The aim of this paper was to study the comparative stability of venlafaxine hydrochloride (VEN) sustained-release pellets prepared by double-polymer coatings and hot-melt subcoating combined Eudragit(®) NE30D outercoating. The uncoated VEN pellets, containing 45% (w/w) VEN, 45% (w/w) MCC (PH101), 10% (w/w) stearic acid and 0.5% (w/w) Carbopol974, were prepared by extrusion-spheronization. Satisfactory release profiles were obtained when VEN pellets were prepared by 4% EC subcoating combined with 4% Eudragit(®) NE30D outercoating and 8% hot-melt subcoating combined with 6% Eudragit(®) NE30D outercoating, respectively. The storage stability was monitored by measuring the drug release over six months storage at 40°C/75% RH and at room temperature (25 ± 2°C/60% RH). The release of pellets with double-polymer coatings increased markedly, while drug release of pellets prepared by hot-melt subcoating combined with polymer coating gradually decreased. Basically, the former may be attributed to the main role of drug migration into the EC subcoating, and the latter may be caused by the fusion and resolidification of stearic acid particles and the further aging of the Eudragit(®) NE30D outercoating. In summary, regardless of the change in release, drug dissolution met the standard requirement and the stability was acceptable during the storage period.
Celsr3 and Fzd3 regulate the development of reciprocal thalamocortical projections independently of their expression in cortical or thalamic neurons. To understand this cell non autonomous mechanism further, we tested whether Celsr3 and Fzd3 could act via Isl1-positive guidepost cells. Isl1-positive cells appear in the forebrain at embryonic day (E) 9.5-E10.5 and, from E12.5, they form 2 contingents in ventral telencephalon and prethalamus. In control mice, corticothalamic axons run in the ventral telencephalic corridor in close contact with Isl1-positive cells. When Celsr3 or Fzd3 is inactivated in Isl1-expressing cells, corticofugal fibers stall and loop in the ventral telencephalic corridor of high Isl1 expression, and thalamic axons fail to cross the diencephalon–telencephalon junction (DTJ). At E12.5, before thalamic and cortical axons emerge, pioneer projections from Isl1-positive cells cross the DTJ from both sides in control but not mutant embryos. These early projections appear to act like a bridge to guide later growing thalamic axons through the DTJ. Our data suggest that Celsr3 and Fzd3 orchestrate the formation of a scaffold of pioneer neurons and their axons. This scaffold extends from prethalamus to ventral telencephalon and subcortex, and steers reciprocal corticothalamic fibers.
Objective: To investigate the clinical characteristics of diabetic patients combined with acute myocardial infarction (AMI) and to compare the prognosis between diabetic and non- diabetic patients in 4-5 years after the onset of AMI. Methods: Followed the certain inclusive and exclusive criteria, a total of 420 patients with acute myocardial infarction were included and divided into diabetes group (group D) and non-diabetes group (group N) with numbers as 161 people and 259 respectively. Baseline data, clinical information, short-term outcome and long-term prognosis of the two groups were compared and analyzed. Results: Among the patients with diabetes, the average age was older (65.65±11.33 vs. 63.30±15.34), with fewer males (64.59% vs. 79.92%); and more likely to have other complications as hypertension (64.60% vs. 53.28%) or hyperlipidemia (42.24% vs. 26.25%). 59.29% of the patients in group D showed pathological changes in 3 major coronary arteries, which were significantly more than its counterpart (40.83%). The proportion of patients that had undergone the coronary artery bypass, grafting (11.11% vs. 5.31%) appeared also higher. There was no significant difference seen in the short-term outcomes between the two groups, but results from the long-term follow-up program showed that both the incidence of Major Adverse Cardiovascular Events (MACE) (50.67% vs. 27.72%) and the all-cause mortality (20.00% vs. 9.90%) in group D were higher than those appeared in group N (27.72%). Conclusions: Patients suffered from the combination of both diabetes and acute myocardial infarction appeared older in age, more in females, with more complications and the coronary artery lesions were more severe and wider. During hospitalization, no significant difference was seen regarding the short-term outcomes between the two groups but the results from long-term follow-up process showing that the risk of MACE events was significantly higher in patients with type2 diabetes.目的： 研究糖尿病急性心肌梗死患者的临床特点，比较糖尿病和非糖尿病患者急性心肌梗死后4~5年预后情况。 方法： 经过一定纳排标准收入420例急性心肌梗死患者，分为糖尿病组161人，非糖尿病组259人，对两组患者的基线资料、病情资料、短期转归及长期预后情况进行对比分析。 结果： 与非糖尿病组相比，糖尿病组患者年龄偏大（65.65±11.33 vs. 63.30±15.34）、男性比例偏低（64.59% vs. 79.92%）、合并高血压病比例（64.60% vs. 53.28%）和高脂血症比例（42.24% vs. 26.25%）等偏高；三支病变比例（59.29% vs. 40.83%）和建议冠脉旁路移植术者（11.11% vs. 5.31%）比例偏高；短期转归方面两组患者没有明显差异，但长期随访结果显示糖尿病组患者不良心血管事件发生概率（50.67% vs. 27.72%）和全因死亡率（20.00% vs. 9.90%）均高于非糖尿病组。 结论： 糖尿病对急性心肌梗死患者的病情及预后有显著的负面影响，主要表现为病变范围和程度的严重性以及长期预后中主要不良心血管事件的风险增加。.
In this paper, we investigate properties of solutions to a space-time fractional variable-order conformable nonlinear differential equation with a generalized tempered fractional Laplace operatorby using the maximum principle. We first establish some new important fractional various-order conformable inequalities. With these inequalities, we prove a new maximum principle with space-time fractional variable-order conformable derivatives and a generalized tempered fractional Laplace operator. Moreover, we discuss some results about comparison principles and properties of solutions for a family of space-time fractional variable-order conformable nonlinear differential equations with a generalized tempered fractional Laplace operator by maximum principle.
In this paper, the authors study a initial boundary value problems (IBVP) for space-time fractional conformable partial differential equation (PDE). Several inequalities of fractional conformable derivatives at extremum points are presented and proved. Based on these inequalities at extremum points, a new maximum principle for the space-time fractional conformable PDE is demonstrated. Moreover, the maximum principle is employed to prove a new comparison principle and estimation of solutions. Beside that, the uniqueness and continuous dependence of the solution of the space-time fractional conformable PDE are demonstrated.
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