Molecular Mechanisms for CFIm-Mediated Regulation of mRNA Alternative Polyadenylation.

Alternative mRNA processing is a critical mechanism for proteome expansion and gene regulation in higher eukaryotes. The SR family proteins play important roles in splicing regulation. Intriguingly, mammalian genomes encode many poorly characterized SR-like proteins, including subunits of the mRNA 3'-processing factor CFIm, CFIm68 and CFIm59. Here we demonstrate that CFIm functions as an enhancer-dependent activator of mRNA 3' processing. CFIm regulates global alternative polyadenylation (APA) by specifically binding and activating enhancer-containing poly(A) sites (PASs). Importantly, the CFIm activator functions are mediated by the arginine-serine repeat (RS) domains of CFIm68/59, which bind specifically to an RS-like region in the CPSF subunit Fip1, and this interaction is inhibited by CFIm68/59 hyper-phosphorylation. The remarkable functional similarities between CFIm and SR proteins suggest that interactions between RS-like domains in regulatory and core factors may provide a common activation mechanism for mRNA 3' processing, splicing, and potentially other steps in RNA metabolism.

Mitochondrial disturbance related to increased caspase-1 of CD4+T cells in HIV-1 infection.

BACKGROUND: In HIV-1 infection, more than 95% of CD4+T cells die of caspase-1 mediated pyroptosis. What governs the increased susceptibility of CD4+T cells to pyroptosis is poorly understood. METHODS: Blood samples were obtained from 31 untreated HIV-infected patients (UNT), 29 antiretroviral therapy treated HIV-infected patients (ART), and 21 healthy control donors (HD). Plasma levels of IL-18 and IL-1ß, caspase-1 expression, mitochondrial mass (MM) and mitochondrial fusion/fisson genes of CD4+T subsets were measured. RESULTS: A significantly higher IL-18 level in plasma and MM level of CD4+T cells were found in HIV-infected patients (UNT and ART) compared to HD, and the MMhigh phenotype was manifested, related to increased caspase-1 expression. Moreover, the increased MM was more pronounced in the early differentiated and inactivated CD4+T cells. However, higher MM was not intrinsically linked to T cell differentiation disorder or excessive activation of the CD4+T cells. Mechanistically, the increased MM was significantly correlated with an elevated level of expression of the mitochondrial fusion gene mitofusin1. CONCLUSION: An increase in MM was associated with heightened sensitivity of CD4+T cells to pyroptosis, even in early differentiated and inactivated CD4+T cells, in patients with HIV-1 infection, regardless of whether patients were on antiretroviral therapy or not. These new revelations have uncovered a previously unappreciated challenge to immune reconstitution with antiretroviral therapy.

UFold: fast and accurate RNA secondary structure prediction with deep learning.

For many RNA molecules, the secondary structure is essential for the correct function of the RNA. Predicting RNA secondary structure from nucleotide sequences is a long-standing problem in genomics, but the prediction performance has reached a plateau over time. Traditional RNA secondary structure prediction algorithms are primarily based on thermodynamic models through free energy minimization, which imposes strong prior assumptions and is slow to run. Here, we propose a deep learning-based method, called UFold, for RNA secondary structure prediction, trained directly on annotated data and base-pairing rules. UFold proposes a novel image-like representation of RNA sequences, which can be efficiently processed by Fully Convolutional Networks (FCNs). We benchmark the performance of UFold on both within- and cross-family RNA datasets. It significantly outperforms previous methods on within-family datasets, while achieving a similar performance as the traditional methods when trained and tested on distinct RNA families. UFold is also able to predict pseudoknots accurately. Its prediction is fast with an inference time of about 160 ms per sequence up to 1500 bp in length. An online web server running UFold is available at https://ufold.ics.uci.edu. Code is available at https://github.com/uci-cbcl/UFold.

Integrated analysis of multimodal single-cell data with structural similarity.

Multimodal single-cell sequencing technologies provide unprecedented information on cellular heterogeneity from multiple layers of genomic readouts. However, joint analysis of two modalities without properly handling the noise often leads to overfitting of one modality by the other and worse clustering results than vanilla single-modality analysis. How to efficiently utilize the extra information from single cell multi-omics to delineate cell states and identify meaningful signal remains as a significant computational challenge. In this work, we propose a deep learning framework, named SAILERX, for efficient, robust, and flexible analysis of multi-modal single-cell data. SAILERX consists of a variational autoencoder with invariant representation learning to correct technical noises from sequencing process, and a multimodal data alignment mechanism to integrate information from different modalities. Instead of performing hard alignment by projecting both modalities to a shared latent space, SAILERX encourages the local structures of two modalities measured by pairwise similarities to be similar. This strategy is more robust against overfitting of noises, which facilitates various downstream analysis such as clustering, imputation, and marker gene detection. Furthermore, the invariant representation learning part enables SAILERX to perform integrative analysis on both multi- and single-modal datasets, making it an applicable and scalable tool for more general scenarios.

Lineage tracing and analog recording in mammalian cells by single-site DNA writing.

Studying cellular and developmental processes in complex multicellular organisms can require the non-destructive observation of thousands to billions of cells deep within an animal. DNA recorders address the staggering difficulty of this task by converting transient cellular experiences into mutations at defined genomic sites that can be sequenced later in high throughput. However, existing recorders act primarily by erasing DNA. This is problematic because, in the limit of progressive erasure, no record remains. We present a DNA recorder called CHYRON (Cell History Recording by Ordered Insertion) that acts primarily by writing new DNA through the repeated insertion of random nucleotides at a single locus in temporal order. To achieve in vivo DNA writing, CHYRON combines Cas9, a homing guide RNA and the template-independent DNA polymerase terminal deoxynucleotidyl transferase. We successfully applied CHYRON as an evolving lineage tracer and as a recorder of user-selected cellular stimuli.

Flexible aqueous supercapacitors with excellent cycling performance and high-energy density based on mesocrystalline NiCo-LDHs.

Flexible aqueous supercapacitors are promising candidates as safe power sources for wearable electronic devices (WEDs). However, the absence of advanced electrode materials with high structural stability has become the most critical factor hindering the development, which is closely related to the poor interface combination between the active substances and flexible collectors. Herein, a unique rigid layered double hydroxide (LDH) nanorod array with the mesocrystalline feature is created using the NiO-Ni layer as the inducer by the electrodeposition strategy. Differing from the traditional NiCo-LDH nanosheets directly grown on a carbon cloth, an elaborately designed NiO-Ni buffer can simultaneously and effectively improve the bidirectional combination with active substances and collectors, also the mesocrystalline LDH showed enhanced intrinsic stability through the reinforcing effect of grain boundaries. Benefiting from these, the assembled supercapacitor exhibited pre-eminent cycle stability (increased from 64% of the initial capacity after 10 000 cycles to no significant attenuation after 50 000 cycles) and ultrahigh energy density. When it was used as a flexible device, a remarkable energy density of 70.4 W h kg-1 could be harvested and processed with high flexibility in the bending state and good temperature adaptability. This study provides an excellent design strategy for the development of next-generation flexible supercapacitors with the goal of better comprehensive performances.

SAILER: scalable and accurate invariant representation learning for single-cell ATAC-seq processing and integration.

MOTIVATION: Single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) provides new opportunities to dissect epigenomic heterogeneity and elucidate transcriptional regulatory mechanisms. However, computational modeling of scATAC-seq data is challenging due to its high dimension, extreme sparsity, complex dependencies and high sensitivity to confounding factors from various sources. RESULTS: Here, we propose a new deep generative model framework, named SAILER, for analyzing scATAC-seq data. SAILER aims to learn a low-dimensional nonlinear latent representation of each cell that defines its intrinsic chromatin state, invariant to extrinsic confounding factors like read depth and batch effects. SAILER adopts the conventional encoder-decoder framework to learn the latent representation but imposes additional constraints to ensure the independence of the learned representations from the confounding factors. Experimental results on both simulated and real scATAC-seq datasets demonstrate that SAILER learns better and biologically more meaningful representations of cells than other methods. Its noise-free cell embeddings bring in significant benefits in downstream analyses: clustering and imputation based on SAILER result in 6.9% and 18.5% improvements over existing methods, respectively. Moreover, because no matrix factorization is involved, SAILER can easily scale to process millions of cells. We implemented SAILER into a software package, freely available to all for large-scale scATAC-seq data analysis. AVAILABILITY AND IMPLEMENTATION: The software is publicly available at https://github.com/uci-cbcl/SAILER. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Longitudinal analysis of new-onset non-AIDS-defining diseases among people living with HIV: A real-world observational study.

OBJECTIVES: We aimed to analyze the incidence rates of new-onset diabetes, hypertriglyceridemia, hypercholesterolemia, liver injury, and renal injury during antiretroviral therapy (ART) among people living with HIV (PLWH) and determine the associated risk factors. METHODS: This study included PLWH enrolled from Beijing Ditan Hospital from November 11, 2004, to December 29, 2018. The incidence rates of new-onset diabetes, hypertriglyceridemia, hypercholesterolemia, liver injury, and renal injury were calculated and stratified based on ART regimen, CD4 count, and HIV-RNA. Risk factors were determined using Cox regression analysis. RESULTS: Overall, 6747 participants were included. Moreover, 4.5%, 43.3%, 25.4%, 11.2%, and 6.2% of patients developed new-onset diabetes, hypertriglyceridemia, hypercholesterolemia, liver injury, and renal injury, respectively, with incidence rates of 1.7, 26.9, 10.2, 3.9, and 5.5 per 100 person-years, respectively. Longitudinally, the incidence rates and percentages of these outcomes were highest in the first year of ART. The percentage of dyslipidemia was significantly higher in protease inhibitor (PI)-based regimen than in non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. However, the percentage of liver injury was significantly higher in NNRTI-based regimen than in PI-based regimen. In multivariate Cox regression analysis, low CD4 count (<200 cells/µL, adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] 1.15-1.57) and high HIV-RNA (>105 copies/mL, aHR = 1.26, 95% CI 1.08-1.48) were risk factors for hypertriglyceridemia. CONCLUSIONS: Clinical outcomes, including new-onset diabetes, dyslipidemia, and liver and renal injuries, are common in PLWH. Regular glucose, lipid, liver, and renal function monitoring is required during ART, especially in high-risk patients.

A novel nonsense PKD1L1 variant cause heterotaxy syndrome with congenital asplenia in a Han Chinese patient.

Heterotaxy syndrome is a very rare congenital disease, which is caused by the disorder of left-right asymmetry during visceral development. However, pathogenic genetic lesions are found in less than 20% of HS patients. In this cohort study, whole-exome sequencing was performed for 110 patients with situs inversus or situs ambiguous. We identified a novel nonsense variant in PKD1L1(c.1387 C > T; p.463Gln*) in a Chinese patient with heterotaxy syndrome and congenital asplenia. This homozygous variant caused the domain of PKD1L1 complete absence. To our knowledge, this novel variant is the first phenotype of congenital asplenia found in patients with PKD1L1 variants, and the first PKD1L1 variant found in China. Our findings expand the spectrum of PKD1L1 variants and provide support for PKD1L1 variant and congenital asplenia, and the critical role of PKD1L1 during left-right patterning in the Han Chinese population.

Low serum vitamin D concentration is correlated with anemia, microinflammation, and oxidative stress in patients with peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is a form of dialysis to replace the function of kidney, that uses the peritoneum as a dialysis membrane to remove metabolites and water retained in the body. Vitamin D deficiency is prevalent in patients treated with PD. This research investigated the correlation between serum 25-hydroxyvitamin D [25(OH)D] concentration and anemia, microinflammation, and oxidative stress in PD patients. METHODS: 62 PD patients and 56 healthy volunteers were recruited in this research. Serum concentrations of 25(OH)D and basic parameters of anemia were detected. The correlation between serum 25(OH)D concentration with anemia, oxidative stress, and microinflammatory state were analyzed. RESULTS: In the PD group, the concentration of 25(OH)D was lower than the healthy control (HC) group (p < 0.001). Hemoglobin, red blood cell count (RBC), and total iron binding capacity (TIBC) in the PD group was significantly lower (all p < 0.001), while high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) concentrations were significantly higher, than the HC group (all p < 0.001). In the PD group, malondialdehyde (MDA) concentration was higher than in the HC group (p < 0.001), while superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were lower (both p < 0.001). Serum 25(OH)D exhibited positive correlation with hemoglobin (r = 0.4509, p = 0.0002), RBC (r = 0.3712, p = 0.0030), TIBC (r = 0.4700, p = 0.0001), SOD (r = 0.4992, p < 0.0001) and GSH-Px (r = 0.4312, p = 0.0005), and negative correlation with hs-CRP (r = - 0.4040, p = 0.0011), TNF-α (r = - 0.4721, p = 0.0001), IL-6 (r = - 0.5378, p < 0.0001) and MDA (r = - 0.3056, p = 0.0157). CONCLUSION: In conclusion, reduced serum 25(OH)D concentrations in PD patients contribute to anemia, oxidative stress and microinflammatory state.

Hepatotoxicity with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer patients: A network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: The efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients diagnosed with non-small-cell lung cancer (NSCLC) has been confirmed by a large number of studies. However, hepatotoxicity caused by EGFR-TKIs has not been widely investigated. This review compares the hepatotoxicity of different EGFR-TKIs through a network meta-analysis. METHODS: PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov were systematically searched from their individual inceptions to 20 May 2020 with the goal of identifying randomized controlled trials (RCTs) reporting hepatotoxicity in NSCLC patients receiving EGFR-TKIs. A random-effects pairwise meta-analysis and network meta-analysis were performed within a frequentist framework. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. RESULTS: Twelve eligible RCTs, including data from 6,280 patients diagnosed with NSCLC, were analysed. In our network meta-analysis, gefitinib was associated with a higher risk for hepatotoxicity compared to placebo (RR, 2.55; 95% CI, 1.32-4.89) and dacomitinib (RR, 2.60; 95% CI, 1.30-5.20) in terms of all-grades alanine transaminase (ALT) elevation. As for all-grades aspartate transaminase (AST) elevation, gefitinib and erlotinib showed a significantly increased risk for hepatotoxicity compared to afatinib, dacomitinib and placebo (erlotinib vs. afatinib: RR, 1.85; 95% CI, 1.05-3.24; erlotinib vs. dacomitinib: RR, 1.68; 95% CI, 1.19-2.36; erlotinib vs. placebo: RR, 3.38; 95% CI, 1.69-6.73; gefitinib vs. afatinib: RR, 2.23; 95% CI, 1.32-3.79; gefitinib vs. dacomitinib: RR, 2.03; 95% CI, 1.51-2.73; gefitinib vs. placebo: RR, 4.08; 95% CI, 2.11-7.91). There was a high risk of high-grade ALT elevation in patients treated with gefitinib compared to patients treated with erlotinib (RR, 4.31; 95% CI, 2.15-8.66), dacomitinib (RR, 6.95; 95% CI, 1.85-26.05) or placebo (RR, 8.38; 95% CI, 1.56-45.01). No statistically significant differences were identified among the five agents analysed in terms of all-grades TB elevation and high-grade AST elevation. The surface under the cumulative ranking curve (SUCRA) revealed that gefitinib showed a potentially higher risk for ALT and AST elevation compared to other EGFR-TKIs regardless of grade. WHAT IS NEW AND CONCLUSION: Current evidence indicates that the association between afatinib or dacomitinib and risk of liver enzyme elevation remains uncertain in patients diagnosed with NSCLC. Some evidence suggests that gefitinib and erlotinib may be associated with a significantly increased risk for hepatotoxicity in patients with NSCLC. However, given that the elevation of liver enzymes was not definitely associated with EGFR-TKIs and publication bias, further studies are required to confirm these results.

The impact of smoking status on the progression-free survival of non-small cell lung cancer patients receiving molecularly target therapy or immunotherapy versus chemotherapy: A meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Smoking has a notable influence on the efficacy of medications for lung cancer. Previous studies illustrated the correlation between smoking and the efficacy of first-line Epidermal Growth Factor Receptors-Tyrosine Kinase Inhibitors (EGFR-TKIs). The benefit of smokers in immunotherapy was still controversial. Here, we investigated the impact of smoking on clinical outcomes of molecularly targeted therapies or immunotherapy in Non-Small Cell Lung Cancer (NSCLC). METHODS: We performed meta-analysis including trials comparing EGFR-TKIs, Anaplastic Lymphoma Kinase (ALK) inhibitors or Immune Checkpoint Inhibitors (ICIs) against chemotherapy in NSCLC. The Progression-Free Survival (PFS)-Hazard Ratios (HRs) of two groups served as the index and we used random effects to pool outcomes. RESULTS AND DISCUSSION: Twenty randomized trials were selected. Compared with chemotherapy, treatment with EGFR-TKIs had similar benefit in never-smokers (PFS: HR = 0.46, 95% CI 0.30 to 0.69) and smokers (PFS: HR = 0.68, 95% CI 0.50 to 0.91; p = 0.135) while non-smokers (PFS: HR = 0.32, 95% CI 0.23 to 0.44) had better benefit from first-line EGFR-TKIs than smokers (PFS: HR = 0.54, 95% CI 0.41 to 0.71; p = 0.02). Treatment with ALK inhibitors had similar benefits in never-smokers (PFS: HR = 0.43, 95% CI 0.35 to 0.53) and smokers (PFS: HR = 0.56, 95% CI 0.44 to 0.71; p = 0.406). The benefit of ICIs in smokers (PFS: HR = 0.79, 95% CI 0.64 to 0.98) was significantly greater than never-smokers (PFS: HR = 1.81, 95% CI 1.27 to 2.57; p = 0.004). WHAT IS NEW AND CONCLUSION: Smoking status is an important clinical predictor of therapy in NSCLC. Never-smokers and smokers have similar benefit with EGFR-TKIs therapy compared with chemotherapy, while never-smokers have greater benefit after first-line EGFR-TKIs therapy. There was similar benefit in never-smokers and smokers when using ALK inhibitors over chemotherapy. Additionally, ICIs treatment over chemotherapy leads to more favourable PFS in smokers both in first-line and second-line settings.

A protective polymorphism in MMP16, improved blood gas levels, and chronic obstructive pulmonary diseases: Family and two population-based studies.

The aberrant expression of matrix metalloproteinases (MMPs) is known to contribute to the pathogenesis of airway remodeling and alveolar disruption in chronic obstructive pulmonary disease (COPD). In the discovery stage, 11 COPD from five families were subjected to whole-genome sequencing, and 21 common polymorphisms in MMPs and TIMPs were identified. These polymorphisms were genotyped in two subsequent verification studies. Of these polymorphisms, c.2392G>A (rs2664370T>C) and c.4158C>A (rs2664369T>G) in MMP16 remained significantly different. Functionally, we found that MMP16 expression was significantly increased in peripheral blood monocytes (PBMCs) from COPD and in cigarette smoke extract-treated 16HBE cells compared with controls. This was also shown by bioinformatics analysis. COPD carrying rs2664370CC showed decreased levels of MMP16 in the plasma and in PBMCs compared with those carrying CT and TT. Treatment with hsa-miR-576-5p mimics led to a greater reduction in luciferase reporter activity in cells transfected with rs2664370CC. Moreover, blood levels of base excess, PCO2 , and PO2 in COPD with rs2664370CC were significantly lower than those with rs2664370CT+TT. Taken together, these results demonstrate that the rs2664370T>C polymorphism in MMP16 protects against the risk of COPD, likely by favoring interaction with hsa-miR-576-5p, leading to reduced MMP16 expression and improved blood gas levels.

Parallel clustering of single cell transcriptomic data with split-merge sampling on Dirichlet process mixtures.

MOTIVATION: With the development of droplet based systems, massive single cell transcriptome data has become available, which enables analysis of cellular and molecular processes at single cell resolution and is instrumental to understanding many biological processes. While state-of-the-art clustering methods have been applied to the data, they face challenges in the following aspects: (i) the clustering quality still needs to be improved; (ii) most models need prior knowledge on number of clusters, which is not always available; (iii) there is a demand for faster computational speed. RESULTS: We propose to tackle these challenges with Parallelized Split Merge Sampling on Dirichlet Process Mixture Model (the Para-DPMM model). Unlike classic DPMM methods that perform sampling on each single data point, the split merge mechanism samples on the cluster level, which significantly improves convergence and optimality of the result. The model is highly parallelized and can utilize the computing power of high performance computing (HPC) clusters, enabling massive inference on huge datasets. Experiment results show the model outperforms current widely used models in both clustering quality and computational speed. AVAILABILITY AND IMPLEMENTATION: Source code is publicly available on https://github.com/tiehangd/Para_DPMM/tree/master/Para_DPMM_package. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

FactorNet: A deep learning framework for predicting cell type specific transcription factor binding from nucleotide-resolution sequential data.

Due to the large numbers of transcription factors (TFs) and cell types, querying binding profiles of all valid TF/cell type pairs is not experimentally feasible. To address this issue, we developed a convolutional-recurrent neural network model, called FactorNet, to computationally impute the missing binding data. FactorNet trains on binding data from reference cell types to make predictions on testing cell types by leveraging a variety of features, including genomic sequences, genome annotations, gene expression, and signal data, such as DNase I cleavage. FactorNet implements several convenient strategies to reduce runtime and memory consumption. By visualizing the neural network models, we can interpret how the model predicts binding. We also investigate the variables that affect cross-cell type accuracy, and offer suggestions to improve upon this field. Our method ranked among the top teams in the ENCODE-DREAM in vivo Transcription Factor Binding Site Prediction Challenge, achieving first place on six of the 13 final round evaluation TF/cell type pairs, the most of any competing team. The FactorNet source code is publicly available, allowing users to reproduce our methodology from the ENCODE-DREAM Challenge.

A common variant of the NOTCH4 gene modulates functional connectivity of the occipital cortex and its relationship with schizotypal traits.

BACKGROUND: Schizotypal traits are considered as inheritable traits and the endophenotype for schizophrenia. A common variant in the NOTCH4 gene, rs204993, has been linked with schizophrenia, but the neural underpinnings are largely unknown. METHODS: In present study, we compared the differences of brain functions between different genotypes of rs204993 and its relationship with schizotypal traits among 402 Chinese Han healthy volunteers. The brain function was evaluated with functional connectivity strength (FCS) using the resting-state functional magnetic resonance image(rs-fMRI). The schizotypal traits were measured by the schizotypal personality questionnaire (SPQ). RESULTS: Our results showed that carriers with the AA genotype showed reduced FCS in the left occipital cortex when compared with carriers with the AG and GG genotypes, and the carriers with the AG genotype showed reduced FCS in the left occipital cortex when compared with carriers with the GG genotype. The FCS values in the left occipital lobe were negatively associated with the SPQ scores and its subscale scores within the carriers with the GG genotype, but not within the carriers with AA or AG genotype. CONCLUSION: Our results suggested that the common variant in the NOTCH4 gene, rs204993, modulates the function of the occipital cortex, which may contribute to schizotypal traits. These findings provide insight for genetic effects on schizotypal traits and its potential neural substrate.

Evaluation of the Diagnostic Accuracy of the CareStart™ Glucose-6-Phosphate Dehydrogenase Deficiency Rapid Diagnostic Test among Chinese Newborns.

Previous studies have shown that the CareStart™ G6PD Deficiency rapid diagnostic test has high diagnostic accuracy on G6PD deficiency in Africa and Thailand, but not in China. As there are regional differences of G6PD genotype distribution, we are attending to verify the effectiveness of the kit in Chinese population. The study cohort included 247 newborns admitted to our hospital for jaundice. The quantitative detection of G6PD enzyme activity and G6PD gene mutations analysis was used to classify the status of G6PD deficiency. The performance of CareStart™ assays was verified by calculating the sensitivity, specificity and area under the receiver operating characteristic curve (AUC) based on the corrected G6PD deficiency status. In male newborns, the sensitivity of the CareStart™ assay was 98.9%, the specificity was 94.2% and the AUC was 0.97. In female newborns, the sensitivity was 58.5% when the cutoff value of residual enzyme activity was 100%; however, the sensitivity was 100% when the cutoff value was 60%. Therefore, the CareStart™ test can effectively screen G6PD deficiency in male newborns and female infants with less than 60% residual enzyme activity, female infants with residual enzyme activities of 60-100% are more likely to be missed diagnosed among Chinese newborns.

Influence of dietary fiber on chronic kidney disease： Base on the gut-kidney axis theory. / åŸºäºŽè‚ -è‚¾è½´ç†è®ºæµ æžè†³é£Ÿçº¤ç»´å¯¹æ ¢æ€§è‚¾ç— çš„å½±å“.

Chronic kidney disease (CKD) can result in alteration of intestinal flora and damage of intestinal barrier function. Intestinal dysbios is contributes to the generation of colon-derived uremic solutes and the translocation of bacteria and endotoxins from gut lumen into the bloodstream, subsequently increasing uremic toxicity and triggering systemic inflammation, which is related to CKD progression and many complications. Studies have revealed that dietary fiber can reduce uremic toxin levels and systemic inflammation in CKD through targeting the "gut-kidney axis". Dietary fiber seems to be a promising measure for CKD treatment.

Cerebral infarction as the first symptom in acute promyelocytic leukemia: A case report and literature review. / ä»¥è„‘æ¢—æ­»ä¸ºé¦–å‘ç—‡çŠ¶çš„æ€¥æ€§æ—©å¹¼ç²’ç»†èƒžç™½è¡€ç— 1例及文献回顾.

In the clinical settings, disseminated intravascular coagulation (DIC) and complications such as hemorrhage are commonly seen in acute promyelocytic leukemia patients, whereas thrombosis is rarely reported. We reported a case here that the patient presented with cerebral infarction as the first manifestation. During the admission, the patient encountered differentiation syndrome, pulmonary embolism, pulmonary hemorrhage, and myocardial ischemia, as well as bleeding and thrombosis complications. Hence the patient was diagnosed as DIC. After the treatment of blood transfusion instead of anticoagulation, his condition was stable and the remission was completely achieved. The treatment experience provides guides for other patients with similar complications of simultaneous bleeding and thrombosis.

Tiotropium added to low- to medium-dose inhaled corticosteroids (ICS) versus low- to medium-dose ICS alone for adults with mild to moderate uncontrolled persistent asthma: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety profile of tiotropium when added to low- to medium-dose inhaled corticosteroid (ICS) regimen versus low- to medium-dose ICS alone for adults with mild to moderate uncontrolled persistent asthma. DATA SOURCES: The online databases Pubmed, Embase and the Cochrane Library were searched for relevant data published up to November 14, 2017; we also conducted a supplementary search using clinicaltrials.gov. STUDY SELECTIONS: Only randomized control trials were included in this review. RESULTS: Four studies met our inclusion criteria for this review. In our review, two crossover studies were rated as "high risk" in the domain of "other bias" because a washout was not performed between each intervention. Lung function was significantly improved in the patient group receiving low- to medium-dose ICS with tiotropium. Results were consistent between each of three subgroups (tiotropium dry powder inhaler 18 µg or Respimat Soft Mist inhaler 5 µg, Respimat Soft Mist inhaler 2.5 µg, and Respimat Soft Mist inhaler 1.25 µg). Although no significant difference in Asthma Control Questionnaire (ACQ) score was found between the two treatment groups, substantial heterogeneity was observed. The incidence of serious adverse events between the two treatment groups was not statistically significant. CONCLUSIONS: Tiotropium as a once daily add-on to low- to medium-dose ICS may be efficacious and well-tolerated treatment in adults with moderate uncontrolled asthma. However, as only a few studies were identified, more studies of better design and long-term trial duration are required in the future.