The prevalence of mild cognitive impairment and its etiological subtypes in elderly Chinese

BackgroundEpidemiologic studies on mild cognitive impairment (MCI) are limited in China.MethodsUsing a multistage cluster sampling design, a total of 10,276 community residents (6096 urban, 4180 rural) aged 65 years or older were evaluated and diagnosed with normal cognition, MCI, or dementia. MCI was further categorized by imaging into MCI caused by prodromal Alzheimer's disease (MCI-A), MCI resulting from cerebrovascular disease (MCI-CVD), MCI with vascular risk factors (MCI-VRF), and MCI caused by other diseases (MCI-O).ResultsThe prevalences of overall MCI, MCI-A, MCI-CVD, MCI-VRF, and MCI-O were 20.8% (95% confidence interval [CI] = 20.0–21.6%), 6.1% (95% CI = 5.7–6.6%), 3.8% (95% CI = 3.4–4.2%), 4.9% (95% CI = 4.5–5.4%), and 5.9% (95% CI = 5.5–6.4%) respectively. The rural population had a higher prevalence of overall MCI (23.4% vs 16.8%, P < .001).ConclusionsThe prevalence of MCI in elderly Chinese is higher in rural than in urban areas. Vascular-related MCI (MCI-CVD and MCI-VRF) was most common.     

Renal injury induced in alloxan diabetic rats. Role of Mycophenolate Mofetil as therapeutic agent

BackgroundRenal injury may develop in uncontrolled chronic hyperglycemia due to increased oxidative stress and release of pro-inflammatory mediators, leading to diabetic complications.MethodsMycophenolate Mofetil (MMF) is an immunosuppressant drug, an inhibitor of inosine monophosphate dehydrogenase (IMPDH), relevant to inflammation processes. MMF effect was tested in alloxan-diabetic rats on selected parameters like oxidative stress, gene expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1), in relation to microalbuminuria and renal function.ResultsWe found that the onset of microalbuminuria preceded the increase in serum glucose after alloxan treatment. Gene expression of TNF-α and TGF-β1 showed gradual increase after one and two weeks of alloxan administration as compared to the normal group. MMF administration decreased the gene expression of TNF-α and TGF-β1 in kidney tissues, serum glucose, fructosamine, urea, creatinine, C-reactive protein, malondialdehyde, urinary microalbumin and total protein. Histological examination of kidney tissues showed significant improvement in MMF treated rats as compared to diabetic control.ConclusionsMMF modulated renal injury of alloxan diabetic rats. Collective data may support its therapeutic effect but further clinical trials may be requested.     

The prevalence of dementia in urban and rural areas of China

ObjectiveThe Chinese population has been aging rapidly and the country's economy has experienced exponential growth during the past three decades. The goal of this study was to estimate the changes in the prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) among elderly Chinese individuals and to analyze differences between urban and rural areas.MethodsFor the years 2008 to 2009, we performed a population-based cross-sectional survey with a multistage cluster sampling design. Residents aged 65 years and older were drawn from 30 urban (n = 6096) and 45 rural (n = 4180) communities across China. Participants were assessed with a series of clinical examinations and neuropsychological measures. Dementia, AD, and VaD were diagnosed according to established criteria via standard diagnostic procedures.ResultsThe prevalence of dementia, AD, and VaD among individuals aged 65 years and older were 5.14% (95% CI, 4.71–5.57), 3.21% (95% CI, 2.87–3.55), and 1.50% (95% CI, 1.26–1.74), respectively. The prevalence of dementia was significantly higher in rural areas than in urban ones (6.05% vs. 4.40%, P < .001). The same regional difference was also seen for AD (4.25% vs. 2.44%, P < .001) but not for VaD (1.28% vs. 1.61%, P = .166). The difference in AD was not evident when the sample was stratified by educational level. Moreover, the risk factors for AD and VaD differed for urban and rural populations.ConclusionsA notably higher prevalence of dementia and AD was found in rural areas than in urban ones, and education might be an important reason for the urban–rural differences.     

Long-circulating and liver-targeted nanoassemblies of cyclic phosphoryl N-dodecanoyl gemcitabine for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a serious cancer with high mortality worldwide. Gemcitabine (GEM) is easily degraded in the circulation and has no tumor-targeted effect. In our previous research, an amphiphilic GEM derivative, cyclic phosphoryl N-dodecanoyl gemcitabine (CPDG) was prepared based on the techniques of HepDirect prodrug and self-assembled drug delivery systems (SADDS), which self-assembled into the stable nanoassemblies in water. In this study, the long-circulating nanoassemblies of CPDG/CHS-PEG1500 (9:1, mol/mol) were prepared for HCC treatment. In vitro and in vivo studies of the long-circulating CPDG nanoassemblies were explored. The degradation rates of CPDG depended on the media. CPDG showed much faster degradation in the acidic environment (pH 2.0) than the weak acidic and neutral media (pH 5.0, pH 7.4). However, the degradation half-life (t_1/2) of CPDG was about 43 h in the mouse plasma, longer than the t_1/2 at pH 2.0. Therefore, the long-circulating CPDG nanoassemblies could keep stable before reaching the targets in vivo. In the biodistribution study, the long-circulating CPDG nanoassemblies were bolus intravenously (i.v.) injected into the hepatocellular tumor-bearing mice. The distribution of CPDG in the tumors was much higher than that in the blood, indicating the tumor targeting of the long-circulating nanoassemblies. In the pharmacodynamic study, the long-circulating CPDG nanoassemblies were i.v. injected into the tumor-bearing mice with doses of (37.5, 75 μmol/kg) compared with GEM (150 μmol/kg). The mice were injected once every 3 days for totally 3 times. The long-circulating nanoassemblies nearly always showed the higher anti-cancer effects than GEM. The tumor inhibitory rates of GEM, the long circulating CPDG nanoassemblies (37.5, 75 μmol/kg) were 49.54, 42.97, 65.10%, respectively. Therefore, the long-circulating CPDG nanoassemblies had the much higher anti-cancer effect than GEM. The long-circulating CPDG nanoassemblies are promising nanomedicines to treat HCC. The combination design of tumor-targeted nanoassemblies based on HepDirect prodrug technique and SADDS theory is an effective method to modify the pharmacologically active nucleosides to treat some liver diseases.     

A homozygote TREX1 mutation in two siblings with different phenotypes: Chilblains and cerebral vasculitis

Three prime repair exonuclease 1 degrades single and double stranded DNA with 3′-5′ nuclease activity and its mutations are related to type 1 IFN mediated autoinflammation due to accumulated intracellular nucleic acids. To date, several cases of systemic lupus erythematosus, Aicardi-Goutieres syndrome, familial chilblain lupus, retinal vasculopathy-cerebral leukodystrophy have been reported with TREX1 mutations.Chilblain lupus is a skin disease characterized by blue-reddish coloring, swelling or ulcers on acral regions of body such as fingertips, heels, nose and auricles. Central nervous system vasculitis is a prominent cause of childhood strokes.10 families with familial chilblain lupus related to TREX1 mutations were reported previously in the literature, in which homozygote D18N variant in TREX1 gene was related to chilblains with cerebral vasculitis.In this report, whole-exome-sequencing revealed a homozygote R114C mutation in TREX1 gene was shown in two siblings with recurrent chilblains whom one of them was the second case accompanied by cerebral vasculitis in the literature. As a result, the approach of WES in clinical use revealed a novel mutation in clinically heterogenous patients to provide genetic counseling.     

依那普利拉抑制大鼠心室成纤维细胞增殖的实验研究

目的观察血管紧张素Ⅰ转换酶抑制剂(ACEI)依那普利拉(enalaprilat,Ena)对血管紧张素Ⅱ(AngⅡ)诱导的心肌成纤维细胞(CFb)增殖作用及作用机制。方法以培养的Wistar大鼠乳鼠CFb为模型,实验分为对照组、AngⅡ组、用药组三个剂量组,采用胰酶消化、差速贴壁法培养CFb,四氮唑盐(MTT)比色法检测CFb增殖;羟脯氨酸法测定胶原含量;流式细胞仪、免疫细胞荧光染色法、免疫印迹法检测细胞周期和p27~(kipl)表达。结果Ena能够抑制AngⅡ诱导的CFb增殖(P<0.01,P<0.05),降低羟脯氨酸含量(P<0.01,P<0.05),提高p27~(kipl)表达(P<0.01,p<0.05)。结论Ena抑制CFb增殖与提高p27~(kipl)表达相关。     

Treatments of unruptured brain arteriovenous malformations: A systematic review and meta-analysis

Background:The best therapeutic option for unruptured brain arteriovenous malformations (bAVMs) patients is disputed.Objective:To assess the occurrence of obliteration and complications of patients with unruptured bAVMs after various treatments.Methods:A systematic literature search was performed in PubMed, EMBASE, Web of Science, and so on to identify studies fulfilling predefined inclusion criteria. Baseline, treatment, and outcomes data were extracted for statistical analysis.Results:We identified 28 eligible studies totaling 5852 patients. The obliteration rates were 98% in microsurgery group (95% confidence interval (CI): 96%–99%, I² = 74.5%), 97% in surgery group (95%CI: 95%–99%, I² = 18.3%), 87% in endovascular treatment group (95%CI: 80%–93%, I² = 0.0%), and 68% in radiosurgery group (95%CI: 66%–69%, I² = 92.0%). The stroke or death rates were 1% in microsurgery group (95%CI: 0%–2%, I² = 0.0%), 0% in surgery group (95%CI: 0%–1%, I² = 0.0%), 4% in endovascular treatment group (95%CI: 0%–8%, I² = 85.8%), and 3% in radiosurgery group (95%CI: 3%–4%, I² = 82.9%). In addition, the proportions of hemorrhage were 2% in microsurgery group (95%CI: 1%–4%, I² = 0.0%), 23% in endovascular treatment group (95%CI: 7%–39%), and 12% in radiosurgery group (95%CI: 12%–13%, I² = 99.2%). As to neurological deficit, the occurrence was 9% in microsurgery group (95%CI: 6%–11%, I² = 94.1%), 20% in surgery group (95%CI: 13%–27%, I² = 0.0%), 14% in endovascular treatment group (95%CI: 10%–18%, I² = 64.0%), and 8% in radiosurgery group (95%CI: 7%–9%, I² = 66.6%).Conclusions:We found that microsurgery might provide lasting clinical benefits in some unruptured bAVMs patients for its high obliteration rates and low hemorrhage. These findings are helpful to provide a reference basis for neurosurgeons to choose the treatment of patients with unruptured bAVMs.