Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Objective:To dry fresh Ginseng Radix et Rhizoma using different drying conditions; To investigate the effects of different drying conditions on the drying characteristics and medicinal quality of Ginseng Radix et Rhizoma.Methods:With moisture, powder color, extract, total polysaccharide and ginsenoside contents of Rg 1, Re, Rf, Rb 1, Rc, Rb 2 and Rd as indexes, the drying characteristics of Ginseng Radix et Rhizoma were studied based on Weibull function model, and the quality of Ginseng Radix et Rhizoma after drying was evaluated by entropy weight-TOPSIS model. Results:The drying method for Ginseng Radix et Rhizoma from its origin can be achieved by controlling the relative humidity of the drying medium to 50%, drying at 70 ℃ for 24 h, and then reducing the drying temperature to 60 ℃ until the moisture content was below 12.0%. This method could achieve high drying efficiency and produce high-quality Ginseng Radix et Rhizoma.Conclusions:The drying process of Ginseng Radix et Rhizoma is a falling rate process controlled by internal moisture diffusion. The drying rate of fresh Ginseng Radix et Rhizoma is affected by temperature and humidity. There is a certain correlation between the color of powder and the content of moisture, alcohol-soluble extractives and ginsenosides.

Objective:To investigate the efficacy of fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet count ratio (APRI), liver stiffness value (LSM), and Agile 3+ score and their combined model in predicting advanced-stage liver fibrosis in patients with chronic hepatitis B (CHB) combined with metabolic-associated fatty liver disease (MAFLD).Methods:A multicenter retrospective cohort study was conducted on the BMOVE population.Nine hundred twenty CHB cases combined with MAFLD who underwent liver biopsy at seven medical centers in China from April 2006 to December 2023 were included. The patients were divided into advanced-stage liver fibrosis (159 cases) and non-advanced-stage liver fibrosis (761 cases) according to the Scheuer's scoring system.The area under the receiver operating characteristic curve (AUROC), decision curve, and calibration curve analysis were used to evaluate the efficacy of the firbrosis-4 index (FIB-4) score, NFS score, APRI index, LSM, and Agile 3+ score and their combined model in predicting advanced-stage fibrosis. The liver fibrosis grade of all patients was diagnosed by liver biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each scoring model and combined model, as well as the proportion of correctly classified patients, were calculated based on different cutoff values.Results:AUROC analysis showed that Agile 3+ (0.814, 95% CI: 0.787-0.838) and LSM (0.805, 95% CI: 0.778-0.829) had similar accuracy and were superior to FIB-4 (0.721, 95% CI: 0.691-0.749), NFS (0.687, 95% CI: 0.656-0.716) and APRI ( 0.689, 95% CI: 0.658-0.718); however, HBV DNA level and HBV e antigen status had no effect on this outcome. Decision curve analysis showed that interventions based on LSM and Agile 3+ had provided higher net benefits compared with serological scores. Calibration curves showed that Agile 3+ had better predicitive accuracy than all other models. Agile 3+ had the highest PPV (0.54), minimal uncertainty interval (11.6%), and the highest proportion of correctly classified patients (76%); followed by LSM (PPV: 0.43, uncertainty interval: 15.5%, correct classification rate: 66%), and FIB-4 (PPV: 0.42, uncertainty interval: 26.1%, correct classification rate: 62.6%) in terms of identifying advanced-stage liver fibrosis. Combined model analysis demonstrated that FIB-4 combined with Agile 3+ had improved the correct classification rate and reduced the proportion of missed patients compared with FIB-4 combined with LSM. Conclusion:The Agile 3+ score is superior than LSM, FIB-4, NFS, and APRI index at identifying advanced-stage fibrosis in patients with CHB combined with MAFLD. This study supports the use of FIB-4 index combined with Agile 3+ for risk stratification in patients with CHB combined with MAFLD.

Objective:To investigate the efficacy of fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet count ratio (APRI), liver stiffness value (LSM), and Agile 3+ score and their combined model in predicting advanced-stage liver fibrosis in patients with chronic hepatitis B (CHB) combined with metabolic-associated fatty liver disease (MAFLD).Methods:A multicenter retrospective cohort study was conducted on the BMOVE population.Nine hundred twenty CHB cases combined with MAFLD who underwent liver biopsy at seven medical centers in China from April 2006 to December 2023 were included. The patients were divided into advanced-stage liver fibrosis (159 cases) and non-advanced-stage liver fibrosis (761 cases) according to the Scheuer's scoring system.The area under the receiver operating characteristic curve (AUROC), decision curve, and calibration curve analysis were used to evaluate the efficacy of the firbrosis-4 index (FIB-4) score, NFS score, APRI index, LSM, and Agile 3+ score and their combined model in predicting advanced-stage fibrosis. The liver fibrosis grade of all patients was diagnosed by liver biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each scoring model and combined model, as well as the proportion of correctly classified patients, were calculated based on different cutoff values.Results:AUROC analysis showed that Agile 3+ (0.814, 95% CI: 0.787-0.838) and LSM (0.805, 95% CI: 0.778-0.829) had similar accuracy and were superior to FIB-4 (0.721, 95% CI: 0.691-0.749), NFS (0.687, 95% CI: 0.656-0.716) and APRI ( 0.689, 95% CI: 0.658-0.718); however, HBV DNA level and HBV e antigen status had no effect on this outcome. Decision curve analysis showed that interventions based on LSM and Agile 3+ had provided higher net benefits compared with serological scores. Calibration curves showed that Agile 3+ had better predicitive accuracy than all other models. Agile 3+ had the highest PPV (0.54), minimal uncertainty interval (11.6%), and the highest proportion of correctly classified patients (76%); followed by LSM (PPV: 0.43, uncertainty interval: 15.5%, correct classification rate: 66%), and FIB-4 (PPV: 0.42, uncertainty interval: 26.1%, correct classification rate: 62.6%) in terms of identifying advanced-stage liver fibrosis. Combined model analysis demonstrated that FIB-4 combined with Agile 3+ had improved the correct classification rate and reduced the proportion of missed patients compared with FIB-4 combined with LSM. Conclusion:The Agile 3+ score is superior than LSM, FIB-4, NFS, and APRI index at identifying advanced-stage fibrosis in patients with CHB combined with MAFLD. This study supports the use of FIB-4 index combined with Agile 3+ for risk stratification in patients with CHB combined with MAFLD.

With rapid development of information technology,blended teaching model has gradually become mainstream teaching model in most colleges and universities.How to evaluate students'learning effect and analyze factors that affect students'per-formance is a key research direction of this teaching model.Taking blended teaching of Medical Immunology course in Xinxiang Medical University as an example,this paper introduces implementation process and evaluation system of blended teaching,analyzes main factors affecting students'performance and learning effect,and focuses on discussing influence of formative evaluation and"flipped classroom"on students'academic performance.

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

OBJECTIVE：To analyze and compare th e contents of 6 kinds of monosaccharide in Astragalus membranaceus from different growth years . METHODS ：2-4 years old A. membranaceus from three areas were extracted with water extraction and alcohol precipitation ，Sevage deproteinization to obtain A. membranaceus polysaccharide. The samples were firstly hydrolyzed with trifluoroacetic acid （TFA）and then derivatized by 1-phenyl-3-methyl-5-pyrazolone（PMP）. HPLC analysis was adopted to determine the contents of 6 kinds of monosaccharide as mannose ，rhamnose，galacturonic acid ，glucose，galactose，arabinose. The determination was performed on Symmetry C 18 column with phosphate buffer solution （pH 6.8）-acetonitrile（84∶16，V/V）as mobile phase at the flow rate of 1.0 mL/min. The detection wavelength was 245 nm，and column temperature was 35 ℃. The sample size was 20 µL. RESULTS ：The contents of mannose ，rhamnose，galacturonic acid ，glucose，galactose and arabinose were 0.50-0.94， 0.76-1.60，3.35-7.86，87.33-275.77，1.95-8.96，2.35-14.04 mg/g，respectively. Total contents of monosaccharide from 2，3，4 years old A. membranaceus were 98.26-139.92，173.81-295.71，122.37-182.41 mg/g，respectively. There was significant difference in the contents of glucose between 3 old years A. membranaceus and 2，4 old years A. membranaceus （162.71-275.77 mg/g vs. 87.33-107.70，111.54-167.26 mg/g，P＜0.05）. CONCLUSIONS ：Above 6 monosaccharides are detected in 2，3，4 years old A. membranaceus，among which the content of glucose is the highest. The content of glucose in 3 years old A. membranaceus is higher than that in 2 and 4 years old A. membranaceus .

Objective To evaluate the efficacy of MoodGYM Internet-delivered Cognitive Behavior-al Therapy in the treatment of anxiety and depression among nurses. Methods A total of 180 nurses with anxiety or depression were randomly divided into three groups,60 in each group,and 2 months of intervention with MoodGYM and health education ( once a week,30-45 minutes each time) in MoodGYM group and health education group,respectively. Another group was as a control group. Before and after intervention,De-pression Anxiety Stress Scale 21 ( DASS-21),Minnesota Satisfaction Questionnaire ( MSQ) and Subjective Happiness Scale (SHS) were used to evaluate psychological status. Results Compared with pre-interven-tion,the scores of anxiety in DASS-21 ((16. 76±7. 61) vs (9. 67±5. 78),t=21. 339,P<0. 01) and depres-sion in DASS-21 ((13. 86±7. 60) vs (10. 91±7. 12),t=16. 716,P<0. 01) decreased,meanwhile job satis-faction in MSQ((65. 11±11. 12) vs (67. 97±11. 10),t=-16. 400,P<0. 01) and subjective well-being in SHS((17. 67 ± 4. 59) vs (21. 83 ± 3. 53),t=-20. 221, P<0. 01) increased in post-intervention in the MoodGYM group. The scores of anxiety((15. 81±8. 24) vs (12. 45± 7. 68),t=17. 566,P<0. 01) and de-pression((12. 44± 8. 23) vs ( 12. 09 ± 7. 95), t=3. 934,P<0. 01) decreased, meanwhile job satisfaction ((67. 37±9. 76) vs (68. 91± 9. 67),t=-4. 474,P<0. 01) and subjective well-being(( 17. 93± 3. 80) vs (19. 85±3. 96),t=-14. 897,P<0. 01) increased in post-intervention in the health education group. After in-tervention,the effect of improving anxiety, depression, job satisfaction and subjective well-being in the MoodGYM group was more obvious than that in the health education group (P<0. 01). Conclusion -MoodGYM intervention can relieve anxiety and depression of nurses,improve their job satisfaction and sub-jective well-being.

Objective To investigate the clinical efficacy and experiences of laparoscopic hepatectomy (LH) for segment Ⅶ and Ⅷ liver tumors.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 94 patients who underwent LH for segment lⅦ or Ⅷ liver tumors in the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine from June 2010 to August 2016 were collected.The operating space for operation was built under laparoscopy.According to liver cirrhosis grading,tumor size,adjacent relationship with major blood vessels and residual liver volume,non-anatomical and anatomical hepatectomies were selected by patients.During the operation,tumors were precisely pinpointed and plane of liver resection was determined,and then proper instruments of liver partition and techniques of hepatic inflow occlusion were selected.Observation indicators:(1) surgical and postoperative recovery situations;(2) postoperative pathological examination;(3) follow-up and survival situation.Follow-up using outpatient examination and telephone interview was performed to detect the patients' survival up to July 2017.Measurement data with normal distribution were represented as (x)±s.Measurement data with skewed distribution were described as M (interquartile range).Survival rate was caculated by the Kaplan-Meier method.Results (1) Surgical and postoperative recovery situations:all 94 patients received successful operations,without perioperative death,including 73undergoing non-anatomical hepatectomy and 21 undergoing anatomical hepatectomy.Fourteen patients had conversion to open surgery and 27 received hepatic inflow occlusion.The median operation time,median volume of intraoperative blood loss and cases with intraoperative blood transfusion were respectively 187.5 minutes (75.0minutes),200 mL (200 mL) and 15.Eighteen patients had postoperative complications,including 6 with pleural effusion,6 with abdominal effusion,1 with wound infection,1 with abdominal infection,1 with venous thrombosis,1 with bleeding,1 with coagulation disorders and 1 with hepatic insufficiency.Clavien-Dindo classification of complications:11,1,5 and 1 patients were detected in grade Ⅰ,lⅡ,Ⅲ and Ⅳ,respectively.All complications were improved by symptomatic treatment.The median duration of hospital stay was 7 days (6 days).(2) Postoperative pathological examination:results of tumor pathological examination showed that 45,5,9 and 35 patients were respectively confirmed as hepatocellular carcinoma,cholangiocarcinoma,metastatic hepatic carcinoma and benign liver tumor.(3) Follow-up and survival situation:59 patients with malignant tumors were followed up for 6.0-52.0 months,with a median time of 42.6 months.Postoperative 1-and 3-year overall survival rates of 59 patients with malignant tumors were 98.3％ and 84.7％,respectively.Conclusions LH for segment Ⅶ and Ⅷ liver tumors which is conducted in experienced medical center is safe and feasible,with definite effects.Building operating space for operation under laparoscopy,determining precise positioning of the tumor and plane of liver resection,and selecting proper instruments of liver partition and techniques of hepatic inflow occlusion are the key points of successful operation.