OBJECTIVES:To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS:Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS:At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS:Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder, and there is an association between it and the development of cardiovascular disease. The aim of this study was to explore whether there is a glutamatergic pathway connecting the medial habenula (MHb) with the rostral ventrolateral medulla (RVLM) that is involved in the regulation of cardiovascular function in a rat model of PTSD. Vesicular glutamate transporter 2 (VGLUT2)-positive neurons in the MHb region were retrogradely labeled with FluoroGold (FG) by the double-labeling technique of VGLUT2 immunofluorescence and FG retrograde tracing. Rats belonging to the PTSD model group were microinjected with artificial cerebrospinal fluid (ACSF) or kynurenic acid (KYN; a nonselective glutamate receptor blocker) into their RVLM. Subsequently, with electrical stimulation of MHb, the discharge frequency of the RVLM neurons, heart rate, and blood pressure were found to be significantly increased after microinjection of ACSF using an in vivo multichannel synchronous recording technology; however, this effect was inhibited by injection of KYN. The expression of N-methyl-D-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits was significantly increased in RVLM of PTSD model rats analyzed by the Western blotting technique. These findings suggest that there may be a glutamatergic pathway connection between MHb and RVLM and that this pathway may be involved in the regulation of cardiovascular function in the PTSD model rats, by acting on NMDA and AMPA receptors in the RVLM.

Post-traumatic stress disorder (PTSD) has been reported to be associated with a higher risk of cardiovascular disease. The amygdala may have an important role in regulating cardiovascular function. This study aims to explore the effect of amygdala glutamate receptors (GluRs) on cardiovascular activity in a rat model of PTSD. A compound stress method combining electrical stimulation and single prolonged stress was used to prepare the PTSD model, and the difference of weight gain before and after modeling and the elevated plus maze were used to assess the PTSD model. In addition, the distribution of retrogradely labeled neurons was observed using the FluoroGold (FG) retrograde tracking technique. Western blot was used to analyze the changes of amygdala GluRs content. To further investigate the effects, artificial cerebrospinal fluid (ACSF), non-selective GluR blocker kynurenic acid (KYN) and AMPA receptor blocker CNQX were microinjected into the central nucleus of the amygdala (CeA) in the PTSD rats, respectively. The changes in various indices following the injection were observed using in vivo multi-channel synchronous recording technology. The results indicated that, compared with the control group, the PTSD group exhibited significantly lower weight gain (P < 0.01) and significantly decreased ratio of open arm time (OT%) (P < 0.05). Retrograde labeling of neurons was observed in the CeA after microinjection of 0.5 µL FG in the rostral ventrolateral medulla (RVLM). The content of AMPA receptor in the PTSD group was lower than that in the control group (P < 0.05), while there was no significant differences in RVLM neuron firing frequency and heart rate (P > 0.05) following ACSF injection. However, increases in RVLM neuron firing frequency and heart rate were observed after the injection of KYN or CNQX into the CeA (P < 0.05) in the PTSD group. These findings suggest that AMPA receptors in the amygdala are engaged in the regulation of cardiovascular activity in PTSD rats, possibly by acting on inhibitory pathways.

Objective To explore the effect of prednisone acetate on renal function, renal inflammatory response and AMP-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1) signaling pathway in diabetic nephropathy (DN) rats. Methods Twelve rats were randomly selected as the control group, and the remaining rats were given high-sugar and high-fat diet supplemented with intraperitoneal injection of streptozotocin (STZ) to construct a DN rat model. The successful model rats were randomly divided into model group, prednisone acetate low (6.25 mg/kg), high (12.5 mg/kg) dose groups, prednisone acetate + CC group (prednisone acetate 12.5 mg/kg+AMPK inhibitor compound C 0.2 mg/kg), with 12 animals in each group. Each group was given corresponding treatment, once a day for 4 weeks. The general state of rats was observed, and the fasting blood glucose (FBG), 24-hour urine microalbumin (U-mAlb), blood creatinine (SCr), blood urea nitrogen (BUN), serum interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected; the pathological changes of renal tissue were observed with hematoxylin eosin (HE) staining and periodate schiff (PAS) staining; The expression of proteins related to the renal tissue AMPK/SIRT1 signaling pathway was detected with Western blot. Results Prednisone acetate can improve the general state of DN rats, reduce FBG, 24 h U-mAlb, serum SCr, BUN, IL-1β, IL-6 and TNF-α levels, and renal tissue acetylation nuclear factor-κB p65 (ac-NF-κB p65)/NF-κB p65 and monocyte chemotactic protein-1 (MCP-1) protein expression (P＜0.05), increase phosphorylated AMPK(p-AMPK)/AMPK and SIRT1 protein expression (P＜0.05), improve kidney disease; compound C could significantly weaken the protective effect of prednisone acetate on DN rats. Conclusions Prednisone acetate can reduce renal inflammatory response and protect renal function in DN rats. Its mechanism may be related to the activation of AMPK/SIRT1 pathway to inhibit the activation of NF-κB.

Objective:This study aimed to explore the feasibility and clinical value of monitoring the progression of early kidney injury in type 2 diabetic patients by assessment of the urinary C-terminal agrin fragment (uCAF) with enzymatic chemiluminescence immunoassay.Methods:A total of 251 patients with type 2 diabetes, who attended the Second Affiliated Hospital of Wenzhou Medical University from October 2018 to March 2020, were included in this retrospective analysis. One hundred and fifty-six participants undergoing health check-up at the Second Affiliated Hospital of Zhejiang University School of Medicine in February 2021 served as controls. Basic clinical information, glycosylated hemoglobin type A 1c and serum creatinine values were recorded, and urine specimens were collected for urinary creatinine, urinary α 1 microglobulin(uα 1M), urinary immunoglobulin G (uIgG), urinary albumin, urinary N-Acetyl-B-D-glycosaminidase (uNAG) and uCAF measurements. Based on the estimated glomerular filtration rate (eGFR), 251 patients were classified into G1~G5 stage groups with 116, 22, 28, 55 and 30 patients in each group. One hundred and sixty-six patients with early diabetic kidney disease (stage G1-G3) were divided into subgroups A1 (79), A2 (48) and A3 (39) according to the urinary albumin/creatinine ratio (UACR), the uα1M levels were divided into uα1M subgroup 1 (83 cases), uα1M subgroup 2 (42 cases), and uα1M subgroup 3 (41 cases), and uIgG subgroup 1 (83 cases), uIgG subgroup 2 (42 cases), and uIgG subgroup 3 (41 cases) according to uIgG levels. The Spearman method was used to analyze the correlation between uCAF levels and eGFR, UACR, uα1M and uIgG levels. Results:(1) The linear range of the uCAF detected by enzymatic chemiluminescence immunoassay was 3.97-2 000.00 ng/ml, with a detection limit of 2.28 ng/ml, intra-batch coefficients of variation of 1.15% and 1.57%, inter-batch coefficients of variation of 1.63% and 5.78%, and a biological reference interval of <95.35 μg/g Cr. (2) The uCAF level and positive rate (UACR≥30 mg/g) increased with the decrease of eGFR from G1-G3, uCAF level was negatively correlated with eGFR value ( r=-0.543, P<0.000 1), and the positive rate increased from 24.14% (28/116) to 85.71% (24/28) from G1-G3. The uCAF level and positivity rate decreased with the decrease of eGFR from G4 to G5. uCAF level was positively correlated with eGFR value ( r=0.495, P<0.001), and the positivity rate decreased from 30.91% (17/55) to 23.33% (7/30) from G4 to G5. (3) In patients with early diabetic kidney disease, uCAF levels and positivity rates increased gradually with the increase of UACR. uCAF levels were positively correlated with UACR values ( r=0.602, P<0.001), and the uCAF positivity rate reached 21.52% (17/79) in the A1 subgroup. (4) uCAF level was positively correlated with uα1M and uIgG levels in patients with early diabetic kidney disease ( r=0.757, 0.596, both P<0.001). Conclusion:Analytical performance of enzyme chemiluminescence immunoassay for the detection of CAF is satisfactory and could be used a biomarker for monitoring damage and progression of early diabetic kidney disease in patients with type 2 diabetes.

目的:探讨以糖尿病为主要表现的Johanson-Blizzard综合征(JBS)患者的临床表型和基因型.方法:收集JBS患者的临床资料、实验室检查、影像学检查,提取相关家庭成员的基因组DNA,使用全外显子组测序及Sanger测序验证.结果:患者以糖尿病为主要表现,伴有眼距增宽,鼻根低平,鼻翼发育不全,发际线低等畸形.基因检测证实UBR1基因存在c.4463T>C(p.Ile1488Thr)纯合错义突变,为新的突变位点,且致病性分析表明该位点为致病性突变.结论:该患者携带新的UBR1基因c.4463T>C纯合突变,提高了临床上对JBS临床表型谱的认识并拓宽了UBR1基因的基因谱.

OBJECTIVE:To investigate the effect of orexin-A on the functionality of ionotropic γ-aminobutyric acid (GABA) receptors in spinal cord ventral horn neurons and its mechanisms. OBJECTIVE:The spinal cord containing the lumbosacral enlargement was isolated from neonatal SD rats (7-12 days old) and sliced. The slices were digested with papain (in 0.18 g/30 mL artificial cerebrospinal fluid) for 40-60 min, and the ventral horn neurons were separated acutely using fire-polished Pasteur pipettes. After the cells adhered to the bottom of Petri dishes, patch-clamp experiments combined with pharmacological methods were performed to test the effects of orexin-A on GABA currents of the neurons treated with SB334867 (a selective OX1R antagonist), TCSOX229 (a selective OX2R antagonist), Bis-Ⅳ (a PKC inhibitor), PMA (a PKC agonist), Rp-cAMP (a PKA inhibitor), or BAPTA (Ca2+ chelator). OBJECTIVE:The isolated neurons maintained good morphologies with diverse shapes of cell body and long protrusions. Treatment with orexin-A significantly inhibited the amplitude of GABA-induced current (P < 0.001, n=49) with an inhibition rate of (67.48±12.50)%. SB334867 and TCSOX229, when applied simultaneously, completely abolished the suppressive effect of orexin-A on the GABA currents (P=0.93, n=6), and their separate use partially relieved the suppressive effect of orexin-A (P=0.001, n=8; P=0.02, n=8). The application of Bis-Ⅳ also abolished the suppressive effect of orexin-A on GABA currents (P=0.31, n=5). PMA mimicked the effect of orexin-A in these neurons and significantly inhibited GABA currents with an inhibition rate of (60.79±10.94)%, and the application of orexin-A did not cause further suppression of GABA currents in PMA-treated neurons (P=0.15, n=6). Orexin-A was still capable of suppressing GABA currents in Rp-cAMP-treated neurons (P=0.001, n=5). The extracellular Ca2+-free solution (P=0.004, n=8) or the presence of BAPTA (P=0.04, n=7) did not significantly affect the inhibitory effect of orexin-A on GABA currents. OBJECTIVE:Orexin-A inhibits GABA currents in the ventral horn neurons of rat spinal cord probably by activating OX1R, OX2R and Ca2+-independent PKC.

This study was aimed to investigate the cardiovascular function in rats with post-traumatic stress disorder (PTSD) and the potential association with the activities of the rostral ventrolateral medulla (RVLM) and the medial habenular nucleus (MHb). Multi-channel in vivo recordings were used to simultaneously acquire spontaneous neuronal firing and peripheral physiological indices, and FluoroGold (FG) retrograde tracing technique was used to observe the projections of labeled neurons in the MHb. The results showed that the discharge frequency of RVLM and MHb neurons, the systolic blood pressure (SBP), and the mean arterial pressure (MAP) in the PTSD group were all increased significantly compared with those in control group (P < 0.05). MHb neurons were retrogradely labeled by FG through microinjection (4% FG, 0.5 μL) into the RVLM. In the control group, electrical stimulation in the MHb increased heart rate (HR) at 100-300 μA (P < 0.05), elevated SBP and MAP at 200-300 μA (P < 0.05), and remarkably increased the RVLM neuronal discharge frequency at 100-500 μA (P < 0.05 or P < 0.01). In the PTSD group, however, only the discharge frequency of RVLM neurons was increased by the electrical stimulation at 100-300 μA (P < 0.05). These results suggest that cardiovascular activities of the PTSD model rat are enhanced, and this change may be related to the activity changes of RVLM and MHb and the potential connection between the two nuclei.

虚拟仿真技术优点卓越,具有极其广阔的应用前景,现如今其已经越来越多地应用于现代教学.该文主要以海马脑片CA1区锥体神经元的突触可塑性实验为切入点,对虚拟仿真实验教学技术在教学中的应用进行了深入研究,以期为今后虚拟仿真技术在教学领域的发展提供一定的指导和帮助.

目的:探讨胰高血糖素样肽1(GLP-1)受体激动剂利拉鲁肽(Lira)早期干预对高脂饮食(HFD)诱导的非酒精性脂肪性肝病(NAFLD)大鼠的影响及沉默信息调节因子1(SIRT1)/AMP活化蛋白激酶(AMPK)通路在其中的作用.方法:SPF级雄性SD大鼠随机分为普通饮食(ND)组、HFD组和HFD+Lira组,每组8只.适应性饲养1周后,按不同分组给药,HFD+Lira组大鼠每日固定时间皮下注射Lira(200μg/kg),其余2组注射等体积生理盐水.干预期间注意观察大鼠体重、毛发、食欲、大小便及活动情况,以便及时调整药量.每周记录体重、进食量和血糖,第16周行葡萄糖耐量实验;第18周末麻醉后行高胰岛素-正葡萄糖钳夹实验,该实验结束后颈动脉取血,处死后取肝脏及不同部位的脂肪组织.血清检测丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)等指标;HE染色法观察肝组织病理损伤变化;油红O染色法观察肝组织脂质蓄积程度;马松染色和天狼星红染色法观察肝脏纤维化程度;活性氧簇(ROS)染色观察肝脏氧化应激情况;免疫荧光染色观察肝脏GLP-1受体表达情况;免疫组织化学染色法观察SIRT1和第172位苏氨酸磷酸化的AMPK[p-AMPK(Thr172)]的表达及定位;Western blot法检测肝组织AMPK、p-AMPK(Thr172)、SIRT1、第372位丝氨酸磷酸化的固醇调节元件结合蛋白1c[p-SREBP-1c(Ser372)]、第79位磷酸化的乙酰辅酶A羧化酶[p-ACC(Ser79)]、肉毒碱棕榈酰转移酶1A(CPT1A)和脂肪酸合成酶(FAS)的蛋白水平.结果:HE和油红O染色结果证实HFD组肝组织结构紊乱,脂质蓄积严重,马松和天狼星红染色显示纤维化程度严重,提示NAFLD大鼠模型建立成功.与ND组相比,HFD组血清总胆固醇(TC)、甘油三酯(TG)、AST和ALT,以及肝组织丙二醛(MDA)、TC、TG和ROS水平均显著升高(P<0.01),超氧化物歧化酶(SOD)活性显著降低(P<0.01),肝组织p-AMPK(Thr172)、SIRT1、p-SREBP-1c(Ser372)、p-ACC(Ser79)和CPT1A蛋白水平显著降低(P<0.05或P<0.01),FAS表达显著增加(P<0.01);与HFD组比较,HFD+Lira组大鼠肝组织脂质蓄积和纤维化程度明显减轻,血清TG、TC、AST和ALT,以及肝组织MDA、TC、TG和ROS水平均显著降低(P<0.05或P<0.01),SOD活性增强(P<0.05),肝组织p-AMPK(Thr172)、SIRT1、p-SREBP-1c(Ser372)、p-ACC(Ser79)和CPT1A蛋白水平显著升高(P<0.05或P<0.01),FAS表达显著减少(P<0.01).结论:Lira能够减轻HFD诱导的NAFLD大鼠胰岛素抵抗、肝纤维化和氧化应激程度,并改善肝脏脂质代谢,其作用可能与SIRT1/AMPK通路有关.

Diabetic nephropathy (DN) is one of the major microvascular complications in diabetic patients, and it is also the main global cause of chronic kidney disease(CKD) and end-stage renal disease(ESRD). Albuminuria and estimated glomerular filtration rate (eGFR) are currently recognized as clinically diagnosed early DN, but their sensitivity and specificity are poor. Therefore, it is very important to find new biomarkers to reflect the potential diabetic nephropathy in the clinical silent period.

患者,女,50岁,因"肢体抖动10余年,心悸1个月"入院.患者于2009年无明显诱因出现肢体抖动,伴易饥多食,怕热多汗,烦躁易怒,于外院诊断为"甲状腺功能亢进",抗甲状腺功能亢进药物治疗1年后自觉无明显改善,自行停药. 10年来多次于外院就诊,抗甲状腺功能亢进药物治疗均无明显改善.

OBJECTIVE:To investigate the effects of etomidate on electrophysiological properties and nicotinic acetylcholine receptors (nAChRs) of ventral horn neurons in the spinal cord. METHODS:The spinal cord containing lumbosacral enlargement was isolated from 19 neonatal SD rats aged 7-12 days. The spinal cord were sliced and digested with papain (0.18 g/30 mL artificial cerebrospinal fluid) and incubated for 40 min. At the ventral horn, acute mechanical separation of neurons was performed with fire-polished Pasteur pipettes, and perforated patch-clamp recordings combined with pharmacological methods were employed on the adherent healthy neurons. In current-clamp mode, the spontaneous action potential (AP) of the ventral horn neurons in the spinal cord was recorded. The effects of pretreatment with different concentrations of etomidate on AP recorded in the ventral horn neurons were examined. In the voltage-clamp mode, nicotine was applied to induce inward currents in the ventral horn neurons, and the effect of pretreatment with etomidate on the inward currents induced by nicotine were examined with different etomidate concentrations, different holding potentials and different use time. RESULTS:The isolated ventral horn neurons were in good condition with large diverse somata and intact processes. The isolated spinal ventral horn neurons (n=21) had spontaneous action potentials, and were continuously perfused for 2 min with 0.3, 3.0 and 30.0 μmol/L etomidate. Compared with those before administration, the AP amplitude, spike potential amplitude and overshoot were concentration-dependently suppressed (P &lt; 0.01), and spontaneous discharge frequency was obviously reduced (P &lt; 0.01, n=12). The APs of the other 9 neurons were completely abolished by etomidate at 3.0 or 30 μmol/L. At the same holding potential (VH=-70 mV), pretreatment with 0.3, 3.0 or 30.0 μmol/L etomidate for 2 min concentration-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine (P &lt; 0.01, n=7). At the holding potentials of - 30, - 50, and - 70 mV, pretreatment with 30.0 μmol/L etomidate for 2 min voltage-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine (P &lt; 0.01, n=6 for each holding potential). During the 6 min of 30.0 μmol/L etomidate pretreatment, the clamped cells were exposed to 0.4 mmol/L nicotine for 4 times at 0, 2, 4, and 6 min (each exposure time was 2 s), and the nicotinic current amplitude decreased gradually as the number of exposures increased. But at the same concentration, two nicotine exposures (one at the beginning and the other at the end of the 6 min pretreatment) resulted in a significantly lower inhibition rate compared with 4 nicotine exposures (P &lt; 0.01, n=6). CONCLUSIONS:etomidate reduces the excitability of the spinal ventral neurons in a concentration-dependent manner and suppresses the function of nAChR in a concentration-, voltage-, and use-dependent manner.

目的:探讨肌肉脂肪比值(SVR)在2型糖尿病(T2DM)患者并发非酒精性脂肪肝(NAFLD)中的临床意义.方法:收集2017年4月至8月于温州医科大学附属第二医院育英儿童医院就诊的394例T2DM患者,分为NAFLD组(159例)及非NAFLD组(235例),比较2组四肢骨骼肌质量、内脏脂肪面积、血糖、血脂等临床资料.采用Pearson相关分析方法分析SVR与代谢危险因素的关系,多因素logistic回归分析SVR对NAFLD发生的影响,ROC曲线分析SVR对NAFLD的预测价值.结果:NAFLD组与非NAFLD组比较,女性比例、体质量、体质量指数、腰围、内脏脂肪面积、体脂肪率、舒张压、血尿酸、糖化血红蛋白水平、总胆固醇、甘油三酯均显著增高,而SVR、四肢骨骼肌质量显著降低(P<0.05).Pearson相关分析显示男性组SVR与体质量指数、腰围、收缩压呈负相关(r=-0.365、-0.437、-0.117,P<0.01),女性组SVR与体质量指数、腰围呈负相关(r=-0.190、-0.212,P<0.01).多因素logistic分析发现SVR是T2DM女性患者并发NAFLD的独立危险因素(OR=4.21,95％CI=1.31～13.52,P=0.016).ROC曲线分析显示SVR在男性组和女性组的AUC分别为0.66和0.63.结论:T2DM患者SVR水平与NAFLD的发生密切相关,可作为临床评估T2DM患者并发NAFLD的一项参考指标.

目的:探讨1,25-二羟维生素D3[1,25(OH)2D3]对软脂酸(PA)诱导的人脐静脉内皮细胞(HUVECs)的胰岛素抵抗的影响及其可能作用机制.方法:用含0.3、0.4、0.5、0.6、0.7、0.8、0.9 mmol/L PA的DMEM培养基培养HUVECs,建立胰岛素抵抗内皮细胞模型.分别用0、0.01、0.1、1.0、10、100 nmol/L 1,25(OH)2D3干预,硝酸盐/亚硝酸盐荧光试剂盒测定NO含量,Western blot法测定pAkt及peNOS蛋白的表达,qPCR法测定VDR、ET-1的表达.结果:0.6 mmol/L的PA培养HUVECs 18 h后,培养液中的葡萄糖浓度耗减显著低于对照组,细胞活力降低,胰岛素抵抗的内皮细胞模型建立.PA干预后NO含量较对照组HUVECs减少(P<0.05),1 nmol/L 1,25(OH)2D3干预胰岛素抵抗的内皮细胞后NO含量增加,在1 min时NO量达最大值.1 nmol/L浓度1,25(OH)2D3干预胰岛素抵抗的内皮细胞后peNOS及pAkt的蛋白表达量明显增加(P<0.05),ET-1的mRNA表达水平明显减少(P<0.05).结论:1,25(OH)2D3增加PA诱导的胰岛素抵抗血管内皮细胞peNOS、pAkt的表达,增加NO产生,降低ET-1的表达,可能对胰岛素抵抗的血管内皮细胞存在一定的保护作用.

Objective::To investigate the association of docosahexaenoic acid (DHA) with the presence of diabetic retinopathy (DR).Methods::This was a multiple-center, hospital-based, case-control study. A total of 197 type 2 diabetes mellitus (T2D) patients aged no less than 35 years old were enrolled from two affiliated hospitals of Wenzhou Medical University and Anhui Medical University. Depending on the fundus photos, they were classified into T2D (controls) and T2D combined with DR (cases). Based on propensity score matching, at a ratio of 1 : 1, by age, sex, body mass index and glycated hemoglobin, 69 pairs of cases and controls were included in the final data analysis. The intensity of DHA was determined using the ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) system. Multiple locally weighted regression and conditional logistic regression models were applied to comprehensively assess the association between DHA and the presence of DR. In addition, the results of a heterogeneity test and the interaction of DHA and the subgroups were displayed by a forest map.Results::A total of 69 pairs of cases and controls were included in the present study. The intensity of DHA in the cases was significantly lower than that of the controls ( t=3.68, P=0.001). After adjusting for potential confounding factors including age, triglyceride, hypertension and diabetes duration, the prevalence of DR was significantly reduced by 53% (odds ratio: 0.47; 95% confidence interval: 0.30, 0.73) with a per interquartile range elevation of DHA. As is shown in the forest map, associations of DHA with the odds of DR were consistent in each subgroup and no interaction effects between the subgroups and DHA were observed. Conclusions::DHA is an independent protective factor of DR and significantly associated with its initiation and progression. Our findings emphasize the clinical and public policy relevance of early screening for DR as well as its secondary prevention, which perhaps should be confirmed by additional large, longitudinal studies.

OBJECTIVE:To investigate the potential neural pathway connecting the nucleus accumbens (NAc) and the rostral ventrolateral medulla (RVLM), and whether the pathway participates in the regulation of cardiovascular function in a model rat of anorexia nervosa (AN).METHODS:Rat models of AN were established by allowing voluntary activity in a running wheel with restricted feeding, with the rats having free access to normal chow without exercise as the control group. FluoroGold (FG) retrograde tracing method and multi-channel simultaneous recording technique were used to explore the possible pathway between the NAc and the RVLM.RESULTS:The rats in AN group exhibited significantly reduced systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) with significantly increased discharge frequency of RVLM neurons in comparison with the control rats. After the injection of FG into the RVLM, retrograde labeled neurons were observed in the NAc of the rats in both the normal control and AN groups. In both groups, SBP and HR were significantly decreased in response to 400 μA electrical stimulation of the NAc accompanied by an obvious increase in the discharge frequency of the RVLM neurons; the diastolic blood pressure (DBP) and MAP were significantly lower in AN model rats than in the normal rats in response to the stimulation.CONCLUSIONS:We successfully established a rat model of AN via hyperactivity and restricted feeding and confirm the presence of a neural pathway connecting the NAc and the RVLM. This pathway might participate in the regulation of cardiovascular function in AN model rats.

目的:探讨中国汉族人群中编码脂肪因子的抵抗素(RETN)、瘦素受体(LEPR)和脂联素(ADIPOQ)基因多态性与2型糖尿病(T2DM)的相关性及其对血脂代谢的影响.方法:入组526例T2DM患者和344例无糖尿病对照者,采用竞争性等位基因特异性PCR(KASP)技术检测RETN(rs1862513、rs3745367),LEPR(rs1137101、rs13306519、rs1805096)和ADIPOQ(rs1501299、rs2241766)的单核苷酸多态性(SNP);并对RETN、LEPR和ADIPOQ基因多态性与T2DM发病风险间的关系以及各SNP基因型与血脂代谢间的关系进行统计学分析.结果:T2DM组中RETN rs1862513 GG基因型和G变异等位基因的频率均高于对照组,差异有统计学意义(42.0％vs.30.0％,P=0.003;65.0％vs.57.1％,P=0.001,OR=1.397,95％CI=1.140～1.712);进一步将总研究人群按不同BMI分析发现,在BMI<25 kg/m2中,T2DM组中RETN rs1862513 GG基因型频率明显高于对照组(42.8％vs.31.0％,P=0.015);进一步分析各基因型与血脂的关系发现,RETN rs3745367在BMI<25 kg/m2时GG或AG基因型具有更低的高密度脂蛋白胆固醇(HDL)水平(P=0.018);LEPR rs13306519在BMI≥25 kg/m2时CC或CG基因型具有更低的HDL水平(P=0.016);ADIPOQ rs1501299在总研究人群中CC或AC基因型的甘油三酯(TG)水平显著高于AA基因型(P=0.044).结论:RETN rs1862513 G等位基因可能与中国汉族人群T2DM的发病风险相关;ADIPOQ rs1501299 CC或AC基因型可能与高TG水平有关,RETN rs3745367 GG或AG基因型在非肥胖人群,LEPR rs13306519 CC或CG基因型在肥胖人群中可能与低HDL水平相关.

It was reported that α7 nicotinic acetylcholine receptor(α7-nAChR) knockout(α7 KO) mice showed few functional pheno-types.The purpose of this study was to investigate the effect of α7 KO on the electrophysiological characteristics of hippocampus in mice.The effect of α7 KO on hippocampal CA3-CA1 synaptic transmission in mice was evaluated by standard extracellular field potential recordings.The electrophysiological phenotype of γ-aminobutyrate A receptors(GABAA-Rs) of single hippocampal neuron was detected by perforated patch-clamp recordings.The results showed that,the slope of field excitatory postsynaptic potential(fEPSP) and carbachol-induced theta oscillation were significantly decreased in the hippocampal CA1 neurons of α7 KO mice,compared with those of wild type mice.Under the treatment of GABAA-R agonist muscimol,the I-V curves of both the hippocampal CA1 and CA3 neurons of α7 KO mice shifted towards depolarizing direction obviously,compared with those of wild type mice.These results suggest that the hippocampal CA3-CA1 synaptic transmission in α7 KO mice was significantly impaired and GABAA-R maturation was significantly delayed,indicating that the deletion of α7-nAChR gene could significantly change the electrophysiological function of the hippocampus.The results may provide a new understanding of the role of α7-nAChR in hippocampal function and associated diseases.

目的:探究荜茇酰胺(PL)对糖尿病心肌病模型中心肌损伤和纤维化的作用.方法:高糖刺激心肌H9C2细胞模拟高糖环境建立细胞模型,随后分为对照组、高糖组、低剂量(2.5μmol/L)PL组及高剂量(5μmol/L)PL组,qPCR检测炎症因子肿瘤坏死因子 α(TNF-α)和白细胞介素6(IL-6)的mRNA表达水平,Western blot检测纤维化指标转化生长因子 β(TGF-β)和Ⅳ型胶原蛋白(collagen IV)的蛋白表达水平.将C57BL/6小鼠随机分为对照组、1型糖尿病模型组、低剂量(2.5 mg/kg)PL组及高剂量(5 mg/kg)PL组,每组6只.除对照组外,其余各组每日腹腔注射链脲佐菌素(STZ)50 mg/kg,连续5日,1周后检测空腹血糖≥12 mmol/L认为造模成功.造模成功后,按不同分组给予不同剂量PL,腹腔注射给药13周,每隔2周尾静脉取血检测空腹血糖,第13周检测超声心动图,第13周末麻醉后处死小鼠,取血清检测肌酸激酶同工酶MB(CK-MB)和乳酸脱氢酶(LDH)水平;取心脏固定包埋切片,HE染色和天狼星红染色观察病理变化.结果:(1)高糖诱导下的H9C2细胞TNF-α 和IL-6的mRNA表达水平以及TGF-β 和collagen IV的蛋白表达水平较对照组明显升高,PL处理后上述指标均有所下降(P<0.05);(2)STZ造模成功后,腹腔注射PL可逆转糖尿病心肌病小鼠心肌组织结构排列紊乱及纤维化等病理改变,并降低心肌损伤血清学指标CK-MB及LDH水平(P<0.05).结论:PL可以减轻糖尿病心肌病模型的炎症反应和心肌组织损伤,延缓纤维化进程.