1.Research progress on the role of SHP-2 in tumor-associated macrophages
Xueliang WU ; Jianchun FAN ; Fei GUO ; Qi ZHANG ; Jun XUE ; Ximo WANG ; Guangyuan SUN ; Jianling LIU ; Lei HAN ; Shuquan GAO
Chinese Journal of Comparative Medicine 2024;34(1):171-176
Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.
2.Effect of Pterostilbene Regulating Nuclear Factor E2-Related Factor 2 on Apoptosis of Colon Cancer Cells in Vitro
Xuehui SHI ; Chongxi FAN ; Quanlong YANG ; Xiaoying WANG ; Donglin ZHAO ; Manhua LI ; Xueliang WU ; Jianchun FAN ; Shoubin NING
Acta Academiae Medicinae Sinicae 2024;46(4):482-489
Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2(Nrf2)in the process of pterostilbene acting on LoVo cells.Methods LoVo cells were treated with different concentrations(5,10,20,40,60,80,100 panol/L)of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Tran-swell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochon-drial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlo-rofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic pro-teins(Bcl2 and Bax)were determined by Western blotting.In addition,cell viability,Nrf2 expression,and ap-optosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane.Results Compared with the control group,40,60,80,100 μmol/L pterostilbene reduced the viability of LoVo cells(P=0.014,P<0.001,P<0.001,P<0.001).Pterostilbene at 5,10,20 μmol/L did not show effects on cell viability but inhibited cell migration(P=0.008,P<0.001,P<0.001)and invasion(all P<0.001).Pterostilbene at 40,60,80 μmol/L increased apoptosis(P=0.014,P<0.001,P<0.001),promoted mitochondrial membrane potential depolarization(P=0.026,P<0.001,P<0.001)and reactive oxygen species accumula-tion(all P<0.001),and down-regulated the expression of phosphorylated Nrf2(P=0.030,P<0.001,P<0.001),heme oxygenase 1(P=0.015,P<0.001,P<0.001),and Bc12(P=0.039,P<0.001,P<0.001)in LoVo cells.Pterostilbene at 60,80 μmol/L down-regulated Nrf2 expression(P=0.001,P<0.001)and up-regulated Bax expression(both P<0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability(P<0.001),apoptosis(P<0.001),and Nrf2 expression(P=0.022).Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.
3.Research progress of SHP2 in digestive system tumors
Peng WANG ; Jianchun FAN ; Juming JIA ; Qingfei DIAO ; Jun XUE ; Xueliang WU
Chinese Journal of Comparative Medicine 2024;34(5):159-168
Malignant tumors are a major disease threatening human health with disability and mortality rates increasing yearly.Protein tyrosine phosphatase 2(SHP2)of Src homology 2,an important member of the protein tyrosine phosphatase family,has a wide range of functions,and its expression is elevated in a wide range of solid tumors.SHP2 plays an important regulatory role in invasion,metastasis,proliferation,apoptosis,and drug resistance.A large number of studies have shown that SHP2 plays a very important role in the genesis and development of many solid tumors,but no systematic studies have reported on the role of SHP2 in digestive system tumors.Here,we reviewed the biological functions and clinical significance of SHP2 in seven tumor types of the digestive system,explored its roles and mechanisms in cancer development stages,and summarized the development of SHP2 inhibitors to further search for potential targets for effective early diagnosis and gene therapy,which is of great significance to improvement the cancer patient survival rate.
4.A novel nomogram-based model to predict the postoperative overall survival in patients with gastric and colorectal cancer
Siwen WANG ; Kangjing XU ; Xuejin GAO ; Tingting GAO ; Guangming SUN ; Yaqin XIAO ; Haoyang WANG ; Chenghao ZENG ; Deshuai SONG ; Yupeng ZHANG ; Lingli HUANG ; Bo LIAN ; Jianjiao CHEN ; Dong GUO ; Zhenyi JIA ; Yong WANG ; Fangyou GONG ; Junde ZHOU ; Zhigang XUE ; Zhida CHEN ; Gang LI ; Mengbin LI ; Wei ZHAO ; Yanbing ZHOU ; Huanlong QIN ; Xiaoting WU ; Kunhua WANG ; Qiang CHI ; Jianchun YU ; Yun TANG ; Guoli LI ; Li ZHANG ; Xinying WANG
Chinese Journal of Clinical Nutrition 2024;32(3):138-149
Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.
5.Clinical study on acupuncture at Zusanli (ST 36) acupoint combined with Traditional Chinese Medicine enema in the treatment of gastroparesis syndrome after gastrointestinal tumor operation
Xueren AO ; Cong LIAO ; Jianchun WU ; Guoxi SHEN ; Kaimin MA
International Journal of Traditional Chinese Medicine 2022;44(3):279-283
Objective:To study the clinical efficacy of acupuncture at Zusanli (ST 36)combined with Traditional Chinese Medicine (TCM) enema in the treatment of gastroparesis syndrome after gastrointestinal tumor operation.Methods:A total of 96 patients with gastroparesis syndrome after gastrointestinal tumor surgery in our hospital from June 2016 to May 2021, who met the inclusion criteria, were randomly divided into three groups by random drawing, with 32 in each group. The control group took mosapride citrate tablets orally, the TCM enema group added TCM enema on the basis of the control group, and the combined group added acupuncture Zusanli (ST 36)on the basis of the TCM enema group. All three groups were treated continuously for 4 weeks. The main syndromes were scored before and after treatment. The levels of serum gastrin (GAS), motilin (MTL) and somatostatin (SS) were detected by radioimmunoassay. The gastric electrophysiological parameters (waveform response area, waveform frequency and average amplitude) were detected by intelligent dual channel gastrointestinal electrograph, the adverse reactions during treatment were recorded, and the clinical efficacy was evaluated.Results:The total effective rate was 96.9% (31/32) in the combined group, 81.3% (26/32) in the TCM enema group and 68.8% (22/32) in the control group. There was significant difference among the three groups ( χ2=8.72, P=0.013). The scores of abdominal fullness and distention, fatigue, belching acid reflux, dry mouth and bitter mouth in the combined group were significantly lower than those in the TCM enema group and the control group ( F values were 16.39, 13.21, 11.28 and 10.23, respectively, P<0.001). After treatment, the levels of GAS [(140.62±15.19) ng/L vs. (128.79±14.34) ng/L, (115.98±12.40) ng/L, F=21.09], MTL [(268.66±28.21) ng/L vs. (245.89±25.24) ng/L, (230.78±22.43) ng/L, F=30.29] and SS [(70.58±8.17) ng/L vs. (65.50±7.76) ng/L, (59.73±7.05) ng/L, F=33.19] in the combined group were significantly higher than those in the TCM enema group and the control group ( P<0.01). The waveform response area [(172.62±17.14) μV/s vs. (158.56± 15.32) μV/s, (145.48±14.13) μV/s, F=20.24], waveform frequency [(3.86±0.61) cpm vs. (3.29±0.50) cpm, (3.01±0.63) cpm, F=13.17] and average amplitude [(86.51±8.98) μV vs. (75.70±7.93) μV, (68.65±7.46) μV, F=28.11] were significantly higher than those in TCM enema group and control group ( P<0.01). During the treatment period, the incidence of adverse reactions was 18.8% (6/32) in the combined group, 15.6% (5/32) in the TCM enema group and 12.5% (4/32) in the control group. There was no significant difference between the three groups ( χ2=0.47, P=0.789). Conclusion:Acupuncture at Zusanli (ST 36) combined with TCM enema can improve the TCM syndrome scores, gastrointestinal hormone level and gastric electrophysiological parameters of patients with gastroparesis syndrome after gastrointestinal tumor operation, improve the curative effect with safety.
6.Chinese Experts Consensus on Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (2020 Version).
Caicun ZHOU ; Jie WANG ; Baocheng WANG ; Ying CHENG ; Zhehai WANG ; Baohui HAN ; You LU ; Gang WU ; Li ZHANG ; Yong SONG ; Bo ZHU ; Yi HU ; Ziping WANG ; Qibin SONG ; Shengxiang REN ; Yayi HE ; Xiaohua HU ; Jian ZHANG ; Yu YAO ; Hongyun ZHAO ; Zhijie WANG ; Qian CHU ; Jianchun DUAN ; Jingjing LIU ; Shukui QIN
Chinese Journal of Lung Cancer 2021;24(4):217-235
Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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7.Clinicopathological features and treatment strategies of intraductal papillary neoplasm of the bile duct
Xin WU ; Binglu LI ; Chaoji ZHENG ; Wei LIU ; Tao HONG ; Yong XIE ; Jianchun XIAO ; Qiang QU ; Xiaodong HE
Chinese Journal of Digestive Surgery 2021;20(8):876-882
Objective:To investigate the clinicopathological features and treatment strategies of intraductal papillary neoplasm of the bile duct (IPNB).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 40 patients with IPNB who were admitted to Peking Union Medical College Hospital from August 2000 to April 2020 were collected. There were 19 males and 21 females,aged (60±14) years. Patients underwent preoperative imaging examination and blood test for evaluation of tumor location, range and resectability. The treatment strategies of patients depended on preoperative examination and their own willingness. Observation indicators: (1) preoperative examinations and tests; (2) treatment; (3) pathological examination; (4) follow-up. Follow-up using outpatient examination, telephone interview and online diagnosis was performed to detect tumor recurrence and survival of patients up to April 2021. Count data were represented as absolute numbers and percentages. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). The Kaplan-Meier method was used to calculate the cumulative survival rate and draw survivla curve. Results:(1) Preoperative examinations and tests: 40 patients received preoperative imaging examination and blood test. Of 40 patients, 33 cases underwent abdominal ultrasonography, 31 cases underwent abdominal computed tomography (CT) examina-tion, 21 cases underwent magnetic resonance imaging (MRI), 15 cases underwent endoscopic retrograde cholangiopancreatography (ERCP), 8 cases underwent position emission tomography CT examination, 6 cases underwent endoscopic ultrasonography; some patients underwent multiple examinations. The main imaging features of IPNB were bile duct dilatation, and intraluminal tumor. Enhanced CT scan showed tumor reinforcement. Preoperative blood tests showed of the 40 patients, 21 cases with abnormal liver function, 17 cases with increased bilirubin, 9 cases with increased carcinoembryonic antigen, and 24 cases with increased CA19-9. (2) Treatment: 35 of 40 patients underwent surgery, 5 patients underwent ERCP and biopsy and didn′t undergo surgery based on their willings. Of 35 patients with surgeries,20 cases underwent hemihepatectomy or lobectomy, 8 cases underwent pancreatico-duodenectomy, 7 cases underwent bile duct tumor resection. The operation time was (262±91)minutes, and volume of intraoperative blood loss was 300 mL(range, 50?2 000 mL). Postopera-tive complications occurred in 6 of 35 patients, including 3 cases with Grade Ⅰ complications and 3 cases with Grade Ⅱ complication according to Clavien-Dindo classi-fication system. (3) Pathological examination: 40 patients were diagnosed as IPNB by pathological examinations. There were 19 and 21 patients with extrahepatic and intrahepatic lesions, respectively. There were 20 benign lesions (15 cases of low or intermediate-grade intraepithelial neoplasia and 5 cases of high-grade intraepithelial neoplasia) and 20 malignant lesions of invasive carcinoma. There were 18 cases with mucus secretion and 22 cases without mucus secretion or information. Five of 35 patients with surgeries had positive margin and the rest of 30 patients had negative margin. A total of 154 lymph nodes were dissected in 21 patients, including 3 positive lymph nodes. (4) Follow-up: 35 of 40 patients were followed up for (53±35)months. Seventeen of 35 patients survived without tumor, and 3 patients survived with tumor of which the time to tumor recurrence were 12, 17, 37 months. Fifteen patients died, with the time interval to death of (30±19)months. The 1-, 3-, and 5-year cumulative survival rates of 35 patients were 88.6%, 73.6%, and 50.7%, respectively.Conclusions:IPNB is rare, with the main imaging features as bile duct dilatation, and intraluminal tumor. The tumor is reinforce-ment after enhanced scan. Surgery is the main treatment for IPNB and lymph node metastasis is rare.
8. The progression of parenteral and enteral nutrition based on new guidelines
Wei CHEN ; Jianchun YU ; Zijian LI ; Guohao WU
Chinese Journal of Surgery 2017;55(1):32-36
As people are getting a better understanding of organism′s metabolism and the concept of disease treatment is being continuously updated, parenteral and enteral nutrition become an inter discipline subject that serves for the clinic and involves a number of disciplines. Just in the past five years, related guidelines at home and abroad have been published as much as more than 40. In order to better serve the clinical decision making, this text attempts to give a carding and interpretation from the three aspects of nutrition screening and assessment, the implementing of nutritional intervention and the progress of special nutrition support. It is observed that the standard clinical nutrition diagnosis and treatment process has been formed consensus. But in the practical application, there are still many details need to confirm and further study.
9.Clinical Characteristics of Lung Cancer with Pancreatic Metastases
DUAN JIANCHUN ; WAN RUI ; SHEN JIANQIN ; LIU XUYI ; WANG JIE ; ZHAO JUN ; WU MEINA ; YANG LU ; AN TONGTONG ; GUO QINGZHI
Chinese Journal of Lung Cancer 2017;20(8):511-515
Background and objective Lacking of typical symptoms, more than 70% of patients with lung cancer are diagnosed as advanced-stage disease. Patients suffer from solid organs metastasis with different clinical features and prog-nosis. With development of new technology, more and more lung cancer patients are diagnosed with pancreatic metastasis. The aim of this study was to investigate clinicopathologic and survival difference by retrospective analysis among lung cancer patients with pancreatic metastases.Methods Of the patients with lung cancer diagnosed by pathology and thorough staging evaluation and treated at Beijing Cancer Hospital with long follow-up during July 1996 and June 2017, 35 cases had pancreatic metastases.Results There were 28 cases diagnosed as small cell lung cancer, 3 cases diagnosed as adenocarcinoma and 4 cases diagnosed as squamous cell carcinoma. There were 15 cases with pancreatic metastases in head of pancreas and 20 cases in body and tail of pancreas, 23 cases presented with isolated metastasis and 12 cases with multiple metastases. Pathological type was prognostic factor for lung cancer patients with pancreatic metastases.Conclusion Pancreatic metastases represents an uncommon site of extrathoracic spread of disease for part of patients with advanced lung cancer. Lung cancer with pancreatic metastases should be treated by combined therapy, especially by systemic chemotherapy. Pathological type was prognostic fac-tor for lung cancer patients with pancreatic metastases.
10.Application of intra-arterial infusion chemotherapy in concurrent chemoradiation therapy of local advanced cervical cancer
Dingquan WU ; Hengwu CUI ; Jianchun YAN ; Jian CHEN
Journal of Practical Radiology 2016;(2):266-269
Objective To investigate the feasibility and clinical efficacy of intra-arterial infusion chemotherapy within concurrent chemoradiation therapy (CCRT)for local advanced cervical cancer (LACC:Stage Ⅰb2 - Ⅳa).Methods 42 LACC patients were treated with CCRT combining with intra-arterial infusion chemotherapy (CCRT group),and another 60 LACC patients were under-went radiotherapy alone (control group).The clinical efficacy,adverse reactions and overall survivals (OAS)were evaluated,be-tween the two groups,respectively.Results Overall response rate was 92.8% in CCRT group.Of 42 patients,24 had achieved complete response (CR)in CCRT group (57.1%).The 5-year overall survival rate in CCRT group was 76.2%,which was signifi-cantly higher than that of control group (49.3%),respectively (P =0.01).Multivariate COX proportional hazards model revealed that the clinical stage(P =0.01 6),pelvic positive lymph nodes (P =0.007)were independent factors of monitoring prognosis of LACC patients treated with CCRT combining with intra-arterial infusion chemotherapy.Conclusion CCRT with intra-arterial infu-sion chemotherapy is a safe and effective method for LCCA,and clinical stage and pelvic positive lymph node were independent fac-tors of the prognosis of patients.

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