1.High-throughput Sequencing of MET Mutational Landscape in Cancer Patients and the Value of IHC Screening for Targeted Therapy
Feicheng YANG ; Lixia JIANG ; Ruobing LIU ; Kai YANG ; Yewei LI ; Yi XIONG ; Hao DENG ; Jie HU
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(1):172-181
ObjectiveTo investigate the mutation status of the MET gene in tumor patients, with a focus on its expression in lung cancer tissues and its impact on patient prognosis, providing theoretical basis and potential targets for precise diagnosis and treatment of the tumors. MethodsA total of 1,627 tumor patient samples were collected from January 2021 to September 2025. High-throughput sequencing technology was used to conduct DNA-level gene detection on 137 tumor patients with MET mutations. The distribution of mutation sites in exons and introns, as well as the occurrence frequencies of MET gene amplification and gene fusion were analyzed, with particular attention paid to the mutation frequencies of each exon and the high-frequency variant types. Immunohistochemical staining was performed to analyze the expression levels of c-MET protein in tumor tissues of the 137 patients. Immunohistochemical analysis was conducted on tumor tissues of 9 patients with MET gene exon 14 skipping mutations to study the association between c-MET protein expression and this specific mutation type. RNA sequencing results, immunohistochemical staining data, and follow-up prognosis of lung cancer from the GEPIA2 database and TCGA database were comprehensively analyzed to explore the potential relationship between MET gene expression in tumor tissues and patient prognosis. ResultsAmong 1,627 tumor patients, 137 MET mutation patients were detected, including 93 males with an average age of (66.85±9.61) years and 44 females with an average age of (59.43±11.08) years. Lung cancer was the most common tumor type (117 cases). MET gene expression was lower in breast cancer and glioblastoma multiforme, but higher in lung cancer and colorectal cancer as compared with the expression in normal tissues. Survival analysis showed that patients with high MET gene expression in lung adenocarcinoma had a shorter overall survival time than those with low expression. A total of 961 mutations were detected by next-generation sequencing, including 547 exon mutations and 374 intron mutations. MET gene amplification was found in 13 cases and gene fusion in 27 cases. The highest mutation frequency was in exon 2, followed by exon 5, exon 4, and exon 19. High-frequency variant types included c.2890C>A (p.L964M) on exon 4 and c.3028G>T (p.D1010Y) on exon 5. The c-MET protein expression was closely related to the type of gene mutation. Missense mutations often led to positive or strongly positive c-MET protein expression, while nonsense mutations often resulted in weak or absent c-MET protein expression. Among the 9 patients with MET gene exon 14 skipping mutations, the c-MET protein expression score was mostly 0 - 1, with only 1 case scoring 2. Among the 117 lung cancer patients, the incidence rate was higher in males than in females, and more common among stage Ⅲ-Ⅳ patients than among stage I-Ⅱ patients. Out of the 41 patients treated with surgery + targeted drugs (gutemitinib, savolitinib), 8 cases of recurrence or metastasis were found during follow-up. ConclusionMET gene mutations exhibit specific mutation characteristics in different tumor types, and its expression levels show significant differences between various tumor tissues and normal tissues. It is closely related to the poor prognosis of lung adenocarcinoma patients. We found that c-MET protein expression is closely related to the type of MET gene mutation, especially in patients with MET gene exon 14 skipping mutations, which presents a characteristic expression pattern. This provides an important basis for the preliminary screening using immunohistochemistry in clinical practice.
2.Analysis of medical malpractice cases of cardiovascular diseases--A study of second-instance cases in henan province
Mengzhu ZHANG ; Yewei YAO ; Caiyuan LIU ; Liya MA ; Zhe ZHENG ; Haojie QIN ; Xinmin PAN
Chinese Journal of Forensic Medicine 2025;40(4):405-410
Objective To analyze the characteristics,causes,influencing factors of compensation,and appraisal features of second-instance medical malpractice cases involving cardiovascular diseases in Henan Province from 2017 to 2022,and to provide reference for forensic appraisal and judicial trial.Methods Cases were retrieved from China Judgments Online between 2017 and 2022.A total of 1,957 documents were reviewed,including 1,397 medical malpractice cases and 130 cardiovascular disease cases.Results The total compensation awarded in these second-instance cases was 27.04 million yuan,with a median of 158,600 yuan.Cases involving patient death accounted for 80.00%(104/130).Among 107 cases with first-instance appraisals,55.14%(59/107)raised objections,while 74.62%(97/130)of the second-instance trials upheld the original judgment.The most common degree of responsibility borne by medical institutions was secondary responsibility(41.54%,54/130).The top three medical faults were:inadequate observation and management of patient conditions(46.15%),omission of auxiliary examinations(37.50%),and insufficient notification(36.54%).In terms of violations-including medical record documentation,inappropriate treatment,misdiagnosis or missed diagnosis,out-of-scope practice,and improper medication use-the actual proportions in judgments(24/113,34/113,12/113,7/113,14/113)were all significantly lower than the patients' claims(all P<0.05).Conclusion Cardiovascular medical malpractice cases in second-instance trials involve substantial compensation and a high proportion of death outcomes.Both medical institutions and patients should pay greater attention to first-instance trials.Appraisal organizations should proactively provide explanation and education regarding issues likely to raise patient doubts,thereby reducing unnecessary appeals.They should also avoid hasty revisions of appraisal opinions when faced with objections and instead focus on improving the quality and credibility of appraisals.In determining medical faults,emphasis should be placed on evaluating whether there was inadequate patient monitoring and management,omission of auxiliary examinations,and insufficient notification.
3.Clinical practice of minimally invasive daytime hepatectomy based on enhanced recovery after surgery whole-process management scheme
Jinghao LIN ; Yewei ZHANG ; Qijiang MAO ; Qifang LIU ; Zhaoyang GE ; Hongxia XU ; Renan JIN ; Xiao LIANG
Chinese Journal of Surgery 2025;63(4):331-337
Objective:To explore the clinical effect of the whole-process management scheme of daytime minimally invasive liver resection surgery based on the enhanced recovery after surgery (ERAS) concept.Methods:This is a retrospective case series study. The data of 55 patients who underwent minimally invasive daytime liver resection surgery under the ERAS concept at the Department of General Surgery,Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2023 to August 2024. There were 22 males and 33 females;aged (48.2±15.1) years (range: 16 to 77 years). All patients were classified as Grade 2 according to the American Society of Anesthesiologists physical status classification. Among them, 7 cases were complicated with liver cirrhosis and 10 cases had fatty liver. A multidisciplinary team was formed, consisting of surgeons, anesthesiologists, rehabilitation physicians, psychologists, pharmacists, acute pain management team, operating room nurses, day surgery ward nurses, and ERAS specialized nurses. After strict evaluation by surgeons and anesthesiologists, patients suitable for daytime liver resection surgery were implemented with the ERAS whole-process management plan for liver resection on the basis of routine nursing care.Results:Among the 55 patients, 50 were discharged smoothly within 48 hours, while 5 were transferred to specialized departments for further treatment due to not meeting the discharge criteria, with a smooth daytime discharge rate of 90.9%. Among the 50 patients, 30 underwent laparoscopic surgery and 20 underwent robotic-assisted surgery. The surgery time was (91.6±28.2)minutes(range:45 to 165 minutes), with the intraoperative blood loss of only (30.5±25.5)ml(range:5 to 100 ml). Pathological examination results showed that among the 50 patients, 13 cases had hepatocellular carcinoma, 21 cases had hepatic hemangioma, 4 cases had hepatic cyst, 8 cases had focal nodular hyperplasia, 1 case had low-grade dysplastic nodule, 1 case had hepatolithiasis, 1 case had lymphoma, and 1 case had vascular, fibrous and lymphoid tissue proliferation. There were 44.0% patients who were able to get out of bed on the day of surgery. The hospital stay was (1.8±0.4)days(range:1 to 2 days), and the hospitalization cost was (34 499±20 330)yuan(range:11 724 to 73 488 yuan). No complications requiring special treatment outside the conventional pathway were observed during the hospital stay and follow-up period. At the 2-week outpatient follow-up, no significant abnormalities were found in all patients, and the wound healing was good.Conclusions:The daytime liver resection surgery based on the ERAS whole-process management plan has shown good feasibility in clinical practice. It helps to simplify medical process, shorten hospital stay, and reduce medical costs.
4.Analysis of medical malpractice cases of cardiovascular diseases--A study of second-instance cases in henan province
Mengzhu ZHANG ; Yewei YAO ; Caiyuan LIU ; Liya MA ; Zhe ZHENG ; Haojie QIN ; Xinmin PAN
Chinese Journal of Forensic Medicine 2025;40(4):405-410
Objective To analyze the characteristics,causes,influencing factors of compensation,and appraisal features of second-instance medical malpractice cases involving cardiovascular diseases in Henan Province from 2017 to 2022,and to provide reference for forensic appraisal and judicial trial.Methods Cases were retrieved from China Judgments Online between 2017 and 2022.A total of 1,957 documents were reviewed,including 1,397 medical malpractice cases and 130 cardiovascular disease cases.Results The total compensation awarded in these second-instance cases was 27.04 million yuan,with a median of 158,600 yuan.Cases involving patient death accounted for 80.00%(104/130).Among 107 cases with first-instance appraisals,55.14%(59/107)raised objections,while 74.62%(97/130)of the second-instance trials upheld the original judgment.The most common degree of responsibility borne by medical institutions was secondary responsibility(41.54%,54/130).The top three medical faults were:inadequate observation and management of patient conditions(46.15%),omission of auxiliary examinations(37.50%),and insufficient notification(36.54%).In terms of violations-including medical record documentation,inappropriate treatment,misdiagnosis or missed diagnosis,out-of-scope practice,and improper medication use-the actual proportions in judgments(24/113,34/113,12/113,7/113,14/113)were all significantly lower than the patients' claims(all P<0.05).Conclusion Cardiovascular medical malpractice cases in second-instance trials involve substantial compensation and a high proportion of death outcomes.Both medical institutions and patients should pay greater attention to first-instance trials.Appraisal organizations should proactively provide explanation and education regarding issues likely to raise patient doubts,thereby reducing unnecessary appeals.They should also avoid hasty revisions of appraisal opinions when faced with objections and instead focus on improving the quality and credibility of appraisals.In determining medical faults,emphasis should be placed on evaluating whether there was inadequate patient monitoring and management,omission of auxiliary examinations,and insufficient notification.
5.Clinical practice of minimally invasive daytime hepatectomy based on enhanced recovery after surgery whole-process management scheme
Jinghao LIN ; Yewei ZHANG ; Qijiang MAO ; Qifang LIU ; Zhaoyang GE ; Hongxia XU ; Renan JIN ; Xiao LIANG
Chinese Journal of Surgery 2025;63(4):331-337
Objective:To explore the clinical effect of the whole-process management scheme of daytime minimally invasive liver resection surgery based on the enhanced recovery after surgery (ERAS) concept.Methods:This is a retrospective case series study. The data of 55 patients who underwent minimally invasive daytime liver resection surgery under the ERAS concept at the Department of General Surgery,Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2023 to August 2024. There were 22 males and 33 females;aged (48.2±15.1) years (range: 16 to 77 years). All patients were classified as Grade 2 according to the American Society of Anesthesiologists physical status classification. Among them, 7 cases were complicated with liver cirrhosis and 10 cases had fatty liver. A multidisciplinary team was formed, consisting of surgeons, anesthesiologists, rehabilitation physicians, psychologists, pharmacists, acute pain management team, operating room nurses, day surgery ward nurses, and ERAS specialized nurses. After strict evaluation by surgeons and anesthesiologists, patients suitable for daytime liver resection surgery were implemented with the ERAS whole-process management plan for liver resection on the basis of routine nursing care.Results:Among the 55 patients, 50 were discharged smoothly within 48 hours, while 5 were transferred to specialized departments for further treatment due to not meeting the discharge criteria, with a smooth daytime discharge rate of 90.9%. Among the 50 patients, 30 underwent laparoscopic surgery and 20 underwent robotic-assisted surgery. The surgery time was (91.6±28.2)minutes(range:45 to 165 minutes), with the intraoperative blood loss of only (30.5±25.5)ml(range:5 to 100 ml). Pathological examination results showed that among the 50 patients, 13 cases had hepatocellular carcinoma, 21 cases had hepatic hemangioma, 4 cases had hepatic cyst, 8 cases had focal nodular hyperplasia, 1 case had low-grade dysplastic nodule, 1 case had hepatolithiasis, 1 case had lymphoma, and 1 case had vascular, fibrous and lymphoid tissue proliferation. There were 44.0% patients who were able to get out of bed on the day of surgery. The hospital stay was (1.8±0.4)days(range:1 to 2 days), and the hospitalization cost was (34 499±20 330)yuan(range:11 724 to 73 488 yuan). No complications requiring special treatment outside the conventional pathway were observed during the hospital stay and follow-up period. At the 2-week outpatient follow-up, no significant abnormalities were found in all patients, and the wound healing was good.Conclusions:The daytime liver resection surgery based on the ERAS whole-process management plan has shown good feasibility in clinical practice. It helps to simplify medical process, shorten hospital stay, and reduce medical costs.
6.The application of improved team-based learning based on the training goal of excellent doctors in ophthalmology internship class
Dan WEN ; Yanyan FU ; Weitao SONG ; Wei ZHENG ; Jia TAN ; Dan LIU ; Yewei YIN ; Zhipeng XUE ; Xiaobo XIA
Chinese Journal of Medical Education Research 2023;22(5):665-669
Objective:To evaluate the effect of the improved team-based learning (TBL) teaching method in the undergraduate probation course of ophthalmology based on the goal of cultivating excellent doctors.Methods:The undergraduates of clinical medicine were randomly divided into experimental group and control group. The control group ( n=50) was given conventional ophthalmology probation teaching, while the experimental group ( n=50) was given ophthalmology probation teaching of improved TBL teaching method. The theoretical examination performance and skill assessment results of students in the two groups were compared, and the subjective evaluation of the students on the teaching was also compared. SPSS 23.0 was used to conduct t-test and Wilcoxon's rank sum test. Results:The theoretical examination performance of experimental group (29.68±4.52) was better than that of control group (27.84±4.33), with significant differences ( P<0.05); the skill assessment results of experimental group (32.88±5.05) were also better than those of the control group (30.88±6.99), with significant differences ( P<0.05); the subjective evaluation of teaching effect in each item of experimental group was better than that of control group ( P<0.05). Conclusion:The improved TBL teaching method can not only improve students' theoretical knowledge and experimental skills, but also improve students' self-study and teamwork ability, which will provide a feasible educational reform plan for achieving the goal of cultivating excellent doctors.
7.Analysis of the disease types of 454 patients with epilepsy in southern Sichuan
Pingping DENG ; Yewei XIAO ; Mei LIU ; Hada S SUSHANT ; Xuntai MA
Journal of Chinese Physician 2019;21(8):1160-1163,1167
Objective To analyze the distribution of disease types of the epilepsy patients in southern Sichuan,and to provide guidances for the clinical diagnosis and treatment of epilepsy.Methods The complete medical records of inpatients with epilepsy in southern Sichuan who were clearly diagnosed in the Affiliated Hospital of Southwest Medical University from August 2014 to July 2017 were collected and sorted,and classified according to the latest revision of the epilepsy disease standard of the International AntiEpilepsy Alliance in 2017,and the distribution of disease types of these patients were statistically analyzed.Results A total of 454 patients with epilepsy were included in the study,with a male to female ratio of 1.54∶ 1,and the average age is (39.38 ±22.38) years.There were 71 patients under 15 years old,139 cases from 15 years old to 40 years old,189 cases from 41 years old to 65 years old,and 55 cases from over 65 years old.The patients in all ages were mainly classified as generalized onset,and the patients with different origins were mainly motor seizures.The focal onset were most common in the patients with epileptiform spasm from 40 days to 14 years old.The patients of generalized onset were mostly tonic-clonic seizures and under 65 years old.And the patients of unknown onset were mainly concentrated in 15-65 years old and mainly epileptic spasms.Conclusions Most of the patients with epilepsy in southern Sichuan are middle-aged and elderly,and the patients of all ages of different origins are mainly motor seizure,and the distribution of disease types of these patients are different.Moreover,the tonic-clonic seizure and epileptiform spasm are the most common types in these patients.
8.Clinical effect of Zhanjinhuoxue Formula combined tower-type pad natural traction for treating pure thoracolumbar compression fracture
Yewei LIU ; Yuxiang ZHANG ; Xiaosong HUANG ; Xiangnan SHEN
Chongqing Medicine 2017;46(9):1246-1248
Objective To investigate the clinical effect of Zhanjinhuoxue Formula combined with the tower-type pad natural traction for the treatment of pure thoracolumbar compression fracture.Methods Fifty patients with thoracolumbar compression fractures treated in our hospital from January to December 2014 were selected and divided into the observation group(n=25) and control group(n=25).The control group was given the tower-type natural traction method,while the observation group was given Zhanjinhuoxue Formula combined with the tower-type pad natural traction method.The curative effect,pain score,activity ability score,analgesic drugs score,bone mineral density (BMD) and the Japanese Orthopedic Association(JOA) score were compared between the two groups.Results The effective rate was 92.00% in the observation group and 68.00% in the control group,the difference between the two groups was statistically significant (x2 =4.50,P<0.05).The pain score,activity ability score and analgesic drugs score after 6-month treatment in the observation group were significantly lower than those in the control group (P<0.05);the BMD and JOA scores in the observation group were significantly higher than those in the control group (P<0.05).Condusion Zhanjinhuoxue Formula coordinated by the tower-type pad natural traction method can conduce to alleviate the pain symptom in the patients with pure thoracolumbar compression fracture,increases the movement function and improves the treatment effect.
9.Application of lymphography in the location and treatment decision of chyle leakage: an analysis of 177 cases.
Dingyi LIU ; Weimu XIA ; Qi TANG ; Jian WANG ; Mingwei WANG ; Chongyu ZHANG ; Wenlong ZHOU ; Jianxin SHI ; Qianjun ZHOU ; Heng ZHANG ; Yewei XIE ; Yuan SHAO
Chinese Journal of Surgery 2016;54(4):281-285
OBJECTIVETo identify the value of lymphography in the location and treatment decision of chyle leakage.
METHODSThe clinic data of 177 patients suffered from chyle leakage admitted in 6 medical centers in Shanghai from February 1998 to December 2014 was analyzed retrospectively. There were 94 male and 83 female patients aging from 9 to 84 years with a mean of 49 years, including 128 cases of chyluria, 34 cases of primary chylothorax and 15 cases of other chyle leakage. All patients had failed to conservative treatment more than 2 weeks. Pedal lymphography was performed in every patient to investigate the site and range of chyle leakage. Effect of surgical or conservative management was compared according to the different results of lymphography.
RESULTSNo serious complication was noticed. For all 177 patients, lymphography showed localized lymphatic diseases in 148 cases (83.6%), including 125 cases of lymphatic renal pelvic leaks, 14 cases of unilateral identified leak within thorax and 9 cases of chyle leakage in neck, heart, abdomen or scrotum. Among these patients, surgical treatment cured 129 and improved 3 patients but failed in 2 patients, while the remaining 14 cases had their leaks decreased after lymphography and cured by conservative management. For those 15 patients having disseminated lymphatic diseases or 14 with no abnormality under lymphography, surgery only cured 2 and improved 1 patient but failed in 8 patients (with 3 death), whereas continuous conservative treatment cured 11 patients, improved 5 patients but only failed in 2 patients (with one death). For localized leakage, surgical treatment showed better efficacy (98.5% vs. 3/11), whereas conservative treatment had significantly higher successful rate than surgical interventions in patients with disseminated lymphatic diseases or no abnormality under lymphography (16/18 vs. 3/11).
CONCLUSIONSLymphography could identify the location and range of complicate chyle leakage failed to primary conservative management. Patients with disseminated lymphatic diseases or no abnormality under lymphography would be better managed by continuous non-operative treatment partly due to therapeutic effect of lymphography, while surgical intervention could be a good option for patients having localized lymphatic etiology.
Abdominal Cavity ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Chyle ; Chylothorax ; diagnosis ; surgery ; Female ; Heart ; Humans ; Kidney Pelvis ; Lymphatic Diseases ; Lymphography ; Male ; Middle Aged ; Neck ; Retrospective Studies ; Scrotum ; Young Adult
10.Inhibition of SIRT6 in prostate cancer reduces cell viability and increases sensitivity to chemotherapeutics.
Yewei LIU ; Qian Reuben XIE ; Boshi WANG ; Jiaxiang SHAO ; Tingting ZHANG ; Tengyuan LIU ; Gang HUANG ; Weiliang XIA
Protein & Cell 2013;4(9):702-710
SIRT6 is an important histone modifying protein that regulates DNA repair, telomere maintenance, energy metabolism, and target gene expression. Recently SIRT6 has been identified as a tumor suppressor and is down-regulated in certain cancer types, but not in other cancers. From deposited gene profiling studies we found that SIRT6 was overexpressed in prostate tumors, compared with normal or paratumor prostate tissues. Tissue micro-array studies confirmed the higher levels of SIRT6 in both prostate tumor tissues and prostate cancer cells than in their normal counterparts. Knockdown of SIRT6 in human prostate cancer cells led to sub-G1 phase arrest of cell cycle, increased apoptosis, elevated DNA damage level and decrease in BCL2 gene expression. Moreover, SIRT6-deficiency reduced cell viability and enhanced chemotherapeutics sensitivity. Taken together, this study provides the first evidence of SIRT6 overexpression in human prostate cancer, and SIRT6 regulation could be exploited for prostate cancer therapy.
Apoptosis
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Cell Cycle Checkpoints
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Cell Line, Tumor
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Cell Proliferation
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Cell Survival
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DNA Damage
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Drug Resistance, Neoplasm
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Gene Knockdown Techniques
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Humans
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Male
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Prostatic Neoplasms
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genetics
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pathology
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therapy
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Proto-Oncogene Proteins c-bcl-2
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metabolism
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Sirtuins
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antagonists & inhibitors
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genetics
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metabolism
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Up-Regulation

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