Objective To explore the diagnostic and prognostic relevance of genes associated with trastuzumab resistance and sensitivity in gastric cancer using machine learning algorithms.Methods The data on resistant and sensitive genes were downloaded from the GEO database and subjected to functional enrichment analysis.Intersection analysis was performed using TCGA and GEO data to identify feature genes related to gastric cancer drug-resistance.LASSO and SVM-RFE methods were used for feature gene selection.The expressions of these feature genes were detected in both test and validation groups,and their diagnostic value was analyzed using receiver operating characteristic curves.The prognostic value of SH3GL2 was assessed using online databases,and its role in patient survival was further explored.CIBERSORT algorithm was used to evaluate the relationship between SH3GL2 and immune cell infiltration in gastric cancer,and analyze its effect on immune microenvironment.Results Fifteen resistance-related genes were identified,and 12 diagnostic biomarkers related to gastric cancer were selected through machine learning,including MMP7,COCH,VCAN,SH3GL2,SYNM,KLK6,STC2,PPP1R1B,CDH3,WNT11,PMEPA1,and BCAT1.SH3GL2 showed low expression in both test and validation groups,and its high expression was associated with poorer prognosis in gastric cancer(P<0.01).SH3GL2 expression level was related to various immune cells(activated CD8+T cells,activated DC cells)and showed positive correlations with immune suppressive factors(such as TGFB1,VTCN1)and negative correlations with immune stimulatory factors(such as CD70,CD80).Conclusion The 12 selected feature genes can serve as potential diagnostic biomarkers for gastric cancer.SH3GL2 has a low expression in gastric cancer,and its high expression might shorten patient survival by inhibiting anti-tumor immunity.

Objective To explore the diagnostic and prognostic relevance of genes associated with trastuzumab resistance and sensitivity in gastric cancer using machine learning algorithms.Methods The data on resistant and sensitive genes were downloaded from the GEO database and subjected to functional enrichment analysis.Intersection analysis was performed using TCGA and GEO data to identify feature genes related to gastric cancer drug-resistance.LASSO and SVM-RFE methods were used for feature gene selection.The expressions of these feature genes were detected in both test and validation groups,and their diagnostic value was analyzed using receiver operating characteristic curves.The prognostic value of SH3GL2 was assessed using online databases,and its role in patient survival was further explored.CIBERSORT algorithm was used to evaluate the relationship between SH3GL2 and immune cell infiltration in gastric cancer,and analyze its effect on immune microenvironment.Results Fifteen resistance-related genes were identified,and 12 diagnostic biomarkers related to gastric cancer were selected through machine learning,including MMP7,COCH,VCAN,SH3GL2,SYNM,KLK6,STC2,PPP1R1B,CDH3,WNT11,PMEPA1,and BCAT1.SH3GL2 showed low expression in both test and validation groups,and its high expression was associated with poorer prognosis in gastric cancer(P<0.01).SH3GL2 expression level was related to various immune cells(activated CD8+T cells,activated DC cells)and showed positive correlations with immune suppressive factors(such as TGFB1,VTCN1)and negative correlations with immune stimulatory factors(such as CD70,CD80).Conclusion The 12 selected feature genes can serve as potential diagnostic biomarkers for gastric cancer.SH3GL2 has a low expression in gastric cancer,and its high expression might shorten patient survival by inhibiting anti-tumor immunity.

The incidence and mortality of colorectal cancer(CRC)have been increasing year by year,and liver metastasis is the main cause of death for CRC patients.Approximately 49%of CRC patients died of liver metastasis,and about 25%of them developed liver metastasis after radical resection.The interaction between various cytokines(such as chemokines,exosomes)and immune cells in the tumor microenvironment(TME)is essential for tumor metastasis.So far,the mechanism of colorectal liver metastases(CRLM)has not been fully elucidated,but some studies have shown that CRLM does not only occur in the late stage of CRC,but also in the early stage of some patients.In this paper,we summarized the current understanding of CRLM pathogenesis from genomics,pathology,and TME perspectives.And we also reviewed the latest molecular regulatory mechanisms of CRLM,as well as the mechanisms of immune cells and cytokines related to TME.Finally,the latest research findings of CRLM immunotherapy are summarized,in order to provide new insights into the comprehensive treatment for CRLM patients.

The incidence and mortality of colorectal cancer(CRC)have been increasing year by year,and liver metastasis is the main cause of death for CRC patients.Approximately 49%of CRC patients died of liver metastasis,and about 25%of them developed liver metastasis after radical resection.The interaction between various cytokines(such as chemokines,exosomes)and immune cells in the tumor microenvironment(TME)is essential for tumor metastasis.So far,the mechanism of colorectal liver metastases(CRLM)has not been fully elucidated,but some studies have shown that CRLM does not only occur in the late stage of CRC,but also in the early stage of some patients.In this paper,we summarized the current understanding of CRLM pathogenesis from genomics,pathology,and TME perspectives.And we also reviewed the latest molecular regulatory mechanisms of CRLM,as well as the mechanisms of immune cells and cytokines related to TME.Finally,the latest research findings of CRLM immunotherapy are summarized,in order to provide new insights into the comprehensive treatment for CRLM patients.

Objective:To investigate the prognostic significance of tumor architecture in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy.Methods:A retrospective study was performed on 958 patients who underwent nephroureterectomy in Second Affiliated Hospital of Zhejiang university (156) and Renji Hospital (802) between January 1998 and June 2019. There were 630 males and 328 females with median age 67 years old, ranging 30-89 years old. Among them, 499 patients suffered with preoperative hydronephrosis, 370 patients suffered with hypertension, 120 patients suffered with diabetes, 252 patients had history of smoking and 119 patients had history of non-muscle invasive bladder cancer (NMIBC) or with NMIBC. 489 patients had tumor in renal pelvic, 394 patients had tumor in ureter and 75 patients had tumor in both sites. Laparoscopic surgery was performed in 543 patients while open surgery was performed in 415 patients. The χ 2 test was used to detect the association between tumor architecture and several clinicopathological features. Kaplan-Meier method with the log-rank test was used to assess survival analysis. Multivariate analyses were conducted using Cox proportional-hazards regression model. Results:516 cases (53.9%) showed papillary architecture(Group A) and 442 cases (46.1%) showed sessile architecture(Group B). 543 patients had a tumor ≤3 cm and 415 had a tumor >3 cm. Low pathological grade and high grade was diagnosed in 275 and 683 patients, respectively. The distribution of pathological stage was pT a-1 in 441 cases, pT 2 in 180 cases, pT 3 in 308 cases and pT 4 in 29 cases. Lymphadenectomy was performed in 227 patients and 62 patients were pathologically confirmed lymph node metastasis. 48 patients were found squamous or glandular differentiation. Lymphovascular invasion (LVI) was observed in 150 patients. 134 patients were multifocality. Positive surgical margin was found in 43 patients. Median follow-up was 39 (ranging, 2-206) months. During follow-up, a total of 304 patients died and 236 died of UTUC. 5-year OS and CSS were 76.6% and 81.8%, respectively, in patients with papillary architecture (group A), which were significantly higher than 54.4% and 60.5% in patients with sessile architecture (group B, all P<0.001). Patients in group B had more female patients (38.9% vs.30.3%, P=0.005), ureteral location (47.1% vs. 36.1, P=0.002), hydronephrosis (55.9% vs.48.8%, P=0.030) and postoperative adjuvant chemotherapy (27.1% vs. 14.7%, P<0.001), higher pathological grade (89.6% vs.55.6%, P<0.001) and stage (79.4% vs.32.4%, P<0.001), lymph node metastasis rate (12.0% vs.1.7%, P<0.001), squamous or glandular differentiation (9.5% vs.1.2%, P<0.001) and LVI (24.4% vs.8.1%, P<0.001) than patients in group A. Cox multivariate regression analysis showed that sessile architecture ( P=0.022, 0.028), age ≥65 years ( P<0.001, <0.001), history of diabetes ( P=0.008, 0.043), history of NMIBC or with NMIBC ( P<0.001, <0.001), higher grade ( P=0.002, <0.001), advanced tumor stage ( P=0.003, 0.005), lymph node metastasis ( P=0.003, 0.044), squamous or glandular differentiation ( P=0.008, 0.027) and positive surgical margin ( P=0.003, 0.010) were independent risk factors for OS and CSS. However, tumor >3 cm ( P=0.013, 0.131) and positive LVI ( P=0.045, 0.174) were independent risk factors for CSS rather than OS. Conclusions:UTUC is high malignancy. Tumor architecture was one of an independent risk factor for OS and CSS in UTUC patients and sessile tumors were more malignant, more aggressive and have worse prognosis.

Objective: To investigate the efficacy and drug related adverse reactions of sorafenib and sunitinib as first-line tyrosine-kinase inhibitors (TKIs) for patients with metastatic renal cell carcinoma (mRCC) and analyze the clinical prognostic factor for survival. Methods: The data of 271 patients with metastatic renal cell carcinoma who had complete clinicopathological data were retrospectively analyzed, including 174 cases in sorafenib group and 97 cases in sunitinib group, to access patients′ overall survival (OS) and progression-free survival (PFS). Prognostic values of all characteristics were determined by using univariate and multivariate Cox regression models. Results: The objective response rates (ORR) of the sorafenib and sunitinib groups were 14.9% and 19.6%, respectively, and the disease control rates (DCR) were 85.1% and 88.6%, respectively. No significant difference was found between the sorafenib and sunitinib group in ORR (P=0.325) or DCR (P=0.408). The most common grade 3 to 4 adverse events in the sorafenib group were hand-foot syndrome (6.7%), diarrhea (2.3%), and rash (2.3%). The most common grade 3 to 4 adverse events in the sunitinib group were neutropenia (6.2%), hand-foot syndrome (6.2%), and thrombocytopenia (4.6%). During the follow-up, 97 cases death occurred and 81 cases disease progression occurred in sorafenib group. The median PFS was 12 months (95% CI: 9-15 months), and the median OS was 25 months (95% CI: 21-29 months) in sorafenib group. While 74 cases death occurred and 40 cases disease progression occurred in sunitinib group, the median PFS was 12 months (95% CI: 10-12 months) and the median OS was 23 months (95% CI: 20-32 months) in sunitinib group. No significant difference was found between the sorafenib and the sunitinib group in PFS (P=0.771) or OS (P=0.548). Multivariate analysis showed Fuhrman grades (HR=1.358, 95%CI: 1.004-1.835), number of metastatic sites (HR=1.550, 95%CI: 1.143-2.101) and MSKCC risk grade (Intermediate risk group: HR=1.621, 95%CI: 1.117-2.232; Poor risk group: HR=2.890, 95%CI: 1.942-4.298) were independent prognostic factors for PFS. Fuhrman grades (HR=2.135, 95%CI: 1.533-2.974), number of metastatic sites (HR=1.774, 95%CI: 1.279-2.461) and MSKCC risk grade (Intermediate risk group: HR=1.415, 95%CI: 1.002-1.998; Poor risk group: HR=3.161, 95%CI: 2.065-4.838) were independent prognostic factors for OS. Conclusions The results of this study indicate that sorafenib and sunitinib are both effective as the first-line TKIs for mRCC patients and sorafenib has comparable efficacy to sunitinib. But they have differences in the incidence of adverse effects. Fuhrman grades, number of metastatic sites and MSKCC risk grade are independent prognostic factors for mRCC patients.

Objective To investigate the prognostic significance of the lymphovascular invasion (LVI) in patients with upper tract urothelial carcinoma (UTUC) after radical nephmureterectomy (RNU).Methods A retrospective review was performed on 812 patients who underwent radical nephroureterectomy for UTUC in our hospital from January 1998 to March 2016.Among all the patients,534 were male and 278 female,with median age 67 years old (ranged 25 to 89 years).Three hundred and three patients had hypertension and 119 patients had diabetes.Hydronephrosis was present in 393 patients.445 patients had tumor in left side and the remaining 367 in right side.The tumor was located in the renal pelvis in 422 patients and was ureteric in 319 patients and multifocal in 71 patients.Low pathological grade and high pathological grade was diagnosed in 239 and 573,respectively.The x2 test was used to detect the association between lymphovascular invasion (LVI) and several clinicopathological features.Kaplan-Meier method with the log-rank test was used to assess overall survival (OS) and cancer-specific survival (CSS).Multivariate analysis was conducted using Cox proportional-hazards regression model.Results There were 396 cases with pathological stage Tis +Ta +T1,135 cases T2,257 cases T3 and 24 cases T4.Of all patients,52 had lymph node metastasis.The median follow-up time was 41 months (ranged 2 to 206 months).Of all 812 patients included,110 patients (13.5％) had LVI,while 702 patients (86.5％) were LV1 negative.The 5-year OS and CSS was 44.8％ and 48.9％ for LVI positive group while 70.1％ and 76.0％ for LVI negative group (P ＜ 0.001).Furthermore,there were statistically significant differences between LVI positive group and LVI negative group in hydronephrosis,tumor grade,tumor stage,muscle invasion and lymph node metastasis (P＜0.05).Cox regression showed LVI,advanced age (≥65 year),higher tumor grade,advanced tumor stage (≥ pT2),lymph node metastasis and multifocal tumor were significant prognostic factors in patients with UTUC after RUN.Conclusion UTUC may have a poor prognosis and LVI could be an independent predictor of both OS and CSS.

Objective To compare the effect of applying low molecular weight heparin calcium in different periods of reteplase for acute myocardial infarction(AMI).Methods Ninety-one cases of AMI were divided into group A(30 cases),group B(30 cases)and group C(31 cases)by random digits table.The patients in three groups were given reteplase intravenous thrombolysis,and 5000 U low molecular weight heparin calcium was abdominal wall subcutaneous injections once 12 h at intravenous thrombolysis immediately(group A),after intravenous thrombolysis 6 h(group B)and 12 h(group C).They all were treated for 7-10 d.The rate of coronary artery recanalization,acute phase complication and adverse reaction were compared among three groups.Results The rate of coronary artery recanalization in group A,B and C was 76.7％(23/30),96.7％(29/30),74.2％(23/31)respectively.The rate of coronary artery recanalization in group B was significantly higher than that in group A and C(P ＜ 0.05).The rate of acute phase complication and adverse reaction in group B[33.3％(10/30)]was significantly lower than that in group A and C[70.0％ (21/30)and 61.3％(19/31)](P ＜ 0.05).Conclusions After reteplase intravenous thrombolysis in 6 h,applying low molecular weight heparin calcium can significantly improve the rate of coronary artery recanalization and reduce the rate of acute phase complication and adverse reaction.