CircARF3 Mitigates Allergic Rhinitis through Targeting microRNA-205-5p/Sirtuin 5 Axis.

INTRODUCTION: Circular RNAs (circRNAs) are essential in the progression of allergic rhinitis (AR). The purpose of this research was to examine the role of circRNA ADP-ribosylation factor 3 (circARF3) in the pathogenesis of AR. METHODS: To generate an animal model of AR, mice were treated with house dust mite (HDM), and mice nasal epithelial cells (NEpCs) were treated with IL-4/IL-13 to imitate the inflammatory damage of AR in vitro. Sanger sequencing, qRT-PCR, and RNAse R digestion assays all validated the circularization structure of circARF3. The levels of circARF3, miR-205-5p, and sirtuin 5 (SIRT5) were determined by qRT-PCR or Western blotting. Luciferase reporter, RNA immunoprecipitation, and pull-down experiments were used to investigate the regulatory network. Flow cytometry was used to investigate the rate of cell apoptosis, and Western blotting was used to determine the levels of apoptotic-related proteins (cleaved caspase 3, cleaved polyadenosine-diphosphate-ribose polymerase) and HMGB1, TLR4, and MyD88. Enzyme-linked immunosorbent assay was used to assess the inflammatory response. Hematoxylin-eosin staining and TUNEL were used to detect the histology of injury and apoptosis of nasal mucosa tissues. RESULTS: CircARF3 and SIRT5 levels were reduced in HDM-treated animals and IL-4/IL-13-treated NEpCs, while miR-205-5p expression was increased. CircARF3 was generated by back-splicing exons 3-5 with a stable circular shape. CircARF3 overexpression mitigated IL-4/IL-13-induced apoptosis in NEpCs by inhibiting miR-205-5p. SIRT5 upregulation attenuated IL-4/IL-13-induced inflammatory injury in NEpCs, and SIRT5 knockdown induced opposite effects. miR-205-5p silencing reversed the effects of SIRT5 knockdown on IL-4/IL-13-induced inflammatory injury. Furthermore, circARF3 overexpression alleviated histological abnormalities, apoptosis, inflammatory response, and HMGB1/TLR4 signaling activation in HDM-treated animals. CONCLUSION: CircARF3 inhibited cell apoptosis and inflammation via the miR-205-5p/SIRT5 axis in IL-4/IL-13-treated NEpCs and HDM-treated mice.

Guanxin Danshen Dripping Pills Improve Quality of Life and Cardiovascular Prognoses of CHD Patients after PCI with Anxiety or Depression (GLAD Study): A Randomized Double-Blind Placebo-Controlled Study.

OBJECTIVE: To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12. RESULTS: In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred. CONCLUSIONS: GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).

Epidemiological characteristics of human adenovirus 2, 3 and 7 genetypes in hospitalized children with respiratory infection in a hospital of pediatric in Hebei Province from 2018 to 2020 / 中华预防医学杂志

Objective: To investigate the epidemiological characteristics of human adenovirus (HADV) 2, 3 and 7 in hospitalized children with respiratory infection. Methods: A total of 25 686 children with respiratory infection hospitalized at Children's Hospital of Hebei Province from January 2018 to December 2020 were retrospectively included.Deep sputum or nasopharyngeal aspirates of those children were collected. Then thirteen common respiratory pathogens were detected by multiplex PCR. 510 HADV positive specimens were randomly selected via random number and classified for type 2, 3 and 7 using a multiplex real-time quantitative PCR. SPSS 21.0 software was used to perform all of the statistical analyses. Enumeration data were expressed by frequency and percentage. χ2 test was used for comparison between groups. Results: The HADV-positive rate was 7.99% (2 052/25 686). Children at age 3-<6 years had the highest HADV-positive rate (11.44%). The HADV-positive rate in 2019 was highest (10.64%). Among the 510 HADV-positive specimens, the proportion of type 3 was the highest (31.16%), followed by type 7 (21.37%) and type 2 (11.18%). The rate of type 2 in 2019 was significantly lower than that in 2018 and 2020 (χ2=8.954 and 16.354; P=0.003 and <0.01), while the rate of type 3 was significantly higher than that in 2018 and 2020 (χ2=5.248 and 4.811; P=0.022 and 0.028). The rate of type 2, type 3 and type 7 were lowest in winter, spring and autumn, respectively. The rate of type 2 increased significantly in autumn and the rate of type 3 and type 7 increased significantly in winter.The co-detection rate of HADV with other respiratory pathogens was 43.33%(221/510). Among, the co-detection rate of type 3 was highest (47.32%), and the co-detection rate of type 2, 3 and 7 was significantly higher than the alone detection rate (χ2=20.438, P<0.01; χ2=42.105, P<0.01; χ2=27.573, P<0.01).The proportion of severe pneumonia in children with type 7 positive (15.89%) was higher than that in children with non-type 7 positive (8.23%) (χ2=5.260, P=0.022). Conclusion: HADV is one of the important pathogens of children with respiratory infection in Children's Hospital of Hebei Province. The susceptible population of HADV is preschool children aged 3 to 6 years. HADV often co-detects with other respiratory pathogens. Type 3 and 7 is likely to be the dominant genotypes in this region, and type 7 may be one of the risk factors of severe pneumonia in children.

Characterization of the complete mitochondrial genome of the tea slug moth, Iragoides fasciata (Lepidoptera: Limacodidae).

Moths of the family Limacodidae are major pests that damage tea trees, fruit trees, and forests. The complete mitochondrial genome of Iragoides fasciata (Lepidoptera: Limacodidae) was sequenced. The genome was found to be 15,645 bp in size (GenBank accession no. MK250437), including 13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and a 431 bp A + T-rich region. Nucleotide composition showed a total A + T content of 82.03% with significant AT-bias. All PCGs were found to start with ATN codons and use the canonical stop codons TAA or incomplete T, except for cox1, which was found to utilize CGA as a start codon. Phylogenetic relationships were based on the 13 PCGs with 24 moths, showing that I. fasciata is more closely related to other slug moths in the family Limacodidae.

Exosomal miR-106a-5p accelerates the progression of nasopharyngeal carcinoma through FBXW7-mediated TRIM24 degradation.

Nasopharyngeal carcinoma (NPC) is prevalent in East Asia and causes increased health burden. Elucidating the regulatory mechanism of NPC progression is important for understanding the pathogenesis of NPC and developing novel therapeutic strategies. Nasopharyngeal carcinoma and normal tissues were collected. Nasopharyngeal carcinoma cell proliferation, migration, and invasion were evaluated using CCK-8, colony formation, wound healing, and transwell assays, respectively. A xenograft mouse model of NPC was established to analyze NPC cell growth and metastasis in vivo. The expression of miR-106a-5p, FBXW7, TRIM24, and SRGN was determined with RT-qPCR and Western blot. MiR-106a-5p, TRIM24, and SRGN were upregulated, and FBXW7 was downregulated in NPC tissues and cells. Exosomal miR-106a-5p could enter NPC cells, and its overexpression promoted the proliferation, migration, invasion, and metastasis of NPC cells, which were suppressed by knockdown of exosomal miR-106a-5p. MiR-106a-5p targeted FBXW7 to regulate FBXW7-mediated degradation of TRIM24. Furthermore, TRIM24 regulated SRGN expression by binding to its promoter in NPC cells. Suppression of exosomal miR-106a-5p attenuated NPC growth and metastasis through the FBXW7-TRIM24-SRGN axis in vivo. Exosomal miR-106a-5p accelerated the progression of NPC through the FBXW7-TRIM24-SRGN axis. Our study elucidates novel regulatory mechanisms of NPC progression and provides potential exosome-based therapeutic strategies for NPC.

Association between Internet gaming disorder and sleep quality among junior middle school student of Xi an City / 中国学校卫生

Objective@#To investigate the association of Internet gaming disorder (IGD) and sleep quality in adolescents of Xi an, thereby providing theoretical evidence for prevention of IGD and improvement of sleep quality of adolescents.@*Methods@#A total of 1 181 adolescents from 3 middle schools of Xi an were randomly selected between August, 2019 and February, 2020. These adolescents were assessed by a series of questionnaires, including basic information questionnaire, IGD and Insomnia Severity Index (ISI). Univariate analysis and multivariate Logistic regression model were used to evaluate the association between IGD and insomnia.@*Results@#Among 929 junior middle school students who participated in online games and the IGD Diagnostic Questionnaire was filled out in the past 12 months, the prevalence of IGD was 20.0%(186). Univariate analyses indicated that gender,whether single family, whether they living with their parents, whether they were addicted to online games, whether they could control the time of online games, and the severity of insomnia influenced IGD ( χ 2=17.11, 8.33, 202.92, 91.23, 29.06, P <0.05). The multivariate Logistic regression of the total population showed that participating in online games was not associated with the severity of insomnia ( OR = 1.62 , 95% CI =0.92-0.85, P >0.05). The people who participated in online games in the past 12 monthsthe severity of insomnia was positively correlated with the risk of IGD ( OR =3.56，95% CI =1.92-6.61, P <0.01).@*Conclusion@#Internet gaming disorder become a severe situation in the middle school students. The severity of insomnia might become the risk factor of IGD, so social should pay more attention to the prevention of internet addiction.

Association between Internet gaming disorder and sleep quality among junior middle school student of Xi an City / 中国学校卫生

Objective@#To investigate the association of Internet gaming disorder (IGD) and sleep quality in adolescents of Xi an, thereby providing theoretical evidence for prevention of IGD and improvement of sleep quality of adolescents.@*Methods@#A total of 1 181 adolescents from 3 middle schools of Xi an were randomly selected between August, 2019 and February, 2020. These adolescents were assessed by a series of questionnaires, including basic information questionnaire, IGD and Insomnia Severity Index (ISI). Univariate analysis and multivariate Logistic regression model were used to evaluate the association between IGD and insomnia.@*Results@#Among 929 junior middle school students who participated in online games and the IGD Diagnostic Questionnaire was filled out in the past 12 months, the prevalence of IGD was 20.0%(186). Univariate analyses indicated that gender,whether single family, whether they living with their parents, whether they were addicted to online games, whether they could control the time of online games, and the severity of insomnia influenced IGD ( χ 2=17.11, 8.33, 202.92, 91.23, 29.06, P <0.05). The multivariate Logistic regression of the total population showed that participating in online games was not associated with the severity of insomnia ( OR = 1.62 , 95% CI =0.92-0.85, P >0.05). The people who participated in online games in the past 12 monthsthe severity of insomnia was positively correlated with the risk of IGD ( OR =3.56，95% CI =1.92-6.61, P <0.01).@*Conclusion@#Internet gaming disorder become a severe situation in the middle school students. The severity of insomnia might become the risk factor of IGD, so social should pay more attention to the prevention of internet addiction.

A novel missense variant in ACAA1 contributes to early-onset Alzheimer's disease, impairs lysosomal function, and facilitates amyloid-ß pathology and cognitive decline.

Alzheimer's disease (AD) is characterized by progressive synaptic dysfunction, neuronal death, and brain atrophy, with amyloid-ß (Aß) plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the brain tissue, which all lead to loss of cognitive function. Pathogenic mutations in the well-known AD causal genes including APP, PSEN1, and PSEN2 impair a variety of pathways, including protein processing, axonal transport, and metabolic homeostasis. Here we identified a missense variant rs117916664 (c.896T>C, p.Asn299Ser [p.N299S]) of the acetyl-CoA acyltransferase 1 (ACAA1) gene in a Han Chinese AD family by whole-genome sequencing and validated its association with early-onset familial AD in an independent cohort. Further in vitro and in vivo evidence showed that ACAA1 p.N299S contributes to AD by disturbing its enzymatic activity, impairing lysosomal function, and aggravating the Aß pathology and neuronal loss, which finally caused cognitive impairment in a murine model. Our findings reveal a fundamental role of peroxisome-mediated lysosomal dysfunction in AD pathogenesis.

The complete mitochondrial genome of the bagworm from a tea plantation in China, Eumeta variegata (Lepidoptera: Psychidae).

The mitochondrial (mt) genome of Eumeta variegata Snellen (Psychidae) has been sequenced and annotated. The mt genome has a total length of 15,793 bp, consisting of 13 protein-coding genes, 22 tRNA, two rRNA genes, and an AT-rich control region (GenBank accession no. MN242985). The nucleotide composition was extremely AT-rich, and the AT content is 81.57%. The gene order is consistent with other sequenced mt genome of moths and butterflies from Ditrysia. The sequence similarity of E. variegate mt genomes between the specimen of China and South Korea is 98.38%, whereas the similarity between the specimen of China and Japan is 90.61%. The sequence of PCGs and rRNAs among different specimens are similar, and many differences are detected at the region of A + T-rich region and the tRNA block 'ARNS1EF'.

Panax Notoginseng Saponin Attenuates Gastric Mucosal Epithelial Cell Injury Induced by Dual Antiplatelet Drugs through COX and PI3K/Akt/ VEGF-GSK-3ß-RhoA Network Pathway.

OBJECTIVE: To elucidate the underlying mechanism of Panax notoginseng saponin (PNS) on gastric epithelial cell injury and barrier dysfunction induced by dual antiplatelet (DA). METHODS: Human gastric mucosal epithelial cell (GES-1) was cultured and divided into 4 groups: a control, a DA, a PNS+DA and a LY294002+PNS+DA group. GES-1 apoptosis was detected by flow cytometry, cell permeability were detected using Transwell, level of prostaglandins E2 (PGE2), 6-keto-prostaglandin F1α (6-keto-PGF1α) and vascular endothelial growth factor (VEGF) in supernatant were measured by enzyme linked immunosorbent assay (ELISA), expression of phosphatidylinositide 3-kinase (PI3K), phosphorylated-PI3K (p-PI3K), Akt, phosphorylated-Akt (p-Akt), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glycogen synthase kinase-3ß (GSK-3ß) and Ras homolog gene family member A (RhoA) were measured by Western-blot. RESULTS: DA induced apoptosis and hyper-permeability in GES-1, reduced supernatant level of PGE2, 6-keto-PGF1α and VEGF (P<0.05). Addition of PNS reduced the apoptosis of GES-1 caused by DA, restored the concentration of PGE2, 6-keto-PGF1α and VEGF (P<0.05). In addition, PNS attenuated the alteration of COX-1 and COX-2 expression induced by DA, up-regulated p-PI3K/p-Akt, down-regulated RhoA and GSK-3ß. LY294002 mitigated the effects of PNS on cell apoptosis, cell permeability, VEGF concentration, and expression of RhoA and GSK-3ß significantly. CONCLUSIONS: PNS attenuates the suppression on COX/PG pathway from DA, alleviates DA-induced GES-1 apoptosis and barrier dysfunction through PI3K/Akt/ VEGF-GSK-3ß-RhoA network pathway.

Precise diagnosis of three top cancers using dbGaP data.

The challenge of decoding information about complex diseases hidden in huge number of single nucleotide polymorphism (SNP) genotypes is undertaken based on five dbGaP studies. Current genome-wide association studies have successfully identified many high-risk SNPs associated with diseases, but precise diagnostic models for complex diseases by these or more other SNP genotypes are still unavailable in the literature. We report that lung cancer, breast cancer and prostate cancer as the first three top cancers worldwide can be predicted precisely via 240-370 SNPs with accuracy up to 99% according to leave-one-out and 10-fold cross-validation. Our findings (1) confirm an early guess of Dr. Mitchell H. Gail that about 300 SNPs are needed to improve risk forecasts for breast cancer, (2) reveal an incredible fact that SNP genotypes may contain almost all information that one wants to know, and (3) show a hopeful possibility that complex diseases can be precisely diagnosed by means of SNP genotypes without using phenotypical features. In short words, information hidden in SNP genotypes can be extracted in efficient ways to make precise diagnoses for complex diseases.

In vivo reflectance confocal microscopy for evaluating seborrheic keratosis, verruca plana, syringoma and lichen nitidus.

BACKGROUND: In clinical, common facial papule dermatosis such as seborrheic keratosis (SK), verruca plana (VP), syringoma and lichen nitidus (LN) is often misdiagnosed. Summarizing in vivo reflectance confocal microscopy (RCM) features of the facial papule dermatosis is helpful in the diagnosis of ambiguous lesions. The purpose of this study was to evaluate the features of SK, VP, syringoma, and LN in RCM. METHODS: We recruited 144 patients referred for unequivocal facial papule dermatosis including 60 patients with SK, 60 patients with VP, 10 patients with syringoma, and 14 patients with LN. The RCM images were evaluated at the epidermis, the dermoepidermal junction, and the dermis from both papule lesions and normal skin. RESULTS: In the epidermis, the cerebriform shape was the main RCM characteristic of SK and the "petal-like" structure was the main RCM characteristic of VP. In the dermoepidermal junction, the RCM features we found were as follows: For SK, the bright dermal papillary rings, the abnormal dermal papilla and the looped vessels were also observed at the abnormal dermal papilla. For VP, the bright dermal papillary rings and the point-like blood vessels were also observed at the round dermal papills. For LN, the round, enlarged, well-circumscribed dermal papillae and the enlarged dermal papillaes were heavily laden with individual highly refractive cells. In the dermis, RCM examination revealed brightly refractile teratogenous sweat tube, designing variably visible bright "moon" structures in all syringoma patients. CONCLUSION: Considering our results, RCM may be useful to non-invasively discriminate SK, VP, syringoma and LN in vivo.

Transcriptome-wide Association Study Identifies Genetically Dysregulated Genes in Diabetic Neuropathy.

BACKGROUND: Complications are the main cause of the disease burden of diabetes. Genes determining the development and progression of diabetic complications remain to be identified. Diabetic neuropathy is the most common and debilitating complication and mainly affects the nerves of legs and feet. In this study, we attempted to identify diabetic neuropathy-specific genes from reliable large-scale genome-wide association studies (GWASs) for diabetes perse. METHODS: Taking advantage of publicly available data, we initially converted the GWAS signals to transcriptomic profiles in the tibial nerve using the functional summary-based imputation (FUSION) algorithm. The FUSION-derived genes were then checked to determine whether they were differentially expressed in the sciatic nerve of mouse models of diabetic neuropathy. The dysregulated genes identified in the sciatic nerve were explored in the blood of patients with diabetes. RESULTS: We found that eleven out of 452 FUSION-derived genes were regulated by diabetes GWAS loci and were altered in the sciatic nerve of mouse models with early-stage neuropathy. Among the eleven genes, significant (P-value<0.05) expression alterations of HSD17B4, DHX32, MERTK, and SFXN4 could be detected in the blood of human patients. CONCLUSIONS: Our analyses identified genes with an effect in the sciatic nerve and provided the possibility of noninvasive early detection of diabetic neuropathy.

miR-223-3p Inhibits Antigen Endocytosis and Presentation and Promotes the Tolerogenic Potential of Dendritic Cells through Targeting Mannose Receptor Signaling and Rhob.

BACKGROUND: The role of miR-223-3p in dendritic cells (DCs) is unknown. This study is aimed at investigating the effect of miR-223-3p on the antigen uptake and presentation capacities of DCs and the underlying molecular mechanism. METHODS: FITC-OVA antigen uptake and cell surface markers in bone marrow-derived DCs (BMDCs) were analyzed by flow cytometry. BMDCs were transfected with the miR-223-3p mimic or inhibitor. Cytokine levels were determined by ELISA. CD4+ T cell differentiation was determined by mixed lymphocyte culture assay. RESULTS: OVA treatment significantly downregulated miR-223-3p in BMDCs. The miR-223-3p mimic significantly inhibited OVA-induced antigen uptake and surface expression of MHC-II on BMDCs (P < 0.01). The miR-223-3p mimic increased TGF-ß1 production in OVA-treated DCs (P < 0.01). Mixed lymphocyte reaction showed that the miR-223-3p mimic significantly promoted Treg cell differentiation. In addition, the miR-223-3p mimic significantly upregulated CD103 in DCs, indicating the promotion of tolerogenic DCs. The miR-223-3p mimic downregulated Rhob protein in OVA-induced DCs. Rhob knockdown significantly suppressed the ability of FITC-OVA endocytosis (P < 0.01) and surface MHC-II molecule expression (P < 0.01) in BMDCs, promoting promoted Treg cell differentiation. Mannose receptor (MR) knockdown significantly upregulated miR-223-3p, downregulated Rhob protein in OVA-treated DCs, inhibited the FITC-OVA endocytosis and surface MHC-II expression in BMDCs, and promoted Treg cell differentiation (all P < 0.01). CONCLUSION: These data suggest that miR-223-3p has an inhibitory effect on the antigen uptake and presentation capacities of BMDCs and promotes Treg cell differentiation, which is, at least partially, through targeting MR signaling and Rhob.

The complete mitochondrial genome of the tea weevil, Myllocerinus aurolineatus (Coleoptera: Curculionidae).

The tea weevil, Myllocerinus aurolineatus (Voss), is a serious pest of tea plants. We have obtained and annotated the complete mitochondrial genome of M. aurolineatus (GenBank accession No. MH197100). The entire mt genome is 17,762 bp long with an A + T content of 75.45%. The mt genome of M. aurolineatus encodes all 37 genes that are typically found in animal mt genomes, consists of 13 protein-coding genes, 2 ribosomal RNA and 22 transfer RNA genes. The gene order is consistent with other weevil mt genomes in Entiminae, within a typical gene order of "RANSEF". Phylogenetic analysis was performed using 13 protein-coding genes among 18 weevils showed that M. aurolineatus is closely related to another Entiminae species, Sympiezomias velatus.

Identification of a functional 339 bp Alu insertion polymorphism in the schizophrenia-associated locus at 10q24.32.

Genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) or small indels robustly associated with schizophrenia; however, the functional risk variations remain largely unknown. We investigated the 10q24.32 locus and discovered a 339 bp Alu insertion polymorphism (rs71389983) in complete linkage disequilibrium (LD) with the schizophrenia GWAS risk variant rs7914558. The presence of the Alu insertion at rs71389983 strongly repressed transcriptional activities in in vitro luciferase assays. This polymorphism may be a target for future mechanistic research. Our study also underlines the importance and necessity of considering previously underestimated Alu polymorphisms in future genetic studies of schizophrenia.

Mutation and association analyses of dementia-causal genes in Han Chinese patients with early-onset and familial Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. It shares clinical and pathological features with other types of dementia, such as vascular dementia (VaD), Lewy body dementia (LBD), and frontotemporal dementia (FTD). We have hypothesized that there might be an overlapping molecular mechanism and genetic basis to the different types of dementia. In this study, we analyzed the mutation pattern of dementia-causal genes in 169 Han Chinese patients with familial and early-onset AD by using whole exome sequencing or targeted resequencing. We identified 9 potentially pathogenic mutations in the AD-causal genes APP, PSEN1, PSEN2, and 6 mutations in a group of non-AD dementia-causal genes including the FTD-causal gene GRN and the VaD-causal gene NOTCH3. A common splice-site variant rs514492 in the FTD-causal gene VCP showed a positive association with AD risk (P = 0.0003, OR = 1.618), whereas the rare missense variant rs33949390 (p. R 1628P) in the LBD-causal gene LRRK2 showed a protective effect on AD risk (P = 0.0004, OR = 0.170). The presence of putative pathogenic mutations and risk variants in these causal genes for different types of dementia in clinically diagnosed familial and early-onset AD patients suggests a need to screen for mutations of the dementia-causal genes in cases of AD to avoid misdiagnosis. These mutations also support the idea that there are overlapping pathomechanisms between AD and other forms of dementia.

Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese.

Alzheimer's disease is the most common neurodegenerative disease, and has a high level of genetic heritability and population heterogeneity. In this study, we performed the whole-exome sequencing of Han Chinese patients with familial and/or early-onset Alzheimer's disease, followed by independent validation, imaging analysis and function characterization. We identified an exome-wide significant rare missense variant rs3792646 (p.K420Q) in the C7 gene in the discovery stage (P = 1.09 × 10-6, odds ratio = 7.853) and confirmed the association in different cohorts and a combined sample (1615 cases and 2832 controls, Pcombined = 2.99 × 10-7, odds ratio = 1.930). The risk allele was associated with decreased hippocampal volume and poorer working memory performance in early adulthood, thus resulting in an earlier age of disease onset. Overexpression of the mutant p.K420Q disturbed cell viability, immune activation and ß-amyloid processing. Electrophysiological analyses showed that the mutant p.K420Q impairs the inhibitory effect of wild type C7 on the excitatory synaptic transmission in pyramidal neurons. These findings suggested that C7 is a novel risk gene for Alzheimer's disease in Han Chinese.

Comparing the effects of depression, anxiety, and comorbidity on quality-of-life, adverse outcomes, and medical expenditure in Chinese patients with acute coronary syndrome.

BACKGROUND: Depression and anxiety have been correlated with elevated risks for quality-of-life (QOL), adverse outcomes, and medical expenditure in patients with acute coronary syndrome (ACS). However, the relevant data are lacking for Chinese ACS populations, especially regarding different effects of major depression, anxiety, and comorbidity. The objective of this study was to evaluate the dynamic changes of depression and/or anxiety over 12 months and examine the effects of depression, anxiety, and comorbidity on QOL, adverse outcomes, and medical expenditure in Chinese patients with ACS. METHODS: For this prospective longitudinal study, a total of 647 patients with ACS were recruited from North China between January 2013 and June 2015. Among them, 531 patients (82.1%) completed 12-month follow-ups. Logistic regression model was utilized for analyzing the association of baseline major depression, anxiety, and comorbidity with 12-month all-cause mortality, cardiovascular events, QOL, and health expenditure. RESULTS: During a follow-up period of 12 months, 7.3% experienced non-fatal myocardial infarction (MI) and 35.8% cardiac re-hospitalization. Baseline comorbidity, rather than major depression/anxiety, strongly predicted poor 12-month QOL as measured by short-form health survey-12 (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.22-2.52, P = 0.003). Regarding 12-month non-fatal MI and cardiac re-hospitalization, baseline anxiety (OR: 2.83, 95% CI: 1.33-5.89, P < 0.01; OR: 4.47, 95% CI: 1.50-13.00, P < 0.01), major depression (OR: 2.58, 95% CI: 1.02-6.15, P < 0.05; OR: 5.22, 95% CI: 1.42-17.57, P < 0.03), and comorbidity (OR: 6.33, 95% CI: 2.96-13.79, P < 0.0001, OR: 14.08, 95% CI: 4.99-41.66, P < 0.0001) were all independent predictors, and comorbidity had the highest predictive value. Number of re-hospitalization stay, admission frequency within 12 months and medical expenditure within 2 months were the highest in patients with ACS with comorbidity. CONCLUSIONS: Major depression and anxiety may predict 12-month non-fatal MI and cardiac re-hospitalization. However, comorbidity has the highest predictive value with greater medical expenditure and worse QOL in Chinese patients with ACS. And depression with comorbid anxiety may be a new target of mood status in patients with ACS.

Characterization of the complete mitochondrial genome of the tea leaf roller Caloptilia theivora (Insecta: Lepidoptera: Gracillariidae).

The tea leaf roller, Caloptilia theivora (Walsingham), is a serious pest of tea plants. We have obtained and annotated the complete mitochondrial genome of C. theivora (GenBank accession No. MK541932). The entire mt genome is 15,297 bp long with an A + T content of 80.66%. The mt genome of C. theivora encodes all 37 genes that are typically found in animal mt genomes, consists of 13 protein-coding genes, 2 ribosomal RNA, and 22 transfer RNA genes. The gene order is consistent with other moths mt genome in Ditrysia. The control region of this genome is 192 bp long with a high A + T content of 96.35%, and located between the rrnS and trnI genes. Phylogenetic analysis was performed using 13 protein-coding genes among 19 moths showed that C. theivora is closely related to species of Gracillariidae.