Rho-associated coiled-coil kinase 1 activation mediates amyloid precursor protein site-specific Ser655 phosphorylation and triggers amyloid pathology.

Rho-associated coiled-coil kinase 1 (ROCK1) is proposed to be implicated in Aß suppression; however, the role for ROCK1 in amyloidogenic metabolism of amyloid precursor protein (APP) to produce Aß was unknown. In the present study, we showed that ROCK1 kinase activity and its APP binding were enhanced in AD brain, resulting in increased ß-secretase cleavage of APP. Furthermore, we firstly confirmed that APP served as a substrate for ROCK1 and its major phosphorylation site was located at Ser655. The increased level of APP Ser655 phosphorylation was observed in the brain of APP/PS1 mice and AD patients compared to controls. Moreover, blockade of APP Ser655 phosphorylation, or inhibition of ROCK1 activity with either shRNA knockdown or Y-27632, ameliorated amyloid pathology and improved learning and memory in APP/PS1 mice. These findings suggest that activated ROCK1 targets APP Ser655 phosphorylation, which promotes amyloid processing and pathology. Inhibition of ROCK1 could be a potential therapeutic approach for AD.

Computerized cognitive training for Chinese mild cognitive impairment patients: A neuropsychological and fMRI study.

BACKGROUND: Computerized multi-model training has been widely studied for its effect on delaying cognitive decline. In this study, we designed the first Chinese-version computer-based multi-model cognitive training for mild cognitive impairment (MCI) patients. Neuropsychological effects and neural activity changes assessed by functional MRI were both evaluated. METHOD: MCI patients in the training group were asked to take training 3-4 times per week for 6 months. Neuropsychological and resting-state fMRI assessment were performed at baseline and at 6 months. Patients in both groups were continuously followed up for another 12 months and assessed by neuropsychological tests again. RESULTS: 78 patients in the training group and 63 patients in the control group accomplished 6-month follow-up. Training group improved 0.23 standard deviation (SD) of mini-mental state examination, while control group had 0.5 SD decline. Addenbrooke's cognitive examination-revised scores in attention (p = 0.002) and memory (p = 0.006), as well as stroop color-word test interference index (p = 0.038) and complex figure test-copy score (p = 0.035) were also in favor of the training effect. Difference between the changes of two groups after training was not statistically significant. The fMRI showed increased regional activity at bilateral temporal poles, insular cortices and hippocampus. However, difference between the changes of two groups after another 12 months was not statistically significant. CONCLUSIONS: Multi-model cognitive training help MCI patients to gained cognition benefit, especially in memory, attention and executive function. Functional neuroimaging provided consistent neural activation evidence. Nevertheless, after one-year follow up after last training, training effects were not significant. The study provided new evidence of beneficial effect of multi-model cognitive training.

Efficacy of Transarterial Chemoembolisation with or without Antiviral Therapy for Patients with Hepatocellular Carcinoma after Radical Hepatectomy.

OBJECTIVE: This study aimed at assessing the effects of transcatheter arterial chemoembolisation (TACE) and antiviral therapy on improving the prognosis of patients with hepatocellular carcinoma (HCC) after radical hepatectomy. METHODS: This study reviewed the data of 120 patients with HCC who received either radical hepatectomy alone (control group), radical hepatectomy with postoperative TACE (TACE group) or radical hepatectomy with combined postoperative TACE, and antiviral therapy (combined group) from January 2000 to May 2015. To reduce the impact of the possible biases on the conclusion of this study to the minimum, the cases with similar demographic and clinicopathological characteristics were collected and 40 cases were assigned into each group. Recurrence, disease-free survival (DFS), and overall survival (OS) rates were compared. RESULTS: Median follow-up period was 54.26 ± 22.65 months with a range of 17-110 months. Recurrence after radical surgery was observed for 39 (97.5%) patients in the TACE group, 32 (80%) in the combined group, and 40 (100%) in the control group with median recurrence duration of 33, 43, and 16.5 months, respectively. Postoperative TACE with or without antiviral therapy significantly prolonged the DFS rate compared with radical hepatectomy alone (P = 0.000). TACE combined with antiviral therapy significantly extended the DFS rate compared with TACE alone (P = 0.008). Postoperative TACE with or without antiviral therapy also significantly prolonged the OS rate compared with radical hepatectomy alone (P = 0.000). In addition, antiviral therapy combined with TACE significantly extended the 5-year OS rate of patients compared with individual TACE and radical hepatectomy (67.5% versus 55% and 2.5%; P = 0.032). CONCLUSION: TACE is an appropriate therapy for HCC patients after radical hepatectomy. When combined with antiviral therapy, this treatment may further prolong the recurrence time and thus lead to high DFS and OS rates.

Effects of a Long-Acting Formulation of Octreotide on Patients with Portal Hypertension.

OBJECTIVE: This study aimed to determine whether the treatment of a long-acting formulation of octreotide (OCT-LAR) exerted a similar effect on improving the prognosis of patients with portal hypertension compared with placement of transjugular intrahepatic portosystemic shunts (TIPSs). METHODS: A total of 24 patients with portal hypertension who underwent TIPS placement or OCT-LAR treatment from January 2010 to January 2015 were reviewed. Hemodynamic studies, biological values, live functions, and treatment complications before and during the treatment were evaluated. RESULTS: Baseline clinical characteristics were similar between two groups. Hepatic venous pressure gradient (HVPG) was improved in OCT-LAR groups (15.9 ± 2.4 to 12.8 ± 1.6 mmHg). Both groups showed a slight decrease in endothelin-1 (ET-1) and urotensin II and a slight increase in oxide metabolite (NOx) concentrations with no significant difference. Aspartate aminotransferase and alanine aminotransferase increased one week after TIPS placement when they improved in the OCT-LAR treatment group. The complications of OCT-LAR treatment were minor and transient. However, one patient who received TIPS placement presented procedure-related complications and required rehospitalization, and 2 patients had developed hepatic encephalopathy during the follow-up period. CONCLUSION: Prolonged administration of OCT-LAR exerted a virtually similar effect on improving hemodynamic parameters and liver function in patients with portal hypertension compared with placement of TIPS, with no apparent serious adverse effects.

Pulmonary enteric adenocarcinoma with pancreatic metastasis: A case report.

Pulmonary enteric adenocarcinoma is a markedly rare pathological type of lung adenocarcinoma. As the pancreas is a relatively uncommon site for metastasis, the present case is even more unusual. A 62-year-old male was admitted to hospital following the identification of masses in the left chest wall, right abdominal wall and right upper limb, but with no respiratory symptoms. Computed tomography (CT) of the chest revealed a lump in the lung and a mass in the left chest wall, and 18F-fluorodeoxyglucose (18F-FDG) uptake by the lumps was increased. An enhanced abdominal CT revealed a hypodense and homogeneous mass on the head of the pancreas, which was slightly enhanced compared with normal pancreatic tissue. In addition, the 18F-FDG uptake of the lesion was increased and the standardized uptake value (SUV) delayed was not evidently decreased compared with SUVearly. A number of other abnormal metabolic lesions were also identified using positron emission tomography/CT, whereas no abnormal 18F-FDG uptake was identified in the gastrointestinal organ. Furthermore, rectocolonoscopy was performed to exclude diagnosis of metastatic colorectal adenocarcinoma. The hematoxylin- and eosin-stained smears of the masses in the right lung and left chest demonstrated an enteric pattern, which shared morphological and immunohistochemical (IHC) features with those of colorectal adenocarcinoma. The IHC detection revealed that the lesions in the right lung were positive for cytokeratin 7 (CK7), and negative for CK20 and thyroid transcription factor 1 (TTF-1), and the expression of caudal type homeobox 2 (CDX2) was weakly positive; the masses in the left chest wall were positive for CK7, negative for TTF-1, and CK20 and CDX2 were weakly expressed.

Biliary stenting with or without sphincterotomy for malignant biliary obstruction: a meta-analysis.

AIM: To investigate the benefits of endoscopic sphincterotomy (EST) before stent placement by meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed, EMBASE, Cochrane Library, and Science Citation Index databases up to March 2014 were searched. The primary outcome was incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and successful stent insertion rate. The secondary outcomes were the incidence of post-ERCP bleeding, stent migration and occlusion. The free software Review Manager was used to perform the meta-analysis. RESULTS: Three studies (n = 338 patients, 170 in the EST group and 168 in the non-EST group) were included. All three studies described a comparison of baseline patient characteristics and showed that there were no statistically significant differences between the two groups. Three RCTs, including 338 patients, were included in this meta-analysis. Most of the analyzed outcomes were similar between the groups. Although EST reduced the incidence of PEP, it also led to a higher incidence of post-ERCP bleeding (OR = 0.34, 95%CI: 0.12-0.93, P = 0.04; OR = 9.70, 95%CI: 1.21-77.75, P = 0.03, respectively). CONCLUSION: EST before stent placement may be useful in reducing the incidence of PEP. However, EST-related complications, such as bleeding and perforation, may offset this effect.

Does hyoscine butylbromide really improve polyp detection during colonoscopy? A meta-analysis of randomized controlled trials.

AIM: To investigate the benefits of hyoscine butylbromide in polyp detection during colonoscopy by a meta-analysis of available randomized controlled trials (RCTs). METHODS: Databases, including PubMed, EMBASE, the Cochrane Library, and the Science Citation Index up to September 2013, were searched. The primary outcome was polyp detection rate, and the secondary outcome was adenoma detection rate. The meta-analysis was performed using the free software Review Manager. Differences observed between the treated and the control groups were expressed as odds ratio (OR) with a 95% confidence interval (CI). A fixed-effects model was used to pool data when statistical heterogeneity was absent. If statistical heterogeneity was present (P < 0.05), a random-effects model was used. RESULTS: The initial search identified nine articles. After screening, five RCTs with a total of 1998 patients were included in this meta-analysis. Of the five studies, all described a comparison of baseline patient characteristics and showed that there was no statistically significant difference between the two groups. Among the 1998 patients, 1006 received hyoscine butylbromide and 992 were allocated to the control group, and the polyp detection rate was reported. There were no significant differences between the treated and the control group (OR = 1.09, 95%CI: 0.91-1.31, P = 0.33). Four RCTs included 1882 patients, of whom 948 received hyoscine butylbromide, and the adenoma detection rate was reported. There were no significant differences between the treated and the control group (OR = 1.13, 95%CI: 0.92-1.38, P = 0.24). CONCLUSION: The use of hyoscine butylbromide did not significantly improve the polyp detection rate during colonoscopy.

Meta-analysis of stapled hemorrhoidopexy vs LigaSure hemorrhoidectomy.

AIM: To compare outcome of stapled hemorrhoidopexy (SH) vs LigaSure hemorrhoidectomy (LH) by a meta-analysis of available randomized controlled trials (RCTs). METHODS: Databases, including PubMed, EMBASE, the Cochrane Library, and the Science Citation Index updated to December 2012, were searched. The main outcomes measured were operating time, early postoperative pain, postoperative urinary retention and bleeding, wound problems, gas or fecal incontinence, anal stenosis, length of hospital stay, residual skin tags, prolapse, and recurrence. The meta-analysis was performed using the free software Review Manager. Differences observed between the two groups were expressed as the odds ratio (OR) with 95%CI. A fixed-effects model was used to pool data when statistical heterogeneity was not present. If statistical heterogeneity was present (P < 0.05), a random-effects model was used. RESULTS: The initial search identified 10 publications. After screening, five RCTs published as full articles were included in this meta-analysis. Among the five studies, all described a comparison of the patient baseline characteristics and showed that there was no statistically significant difference between the two groups. Although most of the analyzed outcomes were similar between the two operative techniques, the operating time for SH was significantly longer than for LH (P < 0.00001; OR= -6.39, 95%CI: -7.68 - -5.10). The incidence of residual skin tags and prolapse was significantly lower in the LH group than in the SH group [2/111 (1.8%) vs 16/105 (15.2%); P = 0.0004; OR= 0.17, 95%CI: 0.06-0.45). The incidence of recurrence after the procedures was significantly lower in the LH group than in the SH group [2/173 (1.2%) vs 13/174 (7.5%); P = 0.003; OR= 0.21, 95%CI: 0.07-0.59]. CONCLUSION: Both SH and LH are probably equally valuable techniques in modern hemorrhoid surgery. However, LigaSure might have slightly favorable immediate postoperative results and technical advantages.

The association between two single nucleotide polymorphisms within the insulin-degrading enzyme gene and Alzheimer's disease in a Chinese Han population.

Several previous studies on the relationship between the insulin-degrading enzyme (IDE) gene and Alzheimer's disease (AD) have connected certain genetic variants to late-onset AD, in the absence of the apolipoprotein E (APOE)ε4 allele. However, the conclusions of these studies remain controversial. We investigated the association between two polymorphisms of IDE with AD in the Chinese population and found that the T/A genotype of rs4646958 had an important role in AD (adjusted p=0.007, odds ratio [OR]=2.796, 95% confidence interval [CI]=1.330-5.878), under the co-dominant genetic model. The T/C genotype of rs1887922 was also significantly associated with AD compared to the T/T genotype (adjusted p=0.003, OR=2.644, 95% CI=1.407-4.970). The C allele of rs1887922 conferred a higher risk of AD under the dominant genetics model (adjusted p=0.001, OR=2.719, 95% CI=1.472-5.022). Compared with the two other variant genotypes, the T/T genotype showed a protective effect in both polymorphisms (adjusted p=0.007, OR=0. 358, 95% CI=0.170-0.752 for rs4646958; adjusted p=0.001, OR=0. 368, 95% CI=0.199-0.679 in rs1887922). In the context of APOEε4-negative status, both variants were significantly associated with AD in some genetic models.

Association study of the GAB2 gene with the risk of Alzheimer disease in the chinese population.

PURPOSE: To assess genetic variations of GAB2 as a risk factor for developing Alzheimer disease (AD). DESIGN AND METHODS: A case-control study (n=310; age>50 y) was conducted to determine the prevalence of 5 single nucleotide polymorphisms (SNPs) of GAB2 (rs2373115, rs1385600, rs4945261, rs7101429, and rs7115850) in patients with AD in Chinese population of mainland China, and was investigated whether these polymorphisms are risk factors for AD. RESULTS: Our results supported a possible implication of 3 tested SNPs of GAB2 (rs4945261, rs7101429, and rs7115850) in AD in the ethnic Chinese Han, of which the maximal significance of association was at SNP rs7101429 C allele (P=4.0×10; odds ratio=2.0; 95% confidence interval, 1.4-2.8), and this observed association was not affected by APOEε4 genotype. In the haplotypes analysis, the minor alleles of the 3 tested SNPs were composed of a TCG haplotype, which had a significant difference in haplotype distribution between the 2 groups (P=3.4×10; odds ratio=8.32; 95% confidence interval, 4.57-15.14). CONCLUSIONS: Our findings implicate an association between genetic variations of GAB2 and AD in Han Chinese, and the minor alleles of the 3 tested SNPs (rs4945261, rs7101429, and rs7115850) might increase the risk of AD.

Association study of clusterin polymorphism rs11136000 with late onset Alzheimer's disease in Chinese Han population.

OBJECTIVE: We conducted a case-control study to investigate whether clusterin polymorphism (rs11136000) was associated with late-onset Alzheimer's disease in Chinese Han population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was performed on genotype rs11136000 and APOEε4 in 127 patients with late-onset Alzheimer's disease and 143 control individuals. Previous published data from other Chinese samples was also included for further meta-analysis. RESULTS: APOEε4 was demonstrated to increase the risk of Alzheimer's disease in Chinese population (odds ratio = 2.35, 95% confidence interval: 1.40-3.96). There is no significant association between clusterin rs11136000 with late-onset sporadic AD in our small cohort. However, meta-analysis revealed significant allele and genotype differences between Alzheimer's disease and controls following a recessive model. CONCLUSION: Clusterin (rs11136000) was associated with Alzheimer's disease in Chinese Han population.

CALHM1 P86L polymorphism is a risk factor for Alzheimer's disease in the Chinese population.

We conducted a case-control study to determine the prevalence of the CALHM1 P86L polymorphism (rs2986017) in patients with Alzheimer's disease (AD) in the Chinese population of mainland China, and also to clarify whether this polymorphism is a risk factor for AD. Fourteen heterozygous P86L carriers were identified among 198 AD patients. One control subject was also found to be a P86L heterozygous carrier. The allelic frequencies of the AD patients and control subjects were found to be significantly different. Our study indicates that the CALHM1-P86L polymorphism is associated with AD in the ethnic Chinese Han.

GIGYF2 Asn56Ser mutation is rare in Chinese Parkinson's disease patients.

Grb10-Interacting GYF Protein-2 gene (GIGYF2) has been suggested as a candidate gene for PARK11 locus since seven different GIGYF2 missense mutations were identified in familial Parkinson's disease (PD) patients of European descent. To evaluate the frequency and distribution of GIGYF2 Asn56Ser mutation in Chinese PD patients, we analyzed 469 patients with PD from mainland China, including 36 cases with familial PD and 433 cases with sporadic PD. A total of 451 subjects without neurological disorders from the same region in China were set as a control group. The result showed that the GIGYF2 Asn56Ser mutation was not present in all subjects. Our finding suggests that the GIGYF2 Asn56Ser mutation is rare in Chinese PD patients.

Economic impact of dementia in developing countries: an evaluation of Alzheimer-type dementia in Shanghai, China.

The main objective of this study was to assess the economic cost of Alzheimer's disease (AD) in Shanghai, China, as a pilot study for future evaluations. Sixty-seven patients with AD were interviewed, and the information of the AD-related cost and resources used was collected from October 2005 to September 2006. By retrospective analysis, annual costs were calculated and expressed in Chinese renminbi (RMB). Direct cost per patient per year averaged approximately 8,432 RMB (1,058 USD), indirect cost per patient per year was 10,568 RMB (1,326 USD), and annual costs were 19,001 RMB (2,384 USD) per patient per year in this investigation. Total cost was significantly associated with the degree of severity including cognitive function (MMSE) and activity of daily living (ADL). With the increase in the number of persons at risk for developing AD, the economic burden of AD patients in China is significantly heavy.