Gallbladder carcinoma is the most common malignancy in biliary tract.Early dissemination,rapid and silent progression and delayed diagnose could portend a dismal prognosis.The 5-year survival rate is less than 10％.Clarifying the etiological feature can improve the early diagnosis.Comprehending surgical indications of benign lesions can provide the methods for rational prophylactic resections.Standardized treatment of accident gallbladder carcinoma could improve the patients' prognosis.Efficient serologic markers could be used for early diagnosis and screening.

Objective To analyze the clinical characteristics,diagnosis,treatment and prognostic factors of primary hepatic neuroendocrine tumor (PHNET).Methods To analyze the clinical data of 21 patients with PHNET who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2012 to January 2019.There were 11 males and 10 females,with ages which ranged from 36 to 75 years.Log-rank test was used for single-factor analysis of the relationship between clinical and pathological indicators and prognosis.Cox proportional risk model was used for multi-factor analysis.Results Among the 21 PHNET patients,10 presented with central and upper abdominal pain,3 abdominal pain accompanied by nausea and vomiting,5 abdominal distension,and 3 were asymptomatic.Carbohydrate antigen (CA) 19-9 was elevated in 6 patients and CA125 in 7 patients.Abdominal enhanced CT showed solid liver space occupying lesions.Four patients had solitary and 17 had multiple lesions.The mean diameter was 58 mm.Fourteen patients had lymph node metastasis.Five patients underwent radical hepatectomy,2 transcatheter hepatic arterial chemoembolization + chemotherapy,12 chemotherapy,and 2 supportive treatment.Factors which were associated with prognosis of PHNET patients were surgery,tumor grading,cytokeratin positivity and lymph node metastasis.Multivariate Cox regression analysis showed that inoperability (HR =8.99,95％ CI:1.13-71.80) was an independent risk factor of prognosis of PHNET patients.The prognosis in patients who underwent surgical resection was better.Conclusion Patients with PHNET had no specific clinical manifestations.Surgical resection gave the best results in treatment.As surgical resection affected prognosis,it should be carried out if technically feasible.

Objective:To investigate the effect of local antibiotics irrigation on chronic proliferative cholangitis (CPC).Methods:CPC model of rabbits was established. Rabbits were divided into CPC group (without local antibiotics irrigation, n=20) and experimental group (with local antibiotics irrigation, n=20). Only the gallbladder was removed, and 20 rabbits with free bile duct (sham operation) were used as normal control. The inflammatory conditions, proliferation of cholangiocytes, biliary fibrosis and biliary stones formation ability were analyzed. Results:Compared with CPC group, the relative expression of inflammation index lipopolysaccharide and interleukin-6 [(1.21±0.13) vs. (3.24±0.21), (1.52±0.22) vs. (3.10±0.23)], biliary cell proliferation index cyclooxygenase-2 and vascular endothelial growth factor [(2.15±0.12) vs. (4.07±0.22), (2.44±0.14) vs. (3.22±0.21)], fibrosis index transforming growth factor-β and Collagen-I [(2.44±0.28) vs. (4.36±0.44), (1.54±0.13) vs. (2.22±0.18)] and biliary stones formation index β-glucuronidase and Mucin 5AC [(1.74±0.20) vs. (3.42±0.31), (1.47±0.15) vs. (2.81±0.22)] were significantly decreased in experimental group (all P<0.05). Conclusion:Local antibiotics irrigation could inhibit CPC by inhibiting the chronic inflammation of the biliary tract and excessive proliferation of cholangiocytes and biliary fibrosis, and reducing the probability of biliary stone formation.

ObjectiveTo investigate the changes in gut microbiota after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients with mild hepatic encephalopathy (MHE) in different prognosis groups. MethodsA total of 28 MHE cirrhotic patients who were hospitalized and underwent TIPS in Xijing Hospital of Digestive Diseases from July 2016 to July 2017 were enrolled. Fecal samples and related clinical data were collected on days 1-3 before surgery and at 1 month after surgery. According to the prognosis after surgery, the patients were divided into none-hepatic encephalopathy (HE) group with 8 patients, MHE group with 12 patients, and overt hepatic encephalopathy (OHE) group with 8 patients. Fecal samples were analyzed by 16S rRNA sequencing to obtain the relative abundance of gut microbiota, and SPSS and R packages were used to analyze the biodiversity, postoperative changes, and differences in such changes of gut microbiota at the genus level between groups. The chi-square test was used for comparison of categorical data between groups; the Kruskal-Wallis H test was used for comparison of continuous data between three groups; the Bonferroni method was used for multiple comparisons of multiple samples; the Wilcoxon signed-rank test was used for comparison before and after surgery within each group. For microbiome beta-diversity analyses, a principal coordinate analysis (PCoA) was performed based on Bray-Curtis distance matrix, and the Adonis method (PerMANOVA) was used for comparison between groups. ResultsPCoA based on Bray-Curtis distance matrix showed that only the MHE group had a significant change in beta diversity after surgery (F=2.71, P=0.049). After surgery, the non-HE group had significant increases in the abundance of the native flora Dialister, Coprococcus, Ruminococcaceae_uncultured, Flavonifractor, and Clostridium_sensu_stricto_1 (Z=2.521, 2.1, 2.1, 2.1, and 1.96, all P＜0.05); the MHE group had significant reductions in the abundance of the harmful flora Granulicatella（Z=2.521,P=0.012）, Enterococcus（Z=2.51,P=0.012）, Streptococcus（Z=2.432,P=0.015）, and Rothia（Z=2.001,P=0.045） and significant increases in the abundance of Veillonella（Z=2.353,P=0.019） and Megasphaera（Z=1.955,P=0.05）; the OHE group only had a significant increase in the abundance of Veillonella after surgery (Z=2.38, P=0.017). There was a significant difference in the change in gut microbiota (postoperative abundance/preoperative abundance) between the non-HE group, the MHE group, and the OHE group ［2.00 (1.11-91.61) vs 1.21 (0.26-679) vs 0.09 (0.01-0.92), χ2=6.249, P=0.043］. ConclusionThere is a significant difference in the change in gut microbiota after TIPS between patients with different prognoses, and the increase in the abundance of native flora may have a certain influence on the remission of MHE.

Objective:To study the impact of additional resection of an intraoperative proximal bile duct positive margin on the survival rate of patients with hilar cholangiocarcinoma (HCCA).Methods:The clinical data of 214 patients with HCCA treated at the First Affiliated Hospital of Zhengzhou University from January 2000 to January 2017 were analyzed. There were 126 males and 88 females, aged (62.3±17.1) years. These patients were divided into three groups according to the pathological status of bile duct margins and whether the proximal bile duct was further resected. Group A consisted of patients with negative margins without additional resection (161 cases). Group B consisted of patients with negative margins after additional resection (21 cases). Group C consisted of patients with R 1 resections (32 cases). The Kaplan-Meier method was used for survival analysis and log-rank test was used for inter-group comparison. Univariate and multivariate Cox regression analysis were used to analyze prognostic factors. Results:The 3-year and 5-year survival rates of patients in groups A, B, and C were 37.1%, 28.6%, 0 and 18.5%, 10.7%, 0, respectively. The cumulative survival rates of patients in group A and group B were significantly higher than that in group C (all P<0.05). Multivariate Cox regression analysis showed that R 1 proximal bile duct margin ( HR=3.728, 95% CI: 2.531-4.936), margin width >5 mm ( HR=0.534, 95% CI: 0.224-0.857), and T 3-4 staging ( HR=5.655, 95% CI: 3.174-8.203) were independent influencing factors for overall survival of patients with HCCA after attempted radical surgery. Conclusion:The survival rate of patients with HCCA with a positive proximal bile duct margin was significantly improved by further resecting the bile duct to obtain a negative margin. The R 1 proximal bile duct margin was an independent risk factor for prognosis in patients with HCCA after attempted radical resection.

Objective To identify lipid metabolism genes in cerebral infarction;To explore the intervention effect of Huoxue Rongluo Prescription.Methods Multi-chip combined differential analysis(GSE61616,GSE30655)was used to identify lipid metabolism genes in cerebral infarction in combination with Reactome database,and the expression differences of lipid metabolism genes in cerebral infarction were identified and verified in GSE97537 chip;Pearson correlation analysis was used to analyze the correlation of 51 cerebral infarction samples in GSE61616,GSE30655,GSE97537,GSE137595,GSE22255,GSE163614,and GSE78731 datasets;PPI,GO and KEGG analysis of lipid metabolism genes in cerebral infarction were performed through STRING database and R clusterProfiler package.SD rats were made to the model of cerebral infarction,and was administered with Huoxue Rongluo Prescription extract 11.7 g/kg by intragastric administration for 7 days.The symptoms of neurological deficit,the changes of Nissl bodies and the mRNA expressions of PLA2G4A,SPHK1,and PTGES key genes in lipid metabolism in cerebral infarction were observed.Results TSPO,CYP1B1,PLIN2,CH25H,PLA2G4A,ANGPTL4,PTGS1,SPHK1,and PTGES were identified as lipid metabolism genes in cerebral infarction,and were significantly highly expressed and positively correlated in cerebral infarction.Among them,PTGS1,PLA2G4A,and SPHK1 interacted with each other,which were the key genes of lipid metabolism in cerebral infarction;the lipid metabolism gene in cerebral infarction mainly exerted molecular functions such as oxidoreductase activity,iron ion binding,heme binding,etc.,mediating arachidonic acid metabolism,phospholipase D signaling pathway,VEGF signaling pathway,involved in regulation of lipid metabolism process,fatty acid metabolism process,fatty acid derivative metabolism process.The symptoms of neurological deficit in the model rats with cerebral infarction were severe(P<0.001),and Huoxue Rongluo Prescription could effectively improve the neurological deficit of model rats(P<0.001).The Nissl staining indicated that the neuronal structure was abnormal and the number was significantly reduced after cerebral infarction(P<0.001).Huoxue Rongluo Prescription could increase the number of neurons(P<0.001)and repair the neuronal structure.RT-qPCR showed that the key genes of lipid metabolism in cerebral infarction were significantly higher in cerebral infarction(P<0.001),corroborated with the bioinformatics results,and Huoxue Rongluo Prescription could reduce the expression of key lipid metabolism genes of PTGS1,PLA2G4A,and SPHK1(P<0.001,P<0.01,P<0.05).Conclusion Huoxue Rongluo Prescription can down-regulate the expressions of PTGS1,PLA2G4A,SPHK1,exert molecular functions such as oxidoreductase activity,iron ion binding,heme binding,and mediate arachidonic acid metabolism,phospholipase D signaling pathway,and VEGF signaling pathway.It participates in the process of lipid metabolism regulation,fatty acid metabolism,and fatty acid derivative metabolism,increases the number of Nissl bodies,improves the symptoms of neurological deficits,and exerts neuroprotective effects.

Malnutrition in liver cirrhosis is associated with ascites, hepatic encephalopathy, infection, and other complications even death. To date, the hazard and disease burden of malnutrition in cirrhosis patients have been severely underestimated. This review summarized the most recent advancement in the field and discussed the techniques and methodologies in detection and evaluation of malnutrition in cirrhosis patients, nutritional support therapy, and future research directions and clinical care of the patients.

Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.
Mice ; Animals ; Humans ; Hepatitis, Autoimmune/pathology* ; Signal Transduction ; Disease Models, Animal ; Stem Cells