Esophageal cancer is a unique malignant disease in China. A fundamental difference exists between the Chinese population and the western population on esophageal cancer in terms of epidemiology, histogenesis, and carcinogenic risk factors. Therefore, ap-plying the western academic achievements to Chinese is difficult. Thus, Chinese scientists have the responsibility to conquer esopha-geal cancer in China. This article reviews the progress of esophageal cancer focused on the molecular mechanism for interactions of ge-netic and environmental risk factors and human esophageal multistage carcinogenesis.

Objective:To investigate the effect of focal adhesion kinase related non kinase (FRNK) on the activation and migration of hepatic stellate cells (HSCs).Methods:Human liver tissue was divided into healthy control group and fibrosis group from March 2019 to September 2019 in Affiliated Hospital of Guizhou Medical University. C57BL/6 mice were divided into wild type (WT) and FRNK gene knockout type (FRNK -/-) groups. The liver fibrosis model was established with carbon tetrachloride (CCl 4). After that, FRNK gene overexpression (Ad-FRNK) was constructed with adenovirus vector. HE and Masson staining were used to evaluate the pathological changes and fiber deposition of liver tissue. Western blot was used to detect the expression of PY397-FAK and α-SMA protein. Mouse primary HSCs were extracted, and the effect of FRNK on HSCs migration was detected by wound healing, activation of Rac and Rho was detected by Western blot. Results:The expression of PY397-FAK protein in human liver tissue with hepatic fibrosis was significantly higher than that in healthy control group (0.88±0.09 vs. 0.73±0.09). FRNK was significantly lower than that in control group(0.68±0.09 vs. 0.79±0.11). After animal model was set up, the degree of liver fibrosis in FRNK -/-mice (153±13)% was more serious than that in WT (100%) group. The expression of PY397-FAK and α-SMA protein was significantly elevated (2.50±0.23 vs. 0.75±0.09, 1.46±0.20 vs. 0.92±0.10). After FRNK gene was re-expressed (100%), the degree of liver fibrosis was mainly reversed [(74±6)%], and the expression of PY397-FAK and α-SMA was accordingly decreased(0.68±0.11 vs. 1.12±0.19,0.68±0.10 vs. 0.85±0.06). In vitro, FRNK inhibited the migration of HSCs [WT∶FRNK -/-∶Ad-FRNK,(339±49)%∶(580±53)%∶(259±33)%] and the activation of Rac and Rho proteins (Rac: 0.54±0.07 vs. 0.91±0.10 vs. 0.77±0.12,Rho:0.45±0.05 vs. 0.64±0.06 vs. 0.53±0.07), all P<0.01. Conclusions:FRNK can inhibit the activation and migration of HSCs which contributed to liver fibrosis. The potential mechanism is related to down regulation of PY397-FAK and inhibition of Rac and Rho activation.

Objective To investigate the common risk factors of primary hepatocellular cancer (PHC) in Guizhou province . Methods The group case-control study was adopted .The main related-factors of primary PHC in Guizhou provincial population and the relation between drinking combined hepatitis B viral infection with the PHC occurrence were analyzed by the unconditional Logistic regression analysis and the stratification analysis .Results Drinking(OR=2 .948 ,95% CI 2 .096-4 .146 ,P=0 .000) ,eco-nomic status 5 years ago(OR=0 .386 ,95% CI 0 .279 -0 .534 ,P= 0 .000) ,family history of PHC(OR= 2 .402 ,95% CI 1 .372 -4 .206 ,P=0 .002) ,cigarette smoking (OR=3 .468 ,95% CI 2 .265 -5 .311 ,P=0 .000) ,chronic liver disease(OR= 1 .502 ,95% CI 1 .054-2 .141 ,P=0 .024) ,HBV infection(OR=31 .999 ,95% CI 19 .318 -53 .002 ,P=0 .000) and diabetes mellitus(OR=4 .750 , 95% CI 2 .761-8 .171 ,P=0 .000) ,the differences between the patients group and the control group had statistical significance ;the OR value of drinking combined with HBV infection was 96 .903(95% CI 35 .265-266 .275 ,P=0 .000) .Conclusion HBV infection is still the common risk factor of PHC in Guizhou provincial population .Drinking can increase the risk in the individuals infected with HBV .

Objective To observe the expression of survivin and Aurora B in human pancreatic cancer BXPC3 cells after the treatment of sulindac and to explore the potential mechanism. Methods MTr assay was used to determine the effect of sulindac on the proliferation of the BXPC3 cells. RT-PCR was used to detect the expression of mRNA level of survivin and Aurora B, western blot was used to detect protein expression of survivin and Aurora B Thr-232. Cell cycle and apoptosis were detected by flow eytometry (FCM). Results The BXPC3 cells were inhibited by sulindac in a dose and time-dependent manner; the expression of mRNA of survivin and Aurora B were both significantly decreased from 1.5644 and 0.6554 to 0. 4372 and 0.1132 (P< 0.01), the expression of survivin protein and the phosphorylation of Aurora B Thr-232 were also decreased from 1.2735 and 0.4680 to 0.2126 and 0.2546 (P<0.01); the proportion of cells in the G0/G1 phase was increased from (56.65±1.93)% to (70.58±3.21)% (P<0.01). Conclusions Sulindac had inhibitory effects on the growth of BXPC3 cells, the possible mechanism was via decreasing the expression of survivin which depressed the activity of Aurora B, then the CPC was influenced. The most of the cells were blocked in the G0/G1 phase, and the cells' mitosis was inhibited.

Objective To investigate the effect of genistein on Notch-1, SHH and HHIP gene expression and on the cell cycle and proliferation of of BxPC3 cells. Methods Human pancreatic cancer cell line BxPC3 was cultured. The BxPC3 cells were treated with genistein and then the total RNA and protein were extracted. RT-PCR was used to detect the expression of Notch-1 mRNA, SHH mRNA and HHIP mRNA. Noteh-1 and SHH protein was determined by western blotting. MTT assay was used to detect proliferation of BxPC3 cells. The cell cycle of BxPC3 cells was measured by Propidium iodide (PI) and flow cytometry. Results The inhibiting rate was 67.17%±2.32% when BxPC3 cell lines were treated by 20μg/ml genistein for 48 hours. Notch-1 mRNA was down-regulated from 2.454±0.068 to 1.304±O.169 ; SHH mRNA was down-regulated from 0.959±0.023 to O.472±0.077 ; HHIP mRNA was up-regulated from 0.625±O.158 to 1.761±0.121. Notch-1 protein expression was down-regulated from 1.361±0.109 to 0.760±0.114; SHH protein expression was down-regulated from 0.265±0.018 to 0.129±0.013. (52.77±9.47)% cells were hindered in G2/M stage. Conclusions Genistein could down-regulate Notch-1 expression and inactivate Hedgehog signaling pathway and inhibit the proliferation of pancreatic cancer cells.

Objective:To investigate the expression level of synaptophysin (Syn), tissue neuronal cell adhesion molecule 56 (CD56) and chromogranin A (CgA) in 92 primary esophageal small cell carcinoma (PESC) and to explore its repationship with clinicopathological features and clinical outcome. Methods:Immunohistochemical studies of CD56, CgA, and Syn were performed in 92 paraffin-embed-ded tissues with clinical-related information obtained from 500,000 esophageal and gastric cardia carcinoma databases established by Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital of Zhengzhou University in Henan, China. Binary logistic regression was used to analyze the correlations of CgA, Syn, and CD56 expression with clinicopathological features. Kaplan-Mei-er survival analysis and Cox proportional hazards regression models were performed for univariate and multivariate survival analyses. Log-rank test was used to compare the difference in survival rates. Results:The CgA-positive expression rate in PESC at lower segment of esophagus (72.2%) was higher than those at the middle and lower segments (41.1%, 10.0%) (P=0.001). The expression level of CD56, CgA, and Syn was not correlated with gender (P=0.262, 0.998, 0.931), age (P=0.250, 0.998, 0.703), tumor invasion (P=0.253, 0.997, 0.061), and lymph node metastasis (P=0.767, 0.998, 0.613). Univariate analysis showed no survival influence in patients with and without lymph node metastasis (P=0.563). Multivariate survival analysis showed that patients with PESC mixed squamous cell car-cinoma (HR=2.58;95%Cl, 1.11-5.98) and higher CgA protein expression (HR=1.87;95%Cl, 1.02-3.43) exhibited a longer survival time than those with pure PESC and without CgA expression. Conclusion:Tissue CgA level was associated with tumor location in PESC. His-tological type and tissue CgA expression were independent important prognostic factors, and lymph node metastasis exerted no influ-ence on survival in PESC.

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease in clinical practice and has a complex pathogenesis. At present, the "two- or three-hit" theory is still widely acknowledged as the major pathogenesis of NAFLD. However, in recent years, the role of liver immunological inflammation in the development and progression of NAFLD has been taken more and more seriously. This article elaborates on the mechanism of liver immunological inflammation in the development and progression of NAFLD from the perspective of liver immunological inflammation.

Objective:To analyze the clinicopathological characterization of primary esophageal benign tumor (EBT). Methods:A total of 1,058 EBTs were enrolled from 500,000 cases in an esophageal and cardiac tumor biological sample and clinical information data-base of Henan Key Laboratory for Esophageal Cancer Research (1973-2015) in the First Affiliated Hospital of Zhengzhou University. SPSS 21.0 software was applied for data analysis. Results:In this database, 1,058 cases with primary EBTs among the 249,246 esopha-geal tumor patients with detailed clinical and pathological information were identified with an incidence of 0.42%(1,058/249,246). A total of 544 patients were male with an average age of 50±11 years old, whereas 514 patients were female, with an average age of 52± 11 years old. Among the 10 types of EBTs, leiomyoma was the most common type (84.50%, 894/1,058), followed by papilloma (6.90%, 73/1058). Adenoma (0.38%, 4/1,058) was the rarest type. Leiomyoma, gastrointestinal stromal tumor, and neurofibroma mainly oc-curred in male patients. By contrast, lipoma, granulosa cell tumor, schwannoma, and hemangioma mainly occurred in female patients.All five cases of hamartoma occurred only in female patients. Given the incidence of≥50%as the common standard, the common EBT in sequence in young male patients was leiomyoma and gastrointestinal stromal tumor, whereas that in young female patients was granulosa cell tumor and lipoma. The common EBT in sequence in older male patients was papilloma, gastrointestinal stromal tumor, and leiomyoma, whereas that in older female patients was schwannoma, papilloma, leiomyoma, gastrointestinal stromal tumor, and hamartoma. Additionally, lipoma, hemangioma, neurofibroma, and adenoma in male patients and neurofibroma in female patients oc-curred in older patients. The different ages of patients with EBTs (P=0.034) and leiomyoma (P=0.004) had a statistical significance. In these EBTs, leiomyoma, papilloma, gastrointestinal stromal tumor, and schwannoma mainly occurred in the middle esophagus, where-as lipoma mainly occurred in the lower esophagus. The major treatment for EBT in the present study was surgery (57.54%, 492/855), which was followed by endoscopic resection (38.01%, 325/855) and others (4.45%, 38/855). Conclusion:The incidence of EBT is low, with a couple of different histological types. Gender, age, and predilection sites are different depending on the histological types of EBTs. Surgery and endoscopic resection are the major treatment methods.

Objective:To elucidate the factors influencing the differences in the survival rates of esophageal squamous cell carcinoma (ESCC) patients between the rural and urban regions in China. Methods:A total of 36,723 ESCC patients derived from the clinical data-bases containing 500,000 esophageal and gastric cardia carcinoma cases (1973-2015) of the Henan Key Laboratory for Esophageal Can-cer Research of the First Affiliated Hospital, Zhengzhou University, were analyzed. Of these patients, 33,625 were from the rural re-gions (91.6%), comprising 20,906 male patients with an average age of 58.98 ± 8.71 years and 12,719 females with an average age of 59.59 ± 8.53 years. The remaining 3,098 were from the urban regions and composed of 2,089 male patients with an average age of 60.84±9.10 years and 1,009 females with an average age of 62.46 ± 9.14 years. All the patients underwent radical esophagectomy, de-tailed histopathological diagnosis, and TNM staging. Chi square test, Kaplan-Meier, Log-rank, and Cox proportional hazards regression model were used to analyze the differences between ESCC patients from rural regions and those from urban regions and among the risk factors in prognosis. Results:Kaplan-Meier and Log-rank analysis results showed that the ESCC patients from the rural regions had significantly higher overall survival than the urban patients (χ2=12.971, P=0.000). Further analysis showed that rural patients≥50 years old and diagnosed with stage IIa and IIb (middle stage) ESCC had higher survival rates than urban patients in males and females (male:χ2=16.188, P<0.001;female:χ2=5.019, P=0.025). However, the survival rates of rural and urban patients with stage 0,Ⅰa,Ⅰb (early stage) and Ⅲa, Ⅲc, and Ⅳ (late stage) were similar (P>0.05). The results of Cox proportional hazards regression model analysis showed that age, gender, and TNM stages were independent risk factors for rural and urban ESCC patients. When the rural and urban ESCC patients were both considered, the Cox proportional hazards regression model analysis results showed that male ESCC patients≥50 years old, urban residence, and TNM stages were independent risk factors. Conclusion:Rural ESCC patients have significantly high-er overall survival than urban patients. Male, age of≥50 years old, urban residence, and TNM stages were independent risk factors for ESCC patient survival.

Objective:To investigate the clinicopathological characteristics, treatments, and survival of patients with esophageal adeno-squamous carcinoma (EASC). Methods:A total of 494 patients with EASC were selected from the clinical information databases of 500, 000 cases with esophageal and gastric cardiac carcinomas in the Henan Key Laboratory for Esophageal Cancer Research. Among the 494 EASC cases, 361 were males with an average age of 61.47 ± 8.32 years, and 133 were females with an average age of 65.56 ± 8.06 years. SPSS 21.0 software was applied to determine the statistical differences among the different groups. A life-table method was also used to calculate the five-year survival rate. A linear regression model was used to analyze the correlation of changes at different peri-ods. Results:The incidence of EASC in our database was 0.196%(494/251707). EASC occurred predominantly in male patients (male:female=2.71:1.00). The peak age was within 60-69 years in both males and females (39.6%vs. 40.6%). Notably, the incidence of male patients showed a downward trend (R2=0.063), whereas that of female patients showed an upward trend (R2=0.004). The prevalence of EASC was obviously higher in low-incidence areas for esophageal cancer than in high-incidence areas (53.1%vs. 46.9%, P<0.001). Ac-cording to the TNM staging criteria for esophageal cancer, phases II and III patients comprised the majority of cases, which accounted for 40.8%(173/424). The positive lymph node metastasis rate was 47.0%(206/438), and the number of positive lymph node metasta-ses ranged within 1-2 (48.5%, 100/206). In addition, preoperative biopsy was performed in 467 cases, and more than half of the pa-tients (53.96%, 252/467) were diagnosed before the operation. Surgical resection was the predominant treatment method for EASC (88.8%, 419/472). Only 1.9%patients (9/472) underwent radiotherapy and chemotherapy. The five-year survival rate of male patients who were neither smoking nor drinking of alcohol was higher than that of male smokers (26.5%vs. 12.1%). In patients with stagesⅠ,Ⅱ, andⅢ+Ⅳcarcinomas with surgery as lone treatment, the three-year survival rates were 64.7%, 50.9%, and 48.5%, respectively. Correspondingly, these rates were 51.7%, 47.8%, and 33.1%after adjuvant radiotherapy and chemotherapy. Conclusion:EASC is a rare type of esophageal malignant tumor. The preoperative biopsy pathological diagnosis has high misdiagnosis rate. Smoking and drinking of alcohol can influence the prognosis of patients. In EASC patients, lymph node metastasis easily occurs, and a simple surgery is bet-ter than other cancer treatments.