Objective To observe the effects of glucagon like peptide-1 (GLP-1) analogues liraglutide on expressions of nitric oxide synthase (NOS) and cyclo-oxygen-ase (COX)2 in renal medulla of type 2 diabetes rats, and the mechanism of its lowering blood pressure and promoting excretion of water and salt in kidney. Methods Type 2 diabetes model rats were generated by high-fat and high-sugar feeding for 8 weeks followed by intraperitoneal injection of streptozotocin (STZ). Subse?quently, eighteen type 2 diabetes rats were divided into two groups: liraglutide treatment group (DMT) and diabetes group (DM). Twelve normal rats were divided into two groups: liraglutide treatment wild type group (WTT) and wild type group (WT). DMT and WTT groups were given liraglutide (200μg/kg) by subcutaneous injection, DM and WT groups were given equivalent normal saline by the same way. The levels of blood glucose and blood pressure were detected at 0, 2, 4 and 6 weeks after treatment in groups of rats. Samples of urine were collected for detecting ion concentrations (K+, Na+and Cl-) af?ter treatment for six weeks. Rats were sacrificed and blood samples were collected for detecting ion concentrations (K+, Na+and Cl-). The expression levels of NOS and COX2 mRNA and protein in renal medulla were detected by real-time PCR and Western blot assay. Results After treating with liraglutide, the values of blood glucose (F=5.933, P<0.05) and blood pres?
sure (F=22.070, P<0.05) were gradually decreased in DMT group. After treatment with liraglutide for 6 weeks, the values of blood glucose (mmol/L:12.78 ± 3.82 vs. 18.75 ± 1.68) and blood pressure (mmHg:119.98 ± 4.43 vs. 136.42 ± 4.48) were signifi?cantly decreased (P<0.05) in DMT group than those of DM group (P<0.05). There were no significant differences in the concentrations of K+, Na+and Cl-between the two groups. There were higher levels of K+(mmol/L:46.55 ± 6.43 vs. 33.13 ± 9.71), Na+(mmol/L:56.33±8.83 vs. 41.20±7.25) and Cl-(mmol/L:159.81±25.06 vs. 71.44±12.99) in urine in DMT group than those of DM group (P<0.05). The mRNA levels and protein expressions of NOS and COX2 in renal medulla were significant?ly increased in DMT group than those of DM group (P<0.05). Conclusion GLP-1 analogues liraglutide may enhance the expression of COX2 by increasing the expression of NOS to excrete water and salt, and decrease blood pressure.

To investigate the alteration of c-Jun N-terminal kinase (JNK) activity after myocardial ischemia reperfusion injury (MIRI) and further explore the effect of naloxone postconditioning on MIRI. Forty male Sprague Dawley rats were randomly divided into five groups: sham operation (sham, n=8); ischemia reperfusion (IR, n=8); IR+naloxone 0.5 mg/kg (Nal L, n=8); IR+naloxone 1.0 mg/kg (Nal M, n=8); IR+naloxone 2.0 mg/kg (Nal H, n=8). Pathological changes of myocardial tissue were visualized by HE staining. The expression of p-JNK, and the apoptosis of cardiomyocytes were investigated with Western blotting and the TUNEL assay, respectively. Irregular arrangement and aberrant structure of myocardial fibers, cardiomyocytes with granular or vacuolar degeneration, and inflammatory cells infiltrating the myocardial interstitial regions characterized MIRI in the IR group. Signs of myocardial injury and inflammatory infiltration were less prominent in the Nal-treated groups. The expression of p-JNK in the sham group and in all Nal-treated groups was significantly lower than that in the IR group (p<0.01). The apoptosis index of cardiomyocytes in the IR group was significantly higher than in the sham group (p< 0.01). The apoptosis indices of cardiomyocytes in all Nal-treated groups were significantly reduced to 55.4%, 26.2%, and 27.6%, respectively, of the IR group (p< 0.01). This study revealed that Naloxone postconditioning before reperfusion inhibits p-JNK expression and decreases cell apoptosis, thus alleviating MIRI.
Animals ; Apoptosis ; Blotting, Western ; Humans ; In Situ Nick-End Labeling ; Ischemia ; JNK Mitogen-Activated Protein Kinases ; Male ; Myocardial Ischemia* ; Myocytes, Cardiac ; Naloxone* ; Rats* ; Rats, Sprague-Dawley ; Reperfusion Injury* ; Reperfusion*

Sarcopenia obesity (SO), a specific disease with co-occurrence of obesity and sarcopenia, is shown clinically as abnormal accumulation of fat, decreased mass and strength of muscle, and increased risk of incidence and mortality of other chronic diseases. Currently, there exist various definitions and diagnoses about SO in the various regions of the world. Its prevalence in populations elevates in an age-dependent manner. This article summarized the possible pathogenesis of SO from the view of chronic inflammation, oxidative stress, insulin resistance, and Hippo pathway, subsequently listed and analyzed potential pharmacological targets (fibroblast growth factor, CD44, adiponectin, etc) involved in treating SO, in order to provide new ideas for clinical diagnosis, treatment of SO patients and research and development of innovative drugs.

OBJECTIVE: To compare the prognostic value of TNM staging systems in the 7th edition and the 8th edition AJCC in Siewert III adenocarcinoma of esophagogastric junction (AEG). METHODS: Data of 160 patients with Siewert III AEG who underwent radical surgery (R0) from January 2009 to January 2013 in PLA General Hospital were collected retrospectively. Exclusion standards:(1)preoperative neoadjuvant chemoradiotherapy;(2)with distant metastasis before or during operation;(3)palliative operation or R1/R2 resection;(4)pathological type as non-adenocarcinoma;(5)number of retrieved lymph nodes less than 16;(6)diagnosed with other malignant tumors concurrently or within 5 years after operation;(7)incomplete clinical or follow-up data. According to the above criteria, 160 patients were included in this study finally. All the patients underwent radical total or proximal gastrectomy by abdominal approach. D1 or D1+ lymph node dissection was performed in early patients and D2 in advanced patients. All the patients were re-staged by the gastric cancer TNM7 (G7), the gastric cancer TNM8 (G8) and the esophageal cancer TNM7(E7). Univariate analysis and Cox regression analysis were performed. Kappa value and Akaike's information criterion (AIC, the less AIC, the better prognosis) value were compared between different staging systems in agreement and predicting prognosis. RESULTS: There were 128 males and 32 females(sex ratio 4:1), and the average age was (60.2±11.6) years and 17 patients with basic disease. Of all the patients, 133 cases (83.1%) underwent radical total gastrectomy and 27 cases (16.9%) underwent proximal gastrectomy. The median number of dissected lymph nodes were 31 and the median number of positive lymph nodes were 4. Multivariate analysis showed that the G7, G8, E7 staging systems were independent prognostic factors (HR=1.374, 1.407 and 1.305 respectively,all P<0.001). Stage migration between G7 and G8 were only observed in IIIA, IIIB and IIIC, and stage migration rate was 8.1% (13/160), and the agreement was very good (weighted Kappa 0.904, P<0.001). However, the difference between G8 and E7 was quite obvious, stage migration rate was 40.6%(65/160), and the agreement between G8 and E7 was not satisfied (weighted Kappa 0.536, P<0.001). AIC value was 811.4 in G8, 812.8 in G7 and 815.9 in E7, respectively. CONCLUSION Compared with G7 and E7 staging systems, the G8 staging system is superior in predicting the prognosis of patients with Siewert III AEG.
Adenocarcinoma ; classification ; pathology ; surgery ; Aged ; Esophageal Neoplasms ; classification ; pathology ; surgery ; Esophagogastric Junction ; pathology ; surgery ; Female ; Gastrectomy ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; methods ; Prognosis ; Retrospective Studies ; Stomach Neoplasms ; classification ; pathology ; surgery

OBJECTIVES: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common operative neurocognitive disorders, which places a heavy burden on patients, families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation. METHODS: This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020, aged 60-80 years old with American Society of Anesthesiologists (ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups (n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction, saline in the C group, dexmedetomidine [0.3 μg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 μg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method (CAM) for assessing POD and Mini Mental State Examination (MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase (NSE), TNF-α, IL-1β, and IL-10 at the different time below: the time before anesthesia (T0), and the first day (T1), the third day (T2), the fifth day (T3), and the seventh day (T4) after operation. RESULTS: Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased (both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group (both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group (both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group (P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%, respectively. The incidences of POCD in the Dex1 group and the Dex2 group declined significantly as compared to the C group (both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group (P>0.05). Compared with the C group, the level of TNF-α and IL-1β decreased and the level of IL-10 increased at each time points (from T1 to T4) in the Dex1 group and the Dex2 group (all P<0.05). Compared with the Dex1 group, the level of IL-1β at T2 and IL-10 from T1 to T3 elevated in the Dex2 group (all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points (from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased (all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group (all P<0.05). CONCLUSIONS Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1β and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.
Aged ; Aged, 80 and over ; Bradycardia ; Cognitive Dysfunction/prevention & control* ; Delirium/prevention & control* ; Dexmedetomidine/therapeutic use* ; Humans ; Hypotension/drug therapy* ; Interleukin-10 ; Middle Aged ; Postoperative Cognitive Complications/prevention & control* ; Postoperative Complications/epidemiology* ; Prospective Studies ; Tumor Necrosis Factor-alpha