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.

Sensory dysfunction is a common clinical problem for children with cerebral palsy.Proprioception plays a key role in maintaining postural adjustment and balance coordination, so proprioceptive assessment is of great significance for further rehabilitation of children with cerebral palsy.At present, proprioception assessment is mainly used in adults such as stroke and joint injury, but there is still a lack of research in children, especially in children with cerebral palsy.Therefore, this paper aims to review the evaluation of proprioception of children with cerebral palsy at home and abroad.

Aim The key genes for necroptosis in atherosclerosis were screened by bioinformatics methods and verified with the help of in vitro experiments to provide new strategies for the prevention and treatment of atherosclerosis from the perspective of necroptosis.Methods Genes related to atherosclerotic plaques were downloaded from GEO da-tabase,and genes related to necroptosis were downloaded from GeneCards database and intersected to obtain atherosclerotic necroptosis genes,and the mechanism of action and signalling pathways of the genes were further analysed by GO and KEGG enrichment analysis,and the protein-protein interaction(PPI)network was constructed and screened for key genes.Finally,macrophages were treated with oxidized low density lipoprotein(oa-LDL)at a final concentration of 100 mg/L,and the expression of key genes was detected by RT-PCR and Western blot.Results A total of 81 atherosclerotic nec-roptosis genes were obtained.GO and KEGG enrichment analyses revealed that they were mainly enriched in the positive regulation of endopeptidase activity,IκB kinase(IKK)/nuclear factor-KB(NF-κB)signalling,and autophagy signalling pathway.Five key genes including HSPA8,STAT3,HMOX1,SQSTM1 and FAS were obtained by using five computa-tional methods of Cytoscape software cytoHubba plug-in.Compared with the normal control group,the HMOX1 gene was highly expressed in THP-1 macrophages treated with ox-LDL(P＜0.05),while the expression of the HSPA8,STAT3,SQSTM1 and FAS genes showed no significant changes(P＞0.05);the HMOX1 and SQSTM1 genes were highly expressed in RAW264.7 macrophages treated with ox-LDL(P＜0.05),while HSPA8,STAT3 and FAS genes showed no significant changes(P＞0.05).The expression of HMOX1 protein in THP-1 macrophages was also increased.Conclusion HMOX1 may be the key gene of atherosclerotic necroptosis,and it is expected to become a new target for the prevention and treatment of atherosclerosis.

OBJECTIVE: To explore the clinical phenotype and genetic features of a child with dilated cardiomyopathy (DCM). METHODS: Clinical data of the child who had presented at the Zhengzhou Children's Hospital on April 28, 2020 was collected. Trio-whole exome sequencing (trio-WES) was carried out for the child and her parents, and candidate variants were validated by Sanger sequencing. "FHL2" was taken as the key word to retrieve related literature from January 1, 1997 to October 31, 2021 in the PubMed database and was also searched in the ClinVar database as a supplement to analyze the correlation between genetic variants and clinical features. RESULTS: The patient was a 5-month-old female infant presented with left ventricular enlargement and reduced systolic function. A heterozygous missense variant c.391C>T (p.Arg131Cys) in FHL2 gene was identified through trio-WES. The same variant was not detected in either of her parents. A total of 10 patients with FHL2 gene variants have been reported in the literature, 6 of them had presented with DCM, 2 with hypertrophic cardiomyopathy (HCM), and 2 with sudden unexplained death (SUD). Phenotypic analysis revealed that patients with variants in the LIM 3 domain presented hypertrophic cardiomyopathy and those with variants of the LIM 0~2 and LIM 4 domains had mainly presented DCM. The c.391C>T (p.Arg131Cys) has been identified in a child with DCM, though it has not been validated among the patient's family members. Based on the guidelines of the American College of Medical Genetics and Genomics, the c.391C>T(p.Arg131Cys) variant was re-classified as likely pathogenic (PS2+PM2_Supporting+PP3+PP5). CONCLUSION The heterozygous missense variant of c.391C>T (p.Arg131Cys) in the FHL2 gene probably predisposed to the DCM in this child, which has highlighted the importance of WES in the clinical diagnosis and genetic counseling.
Female ; Humans ; Cardiomyopathy, Dilated/genetics* ; Cardiomyopathy, Hypertrophic ; Genetic Counseling ; Genomics ; Heterozygote ; Muscle Proteins/genetics* ; Transcription Factors ; LIM-Homeodomain Proteins/genetics*

Objective:To explore whether the regular feedback system in opportunistic screening of colorectal cancer can improve the adenoma detection rate (ADR) of endoscopists.Methods:This study was an observational study, divided into three stages: the baseline stage before intervention (the pre-intervention period), the regular feedback stage (the intervention period) and the post-intervention stage (the post-intervention period). In the pre-intervention period, all patients who underwent opportunistic screening of colorectal cancer in Department of Gastroenterology in Beijing Shijitan Hospital Affiliated to Capital Medical University from June 2017 to May 2018 were reviewed, and the ADR of each endoscopist was calculated. In the intervention period from June 2018 to November 2018, colonoscopies were performed on patients for opportunistic screening of colorectal cancer by endoscopists who participated in the feedback. The ADR of each endoscopist during the previous month was calculated at the beginning of each month and feedback was provided in the form of a report. In the post-intervention period from December 2018 to January 2019, colonoscopies were performed on patients for opportunistic screening of colorectal cancer by endoscopists who participated in the feedback. The ADR of each endoscopist was calculated after the feedback stopped. ADR and polyp detection rate (PDR) of three stages were compared.Results:A total of 1 768, 1 308 and 344 patients were enrolled for opportunistic screening of colorectal cancer during the pre-intervention, the intervention and the post-intervention period respectively. Eight endoscopists participated in the whole process of this study. The total ADR increased from 23.70% (419/1 768) in the pre-intervention period to 33.72% (441/1 308) in the intervention period ( χ2=37.449, P<0.05). Two months after intervention, ADR decreased slightly to 33.14% (114/344), but was still higher compared with before ( χ2=13.602, P<0.05). The total PDR increased from 47.17% (834/1 768) in the pre-intervention period to 52.68% (689/1 308) in the intervention period ( χ2=9.111, P<0.05). Two months after the intervention, PDR increased slightly to 53.78% (185/344), and still higher compared with before ( χ2=5.035, P<0.05). Conclusion:Regular feedback to endoscopists can improve ADR in opportunistic screening of colorectal cancer.

Objective:To explore the clinical significance of recurrent laryngeal nerve inlet zone(RLNIZ) lymph node metastasis in papillary thyroid cancer(PTC).Methods:The clinical data of the clinicopathologic characteristics of 738 cases with papillary thyroid cancer at our centers from Jul 2017 to Jun 2018 was retrospectively reviewed. 108 cases with RLNIZ lymph node dissection for pathological examination were included. The relationship between metastasis of RLNIZ lymph node and clinicopathologic characteristics was analyzed.Results:RLNIZ lymph node was detected in 12.3%(91/738)cases, the mean lymph node number in RLNIZ was 1.5±0.7, and 30.8%(28/91) cases suffered RLNIZ lymph node metastasis. RLNIZ lymph node metastasis(LNM) is associated with tumor size( P=0.028), capsular invasion( P=0.019), No. of central compartment LNM( P<0.001) and lateral neck LNM( P<0.001). No. of central compartment LNM was found to be the independent risk factor of RLNIZ lymph node metastasis. The incidence of dysphagia and inferior parathyroid damage was 0.9%(1/108)respectively. Conclusions:RLNIZ lymph node metastasis is common among PTC patients , therefore, RLNIZ lymph node should be routinely removed especially in patients with tumor size over 1cm、suspected capsular invasion and lateral neck lymph node metastasis confirmed by preoperative imaging examination.

Objective    By applying the mutual corroboration in the diagnosis, we aimed to improve the accuracy of preoperative imaging diagnosis, select the appropriate timing of operation and guide the follow-up time for patients with pulmonary nodules. Methods    Clinical data of 1 368 patients with pulmonary nodules undergoing surgical treatment in our department from July 2016 to October 2019 were summarized. There were 531 males and 837 females at age of 44 (21-67) years. The intraoperative findings, images and pathology were classified and analyzed. The imaging pathology and pathological changes of pulmonary nodules were shown as a dynamic process through mutual collaboration and interaction. Results    Of 1 368 patients with pulmonary nodules, 376 (27.5%) were pure ground-glass nodules, 729 (53.3%) were mixed ground-glass nodules and 263 (19.2%) were solid nodules. Among the pure ground-glass nodules, adenocarcinoma in situ (AIS) accounted for the highest proportion (156 patients), followed by microinvasive adenocarcinoma (MIA, 90 patients), atypical adenomatous hyperplasia (AAH, 85 patients), and benign tumors (20 patients). Among mixed ground-glass nodules, 495 patients were invasive adenocarcinoma (IA) and 207 patients of MIA. no patient was featured by AAH, AIS or MIA. Conclusion    The mutual collaboration and interaction can improve the accuracy of preoperative diagnosis of pulmonary nodules, and it supports the choice of operation timing and the judgment of follow-up time.

Primary hepatic carcinoma（PHC）is the second leading cancer that caused death in the world. The morbidity of PHC is increasing year by year,which threaten people's lives and health. Chronic hepatitis B is considered to be an independent risk factor for PHC,and the incidence of PHC is higher in patients who have progressed to liver cirrhosis. We reviewed the domestic and abroad literatures about the risk factors for hepatitis B cirrhosis progressing to PHC from the year of 1992 to 2018,and concluded that HBV-DNA,HBsAg,HBeAg expression,antiviral treatment time,different antiviral drugs,degree of cirrhosis,alanine transaminase and family history were related to the development of PHC from cirrhosis.

Objective To evaluate intraoperative placement of bile duct decompression drainage tube in CBD primary suture after laparoscopic choledocholithotomy.Methods 152 patients undergoing laparoscopic choledocholithotomy were divided into group A (placement of bile duct decompression drainage tube during operation,82 cases) and group B (no decompression drainage tube placement,70 casas).Results There was no significant difference in operative time and intraoperative bleeding between the two groups (P ＞ 0.05).In group B patients the abdominal drainage tube indwelling time,abdominal drainage volume,peritoneal drainage fluid bilirubin value,postoperative hospitalization time were significantly longer than group A,the difference was statistically significant (P ＜ 0.05).No recurrence of choledocholithiasis and biliary stricture were found in either groups.Conclusions Placement of bile duct decompression drainage tube in laparoscopic choledocholithotomy and CBD primary suture after laparoscopic choledochotomy can significantly reduce the incidence of biliary leakage and shorten the postoperative hospital stay.