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 Jejunal interposition is an important option for restoring gastrointestinal continuity in patients with complex esophageal cancer in whom the stomach is unavailable for reconstruction due to previous gastrectomy, tumor involvement, failed gastric conduit, or other constraints. Although the jejunum offers a caliber similar to the esophagus, a rich blood supply, and preserved peristaltic function, anatomical variations in mesenteric length and vascular arcades render long-segment and high-level reconstruction susceptible to excessive tension, mesenteric torsion, venous congestion, and inadequate distal perfusion. This consensus aims to provide standardized recommendations for the application of jejunal interposition in this specific patient population. Methods This consensus was developed in accordance with the WHO Handbook for Guideline Development and Chinese national guideline development standards, with reference to the Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREE Ⅱ), Reporting Items for Practice Guidelines in Healthcare (RIGHT), and Scientific, Transparent and Applicable Rankings (STAR) checklists. The project was registered on the international practice guidelines registry platform (PREPARE-2026CN1384). The working group systematically searched Chinese and English evidence addressing 12 clinical questions. Evidence was graded using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 system, with structured appraisal of risk of bias, inconsistency, indirectness, and imprecision. Recommendations were formulated through two rounds of Delphi surveys and a face-to-face consensus meeting, with an agreement threshold of ≥75%. Results The consensus generated 12 recommendations covering indications, selection between jejunum and colon, preoperative assessment, surgical approach and reconstruction route, pedicled jejunal interposition (PJI), supercharged pedicled jejunal interposition (SPJ), indocyanine green (ICG) perfusion assessment, perioperative nutrition, management of anastomotic leakage, long-term follow-up, and special treatment scenarios. Given that the available direct evidence is predominantly derived from single-center retrospective cohorts and case series, recommendations extrapolated from general esophagectomy or other gastrointestinal surgical evidence are deliberately phrased with caution. Conclusion Jejunal interposition is a safe and effective approach for digestive tract reconstruction in patients with complex esophageal cancer in whom the stomach is unavailable. This consensus emphasizes that clinical decision-making should be individualized based on the patient's prior treatment history, reconstruction height, vascular anatomy, technical availability, and institutional experience in the Chinese context.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective To explore the application value of targeted next-generation sequencing(tNGS)in the detection of influenza A virus.Methods A retrospective analysis was conducted on the clinical data of 116 patients suspected of having influenza A at our hospital from October 2024 to February 2025.All patients underwent sputum tNGS and throat swab influenza nucleic acid tests due to fever and pulmonary infection,and the diagnostic efficacy of the two methods was compared.Results Among 116 patients,93 were diagnosed with influenza A.Among these 93 influenza A patients,the detection rate of tNGS was higher than that of in-fluenza nucleic acid testing(P<0.05).The results of tNGS and influenza nucleic acid testing for influenza A showed significant consistency with the confirmed diagnosis(P<0.05).There was a statistically significant difference in tNGS sequence counts between the influenza nucleic acid-positive and negative groups(P<0.05).Twenty-three patients excluded from influenza A diagnosis served as the control group.Comparisons of white blood cell(WBC)counts among the influenza nucleic acid-positive group,negative group,and control group showed statistically significant differences(P<0.05),whereas comparisons of C-reactive protein(CRP)and serum amyloid A(SAA)showed no statistically significant differences(P>0.05).Conclusion tNGS demonstrates significant advantages in detecting influenza A virus.Combined with peripheral blood infection-related in-dicators for comprehensive diagnosis,it may provide a more effective approach for early diagnosis and treatment of influenza virus infectious diseases.

Objective To investigate the epidemiological characteristics of patients with postcraniotomy meningitis(PM)caused by Gram-negative bacteria(GNB),and to evaluate the related risk factors for mortal-ity.Methods A total of 202 PM patients in Beijing Tiantan Hospital,Capital Medical University from May 2019 to December 2021 were retrospectively analyzed,including 54 cases in the death group and 148 cases in the survival group.The distribution of microorganisms in the two groups was analyzed,and Cox proportional hazards regression model was established to evaluate the risk factors of death.Results Among the 202 pa-tients with PM caused by GNB,with a mortality rate of 26.7%,Klebsiella pneumoniae(24.8%),Acinetobact-er baumannii(21.8%)and Escherichia coli(8.4%)were the top three isolated pathogens.The proportions of GNB distribution in the survival group and the death group were similar,but the bacteria distribution in the death group was more concentrate.Cox proportional hazards regression model results showed that hyperten-sion(HR=2.384,95%CI 1.229-4.626,P=0.010)and admission to ICU(HR=3.695,95%CI 1.412-9.670,P=0.008)were independent risk factors for death in patients with PM caused by GNB.Conclusion The mortality of PM caused by GNB is high.Hypertension and admission to ICU are independent risk factors for death of patients,and attention should be paid to prevention and treatment in clinical practice.

Objective:To investigate the effectiveness of the Rain Classroom teaching model in the Functional Experiment Science.Methods:A total of 61 clinical medicine students from grade 2021 at a medical college were enrolled and divided into the control group(n=30)who received traditional experimental teaching,and the experimental group(n=31)who was taught using the Rain Classroom teaching model.Ultimately,the outcomes compared between the two groups included scores of experimental assignments,satisfaction with the teaching model,and the experimental group's supporting rate for the Rain Classroom teaching mode.Results:The experimental score in the experimental group was significantly higher than that in the control group(P＜0.05).Additionally,58.06%(18/31)of the experimental group supported the Rain Classroom model.Among the experimental group,77.42%(24/31)and 70.97%(22/31)of the students believed that the Rain Classroom teaching mode could enhance the awareness of autonomous learning and the mastery of key and difficult knowledge.Conclusion:Through the Rain Classroom teaching mode,students'experimental grades have been improved,and it also plays a certain role in promoting the enhancement of their self-study ability.

Objective:To investigate the effectiveness of the Rain Classroom teaching model in the Functional Experiment Science.Methods:A total of 61 clinical medicine students from grade 2021 at a medical college were enrolled and divided into the control group(n=30)who received traditional experimental teaching,and the experimental group(n=31)who was taught using the Rain Classroom teaching model.Ultimately,the outcomes compared between the two groups included scores of experimental assignments,satisfaction with the teaching model,and the experimental group's supporting rate for the Rain Classroom teaching mode.Results:The experimental score in the experimental group was significantly higher than that in the control group(P＜0.05).Additionally,58.06%(18/31)of the experimental group supported the Rain Classroom model.Among the experimental group,77.42%(24/31)and 70.97%(22/31)of the students believed that the Rain Classroom teaching mode could enhance the awareness of autonomous learning and the mastery of key and difficult knowledge.Conclusion:Through the Rain Classroom teaching mode,students'experimental grades have been improved,and it also plays a certain role in promoting the enhancement of their self-study ability.

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 the laboratory tests and clinical characteristics of patients with lupus anticoagulant-positive cerebral infarction.Methods:A retrospective analysis of 216 patients with cerebral infarction hospitalized in Beijing Tiantan Hospital from January 2016 to October 2021 was performed, and the patients were divided into LA-positive cerebral infarction group (168 cases) and LA-negative cerebral infarction group (48 cases) according to the detection of lupus anticoagulant (LA) in cerebral infarction patients, and the laboratory test data between the two groups were compared, and the risk factors related to cerebral infarction, including body mass index (BMI), smoking history, drinking history, hypertension, hyperlipidemia, diabetes history, were included for comparative analysis. LA was performed using the silica clotting time (SCT) method and the modified diluted russell viper venom time (dRVVT) method, respectively. The dRVVT method was used to detect LA. The LA-positive cerebral infarction group was divided into three subgroups according to the positive detection, namely, the dRVVT single-positive group (110 cases), the SCT single-positive group (40 cases) and the double-positive group (18 cases), and the comparison of laboratory indices between different subgroups was performed.The measurement data of normal distribution between the two groups were compared by independent sample t-test, and the mean between multiple groups was compared by ANOVA; The rank sum test was used to compare the median between the measurement data groups that did not conform to the normal distribution, and the χ 2 test was used to compare the counting data groups. Results:The levels of antithrombin Ⅲ and protein C of the LA-positive group ((102.85±14.39)% and (108.52±22.62)%) were all lower than those of the LA-negative group ((110.16±11.10)% and (116.34±18.14)%), the difference was statistically significant ( t values were 3.25, 2.20, P values were 0.001, 0.029, respectively). The levels of fibrinogen, homocysteine, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate, white blood cells and neutrophil were (3.43(3.07,4.03) g/L), (17.92(14.07,23.71) μmol/L), (6.97(2.33,11.46) mg/L), (15.00(6.75,29.00) mm/h), (8.61(6.72,10.86)×10 9/L) and (5.81(4.39,7.91)×10 9/L), all were higher than those in the LA-negative group with values of (3.14(2.68, 3.62) g/L), (14.62(12.49, 18.41) μmol/L), (3.18(2.09,4.32) mg/L), (9.50(3.75,19.00) mm/h), (7.20(6.22,8.33)×10 9/L) and (4.47(4.02,5.57)×10 9/L), and the differences were statistically significant ( Z values were 2.77, 2.89, 3.32, 2.45, 3.15 and 3.76, P values were 0.006、0.004、0.001, 0.014, 0.002 and <0.001, respectively). There were no significant differences in age, gender, BMI, personal history, past medical history and other laboratory indicators between the two groups (all P>0.05). Comparison among different subgroups in LA positive group showed that D dimer and hs-CRP levels in double-positive group were 0.58(0.50,0.84) mg/L and 7.77(5.94,21.61) mg/L, higher than those in SCT single-positive group with values of 0.45(0.32,0.56) mg/L and 2.98(1.09,6.07) mg/L, and protein S level of double-positive group (97.36±25.45)% was lower than that in SCT single-positive group (114.85±22.74)%, the differences were statistically significant (all P<0.05). D dimer, prothrombin time, hs-CRP and neutrophil levels in dRVVT single-positive group were (0.58(0.50,0.84) mg/L), (11.40(11.10,12.10) s), (6.97(4.07,11.97) mg/L) and (5.83(4.51,8.27)×10 9/L), which were higher than those in SCT single-positive group with values of (0.45(0.32,0.56) mg/L), (11.15(10.70,11.43) s), (2.98(1.09,6.07) mg/L) and (5.08(3.92,6.07)×10 9/L), the difference was statistically significant (all P<0.05). Protein C and triglyceride levels were ((105.65±20.62)%) and (1.38(1.05, 1.75) mmol/L) in dRVVT single-positive group, which were lower than those in SCT single-positive group with values of ((117.05±20.86)% and 1.60(1.29,2.36) mmol/L), the differences were statistically significant (all P<0.05). Conclusion:There were significant differences between LA positive and LA negative cerebral infarction patients in laboratory examination. In LA positive cerebral infarction patients, the levels of fibrinogen, homocysteine, hs-CRP, white blood cells, neutrophil and erythrocyte sedimentation rate were higher, while the levels of anticoagulant protein antithrombin Ⅲ and protein C were lower. It is of great significance to pay close attention to the level and change of laboratory related risk factors in patients with LA positive cerebral infarction and give early intervention and treatment for the prevention of the occurrence and recurrence of cerebral infarction.