1.Expression and significance of Twist protein in colorectal cancer
Weijie ZHANG ; Xiaowu CHEN ; Dajian ZHU ; Manzhao OUYANG ; Qiang ZHONG ; Changchun LIU
Chinese Journal of Digestive Surgery 2015;14(5):410-414
Objective To explore the expression of Twist protein in the colorectal cancer (CRC) and its relationship between clinicopathological factors and prognosis of patients.Methods The clinical data of 45 patients with colorectal cancer who were admitted to the First People's Hospital of Shunde from June 2005 to September 2005 were retrospectively analyzed.The colorectal tissue specimens from surgical resection were collected.The expressions of Twist protein in the cancer and paracarcinoma tissues were examined by the immunohistochemistry,and their relationship with clinicopathological factors and prognosis of patients was analyzed.Patients were followed up by outpatient examination and telephone interview until September 2013.The count data were analyzed using the chi-square test and Fisher exact probability.The survival curve was generated using the Kaplan-Meier method,and the survival analysis was conducted using the Log-rank test.The prognosis factors were analyzed by the COX univariate analysis and multivariate analysis.Results The expression of Twist protein in CRC was predominantly detected in the cytoplasm of the tumor cells.The positive expression rates of Twist protein in the CRC and paracarcinoma tissues were 62.2% (28/45) and 20.0% (9/45),respectively,with a significant difference (x2 =18.383,P <0.05).The positive expression rates of Twist protein were 42.1% in patients with Ⅰ-Ⅱ stage of CRC and 76.9% in patients with Ⅲ-Ⅳ stage of CRC.The positive expression rates of Twist protein were 41.7%in patients with N0 stage of CRC and 85.7% in patients with N1-N2 stage of CRC.The expression of Twist protein in patients with CRC was however associated with the TNM stage and lymph node metastasis (x2=5.662,9.244,P < 0.05).A total of 45 patients were followed up for 10-96 months (median,54 months).The median survival time and 5-year cumulative survival rate in 45 patients with positive expression of Twist protein were 44 months and 10.7%,which were compared with 69 months and 82.4% in 45 patients with negative expression of Twist protein,with a statical significance in the survival (x2 =26.147,P < 0.05).The results of univariate analysis showed that the expression of Twist protein was an related factor affecting the prognosis of patients [HR =8.669,95% confidence interval (CI):2.959-25.390,P <0.05].The results of multivariate analysis showed that the positive expression of Twist protein was an independent risk factor affecting the prognosis of patients (HR =5.059,95 % CI:2.888-8.863,P < 0.05).Conclusiors The increasing expression of Twist protein in the CRC is positively correlated with the occurrence and development of CRC.The positive expression of Twist protein is an independent risk factor affecting the prognosis of patients with CRC.
2.Design, synthesis and biological study of BTK/JAK3 dual-target inhibitors
Lifang CEN ; Ming CHENG ; Weijie REN ; Liu YE ; Luhua WANG ; Weibo GUO ; Qiang ZHANG ; Yungen XU
Journal of China Pharmaceutical University 2024;55(1):73-86
Abstract: In the present study, the compound XL-12 from our previous work was utilized as a lead compound. Through the optimization of the terminal phenyl ring, 12 target compounds were designed and synthesized. The structures of all target compounds were confirmed by 1H NMR, 13C NMR, and H RMS. In vitro enzyme activity assay showed that most compounds demonstrated significant inhibitory activity toward Bruton’s tyrosine kinase (BTK) and Janus kinase 3 (JAK3). Among them, compound I-3 exhibited moderate cell proliferation inhibitory activity toward Daudi cells and BaF3-JAK3 cells. In the evaluation of anti-inflammatory activity in vitro, compound I-3 could effectively inhibit the production of inflammatory factors IL-6; besides, it exhibited superior anti-inflammatory activity compared to ibrutinib in xylene-induced ear swelling model in mice.
3.Research model of neurodegenerative diseases based on neuroinflammation and its traditional Chinese medicine treatment strategies
Weijie QIANG ; Ying CHEN ; Weiyan CAI ; Qing YANG ; Yujie LI ; Qi LI ; Yajie WANG ; Xiaogang WENG ; Xiaoxin ZHU
Acta Laboratorium Animalis Scientia Sinica 2017;25(4):461-466
Neurodegenerative diseases are threating our health seriously.Inflammation plays an important role in the initiation and development of neurodegenerative diseases, and its primary characteristics are the activation of microglia and the increasing level of inflammation cytokines.This review describes the relationship between neuroinflammation and several neurodegenerative diseases, and the models in vivo and in vitro.In addition, combining with traditional Chinese medicines knowledge of encephalopathy, we summarizes pharmacological effects and mechanisms of multiple herb extracts and monomer compounds in preventing the activation of microglia and inhibiting neuroinflammation, thus, to provide the basis for gradually revealing the related rules and characteristics of treating encephalopathy by traditional Chinese medicine, and improving the accuracy of the clinical drugs, as well as developing new drugs for the prevention and control of encephalopathy.
4.Effects of pre-operative measurement of proximal tibia varus angle on the prediction for condylar twist angle in total knee arthroplasty
Qiang HE ; Jianbing MA ; Xiangxiang SUN ; Lin XIAO ; Guanghui ZHAO ; Xi WANG ; Kuo JIANG ; Hui LI ; Weijie ZHANG
Chinese Journal of Orthopaedics 2017;37(19):1216-1222
Objective To assess the effects of pre-operative measurement of proximal tibia varus angle (PTA) on predicting condylar twist angle (CTA) in total knee arthroplasty (TKA).Methods The CT-scan of lower limb was performed in sixty-one health female volunteers aged 31.5 (18-38) years with 160 (153-170) cm heights from March 2016 to August 2016.The PTA,medial proximal tibial angle (MPTA) and CTA were determined.The PTA was defined between a line perpendicular to the mechanical axis of the tibia and the tangent on the internal tibial plateau.The MPTA was the medial angle between the mechanical axis of the tibia and the tangent on the internal tibial plateau.The CTA was the angle between the sTEA and the posterior condylar line.The correlations between these parameters were analyzed statistically by linear regression.Results The PTA,MPTA and CTA parameters were conformed to the normal distribution.The PTA was 2.30°± 1.86°,ranged from 1.40° to 6.50°.The MPTA was 87.7°± 1.86°,ranged from 83.50° to 88.60°.The CTA was 3.4°± 1.27°,ranged from 0.50° to 5.80°.The linear regression analysis showed a strong positive correlation between the CTA and PTA in health female knees (r=0.58,P=0.048),while negative correlation was found between the CTA and MPTA in health female knees (r=-0.58,P=0.048).There were fifty-two (85.2%) volunteers with PTA that was more than 2° and less than 4°.Six (9.8%) volunteers had PTA less than 2°,while three (4.9%) had PTA more than 4°.There were eight (13.1%) volunteers with CTA less than 3°.Forty-three (70.5%) volunteers had CTA more than 3° and less than 4°.CTA more than 4° was found in ten volunteers (16.4%).Based on these above results,two formulas were demonstrated for predicting the CTA:CTA=2.52+0.395PTA,CTA=38.06-0.390MPTA.Conclusion The CTA can be predicted by calculating the PTA by CT-scan and standard long-leg standing radiographs before TKA.Using the present method could reduce the risk of femur component malrotation and the flexion gap balancing during TKA.
5.Surgical treatment for knee osteoarthritis subsequent to previous femur fractures
Qiang HE ; Caihong SUN ; Jianbing MA ; Lin XIAO ; Xiangxiang SUN ; Hui LI ; Weijie ZHANG
Chinese Journal of Orthopaedics 2018;38(7):411-417
Objective To investigate the indications and clinical outcomes of total knee arthroplasty or osteotomy for knee osteoarthritis subsequent to previous femur fractures.Methods Six patients (three male and three female) with knee osteoarthritis subsequent to previous femur fractures were analyzed retrospectively between February 2006 and February 2017.The average age of patients was 58.2± 10.3 years old,ranged from 51 to 79 years.Four patients underwent total joint replacement and two underwent osteotomy.The average age of patients in joint replacement group was 60.5±12.3 years old.The age of the two patients in the osteotomy group was 51 and 55 years old,respectively.The extra-articular deformity angle of the coronal plane of the femur,lateral distal femur angle of mechanical axis,hip-knee-ankle angle (HKA) of preoperative and postoperative were determined on long-standing radiography.The mean angle of the extra-articular deformity in the joint replacement group was 17.0±7.7 degrees.The angle of the extra-articular deformity in the osteotomy group was 34 and 20 degrees.Lateral distal femur angle of mechanical axis in the joint replacement group was within the range of 87±7 degrees.Lateral distal femur angle of mechanical axis in the osteotomy group was out of the range of 87±7 degrees.The mean preoperative HKA of the joint replacement group was 161.8±8.0 degrees.The preoperative HKA of the osteotomy group was 155 and 160 degrees,respectively.Knee function was estimated according to knee range of motion and Knee Society Score (KSS).The results of postoperative hip-knee-ankle angle,knee range of motion (ROM) and knee society score were compared between the two groups.Results The mean HKA of the joint replacement group reached 176.0±2.8 degrees at one year postoperatively.The HKA of the osteotomy group improved to 177 and to 175 degrees at one year postoperatively.The average preoperative knee ROM improved significantly from 71 ± 16 degrees preoperatively to 113 ±5degrees postoperatively.The mean knee ROM of the joint replacement group was 113.0±6.8 degrees.The knee ROM of two patients in the osteotomy group was 110 and 115 degrees,respectively.The average preoperative KSS score improved significantly from 46±3 preoperatively to 88±3 postoperatively.The mean KSS of the joint replacement group was 88.8±3.0,while the KSS of the osteotomy group was 85 and 82.No bone nonunion was observed in the two patients in osteotomy group.Conclusion For patients with knee osteoarthritis subsequent to previous femur fractures,satisfactory short-term clinical outcomes could be obtained by total knee arthroplasty or osteotomy with the strict selection of proper operative indications.
6.Regulatory effect of a Chinese medicine Wuji Pill ( WJW) on brain-gut peptides in the rats of post-inflammatory irritable bowel syndrome
Hefei HUANG ; Weijie QIANG ; Qing YANG ; Yujie LI ; Xiaogang WENG ; Yajie WANG ; Qi LI ; Weiyan CAI ; Tao CHEN ; Xiaoxin ZHU ; Ying CHEN
Acta Laboratorium Animalis Scientia Sinica 2018;26(3):265-271
Objective To explore the biological indicators of diagnosis and treatment of irritable bowel syndrome (IBS), and to explore the mechanism of action of a Chinese medicine Wuji Pill (WJW) on irritable bowel syndrome (IBS). Methods (1) Postinflammatory irritable bowel syndrome (PI-IBS) rat model was established by acetic acid plus restraint stress method . (2) The colonic motor ability of rats was evaluated by colon motility index (MI), the number of fecal particles discharged within 2 h, and the time of glass pellet discharge. (3) The formation of PI-IBS model rats and the therapeutic effect of WJW were observed. (4) The levels of calcitonin gene-related peptide (CGRP), motilin (MTL), neuropeptide Y (NPY), substance P (SP), somatostatin (SS), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK) in the brain and colon tissues of PI-IBS rats were measured by ELISA. Results (1) The rat PI-IBS model was successfully established. Compared with the normal group, the body weight of the model rats was decreased, the food intake decreased, the amount of feces increased, loose stools and amorphous soft stools appeared, voluntary movements decreased, colon motility index ( MI) significantly increased ( P < 0. 05 ), the number of fecal particles discharged significantly increased ( P< 0. 05), and the glass pellet discharge time was significantly shortened ( P < 0. 05). (2) WJW treatment for 7 days significantly improved a variety of symptoms. Compared with the normal control, the levels of CGRP, SS and VIP in the brain tissue of PI-IBS rats were significantly increased (P< 0. 05), and the NPY concentration was significantly decreased ( P < 0. 05). However, the treatment with WJW significantly reduced CGRP, SS and VIP levels (P< 0. 05), and significantly increased the NPY concentration level (P < 0. 05). (3) Compared with the normal control group, the levels of CCK, NPY, MTL, SS and VIP in colonic tissues of PI-IBS rats were significantly decreased (P< 0. 05), while WJW significantly increased the CCK and VIP levels. Conclusions WJW can be used to treat IBS by regulating the levels of various brain-gut peptides in the brain and colon tissues of IBS rats. These anomalous and adjustable brain-gut peptides may become a potential biomarker for the diagnosis and treatment of IBS.
7.Survey on status of perioperative aspirin use in thoracic surgery in China
Yingze NING ; Weijie ZHU ; Yang HAO ; Dong LI ; Huayu HE ; Jizheng TANG ; Songlei OU ; Chaoyang LIANG ; Guangliang QIANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(11):680-684
Objective:To understand the current status of the use of aspirin in perioperative period of thoracic surgery in China and the awareness of thoracic surgeons on the prevention and treatment of arterial thromboembolic diseases during the perioperative period.Methods:A survey was conducted among thoracic surgeons nationwide using an electronic questionnaire through a software platform from January 20, 2024 to February 29, 2024. The questionnaire mainly included three parts: basic information, aspirin use, and awareness of arterial thromboembolic diseases, with a total of 27 questions.Results:A total of 1318 valid questionnaires were collected, covering all 33 provincial administrative regions except Taiwan. 69.7%(919/1 318) of thoracic surgeons stopped using aspirin for all patients before surgery; differences could be found in the timing of aspirin withdrawal before surgery and resumption after surgery. 65.1%(858/1 318) of surgeons made perioperative medication decisions based on domestic guidelines or consensus, while 20.9%(276/1 318) of surgeons based their decisions on departmental or personal experience. 87.9%(1 159/1 318) of surgeons believed that it is necessary to develop guidelines for the prevention of arterial thromboembolic diseases in the perioperative period of thoracic surgery.Conclusion:The current use strategy of aspirin in the perioperative period of thoracic surgery in China shows a high degree of inconsistency, and there are also significant differences in the awareness of arterial thromboembolic diseases. It is necessary to establish guidelines for the prevention and treatment of arterial thromboembolic diseases in the perioperative period.
8.A randomized controlled trial to evaluate efficacy and safety of early conversion to a low-dose calcineurin inhibitor combined with sirolimus in renal transplant patients
Xiang ZHENG ; Weijie ZHANG ; Hua ZHOU ; Ronghua CAO ; Zhangfei SHOU ; Shuwei ZHANG ; Ying CHENG ; Xuchun CHEN ; Chenguang DING ; Zuofu TANG ; Ning LI ; Shaohua SHI ; Qiang ZHOU ; Qiuyuan CHEN ; Gang CHEN ; Zheng CHEN ; Peijun ZHOU ; Xiaopeng HU ; Xiaodong ZHANG ; Ning NA ; Wei WANG
Chinese Medical Journal 2022;135(13):1597-1603
Background::The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.Methods::Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.Conclusion::The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.Trial registration::Chinese Clinical Trial Registry, ChiCTR1800017277.