Objective:To explore the relevant risk factors and prognosis of patients with intrahepatic cholangiocarcinoma (ICC) who experienced recurrence within 6 months after surgeryMethods:This retrospective study included a total of 259 patients with ICC a treated at He'nan Provincial People's Hospital and He'nan Cancer Hospital from Jan 2018 to Jan 2020. The clinical and pathological data ,differences between the group with recurrence within 6 months and the group without recurrence within 6 months were compared using the chi-square test. Logistic regression analysis was used to determine the relevant risk factors for recurrence within 6 months. Kaplan-Meier method was used to construct survival and recurrence curves, and survival rates were calculated.Results:The overall survival and recurrence-free survival of patients in the group with recurrence within 6 months were significantly shorter. CA19-9, tumor longitudinal diameter, microvascular invasion, and neural invasion were identified as independent risk factors for recurrence within 6 months after ICC surgery ( P<0.001). Conclusion:The patient population experiencing recurrence within 6 months after ICC surgery has an extremely poor prognosis and possesses a specific tumor microenvironment. CA19-9, tumor longitudinal diameter, microvascular invasion, and neural invasion were identified as independent risk factors for recurrence within 6 months after ICC surgery.

Objective:To study the impact of patients with intrahepatic cholangiocellular carcinoma (ICC) who underwent surgical resection with or without lymph node dissection (LND), negative or positive lymph node metastasis detected by LND, different extents of LND, and prognostic factors on long-term prognosis of these patients.Methods:The clinical data of 162 patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2014 to October 2019 and underwent surgical resection with postoperative histopathological results confirming ICC were retrospectively analyzed. According to the degree of LND, these patients were divided into three groups: the undissected group ( n=68), N0 dissected group (prophylactic dissection) ( n=41) and N1 dissected group (positive dissection, n=53). Of 94 patients who underwent LND, 23 patients underwernt the first station LND (the routine dissection group, n=23), and 71 patients underwent extended LND (the extended dissection group, n=71). The Kaplan-Meier method was used to construct survival curves. Cox regression analysis was used to detect independent factors affecting survival and long-term prognosis of patients. Results:In this study, there were 87 males and 75 females, with a median age of 60 years.The median survival time of these 162 ICC patients was 10 months. The cumulative survival rates at 1-, 3- and 5-year after surgery were 37.6%, 16.5% and 7.9%, respectively. The 1-, 3- and 5-year cumulative survival rates of the N0 dissection group were 52.1%, 31.7% and 25.4%, respectively, which were significantly better than those of the undissected group (34.2%, 12.7%, 3.4%), and the N1 dissection group (30.3%, 11.4%, 0) ( P<0.05). There were no significant differences in postoperative survival between the extended dissection group and the routine dissection group ( P>0.05). Preoperative CA19-9 >50 U/ml ( RR=1.425, 95% CI: 0.962-2.112), maximum tumor diameter > 5 cm ( RR=0.672, 95% CI: 0.456-0.989), without LND ( RR=1.715, 95% CI: 1.140-2.580), positive margin ( RR=0.591, 95% CI: 0.390-0.897), and without postoperative adjuvant therapy ( RR=0.663, 95% CI: 0.504-0.872) were independent risk factors affecting postoperative survival ( P<0.05). Conclusions:LND in ICC patients improved long-term survival outcomes. However, extended LND did not improve prognosis of these patients. The preoperative CA19-9 level, maximum tumor diameter, lymph node dissection, surgical margin status, and postoperative adjuvant therapy were independent risk factors affecting long-term prognosis of these patients.

Objective:To evaluate prognostic significance of metastated lymph nodes (LN) in patients with intrahepatic cholangio carcinoma (ICC) after radical resection.Methods:Data were reviewed on 90 patients at Department of Hepatobiliary and Pancreatic Surgery in our hospital from Feb 2013 to Oct 2019, 37 cases had no LN metastasis (N0 group), 21 cases were in N1 group (positive LN<3) and 32 cases in N2 group (positive LN≥3),and Kaplan-Meier method was used to construct survival curve. Univariate and multivariate COX regression analysis was used to screen independent risk factors.Results:In N0 group the 1-and 3-year survival rates were 57.7% and 35.2%, respectively. In N1 group the 1-and 3-year survival rates were 46.7% and 17.5%, respectively in N2 group. the 1-and 3-year survival rates were 19.6% and 0, respectively. There was statistical significance in overall survival rate among the three groups ( χ2=15.272, P<0.05). Multivariate analysis showed that resection margin ( P=0.009) and the number of positive LN ( P=0.002) were independent risk factors affecting the prognosis of patients. Conclusion:Resection margin and the number of metastasing LN were closely related to postoperative prognosis of ICC patients.

Objective:To investigate the effects of lncRNA LINC00839 on the proliferation, migration and invasion of hepatocellular carcinoma cells and its mechanism.Methods:Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of LINC00839 and miR-3666 in hepatocellular carcinoma tissues and adjacent tissues. Pearson correlation was used to analyze the correlation between LINC00839 and miR-3666 expression in liver cancer tissues. Hepatocellular carcinoma cells MHCC97H were cultured in vitro and divided into si-NC group, si-LINC00839 group, miR-NC group, miR-3666 group, si-LINC00839+ anti-miR-NC group, and si-LINC00839+ anti-miR-3666 group. Methylthiazoletrazolium (MTT) method and clone formation experiment were used to detect cell proliferation. Transwell array was used to detect the cell migration and invasion. Western blot was used to detect the protein expressions of p21, E-cadherin and MMP-2. The double luciferase reporter gene experiment was used to verify the regulatory relationship between LINC00839 and miR-3666.Results:Compared with adjacent tissues, the expression level of LINC00839 in hepatocellular carcinoma tissues increased (2.82±0.27 vs. 0.96±0.10, P<0.001), but the expression level of miR-3666 decreased (0.23±0.02 vs. 1.01±0.10, P<0.001). The expression levels of LINC00839 and miR-3666 in liver cancer tissue were negatively correlated (r=-0.658, P<0.001). The survival rate of MHCC97H cells in the si-LINC00839 group [(53.91±5.41)% vs. (100.53±10.22)%], the number of clones formed (92.0±8.0 vs. 164.0±14.3), the number of migration (131.0±12.7 vs. 247.0±22.4), the number of invasion (66.0±6.4 vs. 120.0±11.6) and the protein level of MMP-2 (0.20±0.02 vs. 0.67±0.06) were lower than those in the si-NC group ( P<0.001). However, the protein levels of p21 (0.76±0.07 vs. 0.25±0.02) and E-cadherin (0.78±0.08 vs. 0.14±0.01) were higher than those in the si-NC group ( P<0.001). LINC00839 targeted and negatively regulated the expression of miR-3666. The survival rate of MHCC97-H cells in the miR-3666 group [(47.93±4.86)% vs. (100.11±10.21)%], the number of clone formation (78.0±7.7 vs. 166.0±15.9), the number of migration (117.0±12.1 vs. 250.0±25.0), the number of invasion (57.0±5.7 vs. 121.0±12.3) and the protein level of MMP-2 (0.16±0.01 vs. 0.69±0.07) were lower than those in the miR-NC group (all P<0.001). However, the protein levels of p21 (0.83±0.08 vs. 0.24±0.02) and E-cadherin (0.87±0.09 vs. 0.13±0.01)were higher than those in the miR-NC group (all P<0.001). The survival rate of MHCC97-H cells in the si-LINC00839+ anti-miR-3666 group [(89.94±9.05)% vs. (54.12±5.39)%], the number of clones (143.0±13.8 vs. 94.0±9.4), the number of migration (208.0±19.8 vs. 129.0±12.6), the number of invasion (108.0±10.1 vs. 65.0±6.4) and the protein level of MMP-2 (0.31±0.03 vs 0.66±0.06) were higher than those in the si-LINC00839+ anti-miR-NC group ( P<0.001). However, the protein levels of p21 (0.31±0.03 vs. 0.74±0.07) and E-cadherin (0.28±0.03 vs. 0.80±0.08) were lower than those int the si-LINC00839+ anti-miR-NC group ( P<0.001). Conclusion:Inhibition of LINC00839 expression may inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells by targeting up-regulation of miR-3666 expression.

Objective:To investigate the effects of lncRNA LINC00839 on the proliferation, migration and invasion of hepatocellular carcinoma cells and its mechanism.Methods:Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of LINC00839 and miR-3666 in hepatocellular carcinoma tissues and adjacent tissues. Pearson correlation was used to analyze the correlation between LINC00839 and miR-3666 expression in liver cancer tissues. Hepatocellular carcinoma cells MHCC97H were cultured in vitro and divided into si-NC group, si-LINC00839 group, miR-NC group, miR-3666 group, si-LINC00839+ anti-miR-NC group, and si-LINC00839+ anti-miR-3666 group. Methylthiazoletrazolium (MTT) method and clone formation experiment were used to detect cell proliferation. Transwell array was used to detect the cell migration and invasion. Western blot was used to detect the protein expressions of p21, E-cadherin and MMP-2. The double luciferase reporter gene experiment was used to verify the regulatory relationship between LINC00839 and miR-3666.Results:Compared with adjacent tissues, the expression level of LINC00839 in hepatocellular carcinoma tissues increased (2.82±0.27 vs. 0.96±0.10, P<0.001), but the expression level of miR-3666 decreased (0.23±0.02 vs. 1.01±0.10, P<0.001). The expression levels of LINC00839 and miR-3666 in liver cancer tissue were negatively correlated (r=-0.658, P<0.001). The survival rate of MHCC97H cells in the si-LINC00839 group [(53.91±5.41)% vs. (100.53±10.22)%], the number of clones formed (92.0±8.0 vs. 164.0±14.3), the number of migration (131.0±12.7 vs. 247.0±22.4), the number of invasion (66.0±6.4 vs. 120.0±11.6) and the protein level of MMP-2 (0.20±0.02 vs. 0.67±0.06) were lower than those in the si-NC group ( P<0.001). However, the protein levels of p21 (0.76±0.07 vs. 0.25±0.02) and E-cadherin (0.78±0.08 vs. 0.14±0.01) were higher than those in the si-NC group ( P<0.001). LINC00839 targeted and negatively regulated the expression of miR-3666. The survival rate of MHCC97-H cells in the miR-3666 group [(47.93±4.86)% vs. (100.11±10.21)%], the number of clone formation (78.0±7.7 vs. 166.0±15.9), the number of migration (117.0±12.1 vs. 250.0±25.0), the number of invasion (57.0±5.7 vs. 121.0±12.3) and the protein level of MMP-2 (0.16±0.01 vs. 0.69±0.07) were lower than those in the miR-NC group (all P<0.001). However, the protein levels of p21 (0.83±0.08 vs. 0.24±0.02) and E-cadherin (0.87±0.09 vs. 0.13±0.01)were higher than those in the miR-NC group (all P<0.001). The survival rate of MHCC97-H cells in the si-LINC00839+ anti-miR-3666 group [(89.94±9.05)% vs. (54.12±5.39)%], the number of clones (143.0±13.8 vs. 94.0±9.4), the number of migration (208.0±19.8 vs. 129.0±12.6), the number of invasion (108.0±10.1 vs. 65.0±6.4) and the protein level of MMP-2 (0.31±0.03 vs 0.66±0.06) were higher than those in the si-LINC00839+ anti-miR-NC group ( P<0.001). However, the protein levels of p21 (0.31±0.03 vs. 0.74±0.07) and E-cadherin (0.28±0.03 vs. 0.80±0.08) were lower than those int the si-LINC00839+ anti-miR-NC group ( P<0.001). Conclusion:Inhibition of LINC00839 expression may inhibit the proliferation, migration and invasion of hepatocellular carcinoma cells by targeting up-regulation of miR-3666 expression.

Objective To study factors affecting prognosis of patients with intrahepatic cholangiocarcinoma (ICC),focusing on the correlation between extent of lymph node dissection and prognosis of patients with ICC.Methods The clinical data of ICC patients who underwent radical resection at the Hepatobiliary and Pancreatic Surgery of Affiliated Cancer Hospital of Zhengzhou University from October 2013 to October 2017 were retrospectively analyzed.According to the extent of lymph node dissection,the patients were divided into the non-dissected lymph node group,the routine dissection lymph node group and the extended lymph node dissection group.The prognoses of the three groups were compared.The Cox stepwise regression model was used to analyze the independent risk factors for prognosis of patients with ICC.Results The 178 patients included 109 males and 69 females.Their ages ranged from 30 to 81 years (average 59 years).There were 80 patients in the non-dissected group,34 patients in the routine lymph node dissection group,and 64 patients in the extended lymph node dissection group.The overall survival rates of the 178 patients at 3 years after liver resection was 29.2％ (52/178),overall median survival 25.8 months.The 3-year survival rates of the non-dissected group,routine dissection group,and extended dissection group were 10.0％ (8/80),52.9％ (18/34),40.6％ (26/64),respectively.The differences among the three groups were significant (P ＜ 0.05).Comparison among the three groups showed that there was no significant difference in survival rates between the routine dissection group and the extended dissection group (P ＞ 0.05).There was a significant difference in survival rates between the non-dissected group and the extended lymph node dissection group (P ＜0.05).Univariate analysis showed that CA19-9,tumor diameter,portal tumor thrombus,and lymph node dissection were related to prognosis of patients with ICC (P ＜ 0.05).Multivariate analysis showed CA19-9,tumor diameter,and extent of lymph nodes clearance were related to patient survival (P ＜ 0.05).Conclusions CA19-9,tumor diameter,and extent of lymph node dissection were independent risk factors of survival in patients with ICC.For patients with ICC who undergo surgical resection,conventional laparoscopic lymph node dissection can achieve good results,and there is no need to extend lymph node dissection.

Objective: To investigate the correlations between the systemic immune inflammatory index (SII) and prognosis of patients with gallbladder cancer. Methods: From April 2005 to January 2019, patients with gallbladder cancer underwent surgical treatment in the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Tumor Hospital of Zhengzhou University were followed up and their SII values were analyzed. The receiver operating characteristic curve (ROC) was used to determine the best clinical boundary value of SII. According to the boundary value, patients were divided into two groups: low SII and high SII. Survival curves were drawn by Kaplan-Meier method. The overall survival time of the two groups was analyzed, and univariate analysis of postoperative survival was performed using log-rank test. Cox regression proportional hazard model was used for multivariate analysis of clinical prognosis. Results: A total of 312 patients were included, including 120 males and 192 females, aged 30.0 to 86.0 (61.5±9.9) years. The best clinical cut off value of preoperative SII was determined by ROC curve to be 510.42. A total of 312 patients with gallbladder cancer were divided into low SII group (SII≤510.42) and high SII group (SII>510.42). Kaplan-Meier survival curve was used to analyze the 1, 3 and 5-year survival rates of gallbladder cancer patients in low SII group and high SII group after operation. The survival rates were 65.7%, 39.6% and 30.2%, and 27.9%, 12.0% and 9.6% respectively. The median survival time was 25 months (95% CI: 16.9-33.1) and 9 months (95% CI: 8.1-9.9), respectively. The survival rate of gallbladder cancer patients in low SII group was better. There were significant differences of the overall survival rate between the two groups (P<0.05). Univariate analysis showed that SII>510.42 (HR=0.086, 95% CI: 0.032-0.289) was a risk factor for overall survival of gallbladder cancer patients. Cox multivariate analysis confirmed that preoperative SII (HR=2.649, 95% CI: 1.981-3.543) was an independent risk factor for overall survival of gallbladder cancer patients. Conclusions SII can be used as an independent prognostic factor to predict the prognosis of patients with gallbladder cancer. The higher the preoperative SII, the worse the prognosis of patients with gallbladder cancer.

OBJECTIVE:To provide reference for formulating drug price regulation policy and promoting reasonable drug price. METHODS:According to WHO and HAI drug price standard investigation,questionnaire survey(supplemented by field investigation)about sale price of 63 commonly used drugs with large consumption sum was conducted among 3 districts of different economic development levels in Hubei province. Median price ratio(MPR)was calculated statistically. Primary interview survey(supplemented by literature investigation)about drug distribution cost was conducted among managerial staff of pharmaceutical wholesale and retail enterprises,hospital pharmacy administrators. Suggestions were put forward to control distribution cost and standardizing drug price based on analysis and discussion. RESULTS:Totally 120 questionnaires were sent out,and 118 were effectively received,with effective recovery of 98.33%. Thirty managerial staff from drug wholesale and retail enterprises,hospital pharmacy department were interviewed for investigation of drug distribution cost. MPR of 63 drugs ranged 0.05-44.55 in different types of sample institutions. Among 67 specifications of 53 kinds of drugs,median retail price of 38 specifications(56.72%)was higher than international reference price in first-level sample medical institutions. Among 79 specifications of 63 kinds of drugs,median retail price of 57 specifications(72.15%)was higher than international reference price in second-level sample medical institutions. Among 80 specifications of 63 kinds of drugs,median retail price of 63 specifications(78.75%)was higher than international reference price in third-level sample medical institutions. Among 50 specifications of 37 kinds of drugs,median retail price of 42 specifications(84.00%)was higher than international reference price in sample pharmaceutical retail enterprises. In all sample institutions,maximum MPR of 13 specification were lower than 1;those of 12 specification ranged from 1 to <2;those of 23 specifications ranged from 2 to <5;15 specification ranged from 5 to <10;those of 17 specification were higher than 10. MPR of third-level medical institution samples were higher than those of second-level and first-level ones,and pharmaceutical retail enterprises(P<0.01). MPR of second-level medical institution samples and pharmaceutical retail enterprises were higher than those of first-level medical institutions(P<0.01). There was no statistical significance in the levels of MPR between second-level medical institutions and pharmaceutical retail enterprises(P>0.05). MPR of sample institutions in well-developed regions were higher than in medium-developed or less-developed regions(P<0.01). MPR of sample institutions in medium-developed regions were higher than in less-developed regions(P<0.01). MPR of original drugs were all higher than those of generic drugs in different types of sample institutions(P<0.01). There was no statistical significance in MPR of original drugs among different types of sample institutions(P>0.05). At the same time,MPR of generic drugs in third-level medical institution samples were higher than in second-level and first-level ones and pharmaceutical retail enterprises (P<0.05 or P<0.01). MPR of second-level medical institution samples and pharmaceutical retail enterprises were higher than in first-level ones(P<0.05). There was no statistical significance between second-level medical institution samples and pharmaceutical retail enterprises(P>0.05). Drug production and circulation cost,centralized bidding and purchasing price in Hubei province were higher than the national level. CONCLUSIONS:The drug price of Hubei province is in high level,especially that of three-level medical institutions is higher than other institutions;drug price of well-developed region is higher than those of medium-level and less-developed region;the price of original drugs are higher than those of generic drugs. The cost of pharmaceutical industry,drug circulation cost and the addition of drug price during application link eventually lead to the higher retailing price of drugs. Comprehensive policy measures need to be taken to control the cost of the whole process of drug distribution and to regulate the price of drugs.

Objective To investigate the effect of miR-10b on migration and invasion of human hepatocellular carcinoma (HCC) cell lines.Methods Transwell assay was used to evaluate the motility and invasiveness in different HCC cell lines,qRT-PCR was then used to detect the expression levels of miR-10b in different HCC cell lines.Artificial mimics of miR-10b were transiently transfected into HepG2 cells,which have low expression of miR-10b,and then the changes in migration and invasion were evaluated by Transwell assay.Antagomirs of miR-10b (miR-10b-AS) were transiently transfected into MHCC97H cells,which have high expression of miR-10b,and then the changes in migration and invasion were evaluated as well.Cell morphology changes were detected by immunofluorescence and electron microscopy,Results There was a significant correlation of miR-10b expression level with cell motility and invasiveness.Low-level expression of miR-10b was observed in HepG2 cells,which exhibited weak motility and invasiveness; whereas high-level expression of miR-10b was observed in MHCC97H cells,which exhibited strong motility and invasiveness.Up-regulation of miR-10b expression in HepG2 cells increased cell motility and invasiveness,whereas inhibition of miR-10b reduced cell motility and invasiveness in MHCC97H cells.Immunofluorescence and electron microscopy results showed that up-regulation of miR-10b in HepG2 cells significantly increased proliferation of filopodia and lamellipodia,whereas inhibition of miR-10b decreased filopodia and lamellipodia amount in MHCC97H cells.Conclusion miR-10b is involved in the invasion and metastasis of HCC cell through regulation of cytoskeleton in vitro and inhibition of miR-10b is likely to be a new molecular target to block metastasis.

ObjectiveTo investigate the clinical features of hepatic follicular dentritic cell sarcoma (FDCS).MethodsClinical data of a patient with hepatic FDCS treated in Cancer Hospital Affiliated to Zhengzhou University in 2004 were retrospectively analyzed. The informed consent of the patient was obtained and the local ethical committee approval had been received. The patient, female, 49-year-old, was admitted to the hospital for the complaint of abdominal pain for 1 month . A 12 cm×12 cm in diameter, hard, poor activity tumor was found below xiphoid by physical examination. Abdominal tenderness was positive and laboratory examinations were essentially normal. CT scan showed a 20 cm in diameter solid lesion in the left lobe of liver. The tumor was observed irregularly enhanced in the arterial phase by enhanced CT scan. The enhancement faded away in the delayed phase, and the tumor revealed a low-density lesion. The initial diagnosis was primary liver cancer.ResultsAfter an active preoperative preparation, the patient underwent left lobectomy under endotracheal general anesthesia on August 31, 2004. A tough tumor measuring 23 cm×20 cm in diameter was found in the left lobe of liver during the surgery. Nodule foci were found beside the tumor and no obvious metastasis was found within the abdomen, pelvic cavity and peritonium. Postoperative pathological examination indicated inlfammatory pseudotumor FDCS and Immunohistochemistry indicated positive CD21, CD23, CD35 and vimentin (VIM). Tumor recurrence and matastasis were observed in the liver, abdomen cavity and chest wall etc. repeatedly and was resected during 2006 to 2014. The patient is currently in stable condition and no recurrence or metastasis was observed during regular follow-up till submission date. ConclusionsHepatic FDCS is a very rare disease. The diagnosis relies on the results of pathological examination. Surgical resection is a reliable treatment and the prognosis is favorable.