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.

Objective To investigate the molecular mechanisms by which SOX7 regulates the SHP-2/Wnt/β-cate-nin/ROS pathway,affecting the proliferation,invasion,and migration of colorectal cancer cells.Methods Twenty nude mice with subcutaneously transplanted tumor models were randomly divided into four groups:SOX7 NC(n=5),SOX mimic(n=5),SOX7 NC+PHPS1(n=5),and SOX7 mimic+PHPS1(n=5)to observe tumor growth.Human colorectal cancer cell line SW480 cells were transfected via lipofection and divided into six groups:SOX7 NC,SOX7 mimic,SOX7 NC+H2 O2,SOX7 mimic+H2O2,SOX7 NC+PHPS1,and SOX7 mimic+PHPS1.The ex-pression of SHP-2/Wnt/β-catenin/ROS pathway-related proteins in SW480 cells of each group was detected by Western blot.The invasion and migration capabilities of SW480 cells were assessed through scratch and Transwell invasion assays,while cell proliferation was evaluated using CCK-8.Results In vivo experiments demonstrated that tumors in the SOX7 mimic group were significantly smaller than those in the SOX7 NC group(P＜0.01).Tumors treated with PHPS1 intervention exhibited a significant increase in volume.There was no statistical significance in the difference in tumor volume between the SOX7 mimic+PHPS1 group and the SOX7 NC+PHPS1 group.In vitro experiments revealed that SOX7 mimic inhibited the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P＜0.01),and promoted the expression of p-SHP-2 protein(P＜0.01).The addition of hydrogen peroxide and SHP-2 inhibitor reversed the effects of SOX7 on SW480 cells(P＜0.05),and significantly promoted the expression levels of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins,with no sig-nificant difference,while significantly reducing the expression levels of SHP-2,p-SHP-2 proteins,with no significant difference.PHPS1 inhibited the expression of SHP-2,p-SHP-2 proteins(P＜0.05)and upregulated the expression of Wnt,β-catenin,NOX2,NOX4,PI3K,P-PI3K,AKT,P-AKT proteins(P＜0.05).Scratch,Transwell invasion and migration assays,and CCK-8 experiments indicated that SOX7 suppressed the migration,invasion,and proliferation of SW480 cells through oxidative stress and the SHP-2 pathway(P＜0.01),while H2O2 and PHPS1 intervention promoted the migration,invasion,and proliferation of SW480 cells(P＜0.05).Conclusion SOX7 can suppress the proliferation,invasion,and migration of colorectal cancer by targeting the SHP-2/Wnt/β-catenin/ROS pathway.

Objective To explore the feasibility and rationality of advanced integrated two-stage laparoscopic simulation training course in standardized training of surgical residents.Methods From December 2019 to December 2021,the advanced integrated two-stage laparoscopic simulation training course was carried out among 2019-2020 surgical residents who received standardized training in our hospital.The course was divided into two stages.In the first stage,BEST(best essential surgical technology training)course,adopted Darwin? endoscopic training system,Tianyan? endoscopic training system,Microport? 3D laparoscopic training system and simple simulative models were used.The second stage,BEST PLUS course,same platform as that in BEST course and in vitro animal models were used.The questionnaire survey method(before and after class questionnaire)was adopted to evaluate the curriculum setting,such as curriculum form,simulators,teaching method,time arrangement,curriculum difficulty,training effect,curriculum satisfaction and so on.Results A total of 37 surgical residents completed the two-stage course training and the questionnaire survey.The overall satisfaction rate with the curriculum setting was 100%.There were 32 residents(86.5%)thought that first stage training course could significantly improve their clinical skills,35 residents(94.6%)thought that second stage training course could significantly improve their clinical skills,and 36 resident(97.3%)thought that the first stage curriculum could significantly help them improve performance in the second stage curriculum.Conclusions The trainees had a high degree of recognition and satisfaction for the advanced integrated two-stage laparoscopic simulation training course.The overall design of course was reasonable and feasible,and was attractive to trainees.

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.

Objective To investigate the targeting of transforming growth factor β1(TGF-β1)expression by Ran-binding protein 9(RANBP9)and its effect on colorectal cancer Colo320 cell apoptosis.Methods Gene expression levels of RANBP9 were analyzed in 625 colon cancer tissues and 20 normal colon tissues in The Cancer Genome Atlas database.The relationship between RANBP9 expression and survival time of patients with colon cancer was analyzed using KMPLOT.The expression of TGF-β1 in normal colon tissues and colon cancer tissues was analyzed using the human protein immunohistochemistry database and the relationship between TGF-β1 expression and the survival of patients with colon cancer was analyzed using the UALCAN database.The relationship between RANBP9 and TGF-β1 was analyzed by dual luciferase experiments.Colo320 cells were transfected with pcDNA3.1-GFP-RANBP9 and control pcDNA3.1-GFP-RANBP9-NC plasmids,respectively,and normal control cells were established without transfection.The cells were cultured and the growth viability of each group of cells was detected by the iazolyl blue tetrazolium bromide method,apoptosis was detected by flow cytometry,the mitochondrial membrane potential was detected by JC-1 staining,and RANBP9 and TGF-β1 protein expression were detected by Western blot.Results RANBP9 expression was significantly reduced in colon cancer tissues.Compared with patients with low RANBP9 expression,patients with high RANBP9 expression had a higher survival curve and significantly higher expression of TGF-β1 in colon cancer tissue.Compared with patients with high TGF-β1 expression,patients with low TGF-β1 expression had a significantly higher survival curve(P＜0.05).RANBP9 targeted the expression of TGF-β1 in colon cancer.Compared with the normal group,cell growth,mitochondrial membrane potential,and TGF-β1 expression were all significantly down-regulated and the apoptosis rate and RANBP9 expression were significantly increased in the experiment group(P＜0.05).Conclusions RANBP9 can target the expression of TGF-β1,promote the growth of Colo320 colon cancer cells,decrease the mitochondrial membrane potential,and induce apoptosis.

Cholangiocarcinoma is a malignant tumor with biliary epithelial features.The early diagnosis of cholangiocarcinoma is currently difficult and the treatment outcomes are poor.Its microenvironment includes abundant fibrotic mesenchyme and a variety of cell types,which promote the development and metastasis of cholangiocarcinoma by interacting with tumor cells through mechanisms such as facilitating migration,suppressing the immune response,and inducing angiogenesis and lymphangiogenesis.Immunotherapy is an important tumor treatment approach,and immunotherapy for cholangiocarcinoma has made some progress.This article reviews the characteristics of the immune microenvironment of cholangiocarcinoma,its relationship with immunotherapy,and cutting-edge therapeutic strategies.

Objective To investigate TXNIP and KLF9 expressions in the tissues of colorectal cancer(CRC)and their impact on clini-cal characteristics and prognosis.Methods This study included 90 CRC patients who were admitted to our hospital between January 2017 and December 2020.The cancer tissue and paired adjacent tissues removed surgically were collected.We performed detection and analysis of TXNIP and KLF9 protein expression levels in cancer and adjacent tissues and their correlation with clinical characteristics and overall survival rate of patients.Results GEPIA database analysis showed that TXNIP and KLF9 mRNA expression levels in READ tissues were significantly lower than those in normal tissues(P＜0.05).The positive expression rates of TXNIP and KLF9 in CRC tissues were 32.22％and 37.78％,respectively,which were lower than those in adjacent tissues(73.33％and 76.67％,respectively;P＜0.05).TXNIP and KLF9 expressions were positively correlated(r=0.519,P＜0.05),and GEPIA database retrieval showed a positive correlation between TXNIP and KLF9 expressions(P＜0.05).TXNIP and KLF9 expressions in patients with clinical stage Ⅲ and lymph node metas-tasis were lower than those in patients with stage Ⅰ/Ⅱ and non-lymph node metastasis(P＜0.05).The overall survival rate of patients with TXNIP and KLF9 expressions was higher than that of patients without TXNIP and KLF9 expressions.Negative expression of TXNIP and KLF9 in TNM stage Ⅲ was a prognostic risk factor(P＜0.05).Conclusion TXNIP and KLF9 expression levels are low in CRC tissues and associated with TNM stage,lymph node metastasis,and poor survival.

Objective To analyze the clinical efficacy of microwave ablation in the colorectal cancer with simultaneously multiple liver metastases that was initially evaluated as potentially resectable.Methods The patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases treated in the De-partment of General Surgery of the First Affiliated Hospital of Hebei North University,the Center of Minimally Invasive Therapy in Oncology of Traditional Chinese and Western Medicine in Dongzhimen Hospital of Beijing U-niversity of Chinese Medicine,and the Second Department of General Surgery in the Fourth Hospital of Hebei Medical University from October 1,2018 to October 1,2020 were selected in this study.The general data,pathological features,treatment methods,and clinical efficacy of the patients were collected.According to the treatment methods,the patients were assigned into a surgical resection group(conversion therapy + laparoscopic primary resection +hepatectomy)and a microwave ablation group(conversion therapy +laparoscopic primary re-section +microwave ablation).The surgical indicators(operation duration,time to first postoperative anal ex-haust,hospital stay,etc.)and postoperative complications(anastomotic stenosis,anastomotic hemorrhage,incision infection,etc.)were compared between the two groups.The survival period was followed up,including the overall survival period and disease-free survival period,and the survival curves were drawn to analyze the clinical efficacy of the two treatment regimens.Results A total of 198 patients with potentially resectable color-ectal cancer with simultaneous multiple liver metastases were included in this study.Sixty-six patients were cured by neoadjuvant chemotherapy(FOLFOX or FOLFIRI),including 30 patients in the surgical resection group and 36 patients in the microwave ablation group(with 57 tumors ablated).After the first ablation,54(94.74%)tumors achieved complete ablation,and all of them reached no evidence of disease status after re-ablation.The microwave ablation group had shorter operation duration,less intraoperative blood loss,shorter time to first post-operative anal exhaust,shorter time of taking a liquid diet,shorter hospital stay,and lower hospitalization cost than the surgical resection group(all P<0.001).In addition,the microwave ablation group had lower visual analogue scale score(P<0.001)than the surgical resection group.The incidences of complications such as inci-sion infection(P =0.740),anastomotic fistula(P =1.000),and anastomotic stenosis(P =1.000),the over-all survival period(P =0.191),and the disease-free survival period(P =0.934)showed no significant differ-ences between the two groups.Conclusions For patients with colorectal cancer with simultaneous multiple liver metastases initially assessed as potentially resectable,laparoscopic primary resection +surgical resection/microwave ablation after conversion therapy was safe,effective,and had similar survival outcomes.Microwave ablation outper-formed surgical resection in postoperative recovery,economy,and tolerability,being worthy of clinical promotion.

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.

Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer.Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were select-ed.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARH-GAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the pa-tients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expres-sion.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups.Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue(P＜0.001).The expression level of ARHGAP8 was correlated with tumor stage(P=0.024),lymph node metastasis(P=0.007),and age(P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tis-sue(P＜0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARH-GAP8 in the cancer tissue was higher than that in the rectal tissue(P=0.011).The expression of ARHGAP8 was correlated with tumor size(P=0.010)and pathological stage(P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 pa-tients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91％(29/44)patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy(P＜0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86％,which was higher than that(53.33％)in the patients with high pro-tein level of ARHGAP8(P=0.033).Conclusions ARHGAP8 is highly expressed in the rectal cancer tissue.The pa-tients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and develop-ment of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.