Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Objective To evaluate the application value of automatic tube current modulation (ATCM) in low dose chest scaning with 64-slices spiral dual-resource CT. Methods Randomly selected healthy people to participate in our hospital from March 2014 to July 2014 in subjects with chest CT examination were 200, 100,received low dose spiral CT examination,as the A group;the other 100 underwent routine CT plain scan,as the B group,All CT images were analyzed by two radiologists with double blind method.Image quality scores (IQS)of lung apex,middle lung and lower lung were made,the image standard deviation(SD)was measured,and the CTDIvol was also recorded,and the statistical analysis was performed. Results SD values in lung apex,middle and lower lungs was (34.34±2.17),(30.63±0.74),(30.74±1.21)in group A,and (36.82±2.51)、(34.15±1.98),(31.69±1.93 )in group B,as well as the corresponding IQS of these three sites were(1.83±0.36),(1.59±0.38),(1.64±0.34)in group A,and(2.31±0.47),(1.68±0.42),(1.73±0.48)in group B,respectively. SD value and IQS of group A were lower than those of group B in lung apex(P<0.05). Conclu-sion The application of ATCM in low dose chest CT scanning plus noise suppression can provide more homogeneous images with better image quality.

Objective To investigate the effects of different doses Alpha-Linolenic acid ( ALA ) on the expressions of fatty acid synthesis-related genes in HepG2 cells.Methods HepG2 cells were divided into two groups, normal control group (NC) and high fat group (HF) in which cells were firstly cultured for 36h in the medium contained 0.5mmol/L stearic acid.Real-time quantitative PCR was taken to detect mRNA expression of genes SREBP1C, FAS and ACC which are related to fatty synthesis.While there are significant differences in fatty synthesis, 10%, 20%, 50%, 70% and 100%ALA took the place of stearic acid, 36h later, real-time quantitative PCR and Western blotting were taken to detect mRNA and protein expression of genes related to fatty synthesis.Results SREBP1C mRNA expression of ALA substitution groups were significantly lower than the high-fat group ( P <0.001) .The FAS of 0.5 mmol/L ALA group and 0.35 mmol/L ALA group were significantly lower than the high-fat group (P <0.001).ACC genes mRNA level was not significantly different from high-fat group.SREBP1C and FAS protein expression were significantly lower than the high-fat group, but ACC showed no significant difference.Conclusions Saturated fatty acids promote hepatocyte fatty acid synthesis, ALA abates fatty acid synthesis by inhibiting FAS and SREBP1C gene expression.

Objective To evaluate previous gastroscopy before percutaneous coronary intervention (PCI) for the risks and benefits of concomitant use of proton pump inhibitors (PPIs) after PCI in patients with non-acute coronary syndrome (non-ACS).Methods The data of 673 non-ACS patients who underwent PCI with stenting were retrospectively analyzed.They were divided into concomitant use of PPIs group and non-PPIs group,then subdivided into high-,moderate-and low-risk groups according to risk factors associated with adverse upper gastrointestinal (GI) events.The incidences of adverse cardiovascular events and adverse upper GI events were compared among groups.Findings of previous gastroscopy were also included.Results Only 82 patients (12.2％) underwent gastroscopy within 5 years before PCI,of whom,27 (32.9％) were diagnosed as having peptic ulcer,and 55.6％ (15/27) of whom were in concomitant use of PPIs.Compared with the non-PPIs group,the rate of adverse cardiovascular events in the concomitant use of PPIs group was significantly higher (22.6％ vs.8.9％,P ＜0.01),and the highest rate (41.7％) was in the high-risk group.However,the corresponding rate of adverse upper GI events was the lowest (4.2％).In the moderate-risk group,90.5 ％ (344/380) of patients were older than 65 years with concomitant use of NSAIDs.The rate of gastroscopy within 5 years before PCI in these patients was remarkably lower than that in patients who had the history of upper GI disease with concomitant use of NSAIDs (concomitant use of PPIs group 14.1％ vs.54.5％ ; non-PPIs group 7.5％ vs.28.0％ ; P ＜ 0.01).In the concomitant use of PPIs group,the rate of adverse cardiovascular events in the former was notably higher than that in the latter (20.5％ vs.9.1％,P ＜0.01),but the rate of adverse upper GI events within 1 year after PCI were similar (9.0％ vs.9.1％).Conclusion Previous gastroscopy before PCI could provide the baseline information of upper GI disease,which may be helpful for the evaluation of concomitant use of PPIs after PCI so as to decrease the incidence of adverse cardiovascular events.Special attention should be paid to those patients older than 65 years in the moderate-risk group and concomitant use of NSAIDs.

Objective To investigate the difference between Asia-Pacific Colorectal Screening (APCS) scoring system and colorectal cancer sequential screening criteria issued by the Health Ministry of China (China sequential criteria) in the evaluation of high-risk colorectal neoplasm in patients undergoing coronary artery angiography (CAG) examination.Methods The data of 870 patients aged from 40 to 74 who underwent CAG examination were retrospectively analyzed.The measurement data were analyzed by t test and the count data were aralyzed by x2 test.Results There were 72 patients aged from 40 to 49 years old.Among them,eight patients were stratified as high-risk population according to the Chinese sequential criteria; however there was no high-risk population by APCS.There were 798 patients aged from 50 to 74 years old.There were 460 patients stratified as high-risk population by APCS.The percentage of CAG negative group (34.7％) was significantly lower than that of the coronary artery disease (CAD) group (68.0％,x2 =77.74,P＜0.01).According to the Chinese sequential criteria,and there were 134 patients stratified as high-risk population,and there was no significant difference between the CAG negative group (17.7 ％) and the CAD group (16.4％,P＞0.05).Among the patients aged from 50 to 74 years old without family history of colorectal cancer in first-degree relatives,72 cases (29.0％) of the CAG negative group and 316 cases (57.5％) of the CAD group were stratified as high-risk according to APCS,however not stratified as high-risk by the Chinese sequential criteria.About 90.5 ％ (351/388) of them were male smokers.According to APCS,30 cases (12.1％) of the CAG negative group and 32 cases (5.8％) of the CAD group were stratified as middle-risk population,however stratified as high-risk population by the Chinese sequential criteria.About 75.8％ (47/62) of them were female non-smokers.Conclusions The percentage of patients stratified as high-risk population by APCS was higher than that by the Chinese sequential criteria.In patients aged from over 50 to 74 years old and without family history of colorectal cancer in first-degree relative,APCS maybe overestimated the risk degree of colorectal neoplasm in male smokers and underestimated the risk degree in female non-smokers.

Comparative pharmacokinetic (PK) analysis is often carried out throughout the entire period of drug development, the common approach for the assessment of pharmacokinetics between different treatments requires that the individual PK parameters, which employs estimation of 90% confidence intervals for the ratio of average parameters, such as AUC and Cmax, these 90% confidence intervals then need to be compared with the pre-specified equivalent interval, and last we determine whether the two treatments are equivalent. Unfortunately in many clinical circumstances, some or even all of the individuals can only be sparsely sampled, making the individual evaluation difficult by the conventional non-compartmental analysis. In such cases, nonlinear mixed effect model (NONMEM) could be applied to analyze the sparse data. In this article, we simulated a sparsely sampling design trial based on the dense sampling data from a truly comparative PK study. The sparse data were analyzed with NONMEM method, and the original dense data were analyzed with non-compartment analysis. Although the trial design and analysis methods are different, the 90% confidence intervals for the ratio of PK parameters based on 1000 Bootstrap are very similar, indicated that the analysis based on NONMEM is a reliable method to treat with the sparse data in the comparative pharmacokinetic study.

Objective To improve the clinic,CT and pathologic knowledge of pleomorphic hyanilizing angiectatic tumor of soft parts(PHAT).Methods Clinical,CT and pathologic characters of PHAT in one case at the right nuchal region were detailedly analysed with literature review.Results The clinical symptoms of PHAT were slight and unspecified.The lesion appeared as a orbicular-ovate tumour with sublobe and clear edge,the density of tumor was uneven on plain scan and uneven enhanced after injected contrast agent,and a part of the tumour was enhanced close to the CT value of blood vessel.The characters of pathology were the presence of clusters of dilated thin-walled vessels,with prominent hyalinization of vessel wall,perivascular and intercellular hyalinization,and pantomorphia neoplastic cell distributed between these dilated vessels.Conclusion PHAT is a low potential malignant soft tissue tumor,it has some specific CT and pathologic characters.

Objective To study the clinical CT manifestations of infective ovarian cysts so as to improve diagnostic ability.Methods All the cases were evaluated on plane scan and enhancement scan.Their manifestations on CT were analysed.Results The cysts lying in the left ovary account for 14 cases, in the right ovary 4 cases. The size of cysts varied from 11 cm?10 cm?11 cm to 4 cm?3 cm?4 cm. The cyst walls thickened to some extent. 15 cases thickened “gradually”. 3 cases thickened “comparatively evenly”. The thickness of the cyst walls was over 1 cm, the thickest being 2 cm. The length of the thickened wall was more than one half circumference of the cyst, with smooth inner side.The cyst wall showed the density of soft tissues and it was mildly intensified after being enhanced.Conclusion The clinical CT manifestations of infective ovarian cysts have certain characteristics.

Objective To investigate the CT features and the diagnostic value in invasive mole. Methods Eleven cases (age, 30 to 53 years, mean 40 years)with invasive mole proved by operation and pathology were studied, including 3 cases during peri menopausal period of eight months, ten months and twelve months respectively. All cases were scanned by CT and enhanced study was done. Results All cases showed enlargement of uterus of varying degrees. On CT, the density of uterine cavity was similar to that of water, intermingled with spotty patchy and hazzy circular isodense shadows. High density stripe like bleeding foci were found in 3 cases.The outline of uterine cavity was locally disrupted in all case and the muscle layer was thickened in 3 cases. On enhanced CT scan, the lesions in the uterine cavity appeared markedly hyperdense, just like “the crater” and the “mole sign” .The muscle layers at the site of disruption showed inhomogeneous enhancement after contrast injection. Conclusion The CT features of invasive mole are characteristic, with important diagnostic value, especially for those during peri menopausal period.

The clinical data of 67 patients underwent orthotopic liver transplantation, including 4 cases of early intra abdominal hemorrhage after orthotopic liver transplantation, were analyzed retrospectively.Anastomotic liver artery hemorrhage was found in 2 cases, hemorrhage of IVC in 1 case and hemorrhage of right adrenal gland in 1 case. All the 4 patients were correctly dignosed and successfully treated by operation in time. It suggests that the early intra abdominal hemorrhage after orthotopic liver transplantation is mostly due to surgical technique. The improvement of surgical technique,correct diagnosis and timely operation are very important for the treatment of intra abdominal hemorrhage.