Objective To construct a Nomogram model that can accurately predict early death of metastatic colon cancer (mCC). Methods A total of 6 669 patients from the SEER database were identified using inclusion and exclusion criteria. Multivariate logistic regression was used to identify risk factors for early mortality and to construct a Nomogram. The predictive performance of the Nomogram was evaluated by C-index, calibration curve, and decision curve analysis (DCA). Results Primary tumor location, differentiation grade, T stage, M stage, bone metastases, brain metastases, CEA, tumor size, age and marital status were independent factors for early death in patients with mCC. A Nomogram was constructed based on these variables. The C-index and the calibration curve of the Nomogram showed the good predictive ability of the nomogram. DCA showed that the Nomogram had a superior clinical net benefit in predicting early death compared with TNM stage. Conclusion The developed Nomogram has good predictive ability and can help guide clinicians to identify patients with high-risk mCC for individualized diagnosis and treatment.

【Objective】 To explore the effect of Zhikepipa Mixture on the treatment of COVID-19 through network pharmacology analysis and molecular docking technology. 【Methods】 First, we performed the network pharmacology method to screen active compounds and targets so as to explore the mixture’s potential mechanisms in the treatment of COVID-19. In line with ADME screening index, like oral bioavailability (OB) ≥30% or drug likeness index (DL) ≥0.18, the active compounds against COVID-19 related targets were selected to construct the 'herb-compound-target’ network. Mechanism prediction of Zhikepipa mixture in the treatment of COVID-19 was analyzed by the interaction of the target sites, the bioinformatic annotation, and the metabolic pathway. Then, we used a molecular docking model to evaluate the binding ability between active compounds and 2019-nCoV (SARS-CoV-2) 3-chymotrypsin-like cysteine protease (3CL^pro) receptor-binding domain (PBD ID 6LU7), which was involved in mediating viral replication and transcription functions. 【Results】 The'herb-compound-target’ network showed 34 key compounds and 30 disease targets after overlapping with disease targets. The network topology analysis showed that those selected compounds with higher degree would produce marked anti-inflammatory effects by regulating 30 targets like PTGS1, IL1B, IL6, IL10, CXCL8 and JUN. AGE-RAGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, and MAPK signaling pathway were involved in regulating hepatitis B and diabetic complications. In addition, Folium eriobotryae and Radix stemonae played important roles in the network. The molecular docking results showed that nine compounds were identified with higher docking score rank against 2019-nCoV 3CL^pro protease, and most of them were attributed to flavonoids. 【Conclusion】 Zhikepipa Mixture could exhibit both anti-inflammatory and anti-virus actions through multi-component, multi-target, and multi-pathway.

Objective:To explore the role and molecular mechanism of hepatocyte nuclear factor 4γ (HNF4γ) in proliferation and stemness of gastric cancer.Methods:A total of 102 cases of paraffin-embedded gastric cancer tissues and matched adjacent gastric tissues and 42 cases of fresh-frozen tissues derived from gastric patients who received radical gastrectomy were collected from the First Affiliated Hospital of Zhengzhou University between 2012 to 2015. The expression of HNF4γ was tested by immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR). HNF4γ overexpressed (AGS-HNF4γ) and shRNA silenced (HGC27-shHNF4γ) gastric cell lines were established. The effects of HNF4γ on cell proliferation and stemness were verified by XTT, clone formation and sphere formation assay. The expression of CD44 was detected by western blot.Results:The mRNA expression level of HNF4γ in fresh-frozen gastric cancer tissue was (12.43±2.702), which was significantly higher than (3.639±1.109) in normal tissue ( P<0.001). The high protein expression rate of HNF4γ in paraffin-embedded gastric cancer tissues was 41.2% (42/102), which was significantly higher than 8.8% (9/102) in normal gastric mucosa tissue ( P< 0.001). The protein expression of HNF4γ was closely related to the tumor differentiation, infiltration depth, lymph node metastasis and tumor stage ( P<0.05). The median survival interval of patients with HNF4γ high expression was 25 months, the 3-year survival rate was 4.8% (2/42), significantly lower than 38 months and 51.7% (31/60) of patients with normal HNF4γ expression ( P<0.001). The proliferation and CD44 protein expression of AGS-HNF4γ cells were significantly higher than those of the AGS-Vector cells. The number of clone formation, sphere formation rate of AGS-HNF4γ cells were 243.5±24.5 and (83.5±3.9)%, significantly higher than 81.0±16.0 and (21.8±5.6)% of AGS-Vector cells ( P=0.030 and P=0.010, respectively). The proliferation and CD44 protein expression of HGC27-shHNF4 cells were significantly lower than those of the HGC27-vector cells. The number of clone formation, sphere formation rate of HGC27-shHNF4 cells were 26.0±1.0 and (20.8±8.4)%, significantly higher than 83.5±4.5 and (72.5±4.8)% of HGC27-vector cells ( P=0.006 and P=0.030, respectively). Conclusions:HNF4γ is upregulated in the gastric cancer tissues and related with the poor prognosis of patients with gastric cancer. Overexpression of HNF4γ promotes the proliferation and remains the stemness of gastric cancer cells by upregulating the expression of CD44.

Objective:To explore the role and molecular mechanism of hepatocyte nuclear factor 4γ (HNF4γ) in proliferation and stemness of gastric cancer.Methods:A total of 102 cases of paraffin-embedded gastric cancer tissues and matched adjacent gastric tissues and 42 cases of fresh-frozen tissues derived from gastric patients who received radical gastrectomy were collected from the First Affiliated Hospital of Zhengzhou University between 2012 to 2015. The expression of HNF4γ was tested by immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR). HNF4γ overexpressed (AGS-HNF4γ) and shRNA silenced (HGC27-shHNF4γ) gastric cell lines were established. The effects of HNF4γ on cell proliferation and stemness were verified by XTT, clone formation and sphere formation assay. The expression of CD44 was detected by western blot.Results:The mRNA expression level of HNF4γ in fresh-frozen gastric cancer tissue was (12.43±2.702), which was significantly higher than (3.639±1.109) in normal tissue ( P<0.001). The high protein expression rate of HNF4γ in paraffin-embedded gastric cancer tissues was 41.2% (42/102), which was significantly higher than 8.8% (9/102) in normal gastric mucosa tissue ( P< 0.001). The protein expression of HNF4γ was closely related to the tumor differentiation, infiltration depth, lymph node metastasis and tumor stage ( P<0.05). The median survival interval of patients with HNF4γ high expression was 25 months, the 3-year survival rate was 4.8% (2/42), significantly lower than 38 months and 51.7% (31/60) of patients with normal HNF4γ expression ( P<0.001). The proliferation and CD44 protein expression of AGS-HNF4γ cells were significantly higher than those of the AGS-Vector cells. The number of clone formation, sphere formation rate of AGS-HNF4γ cells were 243.5±24.5 and (83.5±3.9)%, significantly higher than 81.0±16.0 and (21.8±5.6)% of AGS-Vector cells ( P=0.030 and P=0.010, respectively). The proliferation and CD44 protein expression of HGC27-shHNF4 cells were significantly lower than those of the HGC27-vector cells. The number of clone formation, sphere formation rate of HGC27-shHNF4 cells were 26.0±1.0 and (20.8±8.4)%, significantly higher than 83.5±4.5 and (72.5±4.8)% of HGC27-vector cells ( P=0.006 and P=0.030, respectively). Conclusions:HNF4γ is upregulated in the gastric cancer tissues and related with the poor prognosis of patients with gastric cancer. Overexpression of HNF4γ promotes the proliferation and remains the stemness of gastric cancer cells by upregulating the expression of CD44.

[Abstract] Objective: To investigate the expression of one cut homeobox 2, OC-2 (ONECUT2) gene in human gastric cancer and its clinical significance. Methods: Based on bioinformatics technology, Oncomine, GEPIA, CCLE and EBI databases were searched to analyze the expression level of OC-2 in gastric cancer (GC) and other tumors. Kmplot database was used to verify the correlation between OC-2 expression and the prognosis of gastric cancer patients. STRING database was used to construct proteinprotein interaction network (PPI network), and the co-expressed genes of OC-2 related with gastric cancer were also analyzed. Results: The expression of OC-2 was generally up-regulated in different kinds of tumors with differential OC-2 expression. The expression level of OC-2 increased significantly in gastric cancer tissues and cells (all P<0.05) and might be irrelevant with tissue type and tumor stage (all P>0.05). The expression level of OC-2 was correlated with prognosis of gastric cancer patients. The median overall survival (40.0 vs 26.5 months) and median disease-free survival (26.2 vs 16.1 months) of gastric cancer patients with low OC-2 expression was significantly longer than those patients with high expression (both P<0.01). Fifteen co-expressed genes of OC-2 were obtained; the PPI network predicted 30 functional proteins interacting with OC-2, among which 11 proteins were also related to the occurrence and development of gastric cancer. After Pearson correlation analysis, 4 proteins that closely and positively related to OC-2 were identified: PDX1 (R=0.49), CREB1 (R=0.31), MAPK1 (R=0.26) and CTSS (R=0.25). Conclusion: OC-2 may play an important role in the occurrence and development, as well as invasion and metastasis of gastric cancer, which is expected to become a new target for the diagnosis and treatment of gastric cancer, and also an important indicator for the prognosis prediction of gastric cancer patients.

Aiming at the teaching characteristics of Medical Organic Chemistry in medical colleges and universities and the learning features of students, this article takes information technology as the medium and fully integrates autonomous learning mode of "teaching" and "learning" into the teaching process. In the teaching of Medical Organic Chemistry for students in grade 2017of Air Force Medical University, we adopted flipped classroom that is autonomous learning based on information resources-, student-centered micro-class assisted teaching, and self-learning mode such as self-designed experimental teaching based on network. The comprehensive scores of students of grade 2017 were compared with those of students of grade 2016 who adopted traditional teaching mode. The results showed that this mode of "teaching" and "learning" combined with "dominant-subject" can fully mobilize students' learning enthusiasm and initiative in Medical Organic Chemistry. It is more conducive for students to mastering learning methods, integrating knowledge and improving their ability to analyze and solve practical problems. The application of autonomous "teaching" and "learning" mode has effectively addressed the problems of insufficient interest of medical students in chemistry learning and problems of only one teaching mode for them. To a certain extent, it improves the quality and efficiency of Medical Organic Chemistry teaching.

Objective: To explore the role of microtubule actin cross-linking factor 1(MACF1) in the metastasis of gastric cancer. Methods: From 2009 to 2012, at The First Affiliated Hospital of Zhengzhou University, the paraffin blocks of gastric cancer and normal tissue adjacent to cancer of 107 patients who received radical gastrectomy were collected. The expression of MACF1 in tissues at protein level was detected by immunohistochemical staining. In 2017, at The First Affiliated Hospital of Zhengzhou University, fresh specimens samples of gastric cancer and normal tissue adjacent to cancer of 42 patients who received radical gastrectomy were also collected. The expression of MACF1 at mRNA level was determined by quantitative real-time polymerase chain reaction (PCR). MACF1 knockout gastric cell line was established. The effects of MACF1 on cell migration and invasion were verified by wound-healing test and Transwell assay. The effects of MACF1 on cell microtubule and actin were analyzed by filamentous actin (F-actin) staining. T-test, chi-square test and multivariate analysis were used for statistical analysis. Results: The positive expression rate of MACF1 in gastric carcinoma tissues was 71.0%(76/107), which was significantly higher than that of the corresponding normal tissues adjacent to cancer (22.4%, 24/107), and the difference was significant (t=4.145, P=0.016). The expression of MACF1 at mRNA level in cancer tissues of 42 patients with gastric cancer was 6.463±0.672, which was significantly higher than that of corresponding normal tissue adjacent to cancer (1.727±0.331), and the difference was statistically significant (t=6.326, P<0.01). The differences in positive expression rate of MACF1 in different tumor infiltration depth, different TNM stage and lymph nodes metastasis were statistically significant (χ²=1.170, 7.959 and 5.288; all P<0.01). The five-year survival rate of patients with high expression of MACF1 was 32.9% (25/76), which was significantly lower than that of patients with normal MACF1 expression (64.5%, 20/31), and the difference was statistically significant (χ²=25.093, P=0.034). The high expression of MACF1 was an independent prognostic factor affecting overall survival rate in patients with gastric cancer after surgery(hazard ratio (HR)=0.513, 95%confidence interval (CI): 0.411 to 0.922, P=0.038). The results of wound-healing assay showed that at 24 hour after wound the migration ability of MACF1 knockout AGS- MACF1^-/- cells was (18.77±3.82)%, which was lower than that of wild type AGS cells ((76.24±5.36)%), and the difference was statistically significant (t=6.249, P=0.014). The migration ability of MACF1 knockout HGC27-MACF1^-/-cells was (42.48±7.37)%, which was lower than that of wild type HGC27 cells ((82.35±4.28)%), and the difference was statistically significant (t=5.938, P=0.017). The results of Transwell assay indicated that the number of migration cells of MACF1 knockout AGS-MACF1^-/- cells was 87.0±11.0, which was less than that of wild type AGS cells (200.0±16.0), and the difference was statistically significant (t=5.820, P=0.028). The number of migration cells of MACF1 knockout HGC27-MACF1^-/-cells was 151.0±13.0, which was less than that of wild type HGC27 cells (268.5±20.5), and the difference was statistically significant (t=4.840, P=0.040). The results of F-actin staining demonstrated that the number of actin filaments of MACF1 knockout AGS-MACF1^-/- cells was 216.60±18.09, which was less than that of wild type AGS cells (491.30±5.02), and the difference was statistically significant (t=14.630, P=0.005). Conclusions The abnormally high expression of MACF1 in gastric cancer tissues may be correlated with the poor prognosis of patients with gastric cancer. MACF1 promotes the invasion and metastasis of gastric cancer cells by affecting the formation of F-actin and cell skeleton.

Objective: To observe the clinical efficacy of apatinib combined with chemotherapy for advanced gastric cancer as secondline and above treatment, and to analyze the survival of patients. Methods: Seventy-two patients with advanced gastric cancer that treated at Department of Oncology, the First Affiliated Hospital of Zhengzhou University from March 2016 to April 2017 were included in this study according to the inclusion and exclusion criteria; patients were randomly divided into chemotherapy group, apatinib group, apatinib combined with chemotherapy group. And the clinical efficacy and the survival of patients were investigated. Results: For chemotherapy group, apatinib group, apatinib combined with chemotherapy group, the disease control rate (DCR) and objective response rate (ORR) were 48.3%, 61.1%,72.0% (P>0.05) and 13.8%, 16.7%, 28.0%(P>0.05), respectively; and the incidence rate of adverse reaction at grade three-four was 17.1%, 16.8% and 24.0% (P>0.05), respectively. Compared with the chemotherapy group (93 d), the median progress-free survival (mPFS) time in the apatinib group and apatinib combined with chemotherapy group was 117 d (P=0.128) and 160 d (P=0.001). Furthermore, univariate and multivariate analyses showed that TNM staging (P=0.036), ascites (P=0.041) and treatment regimen (P=0.001) were the independent factors affecting PFS. Conclusion: As the second-line or above treatment in advanced gastric cancer, compared with single chemotherapy and single apatinib group, apatinib combined with chemotherapy displays more satisfactory achievement in remission rate, accompanied by controllable adverse reactions and considerable survival benefit.

Objective: To investigate the associations between genetic variations in DNA mismatch repair genes and sensitivity as well as prognosis to preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Methods: Fourteen haplotype-tagging single nucleotide polymorphisms (htSNPs) of MLH1, MLH3 and MSH2 genes were genotyped by Sequenom MassARRAY method in 146 patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. The associations between genotypes and response to capecitabine-based neoadjuvant chemoradiotherapy (nCRT) were measured by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for sex, age, clinical stages and karnofsky performance score (KPS) by unconditional logistic regression model. The survival analyses were performed by the hazard ratios (HRs) and 95% CIs by Cox proportional regression model. Results: Among 146 cases, 64 patients were nCRT responders with a response rate of 43.8%. MLH3 rs175057 C>T and MSH2 rs13019654 G>T loci were associated with the sensitivity to preoperative chemoradiotherapy. Compared with the rs175057 CC genotype, the adjusted OR for patients with CT and TT genotypes was 0.42 (95% CI: 0.19-0.91; P=0.029). Moreover, for rs13019654, the adjusted OR for patients with the GT or TT genotypes was 0.49 (95% CI: 0.24-0.98; P=0.047) than those with GG genotype. The remaining 12 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs3771273, rs4608577, rs4952887, rs6544991, rs6544997, rs10188090 and rs10191478, were not significantly associated with therapeutic response to preoperative chemoradiotherapy. Meanwhile, MLH3 rs175057 C>T locus was also associated with longer overall survival time in locally advanced rectal cancer (HR=0.44, 95% CI: 0.20-0.96, P=0.038), whereas MSH2 rs3771273 T>A, rs10188090 A>G and rs10191478 T>G loci were associated with shorter overall survival time (HR=1.74, 95% CI: 1.06-2.84, P=0.028; HR=1.64, 95% CI: 1.01-2.66, P=0.046; HR=1.71, 95% CI: 1.01-2.91, P=0.047, respectively). The remaining 10 SNPs, including rs1540354, rs4026175, rs1981929, rs2042649, rs2303428, rs4608577, rs4952887, rs6544991, rs6544997 and rs13019654, were not significantly associated with prognosis. Conclusions Genetic polymorphisms of MLH3 rs175057 and MSH2 rs13019654 loci can predict the nCRT response, while MLH3 rs175057 as well as MSH2 rs3771273, rs10188090 and rs10191478 may predict prognosis in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy. Therefore, these SNPs could be used as potential genetic markers in the personalized therapy of rectal cancer.

Objective: To investigate the expression of ALC1 protein during esophageal squamous cell carcinoma (ESCC) development and progression, so as to explore its association with clinicopathological characteristics and overall survival of ESCC patients, and the effect of ALC1 overexpression on malignant biological behavior of esophageal squamous cells. Methods: Immunohistochemistry (IHC) was used to detect ALC1 protein expression in 245 primary ESCC tissues and their paired normal esophageal mucous membranes, and to determine its correlation to gender, age, tumor cell differentiation, invasion, TNM stage, lymph nodes metastasis, and overall surviv-al rate of ESCC patients. MTT assay, colony formation assay, transwell invasion, and wound healing assay were used to observe the ef-fect of ALC1 on ESCC cell proliferation, invasion, and migration. Results: The expression ratio of ALC1 in esophageal squamous cell car-cinoma was higher compared with that in their paired normal esophageal mucous membranes (41.6% vs . 21.2% , P<0.05). Upregula-tion of ALC1 was associated with ESCC invasion, TNM stage, and lymph node metastasis (P<0.05). The overall survival of ESCC patients with ALC1 overexpression was significantly lower than that in patients with downregulated ALC1 expression (P=0.002). Therefore, ALC1 may promote the proliferation, invasion, and migration of ESCC cells. Conclusions: ALC1 upregulation may play an important role in the progression and development of ESCC. Upregulation of ALC1 leads to poorer disease prognosis, and could promote the prolifera-tion, invasion, and migration of the KYSE30 ESCC cells. Therefore, ALC1 may have potential prognostic value for ESCC patients.