Background: WHSC1 is a histone methyltransferase that facilitates histone H3 lysine 36 dimethylation (H3K36me2), which is a permissive mark associated with active transcription. Colorectal cancer (CRC) is the 4th deadliest and 3rd most frequent cancer globally. However, the role of WHSC1 in CRC progression remains unknown. Methods: qRT-PCR, immunoblotting assays (WB), and immunohistochemistry (IHC) staining was performed to investigate WHSC1 expression levels in CRC tissues and normal tissues. CCK-8 assays, colony formation assays, and flow cytometry were also used to assess the effect of WHSC1 depletion in CRC cell proliferation, apoptosis and oxaliplatin sensitivity in vitro. A cell line-derived xenograft model in nude mice was performed to determine the role of WHSC1 in CRC cell apoptosis in vivo. Results: WHSC1 as well as H3K36me2 were highly expressed in clinical CRC tissues compared with in normal counterparts. High WHSC1 expression was correlated with poorer prognosis in CRC patients. Knockdown of WHSC1 significantly promoted CRC cell apoptosis and inhibited tumour growth in vivo. Further mechanistic investigation revealed that WHSC1 directly binds to the promoter region of BCL2 gene and regulate its H3K36 dimethylation level, so BCL2 expression is markedly decreased after WHSC1 depletion. Conclusions: Our findings demonstrated that knockdown of WHSC1 promoted colon cancer cell apoptosis and suppressed CRC tumorigenesis through targeting BCL2 transcription, suggesting WHSC1 activity may be a potential therapeutic target for the treatment of CRC.

Background: There is a well-established relationship between cell cycle progression and the development of stomach adenocarcinoma. This study aimed to elucidate the molecular mechanism and biological function of APBB2 in gastric cancer. Methods: Gastric adenocarcinoma (GA) data were downloaded from the TCGA-GA and GEO databases and analyzed to explore differentially expressed miRNAs and mRNAs. Moreover, potential target mRNAs were also predicted. The relative level of gene and protein expression in GA cell lines and gastric mucosa cells was detected by q-PCR and Western blot, respectively. Moreover, the influence of APBB2 on proliferation, metastasis, and cell cycle changes in SGC-7901 and BGC-823 cells was evaluated. The binding relationship between the target miRNA and mRNA was confirmed with a dual-luciferase reporter assay. Results: High APBB2 expression was detected in GA patients, indicating that it may be represent a predictive biomarker for poor prognosis. Related experiments confirmed that APBB2 silencing inhibited GA cellular functions, including proliferation, cell cycle progression, migration, and invasion. In addition, to explore the molecular mechanism, our results indicated that the binding sites were located at hsa-mir-30a and the 3'-UTR of APBB2, suggesting that hsa-mir-30a can regulate the expression of APBB2. The biological functions of hsa-mir-30a were also evaluated. Hsa-mir-30a overexpression attenuated the proliferation and metastasis of cancer cells. In rescue experiments, hsa-mir-30a was confirmed to reverse the cell cycle promoting function associated with APBB2 overexpression. Conclusion: Our findings show that hsa-mir-30a can attenuate the development of GA by down-regulating APBB2 expression.

Liver fibrosis is a key phase that will progress to further injuries such as liver cirrhosis or carcinoma. This study aimed to investigate whether transplantation of bone marrow mesenchymal stromal cells (BM-MSCs) can attenuate liver fibrosis in mice and the underlying mechanisms based on the regulation of macrophage subtypes.

Emerging reports suggest microRNAs (miRNAs) play a vital role in the progression of malignant tumors. MiR-30a is downregulated in a variety of cancers and acts as a tumor suppressing gene. However, the molecular mechanisms of miRNA-30a in hepatocellular carcinoma (HCC) are still unclear. Hereby, in this study, we detected that miR-30a expression was significantly down-regulated in both HCC tissues compared with adjacent non-cancerous liver tissues, and we also observed that miR-30a expression was lower in HCC cell lines than that of normal controls. By overexpression of miRNA-30a, we evaluated cell growth with CCK-8 assay and cell apoptosis by flow cytometry. The function of miR-30a on cellular migration in HCC cells was assessed. The potential target genes of miR-30a were analyzed with luciferase activity assay. Our data displayed that miR-30a mimic markedly inhibited HCC cell growth, induced cell apoptosis, and upregulated the expression of apoptotic proteins in HepG2 and MHCC976L cells. We also found that upregulation of miR-30a significantly inhibited HCC cells migration and invasion. Bioinformatics analysis revealed K-Ras was a regulative target gene of miR-30a, and further dual luciferase reporter assay showed that miR-30a directly binds to the 3′-untranslated region (3′-UTR) of K-Ras mRNA. Furthermore, we found that in HepG2 and MHCC97L cancer cells, miR-30a overexpression completely blocked the K-Ras/c-Raf/MEK/ERK pathway activation. Overall, these findings demonstrated that miR-30a might play a certain role in the cell growth, apoptosis and metastasis of HCC cells, partially via regulating K-Ras/c-Raf/MEK/ERK signaling pathway, potentially, it is therefore a candidate targeting biomarker for HCC therapy.

Objective: To investigate the associations of five non-synonymous variants of four DNA repair-relevant genes with gastric cancer (GC) in a large Han Chinese population. Methods: A hospital-based case-control study, comprised of 622 patients diagnosed with gastric cancer and 622 age-and gender-matched controls, was conducted. Blood samples were collected from patients and healthy control subjects to analyze polymorphisms of XRCC1 rs1799782, rs25487, XRCC3 rs861539, hOGG1 rs1052133, and NQO1 rs1800566. Risk estimates were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). Results: All five examined polymorphisms met Hardy-Weinberg equilibrium. Overall, significant differences were found in the genotype/allele distributions of rs1799782 in XRCC1, and rs1800566 in NQO1 (P < 0.05 for both), whereas no significant difference was observed among the other three variants between patients and controls (P > 0.05). The risk of gastric cancer associated with the rs1800566-T mutant allele was higher by 71% (95% CI [confidence interval]: 1.48-1.99; P < 0.001) under the additive model, and by 86% (95% CI: 1.48-2.33; P < 0.001) under the dominant model. The mutant-T allele of variant rs1799782 conferred increased GC risks of 27% (95% CI: 1.06-1.52; P = 0.009) and 42% (95% CI: 1.13-1.77; P = 0.002) under the additive and dominant models, respectively. Conclusions: Results suggest that the XRCC1 rs1799782 and NQO1 rs1800566 polymorphisms confer high susceptibility to GC in the Chinese population.

目的：探讨新型mTORC1／mTORC2双重抑制剂OSI‐027对人结肠癌细胞株HT‐29的体外抑制作用。方法：体外培养的人结肠癌HT‐29细胞株，给予不同浓度（0．1、1、10、25、50 nmol／L）的OSI‐027处理，或以25 nmol／L OSI‐027处理0、24、48、72、96 h后，采用四甲基偶氮唑盐（methyl thiazolyl tetrazolium ，MTT）法、细胞集落形成实验观察HT‐29细胞的生长增殖情况；应用流式细胞仪（FACS）及台盼蓝染色法检测OSI‐027处理后 HT‐29细胞的凋亡和死亡情况；采用蛋白质印迹（Western blotting）法检测HT‐29细胞凋亡相关蛋白cleaved‐caspase‐3和细胞色素C（cytochrome C）的表达。结果：OSI‐027可抑制HT‐29细胞的存活，且呈浓度和时间依赖性；还可抑制HT‐29细胞的增殖，呈浓度依赖性；此外，OSI‐027还能诱导HT‐29细胞的凋亡和死亡，并呈浓度依赖性。OSI‐027处理后，HT‐29细胞中凋亡相关蛋白cleaved‐caspase‐3和cytochrome C的表达水平上调。结论：新型mTORC1／mTORC2双重抑制剂OSI‐027可抑制人结肠癌细胞HT‐29的增殖并诱导细胞凋亡。

Background Gastritis cystica profunda (GCP) is an uncommon disease characterized by multiple cystic gastric glands within the submucosa of the stomach. Case description Here, we present a case of a 63-year-old man with intermittent epigastric discomfort in whom gastroscopy revealed multiple irregular elevated nodular lesions with smooth surfaces at the anterior of the antrum. Surgical resection of the nodular lesions was performed, and the diagnosis of gastritis cystica profunda (GCP) was confirmed by histological examination. Another elevated nodular lesion approximately 10 mm in diameter with an ulcer was found on the gastric side of the remnant stomach near the resection side from 6 to 24 months after the surgical resection. Endoscopic ultrasonography (EUS) and repeated biopsies of the new elevated lesion were performed. Homogeneous, anechoic masses originating from the submucosa without gastric adenocarcinoma in histological examination showed GCP recurrence may occur. Conclusions We report a case of GCP recurrence within 6 months after surgical resection. GCP should be considered in the differential diagnosis of elevated lesions in the stomach.

PURPOSE:To investigate the clinical effect of nutritional supplementation through percutaneous endoscopic gastrostomy on head and neck cancer patients undergoing radiotherapy.METHODS:One hundred and three head and neck cancer patients who received radiotherapy with food intake limitation and need of nutrition supplementation were randomly divided into two groups:PEG group of 47 cases and nasal feeding group of 56 cases.The patients were supplemented with same intensity food through percutaneous endoscopic gastrostomy and nasal intubation.Patients ’ mood,appetite,life quality,tolerance and compliance were observed during treatment.Infection situation was recorded,infection rate and average Defined Daily Dose(DDD) number during whole course were calculated.Nutrition index,including body weight,serum album,transferrin,were also tested before and after radiotherapy respectively.The data was analyzed with SPSS 11.0 software package.RESULTS:In clinical observation,patients' mood,appetite and life quality decreased unobviously after radiotherapy,but tolerance and compliance increased obviously,and social activities were not affected in PEG group.But in nasal intubation group,the status was not optimistic,patients ’ mood,appetite and life quality were depressed,their tolerance and compliance were bad,social activities were reduced.The infection rate in PEG group was 19.1%,which was significantly less than 33.9% of nasal intubation group(P=0.0292).Accordingly,DDDs in PEG group was 1.5,smaller than 4.3 of nasal intubation group.In nutrition index,body weight and serum album decreased sharply from(63.6±4.2) kg and(34.0±4.5) g/L before treatment to(60.7±2.5) kg and(31.4±3.8) g/L after treatment in PEG group,but transferrin increased from(27.6±3.9) μmol/L to(28.4±1.3) μmol/L,although no significant difference was noted.In the same way,body weight,serum album and transferrin decreased from(65.3±5.6) kg,(33.7±3.1) g/L and(28.2±2.1) μmol/L before treatment to(58.4±3.3) kg,(29.6±4.3) g/L and(26.2±2.3) μmol/L after treatment in nasal intubation group obviously(P 0.05).Although nutrition index decreased after radiotherapy,those loss in PEG group was much less than in nasal intubation group,respectively.CONCLUSIONS:Supplementation through percutaneous endoscopic gastrostomy in head and neck cancer patients who undergo radiotherapy does not increase infection rate,and can improve patients’ tolerance and compliance,accordingly improve their nutrition status and enhance their life quality.PEG can be used in head and neck cancer patients’ nutrition who receive radiotherapy.

BACKGROUND/AIMS:TGF-β has dual functions as a tumor promoter or a tumor suppressor. Recent studies suggest the roles of TGF-β might change from a tumor suppressor to a tumor promoter, when lacking SMAD4 expression in CRC (colorectal cancer). However, the precise role of TGF-β as tumor promoter in CRC is still unclear.METHODOLOGY:We evaluated the role of TGF-β in SMAD4-null CRC SW620 cells. In vitro, we measured cell growth and cell cycle distribution by flow cytometry. In vivo, we implanted SW620 cells into mice and measured tumor weight after TGF-β treatment. We also determined cell proliferation ability in tumor by immunohistochemistry of proliferating cell nuclear antigen (PCNA).RESULTS:Cell growth and DNA synthesis in S phase was remarkably enhanced by TGF-β in vitro. Besides, TGF-β-activated ERK1/2 MAPK signal was also observed. In vivo, TGF-β enhanced tumor growth and cell proliferation in tumor.CONCLUSIONS:TGF-β serves as a tumor promoter, which promotes CRC cell growth in vitro and in vivo. These suggest that TGF-β might be developed as an effective therapeutic target for CRC patients.

Objecfive: To evaluate the effects of supplementation through percutaneous endoscopic gastrostomy on oral and maxillofacial malignant tumor patients undergoing comprehensive management. Methods: 163 oral and maxillofacial malignant tumor patients undergoing comprehensive management were divided into two groups: PEG group of 77 cases and nasal feeding group of 86 cases,and were supplemen- ted with same intensity food through percutaneous endoscopic gastrostomy and nasal intubation. Patients ' mood,appetite,life quality,tolerance and compliance were observed during treatment. Changes of body weight,body mass index and percentage of body weight loss were calculated. Nutrition index were also tested before and after treatment respectively. Results: Patients' mood,appetite and life quality didn't decrease after therapy,but tolerance and compliance increased obviously,and social activities were not been affected in PEG group. But in nasal intubation group,data were not optimistic,patients' mood,appe- tite and life quality were depressed,their tolerance and compliance were bad,social activities were re- duced too. Body weights,percentages of body weight loss and body mass indexes of two groups were de- creased,but numbers decreased in PEG group were much less than control group. Although serum album and transferrin of two groups decreased sharply after therapy,those loss in PEG group was much less than those in nasal intubation group. Conclusion: Supplementation through percutaneous endoscopic gastros- tomy in oral and maxillofacial malignant tumor patients undergoing comprehensive management can improve patients' tolerance and compliance,decrease body weight loss effectively and improve the nutrition status.

Ambient air pollution has been associated with increased mortality and morbidity; however, few studies have examined the short-term effect of air pollution specifically on chronic obstructive pulmonary disease (COPD), which is an important cause of mortality and morbidity world wide. In this analysis, we examined the associations between daily air pollution levels [particulate matter less than 10 microns in aerodynamic diameter (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2)] and COPD mortality in four Chinese cities. We used Poisson regression models with natural spline smoothing functions to adjust for long-term and seasonal trends of COPD mortality, as well as other time-varying covariates. We did a meta-analysis to obtain the 4-city average estimates. Air pollution (PM10, SO2, and NO2) was found to be associated with increased risk of COPD mortality in these four cities. Using the random-effects model, an increase of 10 mu g m(-3) of 2-day moving average concentrations of PM10, SO2 and NO2 corresponded to a 0.78% (95% CI, 0.13-1.42), 1.30% (95% CI, 0.61-1.99), and 1.78% (95% CI, 1.10-2.46) increase of COPD mortality, respectively. The concentration response curves indicated linear associations without threshold. Only NO2 remained significant in the multi-pollutant models. To our knowledge, this is the first multi-city study in Asian developing region to report the short-term effect of air pollution on COPD mortality. Our results contribute to very limited data on the effects of air pollution on COPD mortality for high exposure settings typical in developing countries. (C) 2013 Elsevier Ltd. All rights reserved.

一、对象和方法 1.对象:2000年1月至2005年12月,我院老年消化病房共收治上消化道出血患者418例,男297例,女121例;其中老年患者143例,男111例,女32例,年龄60～87岁,平均72.6岁;

Objective To study the effect of mosapride and omeprazole on treatment of reflux esophagitis(RE).Methods 100 RE patients were randomly divided into two groups,the treatment group(50 cases):5 mg of mosapride tid,20 mg of omeprazole qd were taken orally;the control group(50 cases):20 mg omeprazole qd were taken orally.The symptoms were evaluated from pretreatment to every two weeks after the treatment.Recheck the endoscope findings at the end of 6 weeks.24-hour esophageal pH was performed in two groups.Results The clinical curative rates were 100% in the treatment group and 88% in the control group,the efficient rate evaluation under endoscope were 96%,84% respectively.After 6 weeks,the total number of pH4 and the total percentage of pH4 were decreased in two group(P0.05).There was significant difference between the two groups(P0.05).Conclusion The effect of mosapride combined with omeprazole on treating the reflux esophagitis was obviously superior to the other group.

Objective To investigate the clinical effect of mosapride in treating functional dyspepsia(FD).Methods Eighty-four patients meeting Rome Ⅱcriterion were randomly received either mosapride 5mg tid(group,A 42 patients)or domperidone 5mg tid(group,B 42 patients) for 4 weeks.The symptoms were evaluated before treatment and at the end of 4th week.Gastric emptying of solid food was examined by using radiopaque markers in twelve patitens from group A and group B,respectively.Results The clinical curative rates were 85.71% in group A and 66.67% in group B.There was significant difference between two groups(P0.05).After the treatment the average number of barium strip expelled from stomach were 4 in group A and 3 in group B before treatment and was significantly increased to 18 and 12(P0.01),respectively.Conclusion Mosapride has better clinical effect than domperidone on the treatment of FD.

目的 观察以埃索美拉唑为基础的三联短疗程治疗方案对幽门螺杆菌(Hp)阳性的十二指肠溃疡的治疗效果.方法 40例Hp阳性的十二指肠球部溃疡患者随机分为试验组和对照组,每组各20例.试验组给予埃索美拉唑20 mg、阿莫西林1000 mg以及呋喃唑酮100 mg口服,每日2次,共7 d.对照组服用奥美拉唑20 mg、阿莫西林1000 mg和呋喃唑酮100 mg,每日2次,共7 d;7 d后继续给予奥美拉唑20 mg口服,每日1次,共3周.2组患者在入选研究前和第4周后接受胃镜和快速尿素酶试验检查,观察溃疡愈合情况以及Hp根除情况并进行比较和评价.结果试验组的溃疡愈合率为90%,Hp根除率为95%;对照组分别为95%和90%.两组患者的顺应性均很好,均顺利完成了试验,两组不良反应发生率相当.结论以埃索美拉唑为基础的三联短疗程方案可有效根除Hp,促进十二指肠溃疡愈合,具有良好的经济学价值.

Objective To investigate the effect of spironolactone on expression of α1(Ⅰ) and α1(Ⅲ) procollagen mRNA in rat hepatic liver fibrosis.Methods Fifty male SD rats were randomly divided into 3 groups.Hepatic fibrosis model group: the rats were injected with 400 mL/L CCl4 3 mL/kg subcutaneously two times a week for 10 weeks (Group A)or 13 weeks(Group B).Spironolactone group: the rats were injected with 400 mL/L CCl4 3 mL/kg subcutaneously two times a week.Spironolactone equivalent to 20 mg/kg per day was given intragastrically for 10 weeks(Group C)or 13 weeks(Group D).Normal control group: normal chow.The expression of α1(Ⅰ) and α1(Ⅲ) procollagen mRNA were detected by RT-PCR.Results At the end of week 10,the levels of α1(Ⅰ)and α1(Ⅲ) procollagen mRNA were significantly decreased in spironolactone group(P0.05).At the end of week 13,there was no significant difference between two groups.Conclusion Spironolactone may have a certain fibrogenesis-inhibiting effect on CCl4-induced hepatic fibrosis.