1.Interleukin-1β as target to induce synthetic lethality in KRAS mutant biliary tract cancer
Shijie LI ; Yukai SHAN ; Tianen CHEN ; Win TOPATANA ; Sarun JUENGPANICH ; Ziyi LU ; Yuchao SUN ; Tianao XIE ; Ruijing RUIJING ; Lidan HOU ; Jiang CHEN ; Guojun CHEN ; Jiemin LV ; Xianjue MA ; Pengjuan GUO ; Dan Gabriel DUDA ; Xiujun CAI ; Mingyu CHEN
Clinical and Molecular Hepatology 2026;32(2):904-918
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.
2.The application of virtual navigation bronchoscopy assisted localization in thoracoscopic sublobectomy and its impact on perioperative outcomes
Yu HUANG ; Longyu JIN ; Wei FENG ; Yuyang NI ; Yingji CHEN ; Hongchun XU ; Yuchao MA
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(4):212-219
Objective:To investigate the impact of virtual navigation bronchoscopy on perioperative information in patients undergoing thoracoscopic pulmonary resection.Methods:Employed three distinct propensity score matching models to effectively address the baseline data disparities among patients undergoing thoracoscopic pulmonary resection. Categorized the patients into two groups: pulmonary wedge resection and pulmonary segmentectomy. Compared the disparities in clinical characteristics, intraoperative lesion resection, and postoperative recovery between patients who underwent virtual navigation bronchoscopy assisted localization prior to surgery and those who did not employ any specific localization methods.Results:This reserch included a total of 127 patients who underwent localization assisted by virtual navigation bronchoscopy, and 122 patients who did not undergo specialized localization. After propensity score matching, the navigation group demonstrated a statistically significant reduction in intraoperative blood loss[model 3, 40(20, 50) ml vs. 50(20, 100) ml, P=0.027], drainage volume on the first day post-surgery[model 3, 100(50, 175) ml vs. 150(100, 220) ml, P=0.023], and incidence of residual pleural effusion(model 3, 31 cases vs. 38 cases, P=0.046) compared to the non-positioning group among patients undergoing pulmonary wedge resection. In the pulmonary segmentectomy group, we observed a reduction in intraoperative blood loss[model 3, 50(30, 100) ml vs. 100(50, 100) ml, P=0.003] and incidence of residual pneumothorax(model 3, 18 cases vs. 28 cases, P=0.012) in patients who underwent navigation-assisted procedures compared to those without specialized positioning. Conclusion:The utilization of virtual navigation bronchoscopy for preoperative localization assistance in thoracoscopic sublobectomy(including wedge resection and segmental resection) may represent a viable approach to mitigate intraoperative injury and facilitate postoperative recovery.
3.The application of virtual navigation bronchoscopy assisted localization in thoracoscopic sublobectomy and its impact on perioperative outcomes
Yu HUANG ; Longyu JIN ; Wei FENG ; Yuyang NI ; Yingji CHEN ; Hongchun XU ; Yuchao MA
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(4):212-219
Objective:To investigate the impact of virtual navigation bronchoscopy on perioperative information in patients undergoing thoracoscopic pulmonary resection.Methods:Employed three distinct propensity score matching models to effectively address the baseline data disparities among patients undergoing thoracoscopic pulmonary resection. Categorized the patients into two groups: pulmonary wedge resection and pulmonary segmentectomy. Compared the disparities in clinical characteristics, intraoperative lesion resection, and postoperative recovery between patients who underwent virtual navigation bronchoscopy assisted localization prior to surgery and those who did not employ any specific localization methods.Results:This reserch included a total of 127 patients who underwent localization assisted by virtual navigation bronchoscopy, and 122 patients who did not undergo specialized localization. After propensity score matching, the navigation group demonstrated a statistically significant reduction in intraoperative blood loss[model 3, 40(20, 50) ml vs. 50(20, 100) ml, P=0.027], drainage volume on the first day post-surgery[model 3, 100(50, 175) ml vs. 150(100, 220) ml, P=0.023], and incidence of residual pleural effusion(model 3, 31 cases vs. 38 cases, P=0.046) compared to the non-positioning group among patients undergoing pulmonary wedge resection. In the pulmonary segmentectomy group, we observed a reduction in intraoperative blood loss[model 3, 50(30, 100) ml vs. 100(50, 100) ml, P=0.003] and incidence of residual pneumothorax(model 3, 18 cases vs. 28 cases, P=0.012) in patients who underwent navigation-assisted procedures compared to those without specialized positioning. Conclusion:The utilization of virtual navigation bronchoscopy for preoperative localization assistance in thoracoscopic sublobectomy(including wedge resection and segmental resection) may represent a viable approach to mitigate intraoperative injury and facilitate postoperative recovery.
4.A single-blind randomized controlled study of efficacy of internet-based group cognitive-behavioral therapy on major depressive disorder
Jianfang HAN ; Yanxin BAI ; Jiying BAO ; Jun MA ; Yuchao MA ; Yueqin HUANG ; Dongsheng YU
Chinese Mental Health Journal 2024;38(8):660-665
Objective:To explore the effects of internet-based group cognitive-behavioral therapy(IGCBT)on the depressive and anxiety symptoms in patients with major depressive disorder(MDD).Methods:Eighty pa-tients with MDD were recruited and randomly divided into IGCBT combined drug therapy group and control group with drug therapy.Blind assessments were performed using the Hamilton Depression Scale(HAMD)and Hamilton Anxiety Scale(HAMA)three times at baseline,4 weeks after treatment and 8 weeks after treatment,respectively.Results:The effective rates of HAMD and HAMA at the end of the 4th and 8th week,and the effective rates of HAMA at the end of the 8th week were higher in the combined treatment group than those in the control group(Ps<0.05).The total scores of HAMD and HAMA in the combined treatment group and the control group were lower at the end of the 4th and 8th week than those at baseline(Ps<0.001).The total scores of HAMD and HAMA were lower in the combined treatment group than those in the control group at the baseline,4 weeks and 8 weeks after treatment(Ps<0.01).Conclusion:It suggests that intemet-based group cognitive-behavioral therapy combined with antidepressant medication has a better effect on relieving depressive and anxiety symptoms in patients with ma-jor depressive disorder than drug therapy alone,and especially has a better effect on improving anxiety symptom.
5.Research progress in targets and challenges of antibody-drug conjugates in treatment of glioblastoma
Kai LIU ; Yuchao DONG ; Yue LIU ; Hang ZHANG ; Song MIAO ; Chengyuan MA ; Zihao WANG
Chinese Journal of Pharmacology and Toxicology 2024;38(12):945-951
Glioblastoma (GBM) is an exceptionally aggressive tumor that originates in the brain,characterized by a notably high mortality rate and a limited responsiveness to pharmacological interven-tions.In recent years,antibody-drug conjugates (ADCs) have emerged as a focal point in the advance-ment of anti-cancer therapeutic research,merging the precise targeting capabilities of antibodies with the powerful killing power of cytotoxins.In recent years,the outcomes of numerous clinical trials investi-gating ADCs targeted against GBM have been notably encouraging.This article endeavors to provide a comprehensive overview of the prevalent ADCs targets for GBM therapy,which include the epidermal growth factor receptor,the cluster of differentiation,the mannose receptor family,the integrin family,and the galectin family.Furthermore,it will delve into the contemporary landscape of ADCs drug research and the significant challenges encountered in the application of ADCs for GBM treatment.
6.Application value of modified closure of overlap anastomotic common opening in total laparoscopic radical gastrectomy
Wanhong ZHANG ; YuChao MA ; Linjie LI ; Zhenhua WANG ; Yipeng REN ; Xueyi DANG ; Yinan SHI
Chinese Journal of Digestive Surgery 2024;23(10):1354-1358
Objective:To investigate the application value of modified closure of overlap anastomotic common opening in total laparoscopic radical gastrectomy.Methods:The retrospec-tive and descriptive study was conducted. The clinicopathological data of 39 patients with gastric cancer who underwent total laparoscopic radical gastrectomy in Shanxi Hospital of Cancer Hospital, Chinese Academy of Medical Sciences from January 2023 to January 2024 were collected. There were 27 males and 12 females, aged (61±9)years. All patients underwent total laparoscopic radical gastrectomy for gastric cancer, with gastrointestinal reconstruction using overlap anastomosis and a modified closure of overlap anastomotic common opening. Measurement data with normal distribution were represented as Mean± SD, and count data were expressed as absolute numbers. Results:(1) Intraoperative and postoperative conditions. All 39 patients underwent total laparoscopic radical gastrectomy for gastric cancer, with gastrointestinal reconstruction using overlap anastomosis and a modified closure of overlap anastomotic common opening successfully, without conversion to open surgery or thoracotomy. The operation time of 39 patient was (210±52)minutes, with the volume of intraoperative blood loss of (132±55)mL, number of lymph node dissected of 23±11. The time to postoperative first flatus of 39 patients was (3.3±0.3)days, with time to postoperative liquid food intake of (4.4±0.6)days, time to postoperative semi-liquid food intake of (5.2±0.4)days, and duration of postoperative hospital stay of (9.5±3.1)days. (2) Complications. Seven of the 39 patients experienced perioperative complications, including 5 cases with complication classified as Clavien-Dindo grade Ⅱ, and 2 cases with complication classified as Clavien-Dindo grade Ⅲ. After conservative treatment, all patients with complications improved and were discharged. (3) Follow-up. Results of upper gastrointestinal imaging of the 39 patients showed no anastomotic leakage, and all patients were followed up at 1, 3, and 6 months after surgery. There was no other complications, tumor recurrence and metastasis, or mortality during the follow-up period.Conclusion:The modified closure of overlap anastomotic common opening in total laparoscopic radical gastrectomy has good safety and short-term efficacy.
7.Application value of modified closure of overlap anastomotic common opening in total laparoscopic radical gastrectomy
Wanhong ZHANG ; YuChao MA ; Linjie LI ; Zhenhua WANG ; Yipeng REN ; Xueyi DANG ; Yinan SHI
Chinese Journal of Digestive Surgery 2024;23(10):1354-1358
Objective:To investigate the application value of modified closure of overlap anastomotic common opening in total laparoscopic radical gastrectomy.Methods:The retrospec-tive and descriptive study was conducted. The clinicopathological data of 39 patients with gastric cancer who underwent total laparoscopic radical gastrectomy in Shanxi Hospital of Cancer Hospital, Chinese Academy of Medical Sciences from January 2023 to January 2024 were collected. There were 27 males and 12 females, aged (61±9)years. All patients underwent total laparoscopic radical gastrectomy for gastric cancer, with gastrointestinal reconstruction using overlap anastomosis and a modified closure of overlap anastomotic common opening. Measurement data with normal distribution were represented as Mean± SD, and count data were expressed as absolute numbers. Results:(1) Intraoperative and postoperative conditions. All 39 patients underwent total laparoscopic radical gastrectomy for gastric cancer, with gastrointestinal reconstruction using overlap anastomosis and a modified closure of overlap anastomotic common opening successfully, without conversion to open surgery or thoracotomy. The operation time of 39 patient was (210±52)minutes, with the volume of intraoperative blood loss of (132±55)mL, number of lymph node dissected of 23±11. The time to postoperative first flatus of 39 patients was (3.3±0.3)days, with time to postoperative liquid food intake of (4.4±0.6)days, time to postoperative semi-liquid food intake of (5.2±0.4)days, and duration of postoperative hospital stay of (9.5±3.1)days. (2) Complications. Seven of the 39 patients experienced perioperative complications, including 5 cases with complication classified as Clavien-Dindo grade Ⅱ, and 2 cases with complication classified as Clavien-Dindo grade Ⅲ. After conservative treatment, all patients with complications improved and were discharged. (3) Follow-up. Results of upper gastrointestinal imaging of the 39 patients showed no anastomotic leakage, and all patients were followed up at 1, 3, and 6 months after surgery. There was no other complications, tumor recurrence and metastasis, or mortality during the follow-up period.Conclusion:The modified closure of overlap anastomotic common opening in total laparoscopic radical gastrectomy has good safety and short-term efficacy.
8.Research progress in targets and challenges of antibody-drug conjugates in treatment of glioblastoma
Kai LIU ; Yuchao DONG ; Yue LIU ; Hang ZHANG ; Song MIAO ; Chengyuan MA ; Zihao WANG
Chinese Journal of Pharmacology and Toxicology 2024;38(12):945-951
Glioblastoma (GBM) is an exceptionally aggressive tumor that originates in the brain,characterized by a notably high mortality rate and a limited responsiveness to pharmacological interven-tions.In recent years,antibody-drug conjugates (ADCs) have emerged as a focal point in the advance-ment of anti-cancer therapeutic research,merging the precise targeting capabilities of antibodies with the powerful killing power of cytotoxins.In recent years,the outcomes of numerous clinical trials investi-gating ADCs targeted against GBM have been notably encouraging.This article endeavors to provide a comprehensive overview of the prevalent ADCs targets for GBM therapy,which include the epidermal growth factor receptor,the cluster of differentiation,the mannose receptor family,the integrin family,and the galectin family.Furthermore,it will delve into the contemporary landscape of ADCs drug research and the significant challenges encountered in the application of ADCs for GBM treatment.
9.Internet-based group cognitive behavioral therapy for depression and anxiety symptoms
Yanxin BAI ; Dongsheng YU ; Jianfang HAN ; Jiying BAO ; Jun MA ; Yuchao MA
Sichuan Mental Health 2023;36(6):556-561
This paper presents a systematic review of extant research investigating the effectiveness of Internet-based group cognitive behavioral therapy (IGCBT) for depression and anxiety symptoms with an emphasis on the treatment modalities, treatment protocols, efficacy and mechanism, together with a summary of research limitations and suggestions for future research. Cognitive behavioral therapy (CBT) is a structured, short-term and present-oriented psychotherapeutic treatment, its Internet- and group-delivered modalities have led to its wider application, and has proven to be clinically effective in alleviating depression and anxiety symptoms caused by different diseases, whereas some drawbacks have been reported. Thus this paper elaborates the clinical application, therapeutic effect and underlying mechanisms of IGCBT intervention for depression and anxiety symptoms, so as to provide references for its future application. [Funded by the Natural Science Foundation of the Inner Mongolia Autonomous Region (number, 2019MS03038)
10.Modified double-tract reconstruction operation in early SiewertⅡ esophagogastric junction adenocarcinoma
Yuchao MA ; Yanyang SONG ; Jianhong DONG ; Wanhong ZHANG ; Linjie LI
Chinese Journal of General Surgery 2022;37(2):90-93
Objective:To evaluate the safety and efficiency of a modified double-tract reconstruction procedure─proximal gastrectomy with piggyback interposed jejunal single-channel reconstruction (PJIR-STR) for early SiewertⅡ adenocarcinoma of esophagogastric junction (AEG).Method:Data of 8 SiewertⅡ AEG patients at Shanxi Tumor Hospital and undergoing PJIR-STR from May 2018 to Oct 2019 were retrospectively analyzed. The gastroesophageal reflux disease questionnaire (GerdQ) was used to score the patients at 3, 6, 12, and 18 months after surgery. The severity of postoperative reflux esophagitis was assessed by gastroscopy at 3, 6 months after surgery, using the Los Angeles Classification criteria.Result:All patients recovered well after surgery without serious complications. No obvious gastroesophageal reflux was observed in all patients at different periods (All of the GerdQ scores were <8 points.) The results of gastroscopy showed that 1 patient was diagnosed as grade B reflux esophagitis at 3, 6 months after surgery, which was responsive to conservative treatment, and the other 7 patients had no grade B or above reflux esophagitis.Conclusion:PJIR-STR is a feasible, safe reconstruction with excellent efficiency of dual anti-reflux for the SiewertⅡ AEG.

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