Objective To study the antifungal activity of a new series of triazole compounds with n-propyl side chain and disubstituted benzyl structure. Methods Eleven target compounds were designed and synthesized. The structures were confirmed by ¹H NMR, and some compounds were confirmed by ¹³C NMR or HRMS. Three fungal strains were selected as experimental strains, and the antifungal activity was tested in vitro according to the standardized antifungal sensitivity test method recommended by National Committee for Clinical Laboratory Standards (NCCLS). Results Compound B11 showed better activity against candida albicans SC5314 than fluconazole and was comparable to posaconazole; Compounds B10, B11 and B4 showed better activity against cryptococcus neoformanis H99 than fluconazole, while compounds B2, B3, B5, B6 and B7 showed similar activity to fluconazole against cryptococcus neoformanis H99; while all compounds showed poor activity against aspergillus fumigatus. Conclusion Some of the target compounds with n-propyl side chain and disubstituted benzyl group structure had certain antifungal activity and could be identified as potential lead antifungal drugs.

Acute-on-chronic liver failure (ACLF) is a disease of rapid deterioration of liver function caused by the acute exacerbation of chronic liver diseases, and it is often associated with multiple organ failure and has a poorer prognosis than common liver cirrhosis. Many studies suggest that timely liver transplantation can significantly improve the survival rate of patients with ACLF; however, there are currently no reliable guidelines that point out the indications for liver transplantation in patients with ACLF. This article summarizes recent studies and discusses the indication, timing, and prognosis of liver transplantation in ALCF patients.

Teaching quality is directly related to the performance of universities in fostering talents. Being innovative, high-level, and challenging (IHC) is the basic goal of course reform at universities in the new era. It is essential to reform the contents and teaching mode to improve the IHC properties of the existing courses. We first designed the three-dimensional goals of Molecular Biology Experiment teaching and the contents to support these goals. Then, we pinpointed the common points shared by blended teaching and experiment course, and designed the ways of blended teaching for the course. The reformed course contents and teaching mode have enhanced its IHC properties, and achieved good teaching performance. This paper provides a reference for the reform of experiment courses in universities.
Humans ; Molecular Biology ; Students ; Universities

Objective:To compare the treatment outcomes of neoadjoint therapy combined with liver transplantation versus radical hepatectomy for patients with surgically resectable hilar cholangiocarcinoma.Methods:A retrospective study was performed on the data of 64 patients with resectable hilar cholangiocarcinoma operated from January 2009 to December 2014 at the Organ Transplantation Department of the First Central Hospital of Tianjin. There were 43 males and 21 females, with an average age of 61.2 years. There were 45 patients who underwent radical hepatectomy in the liver resection group, and 19 patients who underwent combined neoadjuvant therapy (radiotherapy combined with 5-fluorouracil intravenous drip, transcatheter lumen radiotherapy, capecitabine oral administration) and liver transplantation in the liver transplantation group. The recurrence rates and survival rate were compared between groups.Results:The 1, 3 and 5 years cumulative survival rates of the liver transplantation group were 89.5%, 73.7% and 63.2%, respectively, which were significantly better than those of the liver resection group (80.0%, 53.3% and 35.6%) ( P<0.05). The postoperative tumor recurrence rate in the liver transplantation group was 31.6% (6/19), which was significantly lower than that in the liver resection group of 60.0% (27/45) ( P<0.05). Subgroup analysis using postoperative pathological results showed the cumulative survival rates of patients without lymph node metastasis (N 0) and those with negative resection margins (R 0) were not significantly different between groups ( P>0.05). However, for patients with regional lymph node invasion (N 1) and with R 0 resection margin, the cumulative survival rates at 1, 3 and 5 years after liver transplantation were 83.3%, 66.7% and 50.0%, respectively, which were significantly superior to the 64.3%, 28.6% and 14.3% of the liver resection group ( P<0.05). Conclusion:Hepatectomy is recommended for patients with N 0 R 0 resectable hilar cholangiocarcinoma. For patients with hilar cholangiocarcinoma with marginally resectable N 1R 0, neoadjuvant therapy combined with liver transplantation resulted in significantly better long-term overall survival than resection.

Objective:To evaluate the efficacy of comprehensive anti-cancer treatment for lung metastases after liver transplantation (LT) for hepatocellular carcinoma (HCC).Methods:From March 2012 to July 2016, A total of 36 patients with lung metastasis after LT were divided into comprehensive anti-cancer treatment group (rapamycin + radioactive I 125 seed implantation + pulmonary artery infusion chemotherapy + sorafenib, n=22) and maintenance supportive care group ( n=14). The survival profiles of two groups were evaluated. Results:No significant inter-group differences existed in preoperative basic data, tumor pathology, time of pulmonary metastatic tumor after operation and lung metastasis tumor burden.In comprehensive anti-cancer treatment group, there were partial remission ( n=3), disease stability ( n=12) and disease progression after treatment ( n=7). In maintenance supportive care group, there were disease stability ( n=3) and disease progression after treatment ( n=11). And comprehensive anti-cancer treatment was superior to maintenance supportive care ( χ2=7.901, P=0.019). The median survival time after metastasis was 23 months (95%CI: 19.68-26.32) in comprehensive anti-cancer treatment group and 7 months (95%CI: 3.33-10.67) in maintenance supportive care group; 1-year survival rate 91% and 9%, 2-year survival rate 45% and 0% and 3-year survival rate 10% and 0% respectively.The survival rate of comprehensive anti-cancer treatment group was significantly better than that of maintenance supportive care group ( P<0.001). Conclusions:Comprehensive anti-cancer treatment (rapamycin + radioactive I 125 seed implantation + pulmonary artery infusion chemotherapy + sorafenib) can improve the survival time of patients with lung metastasis after liver transplantation for HCC.

Objective:To evaluate the effect of transfusion-free techniques on the prognosis of liver transplant patients.Methods:The recipients of adult liver transplantation at Tianjin First Central Hospital from August to December 2019 were included in the clinical observation. Liver transplantation without allogeneic blood transfusion was performed through anesthesia management techniques such as acute hemodilution or phlebotomy without volume replacement,maintaining decreased baseline central venous pressure and cell saver. According to the actual results,the patients were divided into two groups: transfusion-free group( n=21) and allogeneic transfusion group( n=28). There were 13 males and 8 females aged of (56.3±11.6) years in the transfusion-free group;and there were 16 males and 12 females aged (54.3±14.2)years in the allogeneic transfusion group. The transplant recipients who had not adopted transfusion management strategy from January to July 2019 were included as control group(27 males and 13 females,aged of (58.9±14.1)years). The clinical data of patients in perioperative period were collected to compare whether there were differences in the recovery of liver function and early complications among the three groups, one-way ANOVA test, rank-sum test, and χ 2 test were used for data analysis. Results:The amount of intraoperative blood loss in both the transfusion-free group and the transfusion group was less than that in the control group((454.2±271.3)ml vs.(673.6±333.4)ml vs.(890.3±346.7)ml; q=-6.342,-5.286,both P<0.05).The duration of stay in ICU of the transfusion-free group was less than that of the transfusion group and control group((36.4±9.1)hours vs.(44.3±14.9)hours vs.(58.2±21.1)hours; q=-4.432,-3.824,both P<0.05).The mean ALT level at 7 days after operation was significantly lower in the transfusion-free group than in the control group((56.8±32.1)U/L vs.(89.6±45.6)U/L; q=-3.358, P<0.05). Conclusions:The improvement of multi-disciplinary transfusion management technology aimed at transfusion-free liver transplantation can effectively reduce intraoperative hemorrhage and help to avoid surgical transfusion. Transfusion-free liver transplantation is beneficial to the early postoperative recovery,and its long-term clinical significance is worthy of further clinical research.

Objective:To evaluate the effect of transfusion-free techniques on the prognosis of liver transplant patients.Methods:The recipients of adult liver transplantation at Tianjin First Central Hospital from August to December 2019 were included in the clinical observation. Liver transplantation without allogeneic blood transfusion was performed through anesthesia management techniques such as acute hemodilution or phlebotomy without volume replacement,maintaining decreased baseline central venous pressure and cell saver. According to the actual results,the patients were divided into two groups: transfusion-free group( n=21) and allogeneic transfusion group( n=28). There were 13 males and 8 females aged of (56.3±11.6) years in the transfusion-free group;and there were 16 males and 12 females aged (54.3±14.2)years in the allogeneic transfusion group. The transplant recipients who had not adopted transfusion management strategy from January to July 2019 were included as control group(27 males and 13 females,aged of (58.9±14.1)years). The clinical data of patients in perioperative period were collected to compare whether there were differences in the recovery of liver function and early complications among the three groups, one-way ANOVA test, rank-sum test, and χ 2 test were used for data analysis. Results:The amount of intraoperative blood loss in both the transfusion-free group and the transfusion group was less than that in the control group((454.2±271.3)ml vs.(673.6±333.4)ml vs.(890.3±346.7)ml; q=-6.342,-5.286,both P<0.05).The duration of stay in ICU of the transfusion-free group was less than that of the transfusion group and control group((36.4±9.1)hours vs.(44.3±14.9)hours vs.(58.2±21.1)hours; q=-4.432,-3.824,both P<0.05).The mean ALT level at 7 days after operation was significantly lower in the transfusion-free group than in the control group((56.8±32.1)U/L vs.(89.6±45.6)U/L; q=-3.358, P<0.05). Conclusions:The improvement of multi-disciplinary transfusion management technology aimed at transfusion-free liver transplantation can effectively reduce intraoperative hemorrhage and help to avoid surgical transfusion. Transfusion-free liver transplantation is beneficial to the early postoperative recovery,and its long-term clinical significance is worthy of further clinical research.

Liver cancer is a common liver malignant tumor and a common cause of death related to malignant tumors, which seriously threatens the lives of patients. In recent years, with the in-depth study of the occurrence and development of liver cancer, a clearer understanding of the occurrence and related molecular pathways of liver cancer has been developed, and a variety of molecular targeted drugs have been developed, mainly including anti-angiogenic drugs and immune checkpoints inhibitors. First-line anti-angiogenic drugs include sorafenib and lenvatinib, both of which can effectively prolong the survival of patients with unresectable advanced liver cancer. For patients with intolerable first-line drug adverse reactions or tumor progression during treatment, second-line drugs such as regorafenib and cabozantinib can also be selected, which may help prolong the survival of patients. Immune checkpoint inhibitors mainly include programmed cell death protein 1 and its ligand inhibitors and cytotoxic T lymphocyte-related antigen 4 inhibitors, both of which can inhibit immune checkpoints through a certain mechanism to prevent immune escape of tumor cells, and can effectively prolong the median survival time of patients with unresectable liver cancer. These two inhibitors are gradually being used in the clinical treatment of liver cancer.

Liver transplantation is the most effective method for hepatitis B-related liver failure, liver cirrhosis and hepatocellular carcinoma. However, the reactivation of hepatitis B virus (HBV) after liver transplantation is not conducive to the recovery of liver function and leads to poor clinical prognosis. The prevention and treatment of HBV reactivation is currently the focus of research by physicians and surgeons. The current viral suppression strategies can not completely eradicate HBV nor completely prevent the recurrence of HBV infection in the future. This article aims to explore the molecular mechanism of HBV reactivation after liver transplantation, in order to more effectively prevent the recurrence of hepatitis B after liver transplantation.

Objective To compare the difference of clinical efficacy between surgical magnifying glass and surgical microscope assisted hepatic artery reconstruction in living donor liver transplantation (LDLT). Methods Clinical data of 272 donors and recipients undergoing LDLT were retrospectively analyzed. According to different patterns of hepatic artery reconstruction, all recipients were divided into the magnifying glass group (n=189) and microscope group (n=83). The operation time, intraoperative blood loss, hepatic artery reconstruction site, diameter of anastomosis, incidence of postoperative complications and survival rate of recipients were statistically compared between two groups. Results Compared with the microscope group, the operation time, hepatic artery reconstruction time and intraoperative blood loss were significantly less in the magnifying glass group (all P < 0.001). The most common site of hepatic artery reconstruction was the right hepatic artery in two groups, and the diameter of anastomosis was (2.1±0.9) mm in the magnifying glass group and (2.1±0.8) mm in the microscope group, with no statistical significance between two groups (P > 0.05). The 1-, 2- and 3-year survival rates of recipients in the magnifying glass group were 88%, 86% and 85%, which did not significantly differ from 89%, 87% and 86% in the microscope group (all P > 0.05). The incidence of postoperative complications did not significantly differ between two groups (all P > 0.05). Conclusions The efficacy and safety of hepatic artery reconstruction in LDLT under surgical magnifying glass are equivalent to those under surgical microscope, with less operation workload and intraoperative blood loss. For experienced transplantation surgeons, it is recommended to perform hepatic artery reconstruction assisted by surgical magnifying glass.