Functional studies of BPGAP1, a novel BCH domain-containing RhoGAP protein

Ph.DDOCTOR OF PHILOSOPH

To Explore the Brain-Gut Interaction Pathway of Intestinal Flora Based on Traditional Chinese and Western Medicine

To Explore the Brain-Gut Interaction Pathway of Intestinal Flora Based on Traditional Chinese and Western Medicin

Body Mass Index of Male Youths Aged 18-20 Years of the Han Nationality Living in Different Regions of China

The study was conducted to assess the nutritional status and levels of body mass index (BMI, kg/m2) and to evaluate the geographical distribution of male youths of the Han nationality in China. In total, 60,773 male youths, aged 18-20 years, of the Han nationality, were categorized into underweight, normal-weight, overweight, and obesity according to the international adult BMI cut-offs. Different levels of nutritional status and BMI of male youths of the Han nationality were compared among different areas. The mean BMI for the whole country was 20.6 in urban areas and 20.0 in rural areas. BMI increased from 20.1 among 18-year old youths to 20.5 among 20-year old youths. The prevalence of underweight among the male youths was 21.6%, while the prevalence of overweight and obesity were 4.6% and 0.6% respectively. For urban youths, the prevalence of underweight, overweight, and obesity were 21.0%, 6.8%, and 1.1% respectively, while these were, respectively, 21.9%, 3.3%, and 0.3% for rural youths. The nutritional status of the male youths in North-China was at the highest level (21.1) among the six areas, and the prevalence of underweight, overweight, and obesity were 14.3%, 9.1%, and 1.4% respectively. The highest prevalence of underweight was 29.8% in the North-West region, and the lowest prevalence of overweight was 2.2% in the South-Middle region, while the lowest prevalence of obesity was 0.2% in the South-West region. The nutritional status of the male youths was significantly different among different areas. Underweight was still prevalent in all male youth groups. Nonetheless, overweight was more prevalent among urban youths than among rural youths and was more prevalent in the North region than in the South region

SnarkFold: Efficient SNARK Proof Aggregation from Split Incrementally Verifiable Computation

The succinct non-interactive argument of knowledge (SNARK) technique is widely used in blockchain systems to replace the costly on-chain computation with the verification of a succinct proof. However, when dealing with multiple proofs, most existing applications require each proof to be independently verified, resulting in a heavy load on nodes and high transaction fees for users. To improve the efficiency of verifying multiple proofs, we introduce SnarkFold, a universal SNARK-proof aggregation scheme based on incrementally verifiable computation (IVC). Unlike previous proof aggregation approaches based on inner product arguments, which have a logarithmic proof size and verification cost, SnarkFold achieves constant verification time and proof size. One core technical advance in SnarkFold, of independent interest, is the ``split IVC\u27\u27: rather than using one running instance to fold/accumulate the computation, we employ two (or more) running instances of different types in the recursive circuit to avoid transferring into the same structure. This distinguishing feature is particularly well-suited for proof aggregation scenarios, as constructing arithmetic circuits for pairings can be expensive. We further demonstrate how to fold Groth16 proofs with our SnarkFold. With some further optimizations, SnarkFold achieves the highest efficiency among all approaches

Increased susceptibility of 129SvEvBrd mice to IgE-Mast cell mediated anaphylaxis

<p>Abstract</p> <p>Background</p> <p>Experimental analyses have identified strain-dependent factors that regulate susceptibility to anaphylaxis in mice. We assessed the susceptibility of the widely used 129SvEvBrd (also known as 129S5) mouse strain to IgE/mast cell-mediated anaphylaxis as compared to BALB/c. Mice were subjected to passive and oral Ovalbumin [OVA]-induced active anaphylaxis. Tissue mast cell, plasma histamine, total IgE and OVA-specific IgE levels and susceptibility to histamine i.v infusion were assessed. Bone marrow mast cell (BMMC)s were examined for Fc_εRI, c-kit, degranulation efficiency, proliferation, apoptosis and cytokine profile.</p> <p>Results</p> <p>129S5 mice had significantly increased susceptibility to passive and oral OVA-induced active anaphylaxis. Increased susceptibility to anaphylaxis was associated with increased homeostatic mast cell levels but not OVA-specific IgE or IgG₁levels. <it>In vitro </it>analyses of BMMCs revealed no difference in Fc_εRI and c-Kit expression, however, 129S5 BMMCs possessed greater proliferative capacity and reduced caspase-3-mediated apoptosis. IgE-BMMC degranulation assays demonstrated no difference in degranulation efficiency. Furthermore, 129S5 mice possessed increased sensitivity to histamine-induced hypothermia.</p> <p>Conclusions</p> <p>We conclude that 129S5 mice have increased susceptibility to anaphylaxis as compared to BALB/c strain and their increased susceptibility was associated with altered mast cell proliferation and homeostatic tissue levels and responsiveness to histamine. Given the wide spread usage of the 129SvEvBrd strain of mice in experimental gene targeting methodology, these data have important implications for studying IgE-reactions in mouse systems.</p

Body Mass Index of Male Youths Aged 18-20 Years of the Han Nationality Living in Different Regions of China

The study was conducted to assess the nutritional status and levels of body mass index (BMI, kg/m2) and to evaluate the geographical distribution of male youths of the Han nationality in China. In total, 60,773 male youths, aged 18-20 years, of the Han nationality, were categorized into underweight, normal-weight, overweight, and obesity according to the international adult BMI cut-offs. Different levels of nutritional status and BMI of male youths of the Han nationality were compared among different areas. The mean BMI for the whole country was 20.6 in urban areas and 20.0in rural areas. BMI increased from 20.1 among 18-year old youths to 20.5 among 20-year old youths. The prevalence of underweight among the male youths was 21.6%, while the prevalence of overweight and obesity were 4.6% and 0.6% respectively. For urban youths, the prevalence of underweight, overweight, and obesity were 21.0%, 6.8%, and 1.1% respectively, while these were, respectively, 21.9%, 3.3%, and 0.3% for rural youths. The nutritional status of the male youths in North-China was at the highest level (21.1) among the six areas, and the prevalence of underweight, overweight, and obesity were 14.3%, 9.1%, and 1.4% respectively. The highest prevalence of underweight was 29.8% in the North-West region, and the lowest prevalence of overweight was 2.2% in the South-Middle region, while the lowest prevalence of obesity was 0.2% in the South-West region. The nutritional status of the male youths was significantly different among different areas. Underweight was still prevalent in all male youth groups. Nonetheless, overweight was more prevalent among urban youths than among rural youths and was more prevalent in the North region than in the South region

Extra-Cerebellar Signs and Non-motor Features in Chinese Patients With Spinocerebellar Ataxia Type 3

Objectives: Our study attempted to systematically explore the prevalence of extra-cerebellar signs and non-motor symptoms, such as anxiety, depression, fatigue, excessive daytime sleepiness (EDS) and sleep disturbances in a cohort of Chinese patients with spinocerebellar ataxia type 3 (SCA3), and further investigated the correlations between non-motor symptoms and clinical characteristics in SCA3 patients.Methods: This study included 68 molecular-proven SCA3 patients. Extra-cerebellar signs were evaluated with the Inventory of Non-Ataxia Symptoms (INAS). The INAS count indicated the number of non-ataxia signs in each patient. The severity of ataxia, fatigue, EDS, sleep quality, anxiety, and depression were assessed using the Scale for the assessment and rating of ataxia (SARA), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Rating Scale (HAMA), and the Hamilton Depression Rating Scale (HAMD) (24 items), respectively.Results: Extra-cerebellar signs were detected in 91.2% of all SCA3 patients and the mean total INAS count was 2.72 ± 1.88. Rigidity was the most frequent extra-cerebellar sign (47.1%, N = 32). Sensory symptoms (2.9%, N = 2) and chorea (5.9%, N = 4) were rare, and myoclonus (0%) was not found in this cohort. High frequencies of sleep disturbances (64.7%), fatigue (52.9%), depression (48.5%), and anxiety (42.6%) were detected in SCA3 patients. The Spearman correlation indicated that the HAMD score was associated with the CAG repeat length and HAMA score, while the PSQI score was correlated with the SARA and FSS score. In addition, multivariate linear regression analysis showed that the CAG repeat length, age of onset, sleep disturbances and depression were significant predictors of fatigue in SCA3 patients.Conclusions: Our study indicates that the vast majority of SCA3 patients display extra-cerebellar signs. Except for EDS, anxiety, depression, fatigue and impaired sleep quality are present in SCA3 patients. The CAG repeat length, age of onset, sleep disturbances and depression are predictors of fatigue in SCA3 patients

De novel heterozygous copy number deletion on 7q31.31-7q31.32 involving TSPAN12 gene with familial exudative vitreoretinopathy in a Chinese family

AIM: To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32. METHODS: A family with familial exudative vitreoretinopathy (FEVR) phenotype was included in the study. Whole-exome sequencing (WES) was initially used to locate copy number variations (CNVs) on 7q31.31-31.32, but failed to detect the precise breakpoint. The long-read sequencing, Oxford Nanopore sequencing Technology (ONT) was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction (QPCR) and Sanger Sequencing. RESULTS: The proband, along with her father and younger brother, were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32, which included the FEVR-related gene TSPAN12. The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del. The proband exhibited a phase 2A FEVR phenotype, characterized by a falciform retinal fold, macular dragging, and peripheral neovascularization with leaking of fluorescence. These symptoms led to a significant decrease in visual acuity in both eyes. On the other hand, the affected father and younger brother showed a milder phenotype. CONCLUSION: The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype. The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders

Distribution of cervical intraepithelial neoplasia on the cervix in Chinese women: pooled analysis of 19 population based screening studies

Abstract Background Controversy remains whether a pattern of cervical intraepithelial neoplasia exists on the cervix. Our study aims at determining if the prevalence of histologically proven lesions differs by cervical four-quadrant location or by 12 o'clock surface locations of diagnosis. Methods We conducted a retrospective, histopathological study of 19 different population based cervical cancer screening studies from 1999 to 2010 by Cancer Hospital of Chinese Academy of Medical Sciences. The Institutional Review Board for human research subjects at CHCAMS approved all of the studies. During the colposcopy procedure, participant received either 4-quadrant biopsy or directed biopsy with/without endocervical curettage. Data of all samples were stratified by the methods of sampling. Kruskal-Wallis test was used to determine overall distribution of normal/CIN1, CIN2 and CIN3+ on the cervix. Results In total, 53,088 cervical samples were included in distribution analysis. 66.9 % samples were obtained by random biopsy, 16.1 % were by directed biopsy, and 17.0 % were by endocervical curettage. 95.9%of the biopsied samples were diagnosed as normal/CIN1, 2.0 % were CIN2, and 2.1 % were CIN3 + . CIN2 and CIN3+ were most often found in quadrants 2 and 3 (χKW2 = 46.6540, p < 0.0001) and at the 4- and 7-o'clock positions by directed biopsy (ORCIN2 = 2.572, 1.689, ORCIN3+ = 3.481, 1.678, respectively), and at the 5-, 6-, 7-, 9- and 12-o’clock positions by random biopsy. CIN3+ was least often found at the 11-o’clock position by directed biopsy (OR = 0.608). Conclusions Our results suggest a predisposition of specific locations on the cervix to CIN occurrence. Quadrants 2 and 3, especially the 4- and 7-o’clock positions should be preferentially targeted during biopsy. The decision for random biopsy should be reconsidered in future studies