The Overexpression of SLC25A13 Predicts Poor Prognosis and Is Correlated with Immune Cell Infiltration in Patients with Skin Cutaneous Melanoma.

Purpose: Skin cutaneous melanoma (SKCM) is one of the most malignant and aggressive cancers with poor prognosis due to its rapid progression towards metastasis. Thus, finding clinically relevant biomarkers for early diagnosis, prognosis, and therapy prediction is essential. This study focused on the identification of SLC25A13 as a novel biomarker for SKCM and is aimed at investigating the biological functions of solute carrier family 25 member 13 (SLC25A13) in the development of SKCM. Methods: GEPIA was used to analyze the diagnostic and prognostic values of SLC25A13 in SKCM using the TCGA dataset. PrognoScan was used to validate the prognostic value of SLC25A13 and its coexpressed genes in SKCM. TISIDB was established to reveal the relationship between the expression of SLC25A13 and immune infiltration in SKCM. The protein expression of SLC25A13 in SKCM was evaluated by the Human Protein Atlas. The signaling pathways and biological functions of SLC25A13 in SKCM were analyzed by LinkOmics. Metascape was applied to analyze the functional enrichment analysis of SLC25A13. Protein-protein interaction analysis of SLC25A13 was performed by GeneMANIA. Results: The mRNA and protein levels of SLC25A13 in the SKCM were much higher than those in the normal tissue. Furthermore, the overexpression of SLC25A13 predicts worse outcomes of SKCM patients. Moreover, the SLC25A13 expression was negatively correlated with the immune infiltration level of SKCM. The overexpression of SLC25A13 coexpressed genes, such as ACLY and AFG3L2, and SCL25A13 interacting genes also predicted the unfavorable prognosis of SKCM patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of SLC25A13 coexpressed genes showed that these genes are enriched in ATPase activity, cell cycle, mTOR, and VEGFA-VEGFR2 signaling pathways, which were relevant to tumor development and angiogenesis. Gene set enrichment analysis (GSEA) demonstrated that the SLC25A13 expression was related to infiltrating immune cells in SKCM. Conclusion: Our findings revealed that SLC25A13 might be a potential prognostic and therapeutic biomarker for SKCM.

Clinical Characteristics of Pediatric Cases of COVID-19 in Hunan, China: A Retrospective, Multi-Center Case Series.

Objective: Aimed to investigate the epidemiological characteristics, clinical features, treatment, and short-term prognosis of COVID-19 in children. Methods: Retrospective analysis was conducted in 48 children with COVID-19 admitted to 12 hospitals in eight cities in Hunan province, China, from January 26, 2020 to June 30, 2020. Results: Of the 48 cases, Familial clusters were confirmed for 46 children (96%). 16 (33%) were imported from other provinces. There were 11 (23%) asymptomatic cases. only 2 cases (4%) were severe. The most common symptom was fever (n = 20, 42%). Other symptoms included cough (n = 19, 40%), fatigue (n = 8, 17%), and diarrhea (n = 5, 10%). In the early stage, the total peripheral blood leukocytes count increased in 3(6%) cases and the lymphocytes count decreased in 5 (10%) cases. C-reactive protein and procalcitonin were elevated respectively in 3 (6%) cases and 2 (4%) cases. There were abnormal chest CT changes in 22 (46%) children, including 15 (68%) with patchy ground glass opacity, 5 (22%) with consolidation, and 2 (10%) with mixed shadowing. In addition to supportive treatment, antiviral therapy was received by 41 (85%) children, 11 (23%) patients were treated with antibiotics, and 2 (4%) were treated with methylprednisolone and intravenous immunoglobulin. Compared to 2 weeks follow-up, one child developed low fever and headache during the 4 weeks follow-up, 3 (6%) children had runny noses, one of them got mild cough, and 4 (12%) children had elevated white blood cells and lymphocytes. However, LDH and CK increased at 2 weeks and 4 weeks follow-up. 2 weeks follow-up identified normal chest radiographs in 33 (69%) pediatric patients. RT-PCR detection of SARS-CoV-2 was negative in all follow-up patients at 2 and 4 weeks follow-up. All 48 pediatric patients were visited by calling after 1 year of discharge. Conclusions: Most cases of COVID-19 in children in Hunan province were asymptomatic, mild, or moderate. Close family contact was the main route of infection. It appeared that the younger the patient, the less obvious their symptoms. Epidemiological history, nucleic acid test, and chest imaging were important tools for diagnosis in children.

Efficacy of cognitive behavioural therapy with medication for patients with obsessive-compulsive disorder: A multicentre randomised controlled trial in China.

BACKGROUND: Meta-analyses support the efficacy of cognitive behavioural therapy (CBT) for obsessive-compulsive disorder (OCD) in Western cultures. However, there are no adequately powered multicentre studies in China. This study aimed to compare the effectiveness of treatment with CBT combined with medication and medication alone in OCD patients in China. METHODS: OCD patients (N = 167) were recruited from outpatient clinics at three large tertiary psychiatric hospitals and one general hospital in China. Participants were randomly allocated to receive either CBT combined with medication (n = 92) or medication alone (n = 75) for a 24-week treatment period. Participants' symptoms and social functioning were assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Anxiety Rating Scale (HAM-A), Global Assessment of Functioning (GAF) and Clinical Global Impression Scale for Severity (CGI-S) at 0, 4, 8, 12 and 24 weeks, and the effectiveness of the two treatments compared using linear mixed-effects models. RESULTS: At 24 weeks, both groups showed large within-group effects in all measures. Significantly more patients receiving combined therapy than medication alone had a decrease in symptom severity of at least 35% (based on Y-BOCS total score). The CGI-S and GAF scores decreased in both groups, and significant differences were found between the groups. LIMITATIONS: Study limitations included lack of consideration of medication types and dosages, and the absence of a CBT-only arm. CONCLUSIONS: CBT combined with medication may be effective in alleviating symptoms and social functioning impairment associated with OCD, and is more effective than medication alone in China, particularly for the treatment of compulsive behaviours.

The effects of cognitive behavioral therapy on resting-state functional brain network in drug-naive patients with obsessive-compulsive disorder.

Objectives: Although cognitive behavioral therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD), the treatment mechanisms remain poorly understood. This study aimed to investigate the effects of CBT on changes in the intrinsic whole-brain functional network of OCD patients. Materials and Methods: Twenty drug-naive and noncomorbid OCD patients were recruited, and resting-state functional magnetic resonance imaging was performed before and after 12 weeks of CBT. Moreover, 20 healthy controls were scanned twice with a 12-week interval. A graph-theory degree centrality (DC) approach and functional connectivity method were used to analyze the whole-brain functional network hub and connectivity changes in OCD patients before and after CBT treatment. Results: A significant group × time interaction on DC was found in the left dorsolateral prefrontal cortex (DLPFC); the DC in the left DLPFC was significantly reduced after CBT treatment. Resting-state functional connectivity (RSFC) between the left DLPFC and right orbitofrontal cortex was increased in the OCD patients at baseline, and normalized after CBT treatment. RSFC changes between the left DLPFC and default mode network (DMN) positively correlated with changes in clinical symptoms in OCD patients. Conclusions: These findings suggest that CBT can modulate changes in intrinsic functional network hubs in the cortico-striato-thalamo-cortical circuit in OCD patients. Cognitive control network and DMN connectivity may be a potential imaging biomarker for evaluating CBT treatment for OCD.

Altered resting state functional connectivity patterns of the anterior prefrontal cortex in obsessive-compulsive disorder.

In this study, we explored different spontaneous functional connectivity patterns between the anterior prefrontal cortex and other brain regions in nonmedicated patients with obsessive-compulsive disorder in a resting state, and examined the relationship between the abnormal spontaneous functional connectivity patterns of the anterior prefrontal cortex and clinical symptoms in patients with obsessive-compulsive disorder. Twenty nonmedicated patients with obsessive-compulsive disorder and 20 sex-matched and age-matched healthy individuals underwent resting state functional MRI scanning. Compared with the healthy controls, significantly increased positive functional connectivity with the right anterior prefrontal cortex was observed in the right insula and the middle cingulate cortex in patients with obsessive-compulsive disorder. Our findings suggest that abnormal intrinsic or spontaneous functional connectivity in the cognitive control system in a resting state may underlie the pathophysiology of obsessive-compulsive disorder.

GAB2 is not associated with late-onset Alzheimer's disease in Chinese Han.

It has recently been shown that GAB2 alleles modify the risk for late-onset Alzheimer disease (LOAD) in apolipoprotein E (ApoE)epsilon4 allele carriers in a genome-wide association study. Some studies subsequently in Caucasians population, though not all, have demonstrated that GAB2 polymorphisms might be associated with LOAD susceptibility. The aim of this study is to evaluate the reported polymorphisms (rs2373115 and rs1385600) and GAB2 haplotypes (rs2373115-rs1385600) for an interaction with the ApoEepsilon4 allele in a cohort of Chinese LOAD. We conducted a case-control study in 292 LOAD and 227 non-demented controls from the Chinese Han population. Our study does not find any association between the two tested SNPs and GAB2 haplotypes and LOAD or any synergetic interaction between the SNPs and ApoE either. However, since the sample size required to show this point is large, our finding needs to be confirmed by a large independent sample of Chinese population.

The Q7R polymorphism in the saitohin gene is rare in a southern Chinese population.

Saitohin (STH) is thought to be involved in the pathogenesis of many neurodegenerative diseases. Recent reports were inconclusive in showing that the Q7R polymorphism in the STH gene is associated with late-onset Alzheimer's disease (LOAD). We examined the Q7R polymorphism in 500 subjects (LOAD: 280; controls: 220) from Guangdong, China, by the Restriction Fragment Length Polymorphism method. Only one QR heterozygous and no RR homozygous variants were found. Our results suggest that the frequency of the R allele in the Han population is lower than that in Caucasian and African populations. The Q7R polymorphism is unlikely to contribute significantly to Alzheimer's disease susceptibility of the Han population in south China and the variation of the Q7R polymorphism among different ethnic groups might account for the varied clinical manifestations of some STH-related diseases.

Evaluation of choline acetyltransferase gene polymorphism (2384 G/A) in Alzheimer's disease and mild cognitive impairment.

BACKGROUND/AIMS: It has been hypothesized that choline acetyltransferase (ChAT) activity might be associated with cognitive impairment in Alzheimer's disease (AD). A functional single nucleotide polymorphism (2384 G/A) of ChAT was proposed to be associated with AD risk and age of onset. The aim of this study was to evaluate this polymorphism in a cohort of Chinese AD patients and patients with mild cognitive impairment (MCI). METHODS: We conducted a case-control study in 273 cases of sporadic AD, 97 MCI patients and 271 nondemented controls from the Chinese Han population. RESULTS: In AD, ChAT 2384 A carriers had a significantly earlier age of onset and worse individual cognitive function in Fuld Object-Memory Evaluation; in MCI, the carriers of both 2384 A and ApoE epsilon4 had a significantly earlier age of onset. CONCLUSION: ChAT 2384 A allele is a risk factor for AD and MCI.

The APOC3 SstI polymorphism is weakly associated with sporadic Alzheimer's disease in a Chinese population.

In order to clarify the relationship of apolipoprotein CIII (APOC3) polymorphism and sporadic Alzheimer's disease (AD) in Chinese, 165 sporadic AD patients and 174 age-matched elderly individuals were genotyped for the APOC3 SstI and apolipoprotein E (APOE) HhaI polymorphisms. As the result, the APOC3 3017G allele was found to be associated with AD in APOE epsilon4 allele noncarriers (chi2=4.433, P=0.035), and the risk estimate of allele C versus G resulted in an OR of 1.56 (95% CI: 1.03-2.37), although in total no significant differences of allelic or genotypic frequencies between patients and controls were found. Assessment of interaction between APOE epsilon4 and APOC3 3017G status presented an adjusted odds ratio of 0.62 (95% CI: 0.37-1.03) with a borderline significant P-value (P=0.066). Therefore, we conclude that the rare APOC3 G allele may offer some protection against the development of sporadic AD in APOE epsilon4 noncarriers in Chinese.

Mutation screening and association study of the neprilysin gene in sporadic Alzheimer's disease in Chinese persons.

Neprilysin has been reported to be a major beta-amyloid peptide (Abeta)-degrading enzyme. The decreased expression and activity of it may contribute to the development of Alzheimer's disease by promoting the accumulation of Abeta. We used denaturing high-performance liquid chromatography to screen the neprilysin gene (NEP) for single nucleotide polymorphisms (SNPs) in 257 Chinese sporadic Alzheimer's disease patients and 242 cognitive normal controls. As a result, eight novel and one known SNP were identified. Three of them, -204G-->C in the promoter region, IVS17-294C-->T, and IVS22+36C-->A showed a significant association with Alzheimer's disease (p = .006,.017, and.003, respectively). Subsequent haplotype analysis provided further evidence of the association (global p < .0001 for the three SNPs mentioned above, and global p < .01 for the eight SNPs with rare allele frequency > 1%). These findings indicate that genetic variations within or extremely close to NEP might influence the susceptibility to Alzheimer's disease in Chinese persons.

[The C224T polymorphism in the cathepsin D gene is not associated with sporadic Alzheimer's disease in Chinese].

Cathepsin D is the major lysosomal/endosomal aspartic protease and exhibits beta- and gamma-secretase-like activity in vitro. Data from German suggest that the C224T polymorphism in the Cathepsin D gene (CTSD) exon 2 is strongly associated with the risk for Alzheimer's disease (AD). Meanwhile other studies have not been able to replicate the result. It's necessary to determine the genotype of the polymorphism in CTSD in Chinese sporadic AD patients and age-matched controls with normal cognition and examine possible association of the polymorphism with the disease. We find no strong evidence of association between the CTSD C224T polymorphism and Chinese sporadic AD. Whereas there may be a weak synergistic interaction between ApoE epsilon4 and CTSD T allele.

[No evidence for genetic association between alpha-2 macroglobulin I1000V polymorphism and sporadic Alzheimer's disease in two independent Chinese populations].

OBJECTIVE: Alpha-2 macroglobulin (alpha2M) is a proteinase inhibitor found in association with senile plaques in Alzheimer's disease (AD). Also alpha2M has been implicated in several pathophysiological processes in AD. In view of the recent contradictory reports on the relationship between AD and a common polymorphism I1000V in A2M gene, the present authors studied a relatively large sample, determined the genotype of the I1000V polymorphism in A2M gene in sporadic AD patients and age-matched controls with normal cognition, and examined the possible association of the polymorphism with AD. METHODS: Genotypes of A2M and apolipoprotein E (apoE) were detected by polymerase chain reaction combined with restriction fragment length polymorphism in 257 patients and 242 controls in Guangzhou, and 112 patients and 113 controls in Chengdu. RESULTS: The 1000Val allele frequencies in the merged AD and control groups were 7.7% and 8.7%, respectively. The differences of allelic and genotypic frequencies between the patients and control subjects were not statistically significant, even after stratification by apoE epsilon4 status or by age-of-onset of the disease. CONCLUSION: The results of this study revealed no association between the I1000V polymorphism of A2M and Chinese sporadic AD in Guangzhou and Chengdu.

[Analysis on association between the polymorphisms in apolipoprotein E, interleukin-1 alpha genes and Alzheimer's disease in Chengdu area].

OBJECTIVE: To investigate the correlation between the polymorphisms of apolipoprotein E(APOE), the interleukin-1 alpha (IL-1 alpha ) genes and the susceptibility to Alzheimer's disease(AD). METHODS: Association study was performed in 114 AD patients and 113 healthy elderly individuals from Chengdu, China. Polymorphisms of APOE and IL-1 alpha genes were analyzed with polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequency of APOE-epsilon 4-carrying genotype in moderate to severe AD patients (28.6%) was higher than that of mild patients (18.5%) and the controls (14.2%), and the difference between moderate to severe AD group and the control group was significant (OR=2.4, 95%CI: 1.1-5.5). The frequency of epsilon 4 was also of significant difference between the group of moderate to severe dementia and the control group (OR=2.6, 95%CI: 1.3-5.3). However, no significant difference in distribution of IL-1 alpha polymorphism between AD patients and controls was observed. CONCLUSION: The APOE epsilon 4 allele was associated with moderate to severe AD while no association between the IL-1 alpha gene polymorphism and AD was found.

[Gln192Arg polymorphism of the paraoxonase-1 gene is not associated with Alzheimer's disease in Chinese].

OBJECTIVE: To explore the relationship between paraoxonase-1 (PON1) gene Gln192Arg polymorphism and sporadic Alzheimer's disease (AD) in Chinese. METHODS: A total of 165 AD patients and 174 age-matched control subjects were enrolled in this study for examination of PON1 Gln192Arg and apolipoprotein E gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The distribution of PON1 allelic and genotypic frequencies did not significantly differ between AD patients and the control subjects, even after the stratification by ApoE-epsilon4 status. CONCLUSION: Gln192Arg polymorphism of the PON1 gene is not associated with sporadic AD in Chinese.

Possible association between Cys311Ser polymorphism of paraoxonase 2 gene and late-onset Alzheimer's disease in Chinese.

The common polymorphism at codon 311 (C311S) of paraoxonase 2 gene (PON2) was investigated in 165 patients with sporadic late-onset Alzheimer's disease (LOAD) and 174 controls in Chinese. The PON2*C allele frequency was significantly increased in the patients as compared with controls. However, no significant difference was observed after stratification of apolipoprotein E (ApoE) epsilon4 allele. These results suggested that the PON2 polymorphism might be a risk factor for LOAD independent of ApoE epsilon4 status in Chinese.

The 1239G/C polymorphism in exon 5 of BACE1 gene may be associated with sporadic Alzheimer's disease in Chinese Hans.

Beta-site amyloid-precursor protein cleaving enzyme (BACE1) is a candidate risk factor for Alzheimer's disease (AD) because of involving in generating beta-amyloid peptide, which is thought to play a central role in the pathogenesis of the disease. A single nucleotide polymorphism 1239G/C in exon 5 of BACE1 gene and a weak association between this polymorphism and AD in Caucasian APOEepsilon4 allele carriers has been reported. To examine possible association of the polymorphism with sporadic AD, two Chinese Han cohorts including 257 patients and 242 age-matched controls in Guangzhou and 112 patients and 113 controls in Chengdu were genotyped using PCR-RFLP techniques. The frequency of the C allele in controls of both cohorts was 0.65, which was higher than that in Caucasian populations [0.39 by Nowotny et al. 2001: Neuroport 12:1799-1802; 0.44 by Nicolaou et al. 2001: Neurogenetics 3:203-206]. There was a significant excess of C allele among the patients in both cohorts (Guangzhou, 0.71 vs. 0.65, chi(2) = 5.20, P = 0.02; Chengdu, 0.74 vs. 0.65, chi(2) = 4.36, P = 0.04). The CC genotype was found to be associated with AD (Guangzhou cohort, OR = 1.56, 95% CI = 1.09-2.23; Chengdu cohort, OR = 1.74, 95% CI = 1.03-2.95; combined sample: OR = 1.61, 95% CI = 1.20-2.17). The association remained in non-APOE epsilon4 allele carriers when all subjects were divided on the basis of the APOEepsilon4 status. Our findings suggest that the 1239G/C polymorphism in exon 5 of BACE1 gene may be associated with sporadic AD in Chinese Hans.

[The prevalence of mild cognitive impairment among residents aged 55 or over in Chengdu area].

OBJECTIVE: To study the prevalence of mild cognitive impairment (MCI) in the urban and the rural areas in Chengdu, Southwest China. METHODS: Residents aged 55 or over were selected by stratified random cluster sampling from 19 districts, cities, and counties of Chengdu area in Sichuan province. A two-stage survey was carried out. In the first stage, CMMSE, CES-D were used as screening instruments. In the second stage, Diagnostic questionnaires of dementia and CDR were used as diagnostic instruments. The diagnostic criteria of mild cognitive impairment adopted from Petersen's were: (1) memory complaint; (2) normal activities of daily living; (3) normal general cognitive function; (4) memory impairment incompatible with age; (5) not demented; (6) CDR = 0.5 and (7) exclusion of the reversible cognitive impairment caused by other factors (i.e. depression). RESULTS: Three thousand, nine hundred and ten subjects were examined. The prevalence rates of MCI was 2.4%. The MCI prevalence rates in the urban and the rural areas were 1.5%, 2.5% respectively, without significant difference. The MCI prevalence in males and females were 1.8%, 2.9% respectively. Prevalence rate in female was higher than in males with significant difference. Prevalence of illiteracy (4.0%) was the highest among different educational levels. The accumulated prevalence increased with age. CONCLUSION: The prevalence of MCI (2.4%) was slightly higher than the prevalence of AD (2.05%) in the same areas of Chengdu. MCI seemed to be a high risk factor for AD which should to be followed up. Early intervention in MCI might be helpful in the prevention of AD.