The incidence of digestive tract cancer is increasing and tends to be younger. With the proposed concept of precision medicine, molecular targeted therapy that kills tumor cells by specifically blocking signal transduction leads a new era of digestive tract cancer therapy. This review takes MET variant digestive tract cancer as the entry point, gives an overview of its clinical features and molecular mechanisms, and summarizes the progress of MET targeted therapy for digestive tract cancer.

Objective:To evaluate the diagnostic efficacy of FibroScan combined with various noninvasive diagnostic models for liver fibrosis in patients with chronic hepatitis B (CHB) complicated with nonalcoholic fatty liver disease (NAFLD), and to establish a new predictive model with common clinical indicators.Methods:From January 2016 to May 2024, the clinical data of 118 CHB patients complicated with NAFLD from the First Affiliated Hospital of Zhengzhou University, who underwent liver biopsy and FibroScan examination were respectively analyzed. According to the Scheuer scoring system, different diagnostic endpoints were set based on the degree of liver fibrosis (S0 to S1, ≥S2, ≥S3, and S4), fibrosis stage ≥S2 was designated as the criterion for significant liver fibrosis. Fibrosis-4 (FIB-4), γ-glutamyl transpeptidase (GGT) to platelet ratio (GPR), GGT-age-platelet-international normalized ratio (GAPI) model, S index, King index and Forns index were calculated according to the common clinical indicators. The independent t test or Mann-Whitney U test was used to compare the two groups. Spearman rank correlation was used to analyze the correlation between each noninvasive diagnostic method and the degree of liver fibrosis. Receiver operating characteristic curve (ROC) was plotted, and the DeLong test was performed to compare the area under the curve (AUC), and to evaluate the predictive value of FibroScan combined with various noninvasive diagnostic models for the diagnosis of liver fibrosis. The laboratory indicators were compared between patients with non-significant liver fibrosis and patients with significant liver fibrosis. And the indicators with statistically significant differences ( P<0.05) in the univariate analysis were further analyzed by multivariate logistic regression to establish a new predictive model for liver fibrosis. Hosmer-Lemeshow test was used to assess the model′s goodness of fit. Results:The results of Spearman rank correlation showed that FIB-4, GPR, FibroScan, GAPI model, S index, King index, and Forns index were positively correlated with the stage of liver fibrosis ( r=0.413, 0.458, 0.512, 0.473, 0.533, 0.380 and 0.478, all P<0.001). The results of ROC analysis indicated that among combination of FibroScan and other diagnostic models, the AUC values of FibroScan+ FIB-4, FibroScan+ Forns index were relatively high in ≥S2 and ≥S3, which were 0.804 and 0.907, respectively. The platelet count ((200.65±50.89)×10 9/L vs. (169.96±63.68)×10 9/L), total cholesterol ((4.69±0.77) mmol/L vs. (4.32±1.00) mmol/L), high-density lipoprotein (HDL) (1.28 (1.05, 1.46) mmol/L vs. 1.08 (0.92, 1.21) mmol/L), total protein (74.00 (70.63, 77.08) g/L vs. 68.80 (64.60, 73.55) g/L), albumin (47.06 (44.65, 48.81) g/L vs. 44.70 (41.55, 46.20) g/L), and globulin (26.80 (24.48, 29.70) g/L vs. 25.80 (23.05, 27.60) g/L) of the non-significant liver fibrosis group were higher than those of the significant liver fibrosis group, and the differences were statistically significant ( t=2.74, 2.09; Z=-3.30, -3.88, -3.95, -2.01; P=0.007, =0.040, =0.001, <0.001, <0.001, =0.044). GGT (27.50 (17.00, 41.75) U/L vs. 37.00 (22.50, 87.00) U/L), the liver stiffness measurement (LSM) in the non-significant hepatic fibrosis group was lower than the significant liver fibrosis group (6.85 (5.60, 9.26) kPa vs. 11.60 (7.08, 17.26) kPa), and the differences were statistically significant ( Z=-2.73, -4.39; P=0.006, <0.001). The result of multivariate logistic regression analysis revealed that globulin, albumin, HDL, and LSM were independent factors of liver fibrosis ( OR (95% confidence interval)=0.865 (0.759 to 0.985), 0.804 (0.691 to 0.935), 0.128 (0.023 to 0.711), and 1.251 (1.091 to 1.433), respectively; P=0.029, 0.025, 0.019, 0.001). A novel model, GLAH, was established with globulin, LSM, albumin, and HDL. The AUC for diagnosing liver fibrosis degree ≥S2, ≥S3, and S4 was 0.847, 0.938, and 0.909, respectively, which were higher than those of the above models. The positive predictive value for diagnosing liver fibrosis degree ≥S2 with GLAH>1.12 as the cutoff value was 95.8%. The negative predictive value for excluding fibrosis stage ≥S2 with GLAH<-1.41 was 92.3%. This approach could reduce the number of liver biopsies by 48.3% (57/118), with an accuracy of 94.7% (54/57). Conclusions:The clinical value of FibroScan combined with FIB-4 or Forns index is better in the diagnisis of fibrosis stage ≥S2 and ≥S3. The GLAH model has higher diagnostic value and can accurately predict the degree of liver fibrosis in CHB patients complicated with NAFLD, thus reducing the need for liver biopsy.

Objective:To evaluate the diagnostic efficacy of FibroScan combined with various noninvasive diagnostic models for liver fibrosis in patients with chronic hepatitis B (CHB) complicated with nonalcoholic fatty liver disease (NAFLD), and to establish a new predictive model with common clinical indicators.Methods:From January 2016 to May 2024, the clinical data of 118 CHB patients complicated with NAFLD from the First Affiliated Hospital of Zhengzhou University, who underwent liver biopsy and FibroScan examination were respectively analyzed. According to the Scheuer scoring system, different diagnostic endpoints were set based on the degree of liver fibrosis (S0 to S1, ≥S2, ≥S3, and S4), fibrosis stage ≥S2 was designated as the criterion for significant liver fibrosis. Fibrosis-4 (FIB-4), γ-glutamyl transpeptidase (GGT) to platelet ratio (GPR), GGT-age-platelet-international normalized ratio (GAPI) model, S index, King index and Forns index were calculated according to the common clinical indicators. The independent t test or Mann-Whitney U test was used to compare the two groups. Spearman rank correlation was used to analyze the correlation between each noninvasive diagnostic method and the degree of liver fibrosis. Receiver operating characteristic curve (ROC) was plotted, and the DeLong test was performed to compare the area under the curve (AUC), and to evaluate the predictive value of FibroScan combined with various noninvasive diagnostic models for the diagnosis of liver fibrosis. The laboratory indicators were compared between patients with non-significant liver fibrosis and patients with significant liver fibrosis. And the indicators with statistically significant differences ( P<0.05) in the univariate analysis were further analyzed by multivariate logistic regression to establish a new predictive model for liver fibrosis. Hosmer-Lemeshow test was used to assess the model′s goodness of fit. Results:The results of Spearman rank correlation showed that FIB-4, GPR, FibroScan, GAPI model, S index, King index, and Forns index were positively correlated with the stage of liver fibrosis ( r=0.413, 0.458, 0.512, 0.473, 0.533, 0.380 and 0.478, all P<0.001). The results of ROC analysis indicated that among combination of FibroScan and other diagnostic models, the AUC values of FibroScan+ FIB-4, FibroScan+ Forns index were relatively high in ≥S2 and ≥S3, which were 0.804 and 0.907, respectively. The platelet count ((200.65±50.89)×10 9/L vs. (169.96±63.68)×10 9/L), total cholesterol ((4.69±0.77) mmol/L vs. (4.32±1.00) mmol/L), high-density lipoprotein (HDL) (1.28 (1.05, 1.46) mmol/L vs. 1.08 (0.92, 1.21) mmol/L), total protein (74.00 (70.63, 77.08) g/L vs. 68.80 (64.60, 73.55) g/L), albumin (47.06 (44.65, 48.81) g/L vs. 44.70 (41.55, 46.20) g/L), and globulin (26.80 (24.48, 29.70) g/L vs. 25.80 (23.05, 27.60) g/L) of the non-significant liver fibrosis group were higher than those of the significant liver fibrosis group, and the differences were statistically significant ( t=2.74, 2.09; Z=-3.30, -3.88, -3.95, -2.01; P=0.007, =0.040, =0.001, <0.001, <0.001, =0.044). GGT (27.50 (17.00, 41.75) U/L vs. 37.00 (22.50, 87.00) U/L), the liver stiffness measurement (LSM) in the non-significant hepatic fibrosis group was lower than the significant liver fibrosis group (6.85 (5.60, 9.26) kPa vs. 11.60 (7.08, 17.26) kPa), and the differences were statistically significant ( Z=-2.73, -4.39; P=0.006, <0.001). The result of multivariate logistic regression analysis revealed that globulin, albumin, HDL, and LSM were independent factors of liver fibrosis ( OR (95% confidence interval)=0.865 (0.759 to 0.985), 0.804 (0.691 to 0.935), 0.128 (0.023 to 0.711), and 1.251 (1.091 to 1.433), respectively; P=0.029, 0.025, 0.019, 0.001). A novel model, GLAH, was established with globulin, LSM, albumin, and HDL. The AUC for diagnosing liver fibrosis degree ≥S2, ≥S3, and S4 was 0.847, 0.938, and 0.909, respectively, which were higher than those of the above models. The positive predictive value for diagnosing liver fibrosis degree ≥S2 with GLAH>1.12 as the cutoff value was 95.8%. The negative predictive value for excluding fibrosis stage ≥S2 with GLAH<-1.41 was 92.3%. This approach could reduce the number of liver biopsies by 48.3% (57/118), with an accuracy of 94.7% (54/57). Conclusions:The clinical value of FibroScan combined with FIB-4 or Forns index is better in the diagnisis of fibrosis stage ≥S2 and ≥S3. The GLAH model has higher diagnostic value and can accurately predict the degree of liver fibrosis in CHB patients complicated with NAFLD, thus reducing the need for liver biopsy.

Colorectal cancer is one of the most common malignant tumors, and its morbidity and mortality increase year by year. In recent years, some patients with colorectal cancer have benefited from precision targeted therapies, but the overall prognosis is still unsatisfactory. Treatment of homologous recombination deficiency represented by BRCA1/2 has become a hot research direction at present. With the wide application and exact curative effect of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in ovarian cancer, breast cancer, pancreatic cancer and other malignant tumors, PARP inhibitors are also gradually being used in colorectal cancer. This review summarizes the current research progress of PARP inhibitors in treatment of colorectal cancer.

Objective:To explore the surgical method and therapeutic effect of repairing thumb pulp defect with pedicled transposition of radial proper palmar digital artery flap of middle finger.Methods:Since June, 2006 to May, 2020, 17 cases(17 fingers) with thumb pulp defect were repaired by pedicled transposition of radial proper palmar digital artery flap of middle finger. The sizes of flap ranged from 1.5 cm × 1.5 cm to 4.2 cm × 2.0 cm. The antegrade pedicled flap of radial proper palmar digital artery of middle finger was used in 2 cases and the retrograde pedicled flap of middle finger was used in 15 cases. After the flap was resected, the donor sites were covered with a medium thickness skin graft transferred from the wrist or elbow. The skin graft did not need to be packed. The dorsal branch of the digital nerve was included in the flap and it was anastomosed with the proper nerve of the injured thumb stump. After 16-22 days of the operation, the pedicles were cut off. The patients were instructed to perform digit function exercise after the pedicle was cut off. After the operation, the patients were included in regularly follow-up through outpatient visit, telephone or WeChat interview. The appearance and sensation of the thumb and finger pulps and the function recovery of the thumb and finger joints were observed through the followed-ups.Results:All 17 flaps and donor site skin grafts survived over 3 to 32 months of follow-up. The flaps achieved good texture and natural appearance. The TPD recovered to 5~11 mm. According to the Michigan Hand Function Questionnaire, all the 17 patients were very satisfied with the overall appearance and function of the hands. According to TAM, the 17 cases were all in excellent.Conclusion:Repairing thumb pulp defect with radial proper palmar digital artery pedicled flap of middle finger, the flap resection is simple, and the donor site is hidden. The appearance and texture of flap is good. It is a safe, effective and good method.

Fusidane-type antibiotics, represented by helvolic acid, fusidic acid and cephalosporin P

Colorectal cancer is the most common gastrointestinal malignant tumor. Advances of targeted therapy and immunotherapy have significantly improved the prognosis of patients with colorectal cancer. In recent years, with the concept of precision medicine, molecular classification of colorectal cancer based on molecular pathology has been widely accepted. Patients with BRAF, HER2, MET, PIK3CA, MEK, BRAC1, BRAC2 and other rare driver gene mutations have been gradually paid attention. This article reviews the treatment advances in colorectal cancer with rare driver gene mutations.

Objective:To investigate the technical points and clinical application of combined infratemporal fossa approaches (CIFA) by analyzing the clinical results with CIFA for lesions involved skull base.Methods:A retrospective study was performed on 11 patients underwent CIFA for skull base lesions dissection from December 2014 to January 2019 in the department of otolaryngology, Peking Union Medical College Hospital. There were 6 male and 5 female patients, with age range of 16-72 years old and median age of 53 years old. Five patients underwent CIFA Type B and D, and the other 6 underwent CIFA A and B. All patients were followed up regularly by CT and MRI to observe possible recurrence.Results:Among the 5 patients with CIFA Type B and D, 3 were giant cell tumor and 2 were giant cell reparative granuloma, and median maximum cross-section size was 42 mm×46 mm (range from 37 mm×18 mm to 56 mm×53 mm). Among the 6 patients with CIFA Type A and B, 4 were paraganglioma of head and neck, 1 was schwannoma of skull base, 1 was petrous cholesteatoma, and median maximum cross-section size was 43 mm×36 mm (range from 24 mm×22 mm to 63 mm×35 mm). Nine patients underwent complete resection of the tumor in the first stage. In 2 patients, the extracranial parts were removed in the first stage, and the intracranial part was removed in the second stage. Tympanum and ossicular reconstruction were done in one of the CIFA Type B and group D, and 1 year′s postoperative hearing was mild conductive hearing loss. There was no cerebrospinal fluid leakage of all patients. All the 5 patients with normal facial nerve function before surgery recovered to H-B grade Ⅰ to Ⅱ within 3 months after surgery. Among the 4 patients whose preoperative facial nerve function were grade Ⅱ, 2 recovered to grade I after surgery and the other 2 were still grade Ⅱ. For the patient whose preoperative facial nerve function was grade Ⅴ, his postoperative recovery was grade Ⅲ. There was 1 patient whose pre-operative FN function was H-B grade Ⅲ, and the post-operative FN function was grade Ⅵ due to FN resection. Except for 2 cases with cochlear involved before surgery, cochleae of the other 9 cases were preserved. The follow-up time was 14 to 58 months. No recurrence was observed in all patients.Conclusions:The CIFA can safely and completely remove the extensive lesions that invade the skull base, and the facial nerve function can be well protected and recovered intro-and post-operation. Appropriate use of combined IFA can not only achieve good exposure and complete resection of lesions, but also create conditions for functional reconstruction.

Fusidic acid is the only fusidane-type antibiotic that has been clinically used. However, biosynthesis of this important molecule in fungi is poorly understood. We have recently elucidated the biosynthesis of fusidane-type antibiotic helvolic acid, which provides us with clues to identify a possible gene cluster for fusidic acid ( cluster). This gene cluster consists of eight genes, among which six are conserved in the helvolic acid gene cluster except and . Introduction of the two genes into the NSAR1 expressing the conserved six genes led to the production of fusidic acid. A stepwise introduction of and revealed that the two genes worked independently without a strict reaction order. Notably, we identified two short-chain dehydrogenase/reductase genes and in the cluster, which showed converse stereoselectivity in 3-ketoreduction. This is the first report on the biosynthesis and heterologous expression of fusidic acid.

Objective: To investigate the safety and feasibility of emergency transcatheter arterial embolization in the treatment with spontaneous rupture of hepatocellular carcinoma. Methods: The data of 42 patients with spontaneous rupture of hepatocellular carcinoma who were treated by emergency transcatheter arterial embolization from January 2015 to December 2018 in Department of Hepatobiliary Surgery of Chongqing Emergency Medical Center were collected. There were 35 males and 7 females, aged 28-78 years, with an average age of 51 years. The success rate of intubation, postoperative mortality and postoperative complications were observed. Results: All patients were successfully intubated, 40 cases improved and discharged, 1case died within 1 month after operation, who with large amount of bleeding, 1 case died after 1 month, who with diffused liver cancer and liver failure, 3 cases were complicated liver or kidney failure, in whom 2 cases improved after active treatment. Conclusion Emergency transcatheter arterial embolization has the advantages of less trauma, short operation time, less postoperative complications and good hemostatic effect, which can increase the survival rate of patients under emergency conditions and lay a foundation for subsequent tumor treatment, it should be popularized in clinical work.