Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.

The growth of solid tumors rely on angiogenesis to establish blood supply, and inducing neovascularization is a necessary condition for the growth of solid tumors. Anti-angiogenic therapies have been developed for tumors based on this theory. Although liver cancer is considered as a highly angiogenic tumor, the effectiveness of these drugs in anti-angiogenic therapies on liver cancer has not met expectations. In recent years, vessel co-option, as a long-standing but overlooked mechanism of vascularization of non-angiogenic tumors, has gradually attracted attention. Tumor tissue can promote its own growth by "hijacking" existing blood vessels in the para-carcinoma tissue instead of inducing angiogenesis, known as vessel co-option or vascular hijacking. Vessel co-option has been observed in a variety of tumors, both primary and metastatic, and is believed to be a key mechanism of anti-angiogenic resistance. The authors systematically examine the evidence, clinical prognosis, and molecular mechanisms of vessel co-option in liver cancer, and discuss its potential role in anti-angiogenic therapeutic resistance and alternative anti-tumor strategies for liver cancer.

Objective:To analyze the influencing factors of abnormal 15-minute retention rate of indocyanine green (ICG R15) (≥10%) in patients with hepatocellular carcinoma, and to construct a nomogram model, and to evaluate the prediction efficiency of the nomogram model.Methods:The clinical data of 190 patients with hepatocellular carcinoma in Zhengzhou University People's Hospital from December 2017 to June 2022 were retrospectively analyzed, including 148 males and 42 females, aged (57.8±9.9) years. According to ICG R15, the patients were divided into ICG R15 normal group ( n=134, ICG R15<10%) and ICG R15 abnormal group ( n=56, ICG R15≥10%). Univariate and multivariate logistic regression were used to analyze the influencing factors of abnormal ICG R15, and the nomogram model was established. The predictive ability of the model was evaluated by receiver operating characteristic (ROC) curve and C-index, and the model was verified by calibration curve and decision analysis curve. Results:Abnormal ICG R15 group the proportion of liver cirrhosis, albumin ≤35 g/L, hemoglobin ≤110 g/L, platelet count ≤100×10 9/L, prothrombin time >13 s, alanine aminotransferase >40 U/L, aspartate aminotransferase >40 U/L, total bilirubin >34.2 μmol/L, and the largest tumor diameter >5.0 cm, spleen volume >383.1 cm 3, spleen volume to of non-tumor liver volume (SNLR) >0.276 and liver tumor volume >117.2 cm 3 were higher than that of ICG R15 normal group, and the differences were statistically significant (all P<0.05). Logistic regression analysis showed that liver cirrhosis ( OR=3.89, 95% CI: 1.28-11.80, P=0.016), spleen volume >383.1 cm 3( OR=5.17, 95% CI: 1.38-19.38, P=0.015), SNLR >0.276 ( OR=5.54, 95% CI: 1.44-21.26, P=0.013) and total bilirubin >34.2 μmol/L( OR=10.20, 95% CI: 1.88-55.39, P=0.007) increased the risk of abnormal ICG R15. A nomogram model was constructed based on the above risk factors. The C-index of the model was 0.915 (95% CI: 0.872-0.957), and the area under the ROC curve predicted by the nomogram model was 0.915 (95% CI: 0.871-0.958). The calibration curve showed that the correlation index of the abnormal ICG R15 predicted by the nomogram was similar to actual situation. Decision analysis curve showed high returns. Conclusion:Liver cirrhosis, spleen volume >383.1 cm 3, SNLR>0.276 and total bilirubin >34.2 μmol/L were indepentlent risk factors for abnormal ICG R15 in patients with hepatocellur carcinoma. The clinical prediction model of ICG R15 abnormality constructed by nomogram has good prediction efficiency, which can provide a reference for evaluating preoperative liver reserve function of patients with hepatocellular carcinoma.

Objective:To investigate the application value of peripheral blood circulating tumor cell (CTC) classification in the prediction of preoperative microvascular invasion of hepato-cellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinico-pathological data of 102 HCC patients who were admitted to Zhengzhou University People's Hospital from September 2018 to September 2020 were collected. There were 71 males and 31 females, aged from 29 to 80 years, with a median age of 57 years. Observation indicators: (1) surgical situations; (2) results of CTC detection and microvascular invasion in HCC patients; (3) results of CTC classification and the best cut-off value of CTC classification in the prediction of microvascular invasion in HCC; (4) influencing factors for microvascular invasion in HCC; (5) comparison of clinicopathological features in HCC patients with different cell counts in mesenchymal phenotype of CTC (M-CTC). Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was analyzed using the nonparametric rank sum U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. The receiver operating characteristic (ROC) curve was used to determine the best cut-off value for the risk of microvascular invasion in patients. Univariate and multivariate analysis were performed using the Logistic regression model. Results:(1) Surgical situations. All 102 patients underwent surgery successfully, including 17 cases undergoing local hepatectomy, 43 cases under-going segmentectomy, 22 cases undergoing hepatic lobectomy, 13 cases undergoing hemilectomy and 7 cases undergoing enlarged hemilectomy. The operation time and the volume of intraoperative blood loss were 235(147,293)minutes and 300(110,500)mL of the 102 patients, respectively. (2) Results of CTC detection and microvascular invasion in HCC patients. Of 102 patients, there were 36 casas with epithelial phenotype of CTC (E-CTC), 86 cases with hybrid phenotype of CTC (H-CTC), 30 cases with M-CTC, respectively, and the total CTC (T-CTC) were positive in 89 cases. Results of postoperative pathological examination showed that there were 40 cases with micro-vascular inva-sion and 62 cases without microvascular invasion in the 102 patients. Of the 40 patients with micro-vascular invasion, the count of E-CTC, H-CTC, M-CTC and T-CTC were 0(0,1) per 5 mL, 4(2,5) per 5 mL, 1(0,2) per 5 mL and 5(3,8) per 5mL, respectively. The above indicators of the 62 cases without microvascular invasion were 0(0,1) per 5 mL, 3(1,5) per 5 mL, 0(0,0) per 5 mL and 3(2,6) per 5 mL, respectively. There were significant differences in the count of M-CTC and T-CTC between patients with and without microvascular invasion ( Z=-4.83, -2.96, P<0.05). (3) Results of CTC classi-fication and the best cut-off value of CTC classification in the prediction of microvascular invasion in HCC. The ROC curve showed that best cut-off value of M-CTC and T-CTC counts in the prediction of microvascular invasion in HCC were 1 per 5 mL and 4 per 5 mL, respectively, with the area under curve, the corresponding specificity, sensitivity were 0.70 (95% confidence interval as 0.60-0.81, P<0.05), 75.8%, 62.9% and 0.67 (95% confidence interval as 0.57-0.78, P<0.05), 60.0%, 72.5%, respec-tively. (4) Influencing factors for microvascular invasion in HCC. Result of univariate analysis showed that alpha fetoprotein (AFP), aspartate aminotransferase (AST), tumor diameter, tumor number, tumor margin, Barcelona clinic liver cancer staging, M-CTC counts and T-CTC counts were related factors influencing microvascular invasion in HCC ( odds ratio=3.13, 0.43, 4.92, 5.65, 2.54, 2.93, 8.25, 4.47, 95% confidence interval as 1.34-7.33, 0.19-0.98, 2.09-11.58, 2.35-13.63, 1.13-5.75, 1.27-6.74, 3.13-21.75, 1.88-10.61, P<0.05). Result of multivariate analysis showed that tumor diameter >5 cm, tumor number as multiple and M-CTC counts ≥1 per 5 mL were independent risk factors influencing microvascular invasion in HCC ( odds ratio=2.97, 4.14, 4.36, 95% c onfidence interval as 1.01-8.70, 1.14-15.02, 1.36-13.97, P<0.05). (5) Comparison of clinicopathological features in HCC patients with different cell counts in M-CTC. The 102 HCC patients were divided into the high M-CTC group of 30 cases with M-CTC counts ≥1 per 5 mL and the low M-CTC group of 72 cases with M-CTC counts <1 per 5 mL, according to the best cut-off value of M-CTC counts. Cases with hepatitis, cases with AFP >400 μg/L, cases with AST >35 U/L, cases with irregular tumor margin, cases with tumor diameter >5 cm, cases with tumor number as multiple and cases with micro-vascular invasion were 22, 17, 13, 21, 18, 16 and 22 in the high M-CTC group of 30 cases. The above indicators were 35, 18, 48, 26, 25, 21 and 18 in the low M-CTC group of 72 cases. There were significant differences in the above indicators between the high M-CTC group and the low M-CTC group ( χ2=5.25, 9.42, 4.80, 9.79, 5.55, 5.35, 20.75, P<0.05). Conclusions:The epithelial-mesen-chymal phenotype of peripheral blood CTC can be used to predict the preoperative microvascular invasion in HCC. Tumor diameter >5 cm, tumor number as multiple and M-CTC counts ≥1 per 5 mL are independent risk factors influencing microvascular invasion in HCC patients.

Objective:This study aimed to compare the clinical outcomes of laparoscopic pancreaticoduodenectomy (LPD) versus open pancreaticoduodenectomy (OPD).Methods:The clinical data of 386 patients who successfully underwent pancreaticoduodenectomy at the People's Hospital of Zhengzhou University from June 2017 to December 2019 were retrospectively analyzed. According to the different surgical methods, patients were divided into the LPD group ( n=122) and the OPD group ( n=264). The differences in operation time, intraoperative blood loss, postoperative hospital stay, postoperative complications, postoperative oncology survival outcomes and prognosis between groups were compared. Results:Of 386 patients in this study, there were 232 males and 154 females, aged (57.8±11.0) years. The operation time of the LPD group was (330.69±80.55) min which was significantly longer than that of the OPD group (241.13±77.24) min. The intraoperative blood loss 300.00(200.00, 400.00) ml was also significantly less than the OPD group 400.00(262.50, 500.00) ml, and the length of postoperative stay in the LPD group (12.21±5.24) d was significantly less than the OPD group (16.61±6.63) d, (all P<0.05). There were 36 patients (29.51%) in the LPD group and 81 patients (30.68%) in the OPD group who developed postoperative complications, with no significant difference between groups ( P>0.05). Postoperative oncology outcomes showed that the number of lymph nodes dissected in the LPD group was significantly more than that in the OPD group [(12.65±5.03) vs (10.07±5.09)], ( P<0.05). There were no significant differences between the two groups in tumor pathology type, size, degree of differentiation and R 0 resection rates (all P>0.05). All patients were followed up for 6-36 months, with a median follow-up of 20 months. The survival rates of patients with malignant tumors after following-up for more than 1 year in the LPD group was 84.72%(61/72), that in the OPD group was 85.81%(133/155), with no significant difference between groups ( P>0.05). Conclusion:LPD was safe and feasible with its advantages of minimally invasiveness.

Objective:To investigate the predictive value of portal vein (PoV) blood circulating tumor cells (CTCs) count in patients with pancreatic cancer on the postoperative prognosis.Methods:The data of 58 patients receiving radical resection of pancreatic cancer and PoV CTCs detection at People's Hospital of Zhengzhou University from Aug 2018 to Jun 2020 were collected. According to the cut-off value of PoV CTCs>10/5 ml made by receiver operating characteristic curve (ROC), patients were divided into high CTCs group and low CTCs group and the differences in clinicopathological parameters and prognosis of the two groups were compared.Results:Postoperative progression-free survival rate of the low CTCs group was higher than that of the high CTCs group ( χ 2=12.97, P<0.001).Univariate COX regression analysis showed that tumor diameter >4 cm, lymph node invasion, TNM staging, CTCs>10/5 ml, postoperative CA199>37 U/m were risk factors for postoperative prognosis. Multivariate COX regression analysis demonstrated that TNM stage ( OR=2.782, P=0.024), CTCs count >10/5 ml ( OR=2.583, P=0.047), postoperative CA199>37 U/m ( OR=3.775, P=0.004) were the independent risk factors of prognosis. Conclusion:A higher PoV CTCs count was a risk factor for poor prognosis of patients with pancreatic cancer after radical resection.

Objective:To investigate the clinical efficacy of laparoscopic radical resection of hilar cholangiocarcinoma.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 25 patients with hilar cholangiocarcinoma who were admitted to Henan Provincial People′s Hospital from January 2017 to July 2019 were collected. There were 16 males and 9 females, aged from 51 to 75 years, with a median age of 64 years. All the 25 patients underwent laparoscopic radical resection of hilar cholangiocarcinoma. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up using out-patient examination and telephone interview was performed to detect local recurrence and distant metastasis of patients up to December 2019. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were described as M (range). Count data were described as absolute numbers. Results:(1) Surgical situations: of the 25 patients, 15 patients in Bismuth typeⅠunderwent laparoscopic radical resection of hilar cholangiocarcinoma+ regional lymph node dissection+ Roux-en-Y choledocho-jejunostomy, 2 patients in Bismuth type Ⅱ underwent laparoscopic radical resection of hilar cholangiocarcinoma+ perihilar resection+ regional lymph node dissection+ Roux-en-Y choledochojejunostomy, 2 patients in Bismuth type Ⅲa underwent laparoscopic radical resection of hilar cholangiocarcinoma+ regional lymph node dissection+ right hemihepatectomy+ hepatic caudate labectomy+ Roux-en-Y choledochojejunostomy, 3 patients in Bismuth type Ⅲb underwent laparoscopic radical resection of hilar cholangiocarcinoma+ regional lymph node dissection+ left hemihepatectomy+ hepatic caudate labectomy+ Roux-en-Y choledochojejunostomy, 3 patients in Bismuth type Ⅳ underwent laparoscopic radical resection of hilar cholangiocarcinoma+ regional lymph node dissection+ hepatic caudate labectomy+ Roux-en-Y choledochojejunostomy. The operation time was (388±118)minutes, and volume of intraoperative blood loss was 200 mL(range, 50-2 000 mL). Six patients were treated with blood transfusion intraoperatively. The operation time of 2 patients in Bismuth type Ⅲa was 375 minutes and 465 minutes, and the volume of intraoperative blood loss was 200 mL and 1 000 mL, respectively; 1 case received blood transfusion. The operation time of 3 patients in Bismuth type Ⅲb was 410 minutes, 465 minutes, 501 minutes, and the volume of intraoperative blood loss was 300 mL, 400 mL, 450 mL, respectively; neither had intraoperative blood transfusion. The operation time of 3 patients in Bismuth type Ⅳ was 415 minutes, 560 minutes, 600 minutes, and the volume of intraoperative blood loss was 300 mL, 600 mL, 800 mL, respectively; 1 case had intraoperative blood transfusion. (2) Postoperative situations: of the 25 patients, 4 patients had grade Ⅰ complications, including 2 cases of biliary fistula (1 case in Bismuth type Ⅰ and 1 case in Bismuth type Ⅲa), 1 case of pulmonary infection (Bismuth type Ⅳ), and 1 case of postoperative liver insufficiency (Bismuth type Ⅲa), all of them were improved after conservative treatment. Results of postoperative pathological examination: bile duct adenocarcinoma and high-grade intraepithelial neoplasia were detected in 23 and 2 patients; there were 8 cases with nerve invasion, 3 cases with lymph node metastasis and no vascular thrombus. The duration of hospital stay and hospitalization expenses were 24 days (range, 10-45 days) and 9.4×10 4 yuan [range, (5.3-18.7)×10 4 yuan] for all the 25 patients; the above indicators were 36 days, 45 days, 15.1×10 4 yuan, 18.7×10 4 yuan for the 2 patients in Bismuth type Ⅲa, 15 days, 26 days, 33 days, 7.3×10 4 yuan, 11.5×10 4 yuan, 15.9×10 4 yuan for 3 patients in Bismuth type Ⅲb, 24 days, 39 days, 41 days, 12.1×10 4 yuan, 15.2×10 4 yuan, 16.7×10 4 yuan for the 3 patients in Bismuth type Ⅳ, respectively. (3) Follow-up: 25 patients were followed up for 2-36 months, with a median follow-up of 16 months. Of the 25 patients, 18 had no recurrence or metastasis, 2 patients in Bismuth type Ⅳ had extensive intraperitoneal metastasis, 1 patients in Bismuth type Ⅲa had trocar hole metastasis, and 4 patients died. Conclusions:Laparoscopic radical resection of hilar cholangiocarcinoma is safe and feasible. Surgeries should be selected strictly based on surgical indications and the Bismuth type.

Objective To evaluate the palatal rugae individual-specific properties and stability before and after orthodontic treatments for investigating the reliability of palatal rugae for individual identification of forensic dentistry based on the palatal rugae model ananlysis. Methods Maxillary models of 70 patients were obtained before and after orthodontic treatments respectively. Palatal rugae morphologic changes and individual identification were examined by model analysis including changes in number, orientation, shape, and length of palatal rugae, as well as mesial and distal endpoint displacement in the anterioposterior(AP) and mesiodistal (MD) direction. Furthermore, The examination of palatal rugae average match accuracy(%) was performed between the pre-treatment and post-treatment orthodontics models and post-treatment and duplicated post-treatment orthodontics models. Results ① The palatal rugae morphological changes were found and the incidence of palatal rugae changes were showed in length(28.6%), segmenta-tion(4.3%); unification(2.9%); orientation(1.4%) and shape(1.4%) after orthodontic treatment. Also the displacement of the distal endpoint of palatal rugae was 45.7% for anterioposterior indirection, 40% for mesiodistal indirection after orthodontic treatment, while the anterioposterior displacement of the mesial endpoint of palatal rugae was 32.9% and mesiodistal displacement was 17.1%. ② The identical palatal rugae patterns were not found both the pre-treatment and post-treatment groups. ③ The palatal rugae average match accuracy was 92.19% between pre-treatment and post-treatment groups, however, the rate had increased by 99.05% when matching the palatal rugae patterns of post-treatment groups to their duplicates. Conclusion Palatal rugae patterns have the high specific properties to each indivi-dual. Although there are some changes in morphology of palatal rugae after orthodontic treatment, it still can be used as a novel method for individual identification in forensic dentistry.

Objective To analyze the morphological matching rate with a digital image recognition system in pre-and post-orthodontic treatments,and to provide forensic dentistry evidence for individual identification.Methods High-resolution digital images of the palatal rugae were taken under particular conditions from each patient in pre-and post-orthodontic treatments.Features of each digital image were extracted using a digital image recognition system and collected in the palatal rugae database.Data of the palatal rugae werematched by MATLAB software system.Results From the matching results,the accuracy rate of individual identification of orthodontic patients was 100％.The accuracy rate in matching palatal rugae patterns in pre-and post-orthodontic treatments was 95.67％.The results were statistically significant with P＜0.05.Conclusion Palatal rugae pattern is highly individual-specific.The morphologyofpalatal rugaecould bechangedby theorthodontic treatment,however,these changes may not greatly influence individual identification in forensic dentistry,providing a new potential to individual identification.

Objective To establish a digital system for forensic identiifcation of the palatal rugae and evaluate its application effects. Methods High-resolution digital images of the palatal rugae were harvested under the standard condition and processed including data collection, noise reduction, contrast enhancement, image segmentation, feature extraction, edge detection, and information matching. Apply an MATLAB software system to develop a digital system for forensic identiifcation of the palatal rugae ,and its application effects were evaluated. Results A digital system for forensic identification of the palatal rugae was successfully established. The digital system had an accuracy rate of 100%. Conclusion Establishing a digital system for forensic identiifcation of the palatal rugae provides a novel method for forensic identiifcation.