Objective To explore the mechanism underlying ITGB1-induced drug resistance in gastric cancer based on the circRNA-miRNA-ITGB1 regulatory network.Methods Tumor tissue samples were collected from 21 patients with gastric cancer.The ITGB1 gene expression levels were determined using real-time fluorescent quantitative polymerase chain reaction,and circRNA sequencing was performed to compare the differences in circRNAs between patients with low and high ITGB1 expression.BGC-823 cells were trans-fected with si-circ_0027189,si-miR-455,or si-NC and divided into the si-circ_0027189,si-miR-455,or si-NC groups,respectively.The circ_0027189,miR-455,and ITGB1 expression levels in each group and the sensitivity to oxaliplatin were measured.Results The circRNA regulatory network showed that circ_0027189 regulated ITGB1 expression through miR-455.Compared to the si-NC group,the si-circ_0027189 group exhibited decreased expression levels of circ_0027189 and ITGB1,increased expression levels of miR-455,and reduced sensitivity to oxaliplatin.In contrast,the si-miR-455 group showed decreased expression levels of miR-455,increased expression levels of ITGB1,and enhanced sensitivity to oxaliplatin compared to the si-NC group.Conclusion circ_0027189 can increase ITGB1 expression levels by targeting miR-455 expression,ultimately increasing drug resistance in gastric cancer cells.

The development of obesity is closely related to the disruption of central appetite regulation. Gastric growth hormone-releasing peptide is the only appetite-promoting peptide known to be present in the circulatory system. Ghrelin may act on the central homeostatic and hedonic feeding neural pathways to promote appetite and feeding behavior, and may be a new target for appetite regulation. In addition, Ghrelin is also involved in the regulation of energy homeostasis via promoting growth, regulating gastrointestinal function, and suppressing inflammatory response. Therefore, the research on the mechanism of ghrelin and its receptors will help understand the pathophysiological changes in the central appetite regulation process of obese patients, and to find potential targets for the treatment of obesity. In this paper, we focus on the molecular mechanism of appetite regulation by Ghrelin and its clinical application.

A 25-year-old female patient took 4 Rupi Sanjie capsules orally (0.55 g/capsule) thrice daily and Xiangshao granules 1 bag (4 g/bag) orally thrice daily by herself for breast nodule. After 2 months, the patient developed yellow urine, skin itching, and yellowish skin and sclera. Laboratory tests showed alanine aminotransferase (ALT) 1 334 U/L, aspartate aminotransferase (AST) 717 U/L, alkaline phosphatase (ALP) 164 U/L, total bilirubin (TBil) 88 μmol/L, and γ-glutamyltransferase (γ-GT) 127 U/L. Liver injury caused by Rupi Sanjie capsules and Xiangshao granules were considered. The 2 drugs were stopped and the treatments of liver protection and cholagogic were given. Three weeks later, her symptoms above-mentioned disappeared and the laboratory tests showed ALT 106 U/L, AST 88 U/L, ALP 88 U/L, TBil 13 μmol/L, and γ-GT 32 U/L. At 1 month of follow-up, the patient′s liver function returned to normal. The patient′s liver injury might be related to the component of bupleurum in Rupi Sanjie capsules and Xiangshao granules and the component of prunella vulgaris in Rupi Sanjie capsules.

A 25-year-old female patient took 4 Rupi Sanjie capsules orally (0.55 g/capsule) thrice daily and Xiangshao granules 1 bag (4 g/bag) orally thrice daily by herself for breast nodule. After 2 months, the patient developed yellow urine, skin itching, and yellowish skin and sclera. Laboratory tests showed alanine aminotransferase (ALT) 1 334 U/L, aspartate aminotransferase (AST) 717 U/L, alkaline phosphatase (ALP) 164 U/L, total bilirubin (TBil) 88 μmol/L, and γ-glutamyltransferase (γ-GT) 127 U/L. Liver injury caused by Rupi Sanjie capsules and Xiangshao granules were considered. The 2 drugs were stopped and the treatments of liver protection and cholagogic were given. Three weeks later, her symptoms above-mentioned disappeared and the laboratory tests showed ALT 106 U/L, AST 88 U/L, ALP 88 U/L, TBil 13 μmol/L, and γ-GT 32 U/L. At 1 month of follow-up, the patient′s liver function returned to normal. The patient′s liver injury might be related to the component of bupleurum in Rupi Sanjie capsules and Xiangshao granules and the component of prunella vulgaris in Rupi Sanjie capsules.

Objective:To investigate the changes of plasma high density lipoprotein cholesterol (HDL-C) and metabolic indicators in obese patients after laparoscopic sleeve gastrectomy (LSG).Methods:The retrospective cohort study was conducted. The clinical data of 69 obese patients who were admitted to the Tenth People′s Hospital of Tongji University from August 2013 to March 2017 were collected. There were 32 males and 37 females, aged (33±12)years, with a range from 18 to 65 years. Of 69 patients, 44 patients with preoperative HDL-C concentration <1.04 mmoL/L were allocated as low HDL-C group, and 25 patients with preoperative HDL-C concentration ≥1.04 mmoL/L were allocated as normal HDL-C group. Sixty-nine patients underwent LSG. Observation indicators: (1) analysis between preoperative HDL-C and clinical indicators; (2) follow-up; (3) stratified analysis of plasma HDL-C. Follow-up was conducted using outpatient examination and hospitalization review to detect changes of plasma HDL-C, insulin resistance index, uric acid, free fatty acids and body mass every 3 months after operation up to September 2017. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M ( P25, P75), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Pearson correlation coefficient was used to analyze measurement data with normal distribution, and Spearman correlation was used to analyze measurement data with skewed distribution. Repeated measurement data were analyzed by ANOVA. Results:(1) Analysis between preoperative HDL-C and clinical indicators: results of correlation analysis showed that the preoperative plasma HDL-C concentration was negative correlated with the body mass, height, abdominal circumference, insulin resistance index and triglyceride in 69 patients ( r=-0.246, -0.307, -0.262, -0.253, -0.301, P<0.05), and the preoperative plasma HDL-C concentration was not correlated with the age, body mass index (BMI), fasting blood glucose, glycosylated hemoglobin, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, uric acid, creatinine, free fatty acid, fasting serum insulin, total cholesterol and low density lipoprotein cholesterol ( P>0.05). The preoperative plasma HDL-C concentration was still negative correlated with the body mass in 69 patients after adjusting for age, BMI, fasting blood glucose, glycosylated hemoglobin, fasting serum insulin and insulin resistance index ( r=-0.277, P<0.05). (2) Follow-up: 69 patients were followed up postoperatively for 6 months (6 months, 12 months). The plasma HDL-C concentration, insulin resistance index, uric acid, free fatty acids, body mass of low HDL-C group at postoperative 3 and 6 months were (0.96±0.18)mmol/L, 2.20(0.51, 11.66), (411±93)μmol/L, 0.57 mmol/L (0.20 mmol/L, 1.00 mmol/L), (92±18)kg and (1.11±0.18)mmol/L, 2.19(0.71, 8.75), (389±100)μmol/L, 0.40 mmol/L(0.13 mmol/L, 1.10 mmol/L), (86±17)kg, respectively. The above indicators of normal HDL-C group at postoperative 3 and 6 months were (1.17±0.24)mmol/L, 2.22(0.24, 7.04), (379±105)μmol/L, 0.60 mmol/L(0.27 mmol/L, 1.10 mmol/L), (84±16)kg and (1.34±0.20)mmol/L, 1.60(0.36, 5.56), (359±92)μmol/L, 0.42 mmol/L (0.16 mmol/L, 2.90 mmol/L), (80±18)kg, respectively. There was significant difference in the changes of postoperative plasma HDL-C concentration between the two groups ( F=41.443, P<0.05), and there was interaction between groups and time points ( F=6.252, P<0.05). There was significant difference between different time points ( F=29.900, P<0.05). There was significant difference in the changes of postoperative insulin resistance index between the two groups ( F=4.313, P<0.05), and there was no interaction between groups and time points ( F=2.298, P>0.05). There was significant difference between different time points ( F=29.800, P<0.05). There was no significant difference in the changes of postoperative uric acid between the two groups ( F=1.669, P>0.05), and there was no interaction between groups and time points ( F=0.111, P>0.05). There was significant difference between different time points ( F=12.796, P<0.05). There was significant difference in the changes of postoperative free fatty acids between the two groups ( F=5.465, P<0.05), and there was no interaction between groups and time points ( F=0.504, P>0.05). There was no significant difference between different time points ( F=1.405, P>0.05). There was significant difference in the changes of postoperative body mass between the two groups ( F=5.614, P<0.05), and there was no interaction between groupsand time points ( F=2.174, P>0.05). There was significant difference between different time points ( F=497.496, P<0.05). (3) Stratified analysis of plasma HDL-C. ① Changes of postoperative plasma HDL-C in obese patients of different genders: of 69 patients, the plasma HDL-C concentration of the 32 male patients before operation and at postoperative 3 and 6 months were (0.91±0.19)mmol/L, (1.02±0.24)mmol/L, (1.18±0.23)mmol/L, respectively, and the percentage increase of plasma HDL-C concentration at postoperative 3 and 6 months were 12.00%(4.00%, 12.00%)and 20.00%(12.00%, 39.25%), respectively. The above indicators of the 37 female patients were (1.05±0.21)mmol/L, (1.06±0.22)mmol/L, (1.22±0.22)mmol/L and 0(-9.50%, 8.25%), 12.00%(2.00%, 23.00%), respectively. There was significant difference in the changes of percentage increase of plasma HDL-C concentration between the male and female patients ( F= 6.716, P<0.05), and there was interaction between groups and time points ( F=3.861, P<0.05). There was significant difference between different time points ( F=37.374, P<0.05). ② Changes of postoperative plasma HDL-C in obese patients of different genders in low HDL-C group and normal HDL-C group: of 44 patients in low HDL-C group, the plasma HDL-C concentration of the 24 male patients before operation and at postoperative 3 and 6 months were (0.82±0.12)mmol/L, (0.99±0.21)mmol/L, (1.12±0.22)mmol/L, respectively, and the percentage increase of plasma HDL-C concentration at postoperative 3 and 6 months were 16.00%(-1.75%, 28.75%) and 27.50%(15.75%, 43.50%), respectively. The above indicators of the 20 female patients in low HDL-C group were (0.89±0.08)mmol/L, (0.93±0.14)mmol/L, (1.10±0.14)mmol/L and 1.50%(-8.25%, 16.50%), 18.00%(9.00%, 23.00%), respectively. There was significant difference in the changes of percentage increase of plasma HDL-C concentration between the male and female patients ( F=4.503, P<0.05), and there was interaction between groups and time points ( F=3.594, P<0.05). There was significant difference between different time points ( F=37.096, P<0.05). Of 25 patients in normal HDL-C group, the plasma HDL-C concentration of the 8 male patients before operation and at postoperative 3 and 6 months were (1.15±0.12)mmol/L, (1.12±0.32)mmol/L, (1.32±0.21)mmol/L, respectively, and the percentage increase of plasma HDL-C concentration at postoperative 3 and 6 months were -1.00%(-14.00%, 12.00%), 13.50%(6.75%, 32.50%), respectively. The above indicators of the 17 female patients in normal HDL-C group were (1.23±0.16)mmol/L, (1.20±0.20)mmol/L, (1.36±0.20)mmol/L and 0(-13.75%, 4.25%), 5.50%(0, 28.50%), respectively. There was no significant difference in the changes of percentage increase of plasma HDL-C concentration between the male and female patients ( F=0.209, P>0.05), and there was no interaction between groups and time points ( F=0.176, P>0.05). There was significant difference between different time points ( F=6.481, P<0.05). Conclusions:For patients with low or normal plasma HDL-C concentration preoperative, there are significant differences in the changes of HDL-C, insulin resistance index, free fatty acids and body mass after LSG. There is significant difference in the changes of postoperative percentage increase of plasma HDL-C concentration between male and female patients who with low plasma HDL-C concentration preoperative.

Objective: To evaluate the cost-utility of different immunization strategies for rabies in China, and to provide a reference for determining the optimal immunization strategy. Methods: The system dynamics model was used to simulate the epidemic of canine rabies and a decision tree model was conducted to analysis different immune strategies. Relevant probabilities were obtained through literature search and on-site investigation. Sensitivity analysis was used to explore the important influenced factors. Results: At baseline, from a social perspective, 70% vaccination of dogs was the optimal strategy compared to current vaccination strategy (43% vaccination in dogs, human category-Ⅱ exposure vaccination/category-Ⅲ exposure vaccination combined with RIG). The total cost was 14 084 354 CNY, and the total utility value was 22 078 616.23 QALYs, and the incremental cost-utility ratio was-62 148 147 CNY/QALY; if human vaccination was considered, 55% vaccination of dogs combined with strategy one was the optimal strategy, its incremental cost-utility ratio was-444 620 557 CNY/QALY. The probability that an injured dog carries rabies virus was the most sensitive parameter. When it was greater than 0.005 03, strategy four was the optimal strategy. When it was less than 82/100 000, strategy one was the optimal strategy; when it was between 82/100 000 and 120/100 000, strategy two was the optimal strategy; when it was between 120/100 000 and 503/100 000, strategy two was the optimal strategy. Conclusion It was conducive to increase the vaccination coverage of canine for the prevention and control of rabies.

To evaluate the cost?utility of different immunization strategies for rabies in China, and to provide a reference for determining the optimal immunization strategy. Methods The system dynamics model was used to simulate the epidemic of canine rabies and a decision tree model was conducted to analysis different immune strategies. Relevant probabilities were obtained through literature search and on?site investigation. Sensitivity analysis was used to explore the important influenced factors. Results At baseline, from a social perspective, 70% vaccination of dogs was the optimal strategy compared to current vaccination strategy (43% vaccination in dogs, human category?Ⅱ exposure vaccination /category?Ⅲ exposure vaccination combined with RIG). The total cost was 14 084 354 CNY, and the total utility value was 22 078 616.23 QALYs, and the incremental cost?utility ratio was-62 148 147 CNY/QALY;if human vaccination was considered, 55% vaccination of dogs combined with strategy one was the optimal strategy, its incremental cost?utility ratio was-444 620 557 CNY/QALY. The probability that an injured dog carries rabies virus was the most sensitive parameter. When it was greater than 0.005 03, strategy four was the optimal strategy. When it was less than 82/100 000, strategy one was the optimal strategy; when it was between 82/100 000 and 120/100 000, strategy two was the optimal strategy; when it was between 120/100 000 and 503/100 000, strategy two was the optimal strategy. Conclusion It was conducive to increase the vaccination coverage of canine for the prevention and control of rabies.

To evaluate the cost?utility of different immunization strategies for rabies in China, and to provide a reference for determining the optimal immunization strategy. Methods The system dynamics model was used to simulate the epidemic of canine rabies and a decision tree model was conducted to analysis different immune strategies. Relevant probabilities were obtained through literature search and on?site investigation. Sensitivity analysis was used to explore the important influenced factors. Results At baseline, from a social perspective, 70% vaccination of dogs was the optimal strategy compared to current vaccination strategy (43% vaccination in dogs, human category?Ⅱ exposure vaccination /category?Ⅲ exposure vaccination combined with RIG). The total cost was 14 084 354 CNY, and the total utility value was 22 078 616.23 QALYs, and the incremental cost?utility ratio was-62 148 147 CNY/QALY;if human vaccination was considered, 55% vaccination of dogs combined with strategy one was the optimal strategy, its incremental cost?utility ratio was-444 620 557 CNY/QALY. The probability that an injured dog carries rabies virus was the most sensitive parameter. When it was greater than 0.005 03, strategy four was the optimal strategy. When it was less than 82/100 000, strategy one was the optimal strategy; when it was between 82/100 000 and 120/100 000, strategy two was the optimal strategy; when it was between 120/100 000 and 503/100 000, strategy two was the optimal strategy. Conclusion It was conducive to increase the vaccination coverage of canine for the prevention and control of rabies.

OBJECTIVETo assess the effects of laparoscopic sleeve gastrectomy (LSG) on insulin secretion mode and metabolism of glucose and lipid in morbidly obese patients.

METHODSClinical data of 65 morbidly obese patients [body mass index (BMI) ≥30 kg/m] undergoing LSG at Shanghai 10th People's Hospital from August 2012 to December 2016 were retrospectively analyzed. According to the result of OGTT, these obese patients were divided into three groups: normal glucose tolerance (NGT, 23 cases), impaired glucose tolerance (IGT, 22 cases) and type 2 diabetes mellitus (DM, 20 cases) groups. Twenty-two healthy people [BMI (23.1±1.4) kg/m] were used as control group. The anthropometries parameters [weight, BMI, waist circumference, body fat percentage, excess weight loss(%EWL)], glucose metabolic indices [fasting plasma glucose (FPG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), homeostasis model assessment-insulin resistance index (HOMA-IR)], lipid profile (TC, TG, HDL-C, LDL-C) and inflammatory factor (UA, TNF-α) of 3 groups were detected before operation and at postoperative 1-, 3-, 6-month. These variables were analyzed among morbidly obese groups before and after surgery and compared to control group. Clinical registration number of this study was ChiCTROCSl2002381.

RESULTSBody weight, waist circumference and BMI of morbidly obese patients all decreased at postoperative 1-, 3-, 6-month. Postoperative %EWL increased obviously to (71.5±24.7)% with the highest range in DM group. Percentage of successful weight loss (%EWL>50%) in NGT, IGT and DM groups was 63.6%, 83.9% and 90.0% at postoperative 6-month respectively, and DM group was also the highest. At postoperative 6-month, HbA1c of 3 morbidly obese groups became normal; FPG and postprandial 2-hour glucose of IGT and DM group decreased to normal level; insulin level of 3 morbidly obese groups decreased obviously compared to pre-operation (all P<0.05), especially FINS and postprandial 2-hour insulin became normal without significant difference of control group (P>0.05), while postprandial 30-minute and 60-minute insulin levels in 3 groups were still higher as compared to control group. The insulin secretion curves of morbidly obese groups showed hyperinsulinemia before surgery. The peak of insulin secretion curve in IGT and DM group moved back to postprandial 120-minute before operation, and returned to 60-minute after operation, with basic normal rhythm of secretion curve. Preoperative HOMA-IR in all 3 morbidly obese groups was higher than that in control group (all P<0.05) and remarkably lower at postoperative 6-month compared to pre-operation(P<0.05). In 3 morbidly obese groups after operation, TG decreased, HDL-C increased, UA and TNF-α decreased significantly compared to before operation (all P<0.05). At postoperative 6-month, the HOMA-IR of DM group was positively correlated with BMI (r=0.236, P=0.004) and TNF-α (r=0.228, P=0.033), and was not correlated with HDL-C(P>0.05).

CONCLUSIONSLSG can effectively ameliorate hyperinsulinemia and insulin secretion curve, and improve metabolic disorder and insulin resistance of different stage in obesity patients with glucose metabolic disorder. Insulin resistance is correlated with body weight and inflammatory factors.

Objective To explore the feasibility of oxygen saturation related diffusion index for assessing oxygenation status,and to establish the critical value of the oxygen saturation related diffusion index,so as to provide more approaches to monitoring oxygenation status.Methods A total of 30 patients with acute respiratory distress syndrome (ARDS) receiving mechanical ventilation support were retrospectively reviewed.Totally 340 cases were collected at corresponding time points,and were divided into mild,moderate and severe groups according to ARDS Berlin criteria.Results There was a positive correlation between oxygen saturation related diffusion index and oxygenation index (r=0.698,P＜0.001);the critical value between the moderate and severe groups of oxygen saturation related diffusion index was 171(sensitivity 84.7％,specificity 68.2％),and the critical value between mild group and moderate group was 440 (sensitivity 56.9％,specificity 91.9％).Conclusion The oxygenation index was consistent with the oxygen saturation related diffusion index in judging the oxygenation status of ARDS patients.As a noninvasive and continuous index,the oxygen saturation related diffusion index provides a new method for nursing assessment.