1.Research advances on chimeric antigen receptor cellular therapy for hepatocellular carcinoma
Jie SHEN ; Jiacheng ZHANG ; Jia YU ; Youming DING
Chinese Journal of Hepatobiliary Surgery 2022;28(3):230-233
Hepatocellular carcinoma is one of the most common cancers and causes of cancer-related death in the world, the insidious onset, rapid progression and poor prognosis make the treatment more difficult. At present, the current therapeutic options, include surgical resection, ablation, postoperative recurrenceare still with disadvantages. The efficacy of targeted drug therapy is also unsatisfactory. Immunotherapy is a promising research direction. Immunosuppressants at the molecular level have shown initial success, while adoptive immunocell therapy at the cellular level has also shown promising results, the typical example is chimeric antigen receptor cell therapy. The purpose of this review is to summarize the recent research progress on chimeric antigen receptor cellular therapy in liver cancer.
2.Risk assessment of investigator initiated trials at the proposal stage
Wenwen LYU ; Tingting HU ; Weituo ZHANG ; Tiantian QU ; Enlu SHEN ; Jiacheng DUAN ; Zhe SUN ; Jian WANG ; Biyun QIAN
Chinese Journal of Hospital Administration 2021;37(11):927-931
Objective:To assess possible risk factors and their respective levels in the whole process of investigator initiated trial(IIT)projects proposed in the proposal stage, for reference in formulation of risk management plans.Methods:Through literature analysis and research group discussions, the risk factors of IIT projects and risk level assessment criteria were preliminarily identified, and a consultation questionnaire was developed as a result. Delphi method was used to further optimize the risk factors and determine their risk levels. Data obtained from the consulfation were analysied by descriptive.Results:The recovery rates of two rounds of expert consultation were both 100%, and the degree of expert authority was 0.942. The survey finalized 38 risk factors, including extremely high risk, high risk, medium risk, low risk and very low risk factors of 17(44.7%), 15(39.5%), 3(7.9%), 2(5.3%) and 1(2.6%) respectively.Conclusions:This study determined a risk evaluation system of IIT projects in the proposal stage. This system can identify risks of IIT projects at an early stage, facilitating early intervention of problems existing in such projects, and minimize risks to the rights and safety of patients.
3.Discussions on risk-based quality management of investigator initiated trials
Wenwen LYU ; Tingting HU ; Jiayuan JIANG ; Weituo ZHANG ; Tiantian QU ; Enlu SHEN ; Jiacheng DUAN ; Tienan FENG ; Biyun QIAN
Chinese Journal of Hospital Administration 2022;38(7):525-529
Effective supervision of the clinical research management department can guarantee and improve the quality of the investigator initiated trials(IIT). The authors analyzed relevant clinical research regulations and literature and summarized the current situation of risk-based IIT project process quality management. On such basis, they determined the risk-based IIT project process quality management method in combination with the previous research of the research group.From 2021 to 2022, this method was used to implement process quality management for 353 IIT projects in Shanghai′s tertiary hospitals. More than 3 000 risk points were identified through centralized supervision, and then on-site supervision was carried out to correct the problems found. As proven by the results, the method could find existing problems in time and define the risk level of the project, and also formulate an individualized risk supervision plan accordingly, so as to effectively ensure the data reliability and scientific results. It is suggested that the clinical research management department implement risk based management for the whole process of IIT projects, increase funding and staffing, and implement hierarchical management for the projects by research types, so as to promote the sustainable development of IITs.
4.Perioperative localization of ectopic functioning parathyroid gland in patients with hyperparathyroidism
Teng ZHAO ; Bojun WEI ; Xing LIU ; Hong SHEN ; Jiacheng WANG ; Qian WANG ; Yunhui XIN
Chinese Journal of General Surgery 2021;36(6):446-450
Objective:To investigate the value and influence factors of preoperative and intraoperative localization of ectopic hyperparathyroidism (EHPT).Methods:Results of 99mTc-sestamibi ( 99mTc-MIBI), neck ultrasound, contrast CT and intraoperative local venous parathyroid hormone (IOLVPTH) were retrospectively analyzed in 205 patients with primary hyperparathyroidism (PHPT) suspected of EHPT. Results:Incidence of EHPT was 16.6% (34 cases), and 36 ectopic lesions were detected. The proportion of EHPT in antero-superior mediastinum, intrathyroidal, in the retropharyngeal region, in carotid sheath, in the prevertebral region and intrapericardial were 44.1% (15 cases), 29.4% (10 cases), 11.8% (4 cases), 5.9% (2 cases), 5.9% (2 cases) and 2.9% (1 cases), respectively. Contrast CT was the most sensitive (86.1%, 31 lesions/36 lesions) for EHPT, followed by 99mTc-MIBI (66.7%, 24 lesions/36 lesions), IOLVPTH monitoring (61.8%, 21 lesions/34 lesions) and neck ultrasound (55.6%, 20 lesions/36 lesions). Contrast CT was most sensitive,100% in detecting deep-located EHPT lesions, whereas IOLVPTH had advantages in detecting intrathyroidal EHPT lesions, with a sensitivity of 100.0%.The combined use of 99mTc-MIBI and neck ultrasound showed a sensitivity of 77.8% in the localization of EHPT. Conclusions:Contrast CT is highly sensitive in the localization of EHPT. The combined use of preoperative imaging and IOLVPTH monitoring helps to higher localization for EHPT.
5.Analyses of risk factors for temporarily inhibited parathyroid hormone secretion of postoperative primary hyperparathyroidism
Xing LIU ; Teng ZHAO ; Jiacheng WANG ; Hong SHEN ; Qian WANG ; Yunhui XIN ; Bojun WEI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2020;55(5):497-500
Objective:To study relative risk factors for temporarily inhibited parathyroid hormone (PTH) secretion after surgery of primary hyperparathyroidism (PHPT).Methods:Seventy-two cases with PHPT from October 2017 to March 2019 in Beijing Chaoyang Hospital were analyzed retrospectively, including 22 males and 50 females aged from 13 to 83 years old. They were reviewed and divided into a complete inhibition group (24 cases, PTH=0 pg/ml), an incomplete inhibition group (23 cases, 0
6.Application of mobile health education platform in continuous nursing for rectal cancer patients with preventive colostomy
Lin SUN ; Hanhui YAO ; Jiacheng WANG ; Hailing ZHANG ; Minjing SHEN ; Jing LU
Chinese Journal of Modern Nursing 2019;25(16):2019-2023
Objective? To investigate the effect of mobile health education platform in the continuous nursing after discharge for rectal cancer patients with preventive colostomy. Methods? From January to December 2017, 60 rectal cancer patients with preventive colostomy in the Department of Gastrointestinal Surgery in the First Affiliated Hospital of University of Science and Technology of China were selected as the subjects by convenient sampling. Patients were divided into two groups: observation group (n=30) and control group(n=30). The control group received regular health education and continuous nursing care of telephone follow-up after discharge, apart from which the observation group received nursing care based on the mobile health education platform. One month after discharge, the two groups were compared in terms of the effects of intervention by the use of Colostomy Patient Colostomy Knowledge Attitude and Practice Scale (CPCKAPS),Ostomy Adjustment Inventory(OAI),and Patients' Satisfactory Questionnaire. Results? One month after surgery, the observation group were higher than the control group in the " knowledge on stoma care(11.80±3.13)", "health belief(51.70±11.72)" and "health behavior (31.73±7.19)"with statistical significances (t=3.76, 2.90, 3.05;P< 0.05). There were statistical significance in the score of OAI between the observation group (43.23±11.90) and the control group (37.43±6.33); the observation group was higher than the control group in the "overall satisfaction degree towards continuous care" (76.67% vs. 43.33%) with statistical significance(χ2=7.69,P< 0.05). Conclusions? Compared with conventional continuous nursing mode, continuous nursing based on mobile health education platform can improve the knowledge, belief and behavior of colostomy care for rectal cancer patients with preventive colostomy, and improve the patients'adaptability on colostomy, as well as their satisfaction.
7.Preparation of Bama miniature pig model of diabetic cardiomyopathy
Shuang YAO ; Yanming SHEN ; Ping YU ; Renmei JIANG ; Caimei WANG ; Disha ZOU ; Minjuan TANG ; Xiaoling LIU ; Rufen MO ; Jiacheng SHI ; Qian HUANG ; Jian YU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2019;26(5):573-576
Objective To observe the changes and significance of the protein expression levels of nuclear factor-κB p65 (NF-κB p65), transforming long factor-β1 (TGF-β1) and apoptosis-related factors Bcl-2 and Bax in myocardial tissue of Bama miniature pig model of diabetic cardiomyopathy (DCM). Methods Ten healthy male Guangxi Bama miniature pigs, aged 4 to 5 months old, were selected and divided into control group and model group according to the random number table method, with 5 pigs in each group. After 12 hours of fasting in the two groups, the DCM model was replicated by intravenous injection of streptozotocin (STZ) 150 mg/kg; for the Bama miniature pigs in the control group, citric acid-sodium citrate buffer 150 mg/kg was injected intravenously. After 10 months of modeling, the basic conditions of the two groups of animals were observed and their fasting blood glucose (FPG) levels were detected. The protein expression levels of NF-κB p65, TGF-β1, Bcl-2 and Bax in myocardial tissue of two groups were detected by Western Blot and the pathological changes of myocardial tissue were observed under electron microscope. Results In the model group, 4 models were successfully established, and 1 died. The model pigs had symptoms such as polydipsia, polyphagia, polyuria and decreased body weight. The FPG level in the model group was significantly higher than that in the control group (mmol/L: 25.53±3.75 vs. 4.68±0.77, P < 0.01). Compared with the control group, the protein expression levels of NF-κB p65, Bax and TGF-β1 in the myocardial tissue of model group were significantly increased (NF-κB p65/GAPDH: 0.46±0.05 vs. 0.38±0.02, Bax/GAPDH: 0.46±0.01 vs. 0.35±0.01, TGF-β1/GAPDH: 0.39±0.01 vs. 0.33±0.01, all P < 0.05) and the expression level of Bcl-2 protein was significantly decreased (Bcl-2/GAPDH: 0.33±0.01 vs. 0.42±0.01, P < 0.01). Electron microscopy results showed that the myofibrils of myocardial tissue in the DCM model group were disordered, and the number of mitochondria in the gap was significantly reduced. A large number of mitochondria with vacuolar degeneration were observed. Conclusions The DCM model of Bama miniature pigs can be successfully replicated after 10 months of high-dose STZ disposable ear vein injection. The DCM model miniature pigs have obvious glucose metabolism disorder, and their myocardial tissue has inflammatory reaction, cardiomyocyte apoptosis and fibrosis.
8.Terpene extract from the stem of Celastrus orbiculatus inhibits actin cytoskeleton remodelling in gastric cancer cells by regulating the protein interaction between PTBP1 and ACTN4
Chu ZEWEN ; Zhu MIAO ; Luo YUANYUAN ; Hu YAQI ; Feng XINYI ; Shen JIACHENG ; Wang HAIBO ; Sunagawa MASATAKA ; Liu YANQING
Journal of Pharmaceutical Analysis 2024;14(8):1158-1175
Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effects,drug resistance,and limited improvements in survival and quality of life.Therefore,it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity.In previous studies,the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity;however,the specific mechanism was unclear.Our research utilising co-immunoprecipitation-mass spectrometry(Co-IP-MS),polypyrimidine tract binding protein 1(ptbp1)clustered regularly interspaced short palindromic repeat-associated protein 9(Cas9)-knockout(KO)mouse model,tissue microarray,and functional experiments suggests that alpha actinin-4(ACTN4)could be a significant biomarker of GC.PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4.Celastrus orbiculatus stem extract(COE)may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4,thereby exerting anti-GC effects.
9.Locking compression plating for treatment of periprosthetic distal femur fractures in the aged
Yake LIU ; Zhenyu ZHOU ; Ran TAO ; Yi CAO ; Jianwei ZHU ; Youhua WANG ; Yue LU ; Hua XU ; Jiacheng XU ; Hongdong MA ; Jining SHEN ; Fengxiang ZHAO ; Kefan WU ; Fan LIU
Chinese Journal of Orthopaedic Trauma 2024;26(9):790-796
Objective:To explore the clinical outcomes of locking compression plating (LCP) in the treatment of periprosthetic fracture (PPF) of the distal femur in the aged patients.Methods:A retrospective study was performed to analyze the 31 aged patients who had been treated at Department of Orthopedic Surgery, The Affiliated Hospital to Nantong University for PPF of the distal femur with LCP between June 2012 and May 2023. There were 27 females and 4 males with an age of (80.2±6.1) years. According to the Unified Classification System (UCS), 18 PPFs were classified as type Ⅴ.3B1 and 6 PPFs as type Ⅴ.3B2 after total knee arthroplasty and 7 PPFs as type Ⅳ.3C after total hip arthroplasty. The patients were fixated with a lateral single plate in 25 cases, and with lateral and medial dual plates in 6 cases. The surgical time, intraoperative blood loss, hospitalization time, postoperative weight-bearing time, fracture healing time, and knee joint function and complications during follow-up were recorded.Results:For the 25 patients undergoing fixation with a lateral single plate, the surgical time was (58.7±7.9) minutes, the intraoperative blood loss (78.0±15.1) mL, the hospitalization time (6.9±1.6) days, the postoperative weight-bearing time (5.9±1.4) days, and the follow-up time 37 (15, 51) months. For the 6 patients undergoing fixation with lateral and medial dual plates, the surgical time was (186.6±9.8) minutes, the intraoperative blood loss (1,256.7±231.2) mL, the hospitalization time (17.8±3.3) days, the postoperative weight-bearing time (3.6±0.6) days, and the follow-up time 17 (16, 21) months. The fracture healing time was (14.9±2.0) and (18.7±2.6) weeks, respectively, for patients fixed with single and double steel plates. By the scoring criteria of the American Hospital for Special Surgery (HSS), the knee joint function was evaluated at the last follow-up as excellent in 10 cases and as good in 15 cases for the 25 patients undergoing fixation with a lateral single plate, and as good for all the 6 patients undergoing fixation with lateral and medial dual plates. No patient experienced such complications as incision infection, bone nonunion, or internal fixation failure during the follow-up period.Conclusions:LCP fixation can achieve satisfactory outcomes in the treatment of PPF of the distal femur in the aged patients. As fixation with a single lateral femoral plate is suitable for most of the aged patients with PPF of the distal femur, it can be used as the first choice. Fixation with dual plates can provide stronger stability, but its indications should be strictly controlled.
10.Time-effect relationship and molecular mechanism of electroacupuncture for repair of gastric mucosal lesion.
Yuan ZHANG ; Caichun LIU ; Linyu LIAN ; Jiacheng SHEN ; Qida HE ; Jiaolong CHEN ; Fuqiang MA ; Zongbao YANG
Chinese Acupuncture & Moxibustion 2018;38(7):747-752
OBJECTIVETo dynamically observe the effects of electroacupuncture (EA) on repair of gastric mucosal lesion in rats with gastric ulcer, and to explore the time-effect relationship and molecular mechanism of EA for gastric ulcer.
METHODSA total of 72 SD rats were randomly assigned to a normal group, a model group, a acupoint group and a sham acupoint group, and each group were further divided into a 1-day subgroup, a 4-day subgroup and a 7-day subgroup, 6 rats in each subgroup. The rat model of gastric ulcer was established by using intragastric administration of ethyl alcohol. The rats in the acupoint group were treated with EA at"Zusanli"(ST 36) and"Liangmen"(ST 21); the rats in the sham acupoint group were treated with EA at points 5 mm next to"Zusanli"(ST 36) and"Liangmen"(ST 21); the EA was given 30 min per treatment, once a day. The rats in the normal group and model group were treated with immobilization for 30 min per day, and no EA was given. PR-PCR method was applied to test the expression of proliferating cell nuclear antigen (PCNA) and substance P (SP); Western blot method was applied to test the expression of neurotensin (NT).
RESULTSAfter 1-day treatment, the ulcer index in the model group was higher than that in the normal group (<0.01), and the expression of PCNA, SP and NT was decreased (<0.01, <0.05); compared with the model group and sham acupoint group, the ulcer index was decreased in the acupoint group (both <0.05), and the expression of PCNA and SP was up-regulated (all <0.05) while that of NT was up-regulated (both <0.01). After 4-day treatment, the ulcer index in the model group was reduced but still higher than that in the normal group (<0.05), and the expression of PCNA, SP and NT was up-regulated and higher than that in the normal group (all <0.01); the ulcer index in the acupoint group was similar to that in the normal group (>0.05), and the expression of PCNA and SP was lower than that in the model group (<0.01, <0.05), and the expression of NT was not significantly different from that in the model group (>0.05). After 7-day treatment, the differences of indexes above were not significant among the four groups (all >0.05).
CONCLUSIONEA at acupoints of stomach meridian has two-way regulation on PCNA and SP and improve the expression of NT in different pathological state of gastric ulcer, which could further improve the repair of gastric ulcer.