Objective:To evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.

Objective:To analyze the clinical characteristics of functional esophagogastric junction outflow obstruction (EGJOO) and to improve the knowledge of functional EGJOO.Methods:From January 2015 to December 2019, at the Gastrointestinal Motility Center of The First Affiliated Hospital with Nanjing Medical University, 91 patients who underwent high resolution esophageal manometry (HREM) and met the EGJOO criteria of Chicago Classification for esophageal motility disorders, 3rd edition and excluded organic diseases by examination such as gastroscopy or upper gastrointestinal radiography were collected. The clinical manifestations, treatment methods, effect and clinical outcome of patients with functional EGJOO, the HREM parameters of patients with different clinical manifestations as well as symptoms and HREM parameters of patients with different treatments were analyzed. Least significant difference test or Tamhanes T2 test, Mann-Whitney U or Wilcoxon test, chi-square test or Fisher exact test were used for statistical analysis. Results:The most common symptom of 91 functional EGJOO patients was dysphagia (34/91, 37.4%). The lower esophageal sphincter pressure (LESP) and the intrabolus pressure during relaxation of the lower esophageal sphincter (IBP LESR) of patients with dysphagia were both higher than those of patients without dysphagia (30.95 mmHg (26.27 mmHg, 39.37 mmHg) (1 mmHg=0.133 kPa) vs. 27.35 mmHg (24.60 mmHg, 34.87 mmHg); (8.25±4.64) mmHg vs. (5.69±4.65) mmHg), and the differences were statistically significant ( Z=2.076, t=2.539; P=0.038, 0.013). Thirty patients (33.0%) had no special treatment, 52 patients (57.1%) were treated with medication, and nine patients (10.0%) underwent peroral endoscopic myotomy (POEM). The incidence of dysphagia before treatment and maximum intrabolus pressure of patients who underwent POEM were both higher than those of patients without special treatment and medication treatment (8/9 vs 43.3%, 13/30 and 25.0%, 13/52; 21.80 mmHg (15.45 mmHg, 28.95 mmHg) vs. 12.20 mmHg (10.00 mmHg, 18.10 mmHg) and 13.70 mmHg (11.07 mmHg, 17.82 mmHg)), and the differences were statistically significant (Fisher exact test, Fisher exact test; Z=2.814, 2.390; P=0.023, P<0.01, P=0.005, 0.017). The incidences of delayed esophageal emptying or esophageal dilation of patients who underwent POEM, without special treatment and with medication treatment was 6/9, 5/14 and 3/18, respectively, and the differences were statistically significant among three groups (Fisher exact test, P=0.039). Among them, the incidence of delayed esophageal emptying or esophageal dilation of patients received POEM before treatment was higher than that of patients with medication treatment (Fisher exact test, P=0.026). The symptoms of 24.2% (22/91) was spontaneously relieved, and two patients (2.2%) developed type Ⅱ achalasia during follow-up. Conclusions:The main manifestation of patients with functional EGJOO is dysphagia. Patients with significantly increased LESP and IBP LESP are more likely to have dysphagia. Patients with obvious signs of esophageal gastric junction obstruction are more inclined to choose POEM treatment. Some patients with functional EGJOO can relieve themselves, and a few patients can develop achalasia.

Objective Aimed to develop the evaluation system and weight of hospital orientation training.Methods Literature review,Delphi,questionnaire,AHP to develop the evaluation system and determined the weight with Satty's method.Results The evaluation system includes 3 division's 13 items.Conclusions Course content,teaching method,course difficultness and occupational plan ning play the most important role,and should be paid more attention.

Objective To perform the ligand-based computer-aided drug design and construct the pharmacophore model of(1,3)-β-D-Glucan Synthase(GS)small molecule inhibitors.Method Six small molecules with diverse structures and good inhibitory activity were selected to construct the training set.The HipHop algorithm in Catalyst pharmacophore generation module was utilized to construct the pharmacophore models.The pharmacophore models were evaluated by constructed Decoy-set 3D database.Results Pharmacophore 02 has a good enrichment factor,sensitivity and specificity parameters.Pharmacoph-ore model validation with Decoyset 3D database proved that the model has good distinguishing capability.Conclusion The pharmacophore model of GS small molecule inhibitors was constructed and tested.It will provide valuable information for de-sign and discovery of novel small molecule GS inhibitors.

Objective To evaluate the safety and efficacy of endoscopic ultrasound (EUS) guided ethanol ablation of benign insulinoma and compare its' advantages and disadvantages with surgical treatment. Methods From April 2011 to February 2016, clinical data of 38 patients with benign insulinoma treated by EUS-guided ethanol ablation or surgical treatment were retrospectively analyzed. Results 97.4% (37/38) patients had a typical clinical manifestation of Whipple's triad, and the I/G ratio of 82.9% patients (29/35) was more than 0.3 with their onset of hypoglycemia. The positive preoperative etiologic diagnosis rates of transabdominal ultrasonography, CT, MRI, PET/CT and EUS were 50.0%, 67.6%, 66.7%, 75.0%, 89.7% respectively. In the current study, 18 patients underwent EUS-guided ethanol ablation (EUS-FNI group) and 20 patients received surgicaltreatment (surgical group). Compared with the surgical group, the operation time, intraoperative hemorrhage volume, postoperative complications, length of stay and hospitalization costs were significantly reduced in the EUS-FNI group (P < 0.05). No treatment-related complications was observed in EUS-FNI group, while 40.0% (8/20) patients in surgical group had complications. During the follow-up period, all these patients maintained stable blood glucose without taking medication, and there's no recurrence of insulinoma in EUS-FNI group after the last treatment with alcohol injection; In surgical group, only 90.0% (18/20) patients had no recurrence, episode of hypoglycemia was less after the operation in 10.0% (2/20) patients. Conclusion EUS-guided ethanol ablation of benign insulinoma is safe and effective, compared with traditional surgical treatment, EUS-guided ethanol ablation is minimally invasive, costs less, recovers fast after treatment and has fewer complications.

AIM: To investigate the effect of nucleolin on diabetic cardiomyopathy in mice.METHODS: A type II diabetic cardiomyopathy mouse model was prepared using a cardiac-specific nucleolin-overexpressing transgenic mice.The mice were divided into wild-type mouse control group, nucleolin transgenic mouse control group, wild-type mouse diabetes group and nucleolin transgenic mouse diabetes group.Wheat germ agglutinin (WGA) fluorescent dye, Masson staining and PowerLab system detection were used to further clarify the role of nucleolin on cardiac hypertrophy, fibrosis and cardiac function in type II diabetic cardiomyopathy mice.RESULTS: Compared with wild-type mouse control group, no significant increase in blood glucose level was found, while genetical myocardial cell hypertrophy was significantly attenuated in nucleolin transgenic mouse diabetes group.The collagen fibers were also significantly reduced, and hemodynamic indexes ± dp/dtmax, left ventricular end-diastolic pressure, left ventricular systolic pressure and heart rate were also improved.The above differences were statistically significant.CONCLUSION: Nucleolin may reduce the occurrence of myocardial hypertrophy and fibrosis, thus improving the cardiac function of diabetic cardiomyopathy mice.

Objective To explore the association of NH2-terminal pro-B-type natriuretic peptide ( NT-proBNP) with the risk of type 2 diabetes.Methods One hundred and twenty-six impaired glucose regulation( IGR) participants from Diabetic Identification Center of Tianjin Metabolic Diseases Hospital were included.NT-proBNP was measured in plasma samples collected from participants at baseline condition.Results At baseline, NT-proBNP was inversely associated with body mass index, waist circumference, fasting glucose, insulin and low-density lipoprotein-cholesterol( LDL-C) levels.During a follow-up of 2 years, 51 participants reported a new diagnosis of diabetes from OGTT.Baseline quartiles of NT-proBNP were inversely associated with diabetes risk, even after multivariable adjustment.Theadjustedrelativerisksfordiabeteswere1.0(reference),0.83(95%CI0.74-0.96),0.78(95%CI 0.68-0.90), 0.74 (95%CI 0.64-0.87) for the 1st, 2nd, 3rd, and 4th quartiles of baseline NT-proBNP, respectively ( P<0.01 ) .Conclus ion In IGRpopulation , lowlevels of NT-proBNP were associated with a significantly increased risk of type 2 diabetes.

BACKGROUNDCopious evidence from epidemiological and laboratory studies has revealed that sleep status is associated with glucose intolerance, insulin resistance, thus increasing the risk of developing type 2 diabetes. The aim of this study was to reveal the interaction of sleep quality and sleep quantity on glycemic control in patients with type 2 diabetes mellitus.

METHODSFrom May 2013 to May 2014, a total of 551 type 2 diabetes patients in Tianjin Metabolic Diseases Hospital were enrolled. Blood samples were taken to measure glycosylated hemoglobin (HbA1c), and all the patients completed the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) questionnaire to evaluate their sleep status. "Good sleep quality" was defined as PQSI <5, "average sleep quality" was defined as PQSI 6-8, and "poor sleep quality" was defined as PQSI >8. Poor glycemic control was defined as HbA1c ≥7%. Sleep quantity was categorized as <6, 6-8, and >8 hours/night. Short sleep time was defined as sleep duration <6 hours/night.

RESULTSIn the poor glycemic control group, the rate of patients who had insufficient sleep was much higher than that in the other group (χ(2) = 11.16, P = 0.037). The rate of poor sleep quality in poor glycemic control group was much greater than that in the average control group (χ(2) = 9.79, P = 0.007). After adjusted by gender, age, body mass index, and disease duration, the adjusted PSQI score's OR was 1.048 (95% CI 1.007-1.092, P = 0.023) for HbA1c level. The sleep duration's OR was 0.464 (95% CI 0.236-0.912, P = 0.026) for HbA1c level. One-way analysis of variance showed that the poor sleep quality group had the highest homeostasis model assessment-insulin resistance (P < 0.01).

CONCLUSIONSInadequate sleep, in both quality and quantity, should be regarded as a plausible risk factor for glycemic control in type 2 diabetes. Poor sleep might bring much more serious insulin resistance and could be the reason for bad glycemic control. A good night's sleep should be seen as a critical health component tool in the prevention and treatment of type 2 diabetes. It is important for clinicians to target the root causes of short sleep duration and/or poor sleep quality.

Adult ; Aged ; Aged, 80 and over ; Blood Glucose ; metabolism ; physiology ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; blood ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Sleep ; physiology ; Young Adult

AIM:To construct myocardium-specific nucleolin ( Ncl) transgenic mice and to provide an animal model for the studies of the myocardial protection of nucleolin .METHODS:To create nucleolin transgenic mice , a myo-cardium-specific expression plasmid of nucleolin ( Alpha-MyHC clone 26-Ncl) was constructed .The gene type of transgenic mice was identified by PCR and the nucleolin protein level was tested by Western blotting .The myocardium morphology , heart weight index (HWI) and left ventricular pressure maximum rise rate were observed in nucleolin transgenic (TG) mice and wild-type ( WT) mice.RESULTS:We gained 4 transgenic mice (51, 52, 56 and 86 lines, only 52 line and 86 line were eugonic) by PCR.Western blotting analysis showed the expression of nucleolin up-regulated specifically in the myocardium .However , the myocardium morphology , HWI and left ventricular pressure maximum rise rate in the nucleolin transgenic mice were similar to those in the wild-type mice.CONCLUSION:We constructed myocardium-specific nucleo-lin transgenic mice successfully .