Objective:This study aims to explore the relationship between the single nucleotide polymorphism (SNPs) of Apo liporoteine E (ApoE), GTP cyclohydrolase 1 (GCH1), and J subfamily member of inward rectifier potassium channel-15 (KCNJ15) gene and cognitive dysfunction in Han nationality patients with schizophrenia in Yunan province.Methods:From September 2018 to August 2020, 182 patients with schizophrenia (patient group) and 176 healthy volunteers (control group) were recruited from the Department of Psychiatry and Physical Examination Center respectively, in the First Affiliated Hospital of Kunming Medical University. The Chinese versions of PANSS and the MATRICS Cognitive Battery (MCCB) were used to evaluate psychiatric symptoms and cognitive function respectively. The SNPs of four loci of GCH1 (rs72713460), KCNJ15 (rs928771), and APOE (rs7412 and rs429358) genes were measured by fluorescence in situ hybridization. The differences of genes and genotypes between the two groups were compared. Then multiple linear regression analyses were performed in the patient group. In the regression models, the T scores of each cognitive function test were entered as dependent variables one by one, while the demographic and clinical data and the four SNPs of ApoE, GCH1, and KCNJ15 as independent variables.Results:The T scores of seven cognitive domains of MCCB were lower in the patient group than in the control group ( t=-25.65 to -18.27, all P<0.001). The genotype frequencies of ApoEε3ε4 (55/182 (30.2%) vs. 22/176 (12.5%)) and allele frequencies of ApoEε4 (65/182 (17.9%) vs. 30/176 (8.5%)) were statistically significantly higher in the patient group than in the control group (χ 2=16.64 and 13.55 respectively, both P<0.001). The genotype and allele frequency of GCH1 in patient group were higher than those in control group (χ 2=8.01 to 21.50), and the difference was statistically significant ( P<0.001 or P<0.05). In the patient group, the T scores of 7 cognitive domains were lower in ApoEε4 allele carriers than in non-carriers ( t=4.99 to 17.69), the T scores of 6 cognitive domains were lower in GCH1-T allele carriers than in non-carriers ( t=5.75 to 13.36), and the T scores of 5 cognitive domains were higher in KCNJ15-G allele carriers than in non-carriers ( t=-2.99 to -2.48). In schizophrenia patients, multiple regression analyses showed that the cognitive domains of information processing speed and word learning were related to carrying ApoEε4 and GCH1-T allele. Conclusion:There is pervasive and significant cognitive dysfunction in Han nationality patients with schizophrenia in Yunan province. The polymorphism of ApoE and GCH1 genes may be related to the pathogenesis of cognitive dysfunction in schizophrenia.

Objective:This study aims to explore the relationship between the single nucleotide polymorphism (SNPs) of Apo liporoteine E (ApoE), GTP cyclohydrolase 1 (GCH1), and J subfamily member of inward rectifier potassium channel-15 (KCNJ15) gene and cognitive dysfunction in Han nationality patients with schizophrenia in Yunan province.Methods:From September 2018 to August 2020, 182 patients with schizophrenia (patient group) and 176 healthy volunteers (control group) were recruited from the Department of Psychiatry and Physical Examination Center respectively, in the First Affiliated Hospital of Kunming Medical University. The Chinese versions of PANSS and the MATRICS Cognitive Battery (MCCB) were used to evaluate psychiatric symptoms and cognitive function respectively. The SNPs of four loci of GCH1 (rs72713460), KCNJ15 (rs928771), and APOE (rs7412 and rs429358) genes were measured by fluorescence in situ hybridization. The differences of genes and genotypes between the two groups were compared. Then multiple linear regression analyses were performed in the patient group. In the regression models, the T scores of each cognitive function test were entered as dependent variables one by one, while the demographic and clinical data and the four SNPs of ApoE, GCH1, and KCNJ15 as independent variables.Results:The T scores of seven cognitive domains of MCCB were lower in the patient group than in the control group ( t=-25.65 to -18.27, all P<0.001). The genotype frequencies of ApoEε3ε4 (55/182 (30.2%) vs. 22/176 (12.5%)) and allele frequencies of ApoEε4 (65/182 (17.9%) vs. 30/176 (8.5%)) were statistically significantly higher in the patient group than in the control group (χ 2=16.64 and 13.55 respectively, both P<0.001). The genotype and allele frequency of GCH1 in patient group were higher than those in control group (χ 2=8.01 to 21.50), and the difference was statistically significant ( P<0.001 or P<0.05). In the patient group, the T scores of 7 cognitive domains were lower in ApoEε4 allele carriers than in non-carriers ( t=4.99 to 17.69), the T scores of 6 cognitive domains were lower in GCH1-T allele carriers than in non-carriers ( t=5.75 to 13.36), and the T scores of 5 cognitive domains were higher in KCNJ15-G allele carriers than in non-carriers ( t=-2.99 to -2.48). In schizophrenia patients, multiple regression analyses showed that the cognitive domains of information processing speed and word learning were related to carrying ApoEε4 and GCH1-T allele. Conclusion:There is pervasive and significant cognitive dysfunction in Han nationality patients with schizophrenia in Yunan province. The polymorphism of ApoE and GCH1 genes may be related to the pathogenesis of cognitive dysfunction in schizophrenia.

Clopidogrel was believed to be superior to aspirin by the well-known CAPRIE trial. However, no other large clinical trials demonstrated the same results, but all focused on the combination use of clopidogrel with aspirin, and combination therapy in CREDO was called the "Emperor's New Clothes". However, no one overturned the results of these clinical trials by quantitatively analyzing them. We reviewed ten large-scale clinical trials about clopidogrel. On the basis of results of CAPRIE, CREDO and CHARISMA trials, we re-estimated their minimal sample sizes and their powers by three well-established statistical methodologies. From the results of CAPRIE, we inferred that the minimal sample size should be 85 086 or 84 968 but its power was only 30.70%. A huge gap existed. The same was also true of CREDO and CHARISMA trials. Moreover, in CAPRIE trial, 0 was included in the 95% confidence interval and 1 was included in the 95% confidence interval for the relative risk. There were some paradoxical data in CAPRIE trial. We are led to conclude that the results in CAPRIE, CREDO, and from the subgroup analysis in CHARISMA trials were questionable. These results failed to demonstrate that clopidogrel was superior to aspirin or that clopidogrel used in combination with aspirin was better than aspirin alone. The cost-effectiveness analyses by some previous studies were not reliable.

Clopidogrel was believed to be superior to aspirin by the well-known CAPRIE trial. However, no other large clinical trials demonstrated the same results, but all focused on the combina-tion use of clopidogrel with aspirin, and combination therapy in CREDO was called the "Emperor's New Clothes". However, no one overturned the results of these clinical trials by quantitatively ana-lyzing them. We reviewed ten large-scale clinical trials about clopidogrel. On the basis of results of CAPRIE, CREDO and CHARISMA trials, we re-estimated their minimal sample sizes and their powers by three well-established statistical methodologies. From the results of CAPRIE, we inferred that the minimal sample size should be 85 086 or 84 968 but its power was only 30.70%. A huge gap existed. The same was also true of CREDO and CHARISMA trials. Moreover, in CAPRIE trial, 0 was included in the 95% confidence interval and 1 was included in the 95% confidence interval for the relative risk. There were some paradoxical data in CAPRIE trial. We are led to conclude that the results in CAPRIE, CREDO, and from the subgroup analysis in CHARISMA trials were questionable. These results failed to demonstrate that clopidogrel was superior to aspirin or that clopidogrel used in combination with aspirin was better than aspirin alone. The cost-effectiveness analyses by some pre-vious studies were not reliable.