BACKGROUND: In China, diabetic patients suffer from various chronic complications with a higher prevalence, which is nearly close to that in developed countries. Especially in Xinjiang, the prevalence is much higher than the average level, and the level of disease control is very poor as a whole.OBJECTIVE: To study the actuality of controlling type 2 diabetes mellitus in Xinjiang so as to analyze its relationship with disease courses.DESIGN: Cluster sampling and stratified analysis.SETTING: Department of Endocrinology, Xinjiang General Hospital of Chinese People's Armed Police Forces.PARTICIPANTS: The survey was conducted at ten treatment centers of Xinjiang(the First Affiliated Hospital of Xinjiang MedicalUniversity, People's Hospital of Xinjiang Uigur Autonomous Region, Urumchi Hospital of Air Force of Chinese PLA, Railway Hospital of Xinjing Uigur Autonomous Region, Military Unit Hospital of Xinjiang, Kuitun Central Hospital of Yili Region of Xinjiang, Kelamay People's Hospital of Xinjiang, Kuler People's Hospital of Xinjiang, the First Division Hospital of Xinjiang Military Unit for Produce and Building, Xinjiang Hospital of Traditional Chinese Medicine). Totally 646 type 2 diabetic patients who had received treatment for diabetes mellitus for 12 months, at any of the centers were randomly recruited with cluster sampling method including 337 males and 309 females. According to different courses of disease, the subjects were divided into 6 groups: 202 cases in group of ＜ 3 years, 89 in group of 3-4 years,89 in group of 5-6 years, 77 in group of 7-9 years, 108 in group of 10-14years, and 81 in group of ≥ 15 years. All the subjects agreed to participate in the survey.METHODS: Patients detected their blood sugar level and urine sugar level themselves with portable diabetograph and test paper. For them, there were at least four days per week to take diabetic diet which was considered as common diet control, and there were at least three days per week to participate in leisure activity and at least half an hour per day to spend in proper exercise which was considered as frequent exercise. Complications of diabetes mellitus were diagnosed with clinical manifestation, disease history and objective examination. The survey was performed through letter,telephone counseling, and patient's reexamination. Enumeration data was analyzed with chi-square test.MAIN OUTCOME MEASURES: Differences in blood sugar, urine sugar, management of living style, prevalence of complications in all the diabetic patients with different courses of disease.RESULTS: There were 645, 645, 643, 646 patients with complete data of blood sugar and urine sugar determined periodically at home, participated in the observation of the management of living style, prevalence of diabetic complications and treatment for diabetes mellitus, respectively. ①There was no significant difference in blood sugar and urine sugar level deter mined at home every month among patients of different courses (P ＞ 0.05). ② There was no difference in diet control and exercise among patients of different courses (P ＞ 0.05). ③In patients with disease course of ＜ 15 years, prevalence of the complication in large vessels and extremity,retinopathy, and positive expression of proteinuria presented an increased tendency; whereas, a decreased tendency was found in patients with the disease course of ≥ 15 years(χ2=34.16,60.64,49.18,P=0.00). ④The proportion of applied therapies, such as diet control and exercise, oral antidiabetic drug, insulin, and insulin plus oral anti-diabetic drug, was different in patients with different disease courses (χ2=97.88 ,P=0.00). In patients with short disease courses, diet control or oral anti-diabetic drug was administrated more usually; in those with long disease courses, insulin treatment or insulin plus oral anti-diabetic drug was applied more frequently.CONCLUSION: ①Whether patients determine their blood sugar and urine sugar levels by themselves is not correlated with patients' disease courses. ②Diet control and exercise are not in correlation with disease courses. ③ For patients with the disease course of less than 15 years, the proportion of prevalence of various diabetic complications is increased with the increase of disease courses; for those with the disease course of more than 15 years, however, it is decreased significantly. ④Simple diet control or oral anti-diabetic drug is often applied in patients with short disease courses while insulin or insulin plus oral anti-diabetic drug are administrated in most patients with long disease courses.

This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.
Animals ; Bile Ducts ; Cell Death ; Cholestasis ; Hepatocytes ; Humans ; Hydrogen ; In Vitro Techniques ; Ligation ; Liver ; Mice ; Nerve Growth Factor ; Phosphotransferases ; Rodentia ; Sirtuin 1

BACKGROUND: Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH. METHODS: Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded. RESULTS: One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]; left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF]; LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH. CONCLUSIONS: PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT02164526.
Coronary Artery Disease/epidemiology* ; Creatinine ; Heart Failure/complications* ; Humans ; Hypertension, Pulmonary/complications* ; Nitrates ; Prevalence ; Prognosis ; Prospective Studies ; Registries ; Risk Factors ; Stroke Volume ; Ventricular Function, Left