Intrahepatic cholangiocarcinoma (ICC) has a high degree malignancy, and its incidence has gradually increased in recent years. Surgery is still the only curative treatment for ICC to achieve long-term survival, but its onset is hidden, and most patients have lost the opportunity of operation when they are diagnosed. ICC shows significant heterogeneity. With the development of the second generation sequencing technology, the tumor patterns of ICC, such as DNA, RNA, epigenetic, protein, microenvironment and so on, have been gradually discovered. The purpose of this article is to review the research progress of molecular typing and clinical application of ICC in recent years.

Objective:To investigate the impact of initial recurrence site on the prognosis of patients with pancreatic cancer after radical operation.Methods:Clinical data of 172 patients who underwent radical resection of pancreatic cancer and were pathologically confirmed as pancreatic ductal adenocarcinoma in Ningbo University Affiliated Lihuili Hospital from January 2015 to June 2021 were analyzed retrospectively. According to the classification of the initial recurrence or metastasis after operation: no recurrence, local recurrence (residual pancreas, mesenteric vein, pancreaticoenterostomy surrounding tissue), liver metastasis, abdominal or retroperitoneum metastasis, multiple site recurrence and other pattern recurrence. The effect on prognosis was analyzed by COX risk ratio model, the overall survival and recurrence-free survival were calculated by Kaplan-Meier, and the survival curve was drawn. Log-rank test was used to compare the survival rate of different recurrence sites and different treatments after recurrence.Results:12 patients had local recurrence, 69 had liver metastasis, 25 had abdominal or retroperitoneal metastasis, 17 had multiple site recurrence, and 5 had other site recurrence and 44 had no recurrence. The median follow-up time was 15.5 months (3-69 months). The median overall survival was 19 months (95% CI 16.273-21.727). The 1- , 3- and 5-year postoperative cumulative survival rate was 71.0%, 27.8% and 20.2%, respectively. Univariate analysis showed that CA125, tumor size, lymph node metastasis, microvascular invasion, tumor differentiation degree, adjuvant chemotherapy, initial recurrence site were significantly correlated with overall survival (All P value <0.05). Multivariate analysis showed that CA125 ≥30 IU/ml ( OR=2.669, P=0.001), microvascular invasion ( OR=1.736, P=0.028), poor tumor differentiation ( OR=1.604, P=0.027), adjuvant chemotherapy ( OR=0.439, P<0.001), initial recurrence site (All P value <0.05) were the independent risk factors for overall survival. The median recurrence-free survival of 172 patients was 9 months (95% CI 7.075-10.925). Univariate analysis showed that CA125, tumor size, lymph node metastasis and microvascular invasion were significantly correlated with recurrence-free survival (All P value <0.05). Multivariate analysis showed that CA125 ( OR=1.640, P=0.026), tumor size ( OR=1.774, P=0.011) and microvascular invasion ( OR=1.563, P=0.034) were the independent risk factors for recurrence-free survival. After surgery, the median survival time of patients with local recurrence, other pattern recurrence, abdominal or retroperitoneal metastasis, multi-site recurrence and liver metastasis was 28, 22, 21, 15 and 14 months, respectively. Among them, the overall survival of patients with postoperative local recurrence was longest, which was significantly longer than that of patients with multi-site recurrence ( P=0.035) and liver metastasis ( P=0.007); the survival of patients with abdominal or retroperitoneal metastasis was also longer than that with liver metastasis ( P=0.005); and all the differences were statistically significant. In 128 patients with recurrence, the median overall survival of 26 patients without adjuvant therapy was 10 months (95% CI 6.877-13.123); the median overall survival of 68 patients with adjuvant chemotherapy was 15 months (95% CI 13.013-16.987); the median overall survival of 34 patients with comprehensive treatment of surgery and radiotherapy was 19 months (95% CI 15.100-22.900), which was significantly higher than the other two groups, and there were significant statistical differences among the three groups ( P<0.001). Conclusions:The initial recurrence site of pancreatic cancer after radical operation is an independent risk factor for overall survival. Compared with local recurrence and abdominal or retroperitoneal metastasis, patients with multi-site recurrence and liver metastasis have a poor prognosis. Comprehensive treatment after recurrence can significantly prolong the overall survival.

Peribiliary glands (PBG) is a kind of microscopic structure around the intra-hepatic bile ducts and extrahepatic bile ducts. PBG not only participates in maintaining the normal physiological function of biliary epithelial tissue, but also plays an important role in its damage and repair process. Biliary tree stem/progenitor cells in PBG are important cell sources of biliary epithelial regeneration and repair. PBG and the surrounding peribiliary vascular plexus are key influencing factors for the occurrence of ischemic-type biliary lesions (ITBL) after liver transplantation. Based on relevant literatures and clinical practice, the authors summarize the function of PBG as well as its relationship with ITBL.

Objective:To analyze the risk factors of newly developed non-alcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) based on a propensity score matching (PSM) analysis.Methods:The clinicopathological data of 219 patients with pancreatic or periampullary tumors undergoing PD in the Ningbo Medical Center Lihuili Hospital from December 2015 to December 2021 were retrospectively analyzed, including 129 males and 90 females, aged (63.68±11.07) years old. The patients were divided into two groups according to the newly occurrence of NAFLD within one year after PD: the NAFLD group ( n=57) and non-NAFLD group ( n=162). A caliper value of 0.1 was employed for 1∶1 matching, resulting in a well-balanced PSM between the groups. Results:A total of 144 patients were successfully matched by PSM. Univariate analysis indicated that gender, body mass index, preoperative serum triglyceride and operative time were risk factors for newly developed NAFLD after PD. Multivariate analysis showed that female ( OR=6.493, 95% CI=2.631-16.129, P<0.001), preoperative serum triglycerides ≥1.5 mmol/L ( OR=3.055, 95% CI=1.220-7.654, P=0.017) and operative time ≥300 min ( OR=5.092, 95% CI=1.374-18.865, P=0.015) were the independent risk factors for newly developed NAFLD after PD. Conclusion:Based on PSM analysis, female, preoperative triglyceride ≥1.5 mmol/L and operative time ≥300 min were independent risk factors for newly developed NAFLD after PD.

The objective of this study was to examine the effects of electroacupuncture on the expression of ATP-binding cassette transporter A1(ABCA1),ATP-binding cassette transporter G1(ABCG1),and class B type Ⅰ scavenger receptor(SR-B Ⅰ)genes and proteins in peritoneal macrophages of atherosclerotic rabbits.The study aimed to explore the mechanism underlying the treatment of atherosclerosis(AS)with electroacupuncture.Methods Twenty-six male New Zealand rabbits were randomly divided into the negative control group(n=7)and the modeling group(n=19)using a random number table method.The negative control group rabbits were fed a regular diet,while the modeling group was induced with a combination of high-fat feed and common carotid artery balloon injury surgery to create an AS model.After successful modeling,the rabbits in the modeling group were further divided into the model group,the electroacupuncture group,and the atorvastatin group,with 6 rabbits in each group.The rabbits in the electroacupuncture group received electroacupuncture at"'Neiguan'(PC6)","'Zusanli'(ST36)",and"'Guanyuan'(ST25)"acupoints,using a density wave,a current of 1 mA,and a frequency of 4 Hz/20 Hz,once a day.The needle was retained for 20 minutes each time,and a total of 4 courses of treatment were conducted,with 6 days per course.The rabbits in the atorvastatin group were administered atorvastatin calcium tablet suspension(1 mg/kg)orally once a day,for 6 days per course,with a total of 4 courses.After the interventions,HE staining was performed to observe the morphological changes in the common carotid artery tissue of the rabbits.Peritoneal macrophages were collected from the rabbits,and the mRNA expression levels of ABCA1,ABCG1,and SR-B Ⅰ were measured using real-time fluorescence PCR.The protein expression levels of ABCA1,ABCG1,and SR-B Ⅰ were detected using Western blotting.Results The negative control group exhibited smooth intima of common carotid artery in rabbits,while the model group displayed damaged intima of common carotid artery,thickened artery walls,and the formation of atherosclerotic plaques.The electroacupuncture group and atorvastatin group showed significant improvements in wall thickening and a reduction in plaque area.Compared with the negative control group,the mRNA and protein expressions of ABCA1,ABCG1,and SR-B Ⅰ in peritoneal macrophages of rabbits in the model group were reduced(P＜0.01).Compared with the model group,the electroacupuncture group and atorvastatin group exhibited increased mRNA and protein expressions of ABCA1,ABCG1,and SR-B Ⅰ in abdominal macrophages of rabbits(P＜0.01).Furthermore,the atorvastatin group demonstrated increased mRNA levels of ABCG1 and SR-B Ⅰ,as well as increased protein expressions of ABCA1,ABCG1,and SR-B Ⅰ in peritoneal macrophages of rabbits,in comparison to the electroacupuncture group(P＜0.01).Conclusion Electroacupuncture can enhance the expressions of ABCA1,ABCG1,and SR-B Ⅰ mRNA and protein in abdominal macrophages of AS rabbits,thereby promoting the process of cholesterol reverse transport.This may be one of the mechanisms underlying the effectiveness of acupuncture in the treatment of AS.

ObjectiveTo investigate the effect of 1，25（OH）₂D₃ on the level of peroxisome proliferator-activated receptor-γ （PPAR-γ） in the liver， the phenotype of hepatic macrophages， and liver inflammation in a rat model of nonalcoholic steatohepatitis （NASH）， as well as the mechanism of 1，25（OH）₂D₃ improving liver inflammation. MethodsAfter 1 week of adaptive feeding， 24 specific pathogen-free Wistar rats were randomly divided into normal group ［choline-supplemented L-amino acid-defined （CSAA） diet］， normal+1，25（OH）₂D₃ group ［CSAA diet+1，25（OH）₂D₃］， model group ［choline-deficient L-amino acid-defined diet （CDAA） diet］， and model+1，25（OH）₂D₃ group ［CDAA diet+1，25（OH）₂D₃］， with 6 rats in each group. The dose of 1，25（OH）₂D₃ was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） were measured， liver histopathology was observed， and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages， and ELISA was used to measure the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in liver tissue， and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups， and the least significant difference t-test was used for further comparison； the Pearson method was used for correlation analysis. ResultsCompared with the normal group， the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT （P=0.019 and P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P<0.001）， as well as a significant increase in the level of TNF-α （P<0.001） and a significant reduction in the level of IL-4 in liver tissue （P=0.025）. The 1，25（OH）₂D₃ group had significant reductions in the serum levels of ALT （P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P=0.001）， the level of IL-1β （P<0.001） and a significant increase in the level of M2 hepatic macrophages （P=0.017）， the level of IL-10 （P=0.039）， the level of IL-4 （P<0.001）， the level of PPAR-γ （P=0.016）. There were significant interactions between CDAA diet-induced NASH model and 1，25（OH）₂D₃ in serum the levels of AST and ALT （P=0.007 and P=0.008）， the SAF scores of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， the level of M2 hepatic macrophages （P=0.008）， the ratio of M1 and M2 of hepatic macrophages （P=0.005）， the level of TNF-α （P<0.001）， the level of IL-10 （P=0.038）， the level of IL-4 （P<0.001） and the level of PPAR-γ （P=0.009）. The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages （r=-0.415， P=0.044） and was positively correlated with M2 hepatic macrophages （r=0.435， P=0.033）， IL-10 （r=0.433， P=0.035）， and IL-4 （r=0.532， P=0.007）. ConclusionThis study shows that 1，25（OH）₂D₃ improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.

Objective To construct an evaluation index system for the capability of comprehensive control of mountain-type zoonotic visceral leishmaniasis based on the One Health concept, so as to provide insights into the control and elimination of mountain-type zoonotic visceral leishmaniasis using the One Health approach. Methods A preliminary evaluation index system was constructed based on literature review, panel discussions and field surveys. Thirty-three experts were selected from 7 provincial disease control and prevention centers in Beijing Municipality, Hebei Province, Shanxi Province, Henan Province, Sichuan Province, Shaanxi Province and Gansu Province where mountain-type zoonotic visceral leishmaniasis was endemic, and two rounds of expert consultations were conducted to screen the indicators. The positive coefficient, degree of concentration, degree of coordination, and authority of the experts were calculated, and the normalized weights of each index were calculated with the analytic hierarchy process. Results The response rates of questionnaires during two rounds of expert consultation were both 100.00% (33/33), and the authority coefficients of the experts were 0.86 and 0.88, respectively. The coefficients of coordination among experts on the rationality, importance, and operability of the indicators were 0.392, 0.437, 0.258, and 0.364, 0.335, 0.263, respectively (all P values < 0.05). Following screening, the final evaluation index system included 3 primary indicators, 17 secondary indicators, and 50 tertiary indicators. The normalized weights of primary indicators “external environment”, “internal support” and “comprehensive control” were 16.98%, 38.73% and 44.29%, respectively. Among the secondary indicators of the primary indicator “external environment”, the highest weight was seen for natural environment (66.67%), and among the secondary indicators of the primary indicator “internal support”, the lowest weight was seen for the scientific research for visceral leishmaniasis control (8.26%), while other indicators had weights of 12.42% to 13.38%. Among the secondary indicators of the primary indicator “comprehensive control”, the weight was 16.67% for each indicator. Conclusions An evaluation index system has been constructed for the capability of comprehensive control of mountain-type zoonotic visceral leishmaniasis based on the One Health concept. In addition to assessment of the effect of conventional mountain-type zoonotic visceral leishmaniasis control measures, this index system integrates the importance of top-level design, organizational management, and implementation of control measures, and includes indicators related to multi-sectoral cooperation.