Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Objective:To understand the incidence of esophageal cancer in population at high risk in Yangzhong of Jiangsu province.Methods:Cluster random sampling method was conducted to select several natural villages from the high risk area of esophageal cancer in Yangzhong during 2011-2017. Local residents aged 40-69 years were selected as the target population and a total of 14 687 persons were diagnosed esophageal cancer by endoscopy and pathology.Results:Precancerous lesions were detected in 341 persons, with the detection rate as 2.32 % (341/14 687). Among them, there were 234 (1.59 %) cases with mild and 107 (0.73 %) cases with moderate esophageal hyperplasia. There were 77 positive cases with esophageal hyperplasia and the detection rate was 0.52 %. Among these positive cases, 41 showed severe esophageal hyperplasia/carcinoma in situ (0.28 %), with another 19 as early esophageal cancer (0.13 %) and 17 with invasive carcinoma (0.12 %). The overall early detection rate of positivity through active screening was 77.92 % (60/77), with trends of upwarding and then downwarding. The detection rate of esophageal lesions in men was higher than that in women ( P<0.05), but without significant gender specific differences seen in the detection rates of early esophageal cancer or invasive carcinoma ( P>0.05). The detection rates of all lesions other than invasive carcinoma, gradually increased with age ( P<0.05). The detection rate of invasive carcinoma reached the highest (0.39 %, 10/2 547) in the age group of 60-years and slightly decreased in the age group of 65-years old. Conclusions:Considerable numbers of patients with cancer and precancerous lesions in groups at high-risk can be found through the screening program for esophageal cancer, suggesting that the screening program is of great significance in improving the survival rate and quality of life. Attention should be paid to men, with elderly groups in particular, at high-risk in order to increase the detection rate of early cases.

Objective: To evaluate the effectiveness and benefit of the upper gastrointestinal cancer screening in Yangzhong city, Jiangsu province, from 2009 to 2015. Methods: From 2009 to 2015, 31 natural villages with high-incidence of upper gastrointestinal cancer were selected from Baqiao town, Youfang town and Xinglong sub-district in Yangzhong city. 13 776 residents aged 40 to 69 years old were recruited and screened for upper gastrointestinal cancer by using endoscopic examination and pathological diagnosis. Two economic evaluation methods, cost-effectiveness analysis and cost-benefit analysis, were performed to evaluate the current screening schemes. Results: The mean age of all respondents were (53.60±8.14) years old and the males accounted for 43.64% (6 012). A total of 502 cases of upper gastrointestinal tract lesions were detected, including 100 cases of cancer (62 cases of esophagus, gastric/cardiac early stage cancer, 38 cases of advanced stage cancer), 38 cases of severe esophageal hyperplasia/carcinoma in situ, and 15 cases of high-grade intraepithelial neoplasia in stomach/cardia, the detection rate was 0.73%, 0.28% and 0.11%, respectively; the early diagnosis rate was 75.16% (115/153). The cost of a precancerous lesion, a case diagnosed at the early stage and a positive case identified through the upper gastrointestinal cancer screening in Yangzhong City was 10 037.17, 30 460.64 and 22 895.25 RMB, respectively. The early detection cost index from 2009 to 2015 was 0.52, 0.56, 0.48, 0.48, 0.21, 0.30, and 0.26, respectively. The effectiveness-cost ratio from 2009 to 2015 was 3.41, 2.77, 2.66, 2.58, 4.99, 3.12, and 3.48, respectively. Conclusions The project of early diagnosis and treatment of upper gastrointestinal tract cancer in Yangzhong city has achieved good results and benefits.

Objective To evaluate the effectiveness and benefit of the upper gastrointestinal cancer screening in Yangzhong city, Jiangsu province, from 2009 to 2015. Methods From 2009 to 2015, 31 natural villages with high?incidence of upper gastrointestinal cancer were selected from Baqiao town, Youfang town and Xinglong sub?district in Yangzhong city. 13 776 residents aged 40 to 69 years old were recruited and screened for upper gastrointestinal cancer by using endoscopic examination and pathological diagnosis. Two economic evaluation methods, cost?effectiveness analysis and cost?benefit analysis, were performed to evaluate the current screening schemes. Results The mean age of all respondents were (53.60 ± 8.14) years old and the males accounted for 43.64% (6 012). A total of 502 cases of upper gastrointestinal tract lesions were detected, including 100 cases of cancer (62 cases of esophagus, gastric/cardiac early stage cancer, 38 cases of advanced stage cancer), 38 cases of severe esophageal hyperplasia/carcinoma in situ, and 15 cases of high?grade intraepithelial neoplasia in stomach/cardia, the detection rate was 0.73%, 0.28% and 0.11%, respectively; the early diagnosis rate was 75.16% (115/153). The cost of a precancerous lesion, a case diagnosed at the early stage and a positive case identified through the upper gastrointestinal cancer screening in Yangzhong City was 10 037.17, 30 460.64 and 22 895.25 RMB, respectively. The early detection cost index from 2009 to 2015 was 0.52, 0.56, 0.48, 0.48, 0.21, 0.30, and 0.26, respectively. The effectiveness?cost ratio from 2009 to 2015 was 3.41, 2.77, 2.66, 2.58, 4.99, 3.12, and 3.48, respectively. Conclusions The project of early diagnosis and treatment of upper gastrointestinal tract cancer in Yangzhong city has achieved good results and benefits.

Objective To evaluate the effectiveness and benefit of the upper gastrointestinal cancer screening in Yangzhong city, Jiangsu province, from 2009 to 2015. Methods From 2009 to 2015, 31 natural villages with high?incidence of upper gastrointestinal cancer were selected from Baqiao town, Youfang town and Xinglong sub?district in Yangzhong city. 13 776 residents aged 40 to 69 years old were recruited and screened for upper gastrointestinal cancer by using endoscopic examination and pathological diagnosis. Two economic evaluation methods, cost?effectiveness analysis and cost?benefit analysis, were performed to evaluate the current screening schemes. Results The mean age of all respondents were (53.60 ± 8.14) years old and the males accounted for 43.64% (6 012). A total of 502 cases of upper gastrointestinal tract lesions were detected, including 100 cases of cancer (62 cases of esophagus, gastric/cardiac early stage cancer, 38 cases of advanced stage cancer), 38 cases of severe esophageal hyperplasia/carcinoma in situ, and 15 cases of high?grade intraepithelial neoplasia in stomach/cardia, the detection rate was 0.73%, 0.28% and 0.11%, respectively; the early diagnosis rate was 75.16% (115/153). The cost of a precancerous lesion, a case diagnosed at the early stage and a positive case identified through the upper gastrointestinal cancer screening in Yangzhong City was 10 037.17, 30 460.64 and 22 895.25 RMB, respectively. The early detection cost index from 2009 to 2015 was 0.52, 0.56, 0.48, 0.48, 0.21, 0.30, and 0.26, respectively. The effectiveness?cost ratio from 2009 to 2015 was 3.41, 2.77, 2.66, 2.58, 4.99, 3.12, and 3.48, respectively. Conclusions The project of early diagnosis and treatment of upper gastrointestinal tract cancer in Yangzhong city has achieved good results and benefits.

Objective · To prepare recombinant human TIGIT protein in E.coli and characterize its ability in binding Fusobacterium nucleatum (Fn). Methods · The gene of immunomodulatory protein of human TIGIT was amplified and cloned into pGEX4T2, and recombinant plasmid was transformed into E.coli BL21 (DE3) for GST-TIGIT fusion proteins were purified by the GST affinity chromatography and the interaction between GST-TIGIT fusion protein and Fn was tested by a pulldown assay. Results · Recombinant GST-TIGIT fusion protein expressed successfully in E.coli and was purified to homogeneity by GST affinity column. This protein could specifically bind to Fn, but not Lactobacillus acidophilus. Conclusion · High purify and activity of human GST-TIGIT fusion protein can be achieved by the prokaryotic expression system, and the adhesion between this protein and Fn has been preliminarily explored, which provides basis for further characterize interaction between them.

α1-Antitrypsin (α1-AT) belongs to serine protease inhibitor (Serpin) superfamily and is the main protease inhibitor in human circulation. It can inhibit many proteases to protect tissues from digradation. The mutant Z (Glu342Lys) of α1-AT predisposes to the early onset of emphysema due to decreased functional α1-AT in the lung and to neonatal hepatitis due to accumulation of α1-AT polymers in the endoplasmic reticulum of hepatocytes, which disrupts the balance between protease and protease inhibitors. This paper reviews recent research progress on the pathogenic mechanism and the prognosis of α1-antitrypsin deficiency.

Objective :To investigate the expression of phosphorylated alpha B-crystallin in hepatocellular carcinoma(HCC) tissues and its significance .Methods : The expression level of phosphorylated alpha B-crystallin in HCC tissues from 403 cases was detected by immunohistochemical staining ,and its correlation with HCC clinicopathologic features and prognosis was analyzed .Results : The expression level of phosphorylate alpha B-crystallin (Ser 59 ) was correlated with tumor size ,tumor encapsulation ,vascular invasion and tissue differentiation ( P < 0 .05 or 0 .01) . However ,it was not correlated with age , gender ,HBsAg ,liver cirrhosis .Multivariate analysis showed that the expression level of phosphorylated alpha B-crystallin (Ser 59 ) was an independent factor for prognosis .Conclusions : The expression level of phosphorylated alpha B-crystallin (Ser 59 ) is correlated with the malignant phenotype and poor prognosis of HCC .

Objective:To establish an improved model of mouse partial hepatectomy for study on liver regeneration .Methods :Healthy 8~10 week old male C57BL/6 mice were anesthetized by intraperitoneal injection .Then ,common hepatic pedicle of left lateral lobe of liver and middle lobe of liver was wrapped around with 6-0 proline suture .6-0 proline was fixed on the sur-face of right middle lobe of liver ,which was 0 .2 cm away from the hepatic pedicle .Hepatic pedicle was ligated and left lateral lobe and middle lobe of liver were resected 0 .2 cm away from ligature .The postoperative survival rate and the situation of liver weight vecovery at 3rd day ,7th day ,and 14th day after the operation were observed .Results:An improved mouse model of partial hepatectomy ,of which left lateral lobe of liver and middle lobe of liver were resected ,was established .The weight of removed liver accounted for 66 .7% of total liver and the survival rate of mice was 100% .After liver resection ,the compensa-tory regeneration of remaining liver achieved 58 .2% of the total liver weight at the 3rd day ,78 .0% at the 7th day ,and 93 .2%at the 14th day after the operation .Conclusions :An improved mouse model of partial hepatectomy was successfully established for study on liver regeneration ,which has advantages such as simplicity ,operability and high success rate .

Objective:To study the expression of UHRF1 and its relationships with the clinicopathological characteristics in hepatocellular carcinoma(HCC) .Methods :The expression of UHRF1 was analyzed in 556 cases of tumor tissues and peritumor tissues of HCC by immunohistochemistry .The relationships of UHRF1 with the clinicopathological characteristics of HCC were assayed .Results:Immunohistochemistry showed that positive staining of UHRF1 located in the nucleus of HCC cells .The ex-pression levels of UHRF1 protein were higher in tumor tissues than in peritumor tissues .HCC patients with positive expression of UHRF1 protein accounted for 59% of the whole cohort .The expression of UHRF1 protein was significantly correlated with the size of tumor ( P<0 .01) ,differentiation (P<0 .05) and microvessel invasion(P<0 .01) .Conclusions :The overexpression of UHRF1 is correlated with the malignant phenotypes of HCC and probably implicated in the invasion and metastasis of HCC .