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.

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.

[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.

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.

OBJECTIVETo evaluate the outcome of radical surgery combined with adjuvant radiotherapy for patients aged over 75 years with stage II( or III( rectal cancer.

METHODSFrom 2000 to 2010, 178 patients aged over 75 years at diagnosis who underwent radical surgery in National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were selected from 3995 patients with stage II( or III( rectal cancer in the database of the above center and enrolled into this retrospective cohort study, which was approved by ethics committee of the above hospital (ClinicalTrials.gov number, NCT02312284).

RESULTSMedian age of patients was 77 years (range 75-87). There were 37 (20.8%), 69 (38.8%), and 72 (40.4%) patients with tumors locating in the high, middle and low rectum respectively; 89(50%) patients of pathological stages II( and III( respectively; 21(11.8%), 137(77%), 19(10.7%), and 1(0.6%) patients with poorly, moderately, well differentiated adenocarcinoma, and mucinous adenocarcinoma respectively. The Charlson/Deyo comorbidity index (CCI) score was 0 in the majority (73.6%) of patients. Fifty-three patients underwent abdominoperineal resection, 116 underwent low anterior resection and 9 underwent Hartmann resection. All the patients received computed tomography-based simulation and treatment planning using an anal marker in a prone or supine position. Patients were treated with linear accelerator by megavoltage photons (6MV), with 2D technique in early years and 3D conformal or simplified intensity-modulated radiotherapy technique later, at a dose of 50 Gy in 25 fractions to the pelvis within an overall treatment time of 35 days. Sixty-one patients (34.3%) received surgery combined with radiation (ART group), in whom 16 received radiation alone 117 patients did not receive radiation(NORT group). The baseline data between ART and NORT group were not significantly different(all P>0.05). There was no significant difference in 5-year overall survival between ART and NORT groups (61.0% vs. 63.0%, P=0.586). The cumulative local relapse was 10.9% and 25.4% in ART and NORT group respectively (P=0.032). Cox multivariate analysis revealed that surgery combined with radiation improved local control significantly(HR=0.27, 95%CI:0.11-0.68, P=0.005).

CONCLUSIONSFor elderly patients aged over 75 years with stage II( or III( rectal cancer, radical surgery combined with radiation does not increase the overall survival, but can improve local control rate. It is reasonable to selectively apply adjuvant radiotherapy to the elderly patients in the setting of radical surgery.

Adenocarcinoma ; radiotherapy ; surgery ; Aged ; Aged, 80 and over ; Humans ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Rectal Neoplasms ; radiotherapy ; surgery ; Retrospective Studies

Objective To investigate the role of cell adhesion molecule L1 like (CALL) in the genesis and development of esophageal squamous cell carcinoma (ESCC).Methods From July 2007 to December 2010,a total of 100 patients with ESCC who received radical resection of esophageal cancer were enrolled.The ESCC tissues and corresponding tumor-adjacent normal tissues were obtained.The expression of CALl was determined by tissue microarray technology and immunohistochemical staining.The CALL over-expressed esophageal cancer cell line was established.The effects of CALL on cell migration and invasion were detected by wound-healing assay and Transwell assay,respectively.The effects of CALL on actin microfilament was analyzed by filamentous actin (F-actin) staining.Chi square test,Fisher's exact test,multivariate analysis and t test were performed for statistical analysis.Results The positive expression rate of CALL in ESCC tissues was 56 ％ (56/100),which was lower than that of tumor-adjacent normal tissues (95％,95/100),and the difference was statistically significant (x2=41.114,P＜0.01).There were statistically significant differences in CALL expression at protein level among patients with ESCC of different differentiation degree,different pathological T stage,lymph node metastasis and different TNM stage (x2=13.702,5.317,21.453,Fisher's exact test;all P＜ 0.05).The five year disease related survival rate of ESCC patients with down-regulated expression of CALL was 0(0/49),which was lower than those with normal CALL expression (25.5％,13/51),and the difference was statistically significant (x2 =43.338,P＜0.01).The median survival time of CALL expression down-regulated group was 17 months,and that of normal expressed group was 38 months.CALL expression was an independent risk factor of disease special survival rate (hazard ratio (HR) 0.353,95％ confidence interval (CI) 0.188 to 0.666,P=0.001).The results of wound-healing assay showed that the migration ability of CALL overexpressed CALL-k30 cells was lower than that of Vec-k30 cells in control group on 24 hours after wound.The results of Transwell invasion test showed the number of migrating cells penetrating CALL k30 cells attached to the inferior surface of the membrane was 44.000±13.748,which was less than that of the Vec k30 cells (154.333±25.007),and the difference was statistically significant (t=5.136,P=0.036).The results of F-actin staining demonstrated that actin filaments of CALL-k30 cells was 234.667 ± 65.118,which was lower than that of Vec-k30 cells (597.000± 119.929),and the difference was statistically significant (t=4.707,P=0.042).Conclusions CALL lowers the migration and invasion abilities of esophageal cancer cells by inhibiting F-actin microfilaments.Its abnormal expression may play an important role in the genesis,development and prognosis of ESCC.

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.