.20±0.75) m/s, P<0.01, max-PG reduced from(101.3±30.4) mmHg to (72.9.0±23.3) mmHg, P<0.01, mean-PG reduced from (62.4±19.0) mmHg to (44.9±15.1) mmHg, P<0.01;while left ventricular diastolic dimension and LVEF were similar at per- and post-operation, P>0.05. NT-proBNP was decreased from (13 889±12 303) pg/ml to (5 412±4 923) pg/ml, P<0.01. The average post-operative follow-up time was (3-27) months and the median NYHA grade improved from IV to II. Conclusion: Palliative and bridging PBAV was reliable and safe in severe AS-HF patients for short time, it had less complication and could be used as an optional treatment.

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