Abstract Purpose Liraglutide (LIRA), a Glucagon-like peptide-1 receptor agonist (GLP-1RA), showed potent cardioprotective effects of diabetic cardiomyopathy (DCM) with the mechanism remained incompletely understood. Methods T2DM rats were used as study subjects and randomly divided into four groups: 1) CON group, 2) CON + L group, 3) DM group and 4) DM + L group. All rats received either saline or LIRA 0.2 mg/kg (by i.p injection) per day for 4 weeks. After the model was successfully established, cardiac function was determined by invasive hemodynamic evaluation methods. Immunohistochemistry and western blot were performed to understand the molecular mechanism between cardiac function and LIRA. Cultured H9C2 cells with small interfering RNA (siRNA) of Cav3 under high glucose (HG), western blot was performed to understand the molecular mechanism between Cav3 and RyR2 with LIRA. Results Based on our results, LIRA treatment showed a trend to enhance LVSP (110.76 ± 5.61 mmHg) and ± dp/dtmax (5860.41 ± 200.32 mmHg and 3996.8 ± 179.3 mmHg), decreased LVEDP (7.23 ± 0.58 mmHg). The expression of Cav3, eNOS and RyR2 was significantly decreased in the myocardium in DM group, which increased in DM + L group after LIRA administrated. LIRA improved cardiac systolic and diastolic function, attenuate diabetic cardiomyopathy injury by improving Cav3/eNOS/NO signaling and increasing interaction of Cav3 and ryanodine receptor 2 (RyR2) in diabetic cardiac tissues. Conclusion In summary, we found that Liraglutide ameliorates cardiac dysfunction in rats with type 2 diabetes mellitus via improving Cav3/eNOS/NO signaling and increasing interaction of Cav3 and RyR2.

Abstract Background Liraglutide (LIRA), a Glucagon-like peptide-1 receptor agonist (GLP-1RA), showed potent cardioprotective effects with the mechanism remained incompletely understood. Caveolin-3 (Cav3) is the cardiomyocytes specific caveolae structural protein, decreased in the diabetic heart. Therefore, this study aimed to investigate whether LIRA exerts its effect on cardiac function in rats with type 2 diabetes mellitus (T2DM) via enhance Cav3 expression. Methods T2DM rats were used as study subjects and randomly divided into four groups: 1) CON group, 2) CON+L group, 3) DM group and 4) DM+L group. All rats received either saline or LIRA 0.2 mg/kg (by i.p injection) per day for 4 weeks. After the model was successfully established, cardiac function was determined by invasive hemodynamic evaluation methods. Immunohistochemistry and western blot were performed to understand the molecular mechanism between cardiac function and LIRA. Results Based on our results, DM group displayed higher blood glucose than Con group (20.57±2.75 mol/L vs. 4.34±0.21 mol/L), while blood glucose level in DM+L group was lower than DM group after received LIRA (10.36±1.84 mol/L). LVSP (91.39±4.98 mmHg), LV +dp/dtmax (4040.74±197.72 mmHg/s) were significantly reduced in DM group, and diabetic rats also exhibited reduced -dp/dtmax (2926.5±142.3 mmHg/s) and elevated LVEDP (10.87±0.83 mmHg). LIRA treatment showed a trend to enhance LVSP (110.76±5.61 mmHg) and ± dp/dtmax (5860.41±200.32 mmHg and 3996.8±179.3 mmHg), decreased LVEDP (7.23±0.58 mmHg). The expression of Cav3, eNOS and RyR2 was significantly decreased in the myocardium in DM group, which increased in DM+L group after LIRA administrated. Hemodynamic data showed DM rats exhibited impairment of myocardial function, while LIRA improved cardiac systolic and diastolic function, attenuate diabetic cardiomyopathy injury by improving Cav3/eNOS/NO signaling, reducing ROS level in cardiac tissues, and increasing interaction of Cav3 and ryanodine receptor 2 (RyR2). Conclusions Liraglutide ameliorates cardiac dysfunction in rats with type 2 diabetes mellitus via reducing ROS level in cardiac tissues, improving Cav3/eNOS/NO signaling and increasing interaction of Cav3 and RyR2. Keywords Type-2 diabetes Mellitus, liraglutide, caveolin-3, ryanodine receptor2, myocardial dysfunction

目的:观察间歇性低氧(IH)对人膀胱逼尿肌细胞凋亡和钙离子通道的影响,并初步探讨中药益智仁(AOF)的调节机制.方法:建立人膀胱逼尿肌细胞IH模型,IH模式为5％O260 min-20％O230 min,6个循环.体外培养人膀胱逼尿肌细胞,随机分为6组,每组设8孔,分别为P2X3受体拮抗剂+IH组(A组)、M3受体拮抗剂+IH组(B组)、β3受体拮抗剂+IH组(C组)、AOF+IH组(D组)、生理盐水+IH对照组(NC组)和空气模拟对照(AC)组.干预结束后普通光镜下细胞板计数比较各组细胞密度,免疫荧光法观察细胞形态改变,流式细胞术检测细胞凋亡,膜片钳法测定细胞钙离子表达变化.结果:(1)与AC组细胞比较,NC组细胞密度增高、反应活跃,部分细胞出现突起、变圆,细胞边界模糊;A组和D组细胞密度较NC组有显著减低(P<0.05);(2)免疫荧光检测细胞α-肌动蛋白(α-SMA)表达情况:与AC组比较;NC组的平均吸光度(MA)显著增高(F=3.25,P<0.05);A组、D组细胞分别与NC组比较均有不同程度显著降低(P<0.05).(3)与AC组细胞比较,NC组细胞凋亡率显著减低(P<0.05);A组与D组的细胞凋亡率分别与NC比较有显著增高(P<0.05);(4)与AC组细胞比较,NC组细胞钙离子通道表达显著减低(P<0.05);与NC组细胞比较,AOF组(100 mg/L)和AOF组(50 mg/L)钙离子通道表达显著增高(P均<0.05).结论:IH可通过P2X3膀胱神经受体调节逼尿肌细胞增殖和凋亡,中、高剂量AOF可改变钙离子通道并对IH诱导的细胞损害起保护作用.

The objective of this study was to explore the effect of Alpiniae oxyphyllae Fructus (AOF) on a rat model of chronic intermittent hypoxia (CIH)–induced enuresis. Findings of this study may help identify therapeutic targets in children with nocturnal enuresis (NE).

Purpose. Limited studies have preliminarily identified a positive association between nonalcoholic fatty liver disease (NAFLD) and hemoglobin glycation index (HGI). However, this association has not been fully established. We aim to investigate the association between NAFLD and HGI in Chinese nondiabetic individuals and to construct a risk score based on HGI to predict a person’s risk of NAFLD. Methods. After strict exclusion criteria, 5,903 individuals were included in this retrospective cross-sectional study. We randomly selected 1,967 subjects in the enrollment to obtain an equation of linear regression, which was used to calculate predicted HbA1c and drive HGI. The other subjects were classified into four categories according to HGI level (≤−0.22, −0.21∼0.02, 0.03∼0.28, and ≥0.29). All subjects retrospectively reviewed the baseline characteristics, laboratory examinations, and abdominal ultrasonography. Results. The prevalence of NAFLD in this population was 20.7%, which increases along with the growth of HGI levels (P<0.001). Adjusted to multiple factors, this trend still remained significant (OR: 1.172 (95% CI, 1.074–1.279)). The combined NAFLD risk score based on HGI resulted in an area under the receiver operator characteristic curve (AUROC) of 0.85 provided sensitivity, specificity, positive predictive value, and a negative predictive value for NAFLD of 84.4%, 71.3%, 65.0%, and 88.0%, respectively. Conclusions. NAFLD is independently associated with HGI levels in Chinese nondiabetic individuals. And, NAFLD risk score may be used as one of the risk predictors of NAFLD in nondiabetic population.

BACKGROUND:Obstructive sleep apnea (OSA) and nocturnal enuresis (NE) are common clinical problems in children. OSA and NE are thought to be interrelated, but the exact pathophysiological mechanisms are not yet clear. This review aims to explain the possible pathogenesis of NE in children with OSA.DATE SOURCES:We have retrieved all relevant original articles from Database that have been published so far, including the prevalence studies of NE and OSA in children, sleep characteristic studies that use polysomnography (PSG) to focus on children with NE, and studies on the relationship between OSA and NE.RESULTS:Clinical studies have revealed that the risk of NE in children with OSA was increased compared with that of their healthy peers. This increased risk may be associated with sleep disorders, bladder instability, detrusor overactivity, nocturnal polyuria, endocrine and metabolic disorders, and inflammation.CONCLUSIONS:Cardiopulmonary and renal reflex-induced neuroendocrine disorder may play an important role in the mechanism of NE in children with OSA, but this remains to be confirmed by animal studies. Other causes such as oxidative stress and inflammatory responses need to be further researched.

This study aimed to examine clinical effect of vacuum sealing drainage in treating the wound tissue of patients with diabetes; and investigate the expression of periostin and connective tissue growth factor in wound tissue. We selected 40 patients with diabetes and chronic ulcers, and assigned randomly into two groups: the vacuum sealing drainage group and routine dressing group (controls). Tissues were cut at day 1 before treatment and day 7 after treatment. Immunohistochemistry was used to observe periostin and connective tissue growth factor expression. Cure time and cure rate between the two groups was observed. Connective tissue growth factor and periostin were rarely expressed in wound tissue before treatment, but were increased after treatment. The mean count of periostin-positive cells was 25.2 +/- 3.50 in the vacuum sealing drainage group and 12.9 +/- 1.8 in the control group (P < 0.05). The mean count of connective tissue growth factor-positive cells was 19.7 +/- 2.54 in the vacuum sealing drainage group and 6.8 +/- 1.58 in the control group (P < 0.05). The mean duration of hospitalization of the vacuum sealing drainage group was 33.4 +/- 7.91 days, and 17 (85%) patients were cured. The mean duration of hospitalization of the routine treatment group was 50.45 +/- 6.77 days, and 13 (65%) patients were cured (both P < 0.05). This study shows that vacuum sealing drainage can shorten the healing time of diabetic chronic wounds and was addition to the mechanism of the vacuum sealing drainage treatment of diabetic wound.

Objective: To investigate the risk factors alert mechanism in children with obstructive sleep ap-nea and hypopnea syndrome (OSAHS), and to determine the correlation of arousal and systematic inlfammation response.Methods: Two hundred and eighty-ifve cases of snoring children aged 6-11 years old were included, sleep questionnaires were completed by their parents. All the children performed the whole night polysommong-raphy (PSG), the total sleep time (TST), sleep efifciency, sleep structure, oxygen desaturation, and various respi-ratory disorder index were assessed by physician. Thirty children at high risk and low risk for obstructive sleep apnea syndrome (OSAHS) were randomly selected to detect the blood routine, C reactive protein (CRP) and interleukin-1β (IL-1β) levels.Results: Fifty-six cases (19.6%) of snoring children were diagnosed OSAHS by PSG. Logistic regression analysis showed that tonsil and adenoid hypertrophy, habitual snoring, obesity, mouth breathing, enuresis, hyperactivity and irascibility were the main risk factors. PSG study showed that TST, sleep efifciency, deep sleep (stage III and IV) and REM sleep time decreased, light sleep (stage I and II), arousal index (AI), OAI, AHI and RDI increased in OSAHS children. IL-1β and CRP levels increased in OSAHS children. Pearson correlation analysis showed there was positive correlation between AI and RDI (r=7.56,P<0.01). Fur-thermore, AI correlated with the level of IL-1β (r=6.85,P<0.01).Conclusion: Tonsil and adenoid hypertrophy, habitual snoring, obesity, mouth breathing, enuresis, hyperactivity and irascibility are the main risk factors of&nbsp;OSAHS children. AI increases in accord with RDI and this phenomenon may correlate with systematic mild in-lfamation reponse.

Vitamin D as an immune regulator,playing an important role in the bronchial asthma (asthma).But about the T cell signal transduction pathways involved research is unclear.The active form of vitamin D,1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] with vitamin D receptor has been shown to play a role of immune regulation.This article mainly summarized the 1,25(OH)2 D3 and its receptor mediated the role of regulatory T cells in the immune mechanism of asthma,and the signal transduction pathways that 1,25(OH)2 D3 biological effects may play.Understanding the immune mechanism of asthma control is of great importance.