Publications by authors named "Xiaochuan Wang"

132 Publications

The predictive value of RNA binding proteins in colon adenocarcinoma.

J Gastrointest Oncol 2021 Aug;12(4):1543-1557

Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou, China.

Background: RNA binding proteins (RBPs) play an important role in regulating post-transcriptional gene expression and have been reported to be closely associated with the occurrence and development of tumors. However, the effect of RBPs in colon cancer remains unclear.

Methods: We downloaded clinical information and transcriptome data of colon adenocarcinoma (COAD) from The Cancer Genome Atlas database (TCGA) database. After combining this data, we identified differentially expressed RBPs in normal and cancer tissues and subsequently performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Prognosis-related RBPs were identified via Cox regression analysis. The samples were randomly divided into two groups; an experimental group and a control group. A predictive model was constructed by dividing the experimental group into high- and low-risk subgroups based on the scores of the prognostic-related RBPs, and the prognosis of samples in these two subgroups was compared. Then, this model was applied to the control group. Finally, the model results were verified based on an online survival database and the Human Protein Atlas (HPA) database.

Results: A total of 469 differentially expressed RBPs were identified in normal and cancer tissues. Ten prognosis-related RBPs were determined by Cox regression analysis. In the prognostic prediction model, the prognosis of high-risk patients in the experimental group was worse than that in the low-risk group, and the same result was obtained in the control group. In addition, the risk score in the Cox regression analysis showed that the model could be used as an independent prognostic factor (P<0.001). The results of the online survival analysis tool, HPA database, and the model were consistent.

Conclusions: Some specific RBPs are significantly associated with the prognosis of patients with COAD, and this finding may provide important information for the future diagnosis and treatment of patients with COAD.
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http://dx.doi.org/10.21037/jgo-21-318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421876PMC
August 2021

Role of Nursing Home Quality on COVID-19 Cases and Deaths: Evidence from Florida Nursing Homes.

J Gerontol Soc Work 2021 Aug 26:1-17. Epub 2021 Aug 26.

Doctoral Program in Public Affairs, School of Public Administration, University of Central Florida, Orlando, Florida, USA.

The Coronavirus disease 2019 (COVID-19) disproportionately affects nursing home residents, resulting in an elevated risk for COVID-19 morbidity and mortality for this frail population. It is critical to understand whether nursing home quality is related to COVID-19 cases and deaths. Using publicly available data obtained from Centers for Medicare & Medicaid Services COVID-19 Nursing Home Dataset, Nursing Home Compare and Long-Term Care Focus, this study compares key nursing home characteristics, infection prevention and control deficiencies, and five-star ratings among Florida nursing homes with and without resident COVID-19 cases and deaths. The study further examines the association between facility and resident characteristics, quality indicators, and COVID-19 cases and deaths. Findings from our study indicate that through late October 2020, over 90% of Florida nursing homes have at least one resident case and 65% have at least one resident death. The likelihood of having COVID-19 cases is more related to ownership status, facility size and average occupancy rate, rather than quality indicators. Associations between infection prevention and control deficiencies, overall quality ratings, and presence of COVID-19 resident deaths varied across different phases of the pandemic (e.g., overall five-star rating was found related to the odds of having resident deaths after, but not during, the surging stage). Training, uptake, and adherence to infection control procedures are needed to better protect the vulnerable nursing home resident population.
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http://dx.doi.org/10.1080/01634372.2021.1950255DOI Listing
August 2021

Role of Nursing Home Quality on COVID-19 Cases and Deaths: Evidence from Florida Nursing Homes.

J Gerontol Soc Work 2021 Aug 26:1-17. Epub 2021 Aug 26.

Doctoral Program in Public Affairs, School of Public Administration, University of Central Florida, Orlando, Florida, USA.

The Coronavirus disease 2019 (COVID-19) disproportionately affects nursing home residents, resulting in an elevated risk for COVID-19 morbidity and mortality for this frail population. It is critical to understand whether nursing home quality is related to COVID-19 cases and deaths. Using publicly available data obtained from Centers for Medicare & Medicaid Services COVID-19 Nursing Home Dataset, Nursing Home Compare and Long-Term Care Focus, this study compares key nursing home characteristics, infection prevention and control deficiencies, and five-star ratings among Florida nursing homes with and without resident COVID-19 cases and deaths. The study further examines the association between facility and resident characteristics, quality indicators, and COVID-19 cases and deaths. Findings from our study indicate that through late October 2020, over 90% of Florida nursing homes have at least one resident case and 65% have at least one resident death. The likelihood of having COVID-19 cases is more related to ownership status, facility size and average occupancy rate, rather than quality indicators. Associations between infection prevention and control deficiencies, overall quality ratings, and presence of COVID-19 resident deaths varied across different phases of the pandemic (e.g., overall five-star rating was found related to the odds of having resident deaths after, but not during, the surging stage). Training, uptake, and adherence to infection control procedures are needed to better protect the vulnerable nursing home resident population.
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http://dx.doi.org/10.1080/01634372.2021.1950255DOI Listing
August 2021

The Implication of STEP in Synaptic Plasticity and Cognitive Impairments in Alzheimer's Disease and Other Neurological Disorders.

Front Cell Dev Biol 2021 14;9:680118. Epub 2021 Jun 14.

Cognitive Impairment Ward of Neurology Department, The Third Affiliated Hospital, Shenzhen University, Shenzhen, China.

STriatal-Enriched protein tyrosine Phosphatase (STEP) is a tyrosine phosphatase that has been implicated in Alzheimer's disease (AD), the most common form of dementia, and many other neurological diseases. The protein level and activity of STEP have been found to be elevated in most of these disorders, and specifically in AD as a result of dysregulation of different pathways including PP2B/DARPP32/PP1, PKA as well as impairments of both proteasomal and lysosomal systems. The upregulation in STEP leads to increased binding to, and dephosphorylation of, its substrates which are mainly found to be synaptic plasticity and thus learning and memory related proteins. These proteins include kinases like Fyn, Pyk2, ERK1/2 and both NMDA and AMPA receptor subunits GluN2B and GluA2. The dephosphorylation of these molecules results in inactivation of these kinases and internalization of NMDA and AMPA receptor complexes leading to synapse loss and cognitive impairments. In this study, we aim to review STEP regulation and its implications in AD as well as other neurological disorders and then summarize data on targeting STEP as therapeutic strategy in these diseases.
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http://dx.doi.org/10.3389/fcell.2021.680118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236946PMC
June 2021

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.

Genome Biol 2021 06 29;22(1):194. Epub 2021 Jun 29.

Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

Background: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.

Results: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.

Conclusion: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
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http://dx.doi.org/10.1186/s13059-021-02398-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243879PMC
June 2021

Prevalence of monogenic disease in paediatric patients with a predominant respiratory phenotype.

Arch Dis Child 2021 Jun 16. Epub 2021 Jun 16.

Division of Pulmonary Medicine, Children's Hospital of Fudan University, Shanghai, China

Objective: This study aimed to investigate the prevalence and clinical characteristics of monogenic disease in paediatric patients with a predominant respiratory phenotype.

Methods: Exome sequencing was performed in a cohort of 971 children with a predominant respiratory phenotype and suspected genetic aetiology. A total of 140 positive cases were divided into subgroups based on recruitment age and the primary biological system(s) involved.

Results: There were 140 (14.4%) patients with a positive molecular diagnosis, and their primary clinical manifestations were respiratory distress (12.9%, 18 of 140), respiratory failure (12.9%, 18 of 140) and recurrent/persistent lower respiratory infections (66.4%, 93 of 140). Primary immunodeficiency (49.3%), multisystem malformations/syndromes (17.9%), and genetic lung disease (16.4%) were the three most common genetic causes in the cohort, and they varied among the age subgroups. A total of 72 (51.4%) patients had changes in medical management strategies after genetic diagnosis, and the rate in those with genetic lung disease (82.6%, 19 of 23) was far higher than that in patients with genetic disease with lung involvement (45.3%, 53 of 117) (p=0.001).

Conclusion: Our findings demonstrate that exome sequencing is a valuable diagnostic tool for monogenic diseases in children with a predominant respiratory phenotype, and the genetic spectrum varies with age. Taken together, genetic diagnoses provide invaluable clinical and prognostic information that may also facilitate the development of precision medicine for paediatric patients.
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http://dx.doi.org/10.1136/archdischild-2021-322058DOI Listing
June 2021

Targeting the Transnitrosylation Cascade Provides a Novel Therapeutic Strategy for Alzheimer's Disease.

Neurosci Bull 2021 Sep 27;37(9):1373-1376. Epub 2021 May 27.

Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

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http://dx.doi.org/10.1007/s12264-021-00710-yDOI Listing
September 2021

Prospective Evaluation of the Addition of Polygenic Risk Scores to Breast Cancer Risk Models.

JNCI Cancer Spectr 2021 Jun 2;5(3):pkab021. Epub 2021 Mar 2.

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Background: The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm and the International Breast Cancer Intervention Study breast cancer risk models are used to provide advice on screening intervals and chemoprevention. We evaluated the performance of these models, which now incorporate polygenic risk scores (PRSs), using a prospective cohort study.

Methods: We used a case-cohort design, involving women in the Melbourne Collaborative Cohort Study aged 50-75 years when surveyed in 2003-2007, of whom 408 had a first primary breast cancer diagnosed within 10 years (cases), and 2783 were from the subcohort. Ten-year risks were calculated based on lifestyle factors, family history data, and a 313-variant PRS. Discrimination was assessed using a C-statistic compared with 0.50 and calibration using the ratio of expected to observed number of cases (E/O).

Results: When the PRS was added to models with lifestyle factors and family history, the C-statistic (95% confidence interval [CI]) increased from 0.57 (0.54 to 0.60) to 0.62 (0.60 to 0.65) using IBIS and from 0.56 (0.53 to 0.59) to 0.62 (0.59 to 0.64) using BOADICEA. IBIS underpredicted risk (E/O = 0.62, 95% CI = 0.48 to 0.80) for women in the lowest risk category (<1.7%) and overpredicted risk (E/O = 1.40, 95% CI = 1.18 to 1.67) in the highest risk category (≥5%), using the Hosmer-Lemeshow test for calibration in quantiles of risk and a 2-sided value less than.001. BOADICEA underpredicted risk (E/O = 0.82, 95% CI = 0.67 to 0.99) in the second highest risk category (3.4%-5%); the Hosmer-Lemeshow test and a 2-sided valuewas equal to .02.

Conclusions: Although the inclusion of a 313 genetic variant PRS doubles discriminatory accuracy (relative to reference 0.50), models with and without this PRS have relatively modest discrimination and might require recalibration before their clinical and wider use are promoted.
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http://dx.doi.org/10.1093/jncics/pkab021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099999PMC
June 2021

The blue light receptor CRY1 interacts with GID1 and DELLA proteins to repress GA signaling during photomorphogenesis in Arabidopsis.

Mol Plant 2021 Aug 7;14(8):1328-1342. Epub 2021 May 7.

College of Biology, Hunan Province Key Laboratory of Plant Functional Genomics and Developmental Regulation, Hunan Hybrid Rape Engineering and Technology Research Center, Hunan University, Changsha 410082, China; Shenzhen Institute, Hunan University, Shenzhen 518057, China. Electronic address:

Light is a critical environmental cue that regulates a variety of diverse plant developmental processes. Cryptochrome 1 (CRY1) is the major photoreceptor that mediates blue light-dependent photomorphogenic responses such as the inhibition of hypocotyl elongation. Gibberellin (GA) participates in the repression of photomorphogenesis and promotes hypocotyl elongation. However, the antagonistic interaction between blue light and GA is not well understood. Here, we report that blue light represses GA-induced degradation of the DELLA proteins (DELLAs), which are key negative regulators in the GA signaling pathway, via CRY1, thereby inhibiting the GA response during hypocotyl elongation. Both in vitro and in vivo biochemical analyses demonstrated that CRY1 physically interacts with GA receptors-GA-INSENSITIVE DWARF 1 proteins (GID1s)-and DELLAs in a blue light-dependent manner. Furthermore, we showed that CRY1 inhibits the association between GID1s and DELLAs. Genetically, CRY1 antagonizes the function of GID1s to repress the expression of cell elongation-related genes and thus hypocotyl elongation. Taken together, our findings demonstrate that CRY1 coordinates blue light and GA signaling for plant photomorphogenesis by stabilizing DELLAs through the binding and inactivation of GID1s, providing new insights into the mechanism by which blue light antagonizes the function of GA in photomorphogenesis.
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http://dx.doi.org/10.1016/j.molp.2021.05.011DOI Listing
August 2021

Time Distributions of Common Respiratory Pathogens Under the Spread of SARS-CoV-2 Among Children in Xiamen, China.

Front Pediatr 2021 12;9:584874. Epub 2021 Apr 12.

Xiamen Key Laboratory of Neonatal Diseases, Xiamen Children's Hospital (Children's Hospital of Fudan University Xiamen Branch), Xiamen, China.

The aim of this study was to observe the effect of COVID-19 prevention and control measures on the transmission of common respiratory viruses in a pediatric population. This was a retrospective observational study. The study population was selected from children with respiratory diseases who attended Xiamen Children's Hospital from January 1, 2018 to January 31, 2021. All children were screened for influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), adenovirus, and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The changes in respiratory virus detection rates before and after the SARS-CoV-2 intervention were analyzed using an interrupted time-series model. Polynomial curve fitting was also used to predict future short-term trends in respiratory virus detection. A total of 56,859 children were seen at Xiamen Children's Hospital from January 1, 2018 to Jan 31, 2021, of which 32,120 were tested for respiratory viruses via pharyngeal swabs. The overall positive detection rates of the four respiratory viral infections decreased significantly ( = 0.0017) after the implementation of the quarantine and school suspension measures in January 2020. Among them, the detection rate of RSV decreased most significantly ( = 0.008), and although there was no statistically significant difference in the detection rates of the influenza virus, parainfluenza virus, and adenovirus, a downward trend in the graph was observed. The positive detection rates of RSV in the 0-1-, 1-3-, and 3-7-year-old groups all decreased significantly ( = 0.035, 0.016, and 0.038, respectively). The change in the positive detection rate of RSV was relatively stable in the 7-18-year-old group. A total of 10,496 samples were tested for SARS-CoV-2, and no positive cases were reported. The combination of preventive and control measures for COVID-19 reduced the detection rate of four common respiratory viruses, with the greatest impact on RSV. If prevention and control measures continue to be maintained, the overall detection rate or absolute number of detections for the four respiratory viruses will remain low in the short term. However, this trend is likely to vary with the changes in measures.
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http://dx.doi.org/10.3389/fped.2021.584874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075055PMC
April 2021

Serious Mental Illness in Nursing Homes: Roles and Perceived Competence of Social Services Directors.

J Gerontol Soc Work 2021 Apr 14:1-19. Epub 2021 Apr 14.

School of Social Work, University of Iowa, Iowa City, Iowa, USA.

Providing nursing home psychosocial care to persons with serious mental illnesses (SMI) requires understanding of comorbidities and attention to resident rights, needs and preferences. This quantitative study reports how 924 social service directors (SSDs) taking part in the National Nursing Home Social Service Director survey identified their roles and competence, stratified by the percentage of residents with SMI. More than 70% of SSDs, across all categories of homes, reported the social services department was "always" involved in conducting depression screening, biopsychosocial assessments and PASRR planning. SSDs in homes with lower concentrations of residents with SMI reported less involvement in anxiety screening. Those employed in homes with higher concentrations of residents with SMI reported lower involvement conducting staff interventions for resident aggression or making referrals. More than one-fifth of SSDs lacked confidence in their ability to compare/contrast dementia, depression, and delirium or to develop care plans for residents with SMI. SSDs' perceived competence in developing care plans for residents with SMI was associated with education and involvement in care planning. About one-quarter of social services directors reported not being prepared to train a colleague on how to develop care plans for residents with SMI. Training in SMI could enhance psychosocial care.
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http://dx.doi.org/10.1080/01634372.2021.1912241DOI Listing
April 2021

Efficacy of tocilizumab therapy in a patient with severe pancytopenia associated with a STAT3 gain-of-function mutation.

BMC Immunol 2021 03 17;22(1):19. Epub 2021 Mar 17.

Department of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China.

Background: We aimed to report the clinical characteristics, immunological features, and treatment of one patient with a de novo STAT3 gain-of-function mutation identified by next generation sequencing. We investigated the efficacy of tocilizumab therapy in immune dysregulation diseases caused by STAT3 mutation.

Results: The patient was a 16-year-old girl. She presented with recurrent respiratory infections and chronic diarrhea after birth. She had life-threatening autoimmune pancytopenia at 14 years old. After receiving glucocorticoid therapy, she developed diabetes. However, her pancytopenia relapsed when the glucocorticoid was tapered. Next-generation sequencing showed a de novo heterozygous mutation in the STAT3 gene, c.1261G > A (p. G421R), which was previously described as a gain-of-function mutation. After tocilizumab therapy, her pancytopenia fully resolved, and insulin and glucocorticoid therapies were gradually discontinued within 12 months. She had lymphopenia and an inverted CD4/CD8 ratio before therapy. Lymphocyte subpopulation analysis indicated an expansion of effector memory CD4+, effector memory CD8+ and central memory CD4+ T cells. The proportions of memory B cells and naive CD4+ T cells were decreased, and the proportion of naïve B cells was increased. None of the abnormal lymphocytic changes improved significantly. STAT3 GOF mutations were identified by next gene sequencing in those with early-onset multi-organ autoimmunity. Including our patient, 13 patients with STAT3 GOF mutations received targeted treatment. Twelve of them were treated with tocilizumab alone or combination tocilizumab with JAK inhibitor, and ten patients improved.

Conclusions: Gene sequencing should be performed for patients with early-onset refractory or multiorgan immune dysregulation diseases. Targeted drugs can effectively improve the clinical problems associated with STAT3 gain-of-function mutations, while nontargeted immunosuppressive therapy is usually insufficient.
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http://dx.doi.org/10.1186/s12865-021-00411-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968248PMC
March 2021

Complete IFN-γR1 Deficiency in a Boy Due to UPD(6)mat with IFNGR1 Novel Splicing Variant.

J Clin Immunol 2021 05 27;41(4):834-836. Epub 2021 Jan 27.

Center for Molecular Medicine, Pediatrics Research Institute, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.

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http://dx.doi.org/10.1007/s10875-021-00970-3DOI Listing
May 2021

Old men with prostate cancer have higher risk of Gleason score upgrading and pathological upstaging after initial diagnosis: a systematic review and meta-analysis.

World J Surg Oncol 2021 Jan 20;19(1):18. Epub 2021 Jan 20.

Department of Urology, Capital Medical University affiliated Beijing Friendship Hospital, No. 95, Yongan Road, Xicheng District, 100050, Beijing, People's Republic of China.

Background: To evaluate the predictive performance of age for the risk of Gleason score change and pathologic upstaging.

Evidence Acquisition: Ovid MEDLINE, Ovid Embase, and the Cochrane Library were searched from inception until May 2020. Quality of included studies was appraised utilizing the Newcastle-Ottawa Quality Assessment Scale for case-control studies. The publication bias was evaluated by funnel plots and Egger's tests.

Evidence Synthesis: Our search yielded 27 studies with moderate-to-high quality including 84296 patients with mean age of 62.1 years. From biopsy to prostatectomy, upgrading and upstaging occurred in 32.3% and 9.8% of patients, respectively. Upgrading from diagnostic biopsy to confirmatory biopsy was found in 16.8%. Older age was associated with a significant increased risk of upgrading (OR 1.04, 95% CI 1.03-1.05), and similar direction of effect was found in studies focused on upgrading from diagnostic biopsy to confirmatory biopsy (OR 1.06, 95% CI 1.04-1.08). For pathologic upstaging within older men compared with younger, the pooled odds was 1.03 (95% CI 1.01-1.04).

Conclusion: Thorough consideration of age in the context of effect sizes for other factors not only prompts more accurate risk stratification but also helps providers to select optimal therapies for patients with prostate cancer.
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http://dx.doi.org/10.1186/s12957-021-02127-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818761PMC
January 2021

Predicting Gleason sum upgrading from biopsy to radical prostatectomy pathology: a new nomogram and its internal validation.

BMC Urol 2021 Jan 6;21(1). Epub 2021 Jan 6.

Department of Urology, Capital Medical University Affiliated Beijing Friendship Hospital, No. 95, Yongan Road, Xicheng District, Beijing, People's Republic of China.

Background: To explore the rate of Gleason sum upgrading (GSU) from biopsy to radical prostatectomy pathology and to develop a nomogram for predicting the probability of GSU in a Chinese cohort.

Methods: We retrospectively reviewed our prospectively maintained prostate cancer (PCa) database from October 2012 to April 2020. 198 patients who met the criteria were enrolled. Multivariable logistic regression analysis was performed to determine the predictors. Nomogram was constructed based on independent predictors. The receiver operating curve was undertaken to estimate the discrimination. Calibration curve was used to assess the concordance between predictive probabilities and true risks.

Results: The rate of GSU was 41.4%, whilst GS concordance rate was 44.4%. The independent predictors are prostate specific antigen (PSA), greatest percentage of cancer (GPC), clinical T-stage and Prostate Imaging Reporting and Data System (PI-RADS) score. Our model showed good discrimination (AUC of 0.735). Our model was validated internally with good calibration with bias-corrected C-index of 0.726.

Conclusions: Utilization of basic clinical variables (PSA and T-stage) combined with imaging variable (PI-RADS) and pathological variable (GPC) could improve performance in predicting actual probabilities of GSU in the 24-core biopsy scheme. Our nomogram could help to assess the true risk and make optimal treatment decisions for PCa patients.
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http://dx.doi.org/10.1186/s12894-020-00773-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789761PMC
January 2021

Corrigendum to: Civil Money Penalty Enforcement Actions for Quality Deficiencies in Nursing Homes.

Gerontologist 2021 Aug;61(6):998

School of Social Work, College of Health Professions and Sciences, University of Central Florida, Orlando.

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http://dx.doi.org/10.1093/geront/gnaa171DOI Listing
August 2021

Influence of Body Mass Index on the Surgical Outcomes of Flexible Ureteroscopy for Pediatric Upper Urinary Tract Aalculi-A Single Surgeon Experience.

Urology 2021 Jul 20;153:291-297. Epub 2020 Nov 20.

Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China. Electronic address:

Objective: To examine the association between body mass index (BMI) and surgical outcomes of flexible ureteroscopy (FURS) for pediatric upper urinary tract calculi and to estimate the influence of BMI percentile on the learning curve of pediatric FURS.

Materials And Methods: We reviewed our prospectively maintained database containing children who had kidney or ureteral stones from June 2014 to April 2019. We calculated BMI and plotted it on the Centers for Disease Control and Prevention growth chart for sex and age to estimate BMI percentile. Patient demographics, intraoperative data, stone characteristics, stone-free rate (SFR), and complication rate (CR) were analyzed. Learning curves stratified by BMI percentile groups were generated.

Results: The final analysis included 161 children, of whom 63 (39.1%) had upper body weight percentile (UBW), 64 (39.8%) had normal body weight percentile (NBW), and 34 (21.1%) had lower body weight percentile (LBW). The median stone burden of the 3 groups were 1.14 (IQR 0.50-3.41), 1.13 (IQR 0.70-3.14), and 0.95 (IQR 0.50-1.77), respectively (P = .17). The SFRs were 90.5% (57/63) in the UBW group, 81.2% (52/64) in the NBW group and 70.6% (24/34) in the LBW group (P = .04). The CRs were 15.9% (10/63), 21.9% (14/64), and 29.4% (10/34), respectively (P = .29). The learning curves showed that the SFR of FURS could be improved after about 100 cases. And decreasing BMI could steepen the learning curve of SFR.

Conclusions: BMI is associated with the SFR of FURS. LBW children had the lowest SFR compared to UBW and NBW children. Lower BMI percentile makes the success of FURS more challenging.
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http://dx.doi.org/10.1016/j.urology.2020.11.013DOI Listing
July 2021

Optical rotation and electromagnetically induced transparency in a chiral metamaterial with C symmetry.

Opt Express 2020 Sep;28(20):29496-29512

We design and fabricate a double-layered chiral metamaterial with 4-fold rotational symmetry, which simultaneously exhibits optical rotation and electromagnetically induced transparency (EIT) effects. Using analytical equivalent circuit model and Lorentz's coupled oscillator model, we interpret the physical mechanisms and derive material equations. Importantly, we find that magnetic dipole and electric quadrupole play important roles in optical rotation and keeping the symmetry of the material equations. Our work offers a better understanding of optical rotation in chiral metamaterials, and provides a new and simple approach to combine optical rotation and EIT effects into a single metamaterial.
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http://dx.doi.org/10.1364/OE.403421DOI Listing
September 2020

Men with High Prostate Specific Antigen Have Higher Risk of Gleason Upgrading after Prostatectomy: A Systematic Review and Meta-analysis.

Urol J 2020 Oct 21. Epub 2020 Oct 21.

Department of Urology, Capital Medical University affiliated Beijing Friendship Hospital, No. 95, Yongan Road, Xicheng District 100050, Beijing, People's Republic of China.

Purpose: To examine the correlation between prostate specific antigen (PSA) and the risk of Gleason sum upgrading (GSU) from biopsy Gleason sum (bGS) to prostatectomy Gleason sum (pGS).

Materials And Methods: Five electronic databases (Web of Science, Ovid Medline, Ovid Embase, SCOPUS and the Cochrane Library) were searched from inception until March 2020. Studies were included if they focused on the relationship between PSA and GSU analyzed in multivariable analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized. Quality of included studies was appraised utilizing the Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control studies. The publication bias was evaluated by funnel plot and Egger's test.

Results: Our search yielded 19 studies with high quality including 42193 patients. GSU was found in 28.2% of patients. Higher PSA level was associated with a significant increased risk of GSU (pooled OR = 1.14, 95% CI: 1.10-1.18; P < .05; I2 = 92%). For the definition of upgrading from bGS ≤ 6 to pGS ≥ 7, the odds of upgrading with higher PSA level as opposed to lower PSA level was 1.12 (95% CI: 1.11-1.14; P < .05; I2 = 13%), while the odds of upgrading with other definitions were 1.11 (95% CI: 1.05-1.18; P < .05; I2 = 89%).

Conclusion: Patients with high level of serum PSA are at high risk of undergoing pathologic upgrading at prostatectomy. Combined with other risk factors, PSA prompts risk reclassification and improve confidence of urologists in management decisions for optimal therapy. Nevertheless, further robust studies are necessitated to confirm these results.
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http://dx.doi.org/10.22037/uj.v16i7.6127DOI Listing
October 2020

Polyphyllin I attenuates cognitive impairments and reduces AD-like pathology through CIP2A-PP2A signaling pathway in 3XTg-AD mice.

FASEB J 2020 12 18;34(12):16414-16431. Epub 2020 Oct 18.

Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Polyphyllin I (PPI) is a natural phytochemical drug isolated from plants which can inhibit the proliferation of cancer cells. One of the PPI tumor-inhibitory effects is through downregulating the expression of Cancerous Inhibitor of PP2A (CIP2A), the latter, is found upregulated in Alzheimer's disease (AD) brains and participates in the development of AD. In this study, we explored the application of PPI in experimental AD treatment in CIP2A-overexpressed cells and 3XTg-AD mice. In CIP2A-overexpressed HEK293 cells or primary neurons, PPI effectively reduced CIP2A level, activated PP2A, and decreased the phosphorylation of tau/APP and the level of Aβ. Furthermore, synaptic protein levels were restored by PPI in primary neurons overexpressing CIP2A. Animal experiments in 3XTg-AD mice revealed that PPI treatment resulted in decreased CIP2A expression and PP2A re-activation. With the modification of CIP2A-PP2A signaling, the hyperphosphorylation of tau/APP and Aβ overproduction were prevented, and the cognitive impairments of 3XTg-AD mice were rescued. In summary, PPI ameliorated AD-like pathology and cognitive impairment through modulating CIP2A-PP2A signaling pathway. It may be a potential drug candidate for the treatment of AD.
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http://dx.doi.org/10.1096/fj.202001499RDOI Listing
December 2020

Hyperglycemia-reduced NAD biosynthesis impairs corneal epithelial wound healing in diabetic mice.

Metabolism 2021 01 11;114:154402. Epub 2020 Oct 11.

State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China. Electronic address:

Objective: Nicotinamide adenine dinucleotide (NAD) is an essential molecule participating in multiple physiological and pathophysiological processes. In diabetic cornea, the NAD-consuming enzyme SIRT1 was down-regulated and contributed to the delayed wound healing. However, the impact of hyperglycemia on corneal NAD biosynthesis remained elusive. This study was to investigate the relationship of NAD biosynthesis and the delayed corneal wound healing in diabetic mice.

Methods: Type 1 diabetes mellitus (DM) mice were induced by streptozotocin and corneal epithelial wound healing models were constructed by epithelial scraping. The NAD contents of corneal epithelium were measured using the NAD/NADH quantification kit. Expression of key enzymes involved in the NAD biosynthesis in type 1 DM mice and type 2 DM patients were analyzed. The nicotinamide phosphoribosyltransferase (NAMPT)-specific siRNA and the selective inhibitor FK866 were used to achieve the blockade of NAMPT, whereas exogenous NAD and its precursors were replenished to the corneal epithelial cells and DM mice.

Results: Hyperglycemia attenuated NAD content and NAMPT expression in the corneal epithelium of both type 1 DM mice and type 2 DM patients. Local knockdown of NAMPT by siRNA or FK866 consistently recapitulated the delayed corneal epithelial wound healing in normal mice. Moreover, NAD replenishment recovered the impaired proliferation and migration capacity by either FK866 or high glucose treatment in cultured corneal epithelial cells. Furthermore, in DM mice, NAD and its precursors nicotinamide mononucleotide and nicotinamide riboside also facilitated corneal epithelial and nerve regeneration, accompanied with the recovered expression of SIRT1 and phosphorylated EGFR, AKT, and ERK1/2 in epithelium and corneal sensitivity.

Conclusion: Hyperglycemia-reduced NAD biosynthesis and contributed to the impaired epithelial wound healing in DM mice. The replenishment of NAD and its precursors facilitated diabetic corneal wound healing and nerve regeneration, which may provide a novel therapeutic strategy for the treatment of diabetic corneal complications.
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http://dx.doi.org/10.1016/j.metabol.2020.154402DOI Listing
January 2021

Blockage of AEP attenuates TBI-induced tau hyperphosphorylation and cognitive impairments in rats.

Aging (Albany NY) 2020 Oct 20;12(19):19421-19439. Epub 2020 Oct 20.

Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Traumatic brain injury (TBI) is regarded as a high-risk factor for Alzheimer's disease (AD). Asparaginyl endopeptidase (AEP), a lysosomal cysteine protease involved in AD pathogenesis, is normally activated under acidic conditions and also in TBI. However, both the molecular mechanism underlying AEP activation-mediated TBI-related AD pathologies, and the role of AEP as an AD therapeutic target, still remain unclear. Here, we report that TBI induces hippocampus dependent cognitive deficit and synaptic dysfunction, accompanied with AEP activation, I (inhibitor 2 of PP2A, also called SET) mis-translocation from neuronal nucleus to cytoplasm, an obvious increase in AEP interaction with SET, and tau hyperphosphorylation in hippocampus of rats. Oxygen-glucose deprivation (OGD), mimicking an acidic condition, also leads to AEP activation, SET mis-translocation, PP2A inhibition, tau hyperphosphorylation, and a decrease in synaptic proteins, all of which are abrogated by AEP inhibitor AENK in primary neurons. Interestingly, AENK restores SET back to the nucleus, mitigates tau pathologies, rescuing TBI-induced cognitive deficit in rats. These findings highlight a novel etiopathogenic mechanism of TBI-related AD, which is initiated by AEP activation, accumulating SET in cytoplasm, and favoring tau pathology and cognitive impairments. Lowering AEP activity by AEP inhibitor would be beneficial to AD patients with TBI.
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http://dx.doi.org/10.18632/aging.103841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732271PMC
October 2020

The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations.

Allergy Asthma Clin Immunol 2020 22;16:65. Epub 2020 Jul 22.

Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102 China.

Background: Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases. We retrospectively analyzed the age, common clinical symptoms, immunologic and molecular manifestations in 11 patients with LOF STAT3 mutations and 1 patient with a GOF STAT3 mutation.

Methods: Twelve patients were enrolled in our study. Serum immunoglobulin measurements, lymphocyte subset detection and whole-exome sequencing were performed.

Results: The median age at diagnosis of STAT3-HIES patients was 4.74 years. Eczema, recurrent respiratory infections, fevers, abscesses and infections were the classic manifestations. Elevated serum IgE levels are not always observed in conjunction with high eosinophil counts. A moderate viral DNA load was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common mutation site, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients achieved notable improvement after receiving intravenous immunoglobulin.

Conclusion: We updated the current knowledge of this topic. We found an earlier median age at diagnosis, a higher survival rate, and a general lack of nonimmunological abnormalities; we also described the treatment details and novel mutations involve in STAT3-HIES and compared STAT3 LOF and GOF mutations.
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http://dx.doi.org/10.1186/s13223-020-00462-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491347PMC
July 2020

Insulin Promotes Corneal Nerve Repair and Wound Healing in Type 1 Diabetic Mice by Enhancing Wnt/β-Catenin Signaling.

Am J Pathol 2020 11 26;190(11):2237-2250. Epub 2020 Aug 26.

State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, China. Electronic address:

The insulin and Wnt signaling pathways are involved in cell proliferation, tissue homeostasis, and tumorigenesis. However, their interrelationship in the pathophysiological process of diabetic corneal injury remains unclear. In this study, the role of insulin in the diabetic cornea was investigated in vitro, using cultured TKE2 cells and trigeminal ganglion neurons, and in vivo, by assessing corneal wound-healing responses in diabetic mice. A selective Wnt antagonist (XAV-939) and activator (BML-284) were used to regulate the interactions between insulin and the Wnt pathway. The results demonstrated that insulin promoted corneal epithelial wound healing and sensation recovery, whereas the expression of molecules involved in the Wnt/β-catenin pathway was also up-regulated in the injured corneal epithelium. However, XAV-939 limited the insulin-induced epithelial and corneal nerve repair. By contrast, BML-284 treatment promoted the healing of the corneal epithelium and corneal nerve repair in diabetic mice. These results indicate that insulin, via Wnt signaling, contributes to diabetic corneal epithelial wound healing and nerve injury recovery and is, therefore, a potential protective factor for diabetic corneal epithelial wounds and nerve injury.
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http://dx.doi.org/10.1016/j.ajpath.2020.08.006DOI Listing
November 2020

Case Report: Clinical and Immunological Features of a Chinese Cohort With -Induced Rash and Mucositis.

Front Pediatr 2020 22;8:402. Epub 2020 Jul 22.

Department of Allergy and Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.

Dermatological disorders are the most common extrapulmonary complications of , of which Mycoplasma-induced rash and mucositis (MIRM) has recently been proposed to be a separate diagnostic entity. MIRM could easily be misdiagnosed as atypical Stevens-Johnson syndrome by clinicians due to the unawareness of this rare disease. We retrospectively reviewed the inpatient database from Jan. 2016 to Dec. 2019 of the Children's Hospital of Fudan University. In total, five patients (mean age 5.5 years, three male) matched the diagnostic criteria of MIRM. All patients had scattered lesions and more than two sites of mucosal involvement. The serum IgA level of three patients was higher than normal. Two patients had a significant decrease in peripheral blood CD3+ T and CD4+ T cells that improved with recovery. The percentage of TCRαβ+ CD4-CD8-T cells of Patient five was higher than normal. All patients received treatments with antibiotics and corticosteroids, 3 patients received intravenous immunoglobulin. Among five patients, three patients complained of dyspigmentation, and two patients had an uneventful recovery. MIRM is a separate entity with predominant mucosal involvement and excellent prognosis that more often affects younger patients. Excessive inflammatory reactions may lead to immune disorders, including lymphopenia and a redistribution of CD4+ T cells. We recommend that pneumonia accompanied by mucocutaneous eruptions, especially in young patients, should raise clinical suspicion of MIRM.
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http://dx.doi.org/10.3389/fped.2020.00402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387509PMC
July 2020

PTEN Inhibition Facilitates Diabetic Corneal Epithelial Regeneration by Reactivating Akt Signaling Pathway.

Transl Vis Sci Technol 2020 02 7;9(3). Epub 2020 Feb 7.

State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China.

Purpose: To investigate the contribution of phosphatase and tensin homologue (PTEN) on the delayed epithelial regeneration and impaired Akt activation in diabetic mice.

Methods: The expression of PTEN on cornea was compared between normal and diabetic mice. The corneal epithelial and nerve regeneration rate was evaluated in diabetic mice after the treatment with PTEN small interfering RNA (siRNA), PTEN inhibitors, or Akt inhibitor. The reactivation of epithelial regeneration-related signaling, including phosphorylated ()-Akt, -Stat3, Sirt1, and Parkin, were assessed with Western blot and immunofluorescence staining. The effects of PTEN inhibition on cellular proliferation and migration were further evaluated in cultured mouse corneal epithelial cells.

Results: PTEN messenger RNA and protein levels exhibited up-regulation in diabetic cornea. Upon central epithelial debridement, the epithelial regeneration rate was significantly promoted in diabetic mice with the treatment of PTEN inhibition than that of vehicle control ( < 0.05), which accompanied with the recovered levels of -Akt, -Stat3, Sirt1, and Parkin. However, the promotion of diabetic corneal epithelial regeneration rate and Akt reactivation was completed reversed by Akt inhibitor. In vitro, PTEN inhibition promoted their migration, but not the proliferation capacity. In addition, PTEN inhibitor treatment also improved the recovery of corneal nerve fiber density and sensitivity that was impaired in diabetic mice.

Conclusions: Elevated PTEN expression contributes to the impaired corneal epithelial regeneration and Akt activation in diabetic mice, which can be improved with PTEN inhibition.

Translational Relevance: Our study suggests that PTEN inhibition may serve as a new strategy for restoring the impaired corneal epithelial regeneration ability in patients with diabetes.
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http://dx.doi.org/10.1167/tvst.9.3.5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347282PMC
February 2020

Nedd4l downregulation of NRG1 in the mPFC induces depression-like behaviour in CSDS mice.

Transl Psychiatry 2020 07 23;10(1):249. Epub 2020 Jul 23.

Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

The occurrence of major depressive disorders has been closely related to the vulnerability of stress. The medial prefrontal cortex (mPFC) is involved in regulating pathological reactivity to stress, changes in affective behaviour and cognitive functions by distress. Increasing evidence indicates that neuregulin 1 (NRG1) plays an important role in psychiatric illnesses, including depression, schizophrenia and bipolar disorder. However, whether NRG1 in the mPFC is related to stress vulnerability remains unclear. We here assessed the regulation of NRG1 by the E3 ubiquitin ligase Nedd4l (neural precursor cell expressed developmentally downregulated 4-like) and investigated whether NRG1 changes in the mPFC might lead to vulnerability to depression-like behaviours. We've identified a deficiency of NRG1 in the mPFC as a key factor that contributes to the regulation of stress susceptibility in mice, as further suggested by the finding that overexpression of NRG1 attenuated depression-like behaviours in the animal model of chronic social defeat stress (CSDS). Interestingly, RNA sequencing in the mPFC brain region showed no differences in NRG1 mRNA levels between control animals and stress-susceptible (SS) or resilient mice (RES) following CSDS. However, mRNA and protein levels of Nedd4l were markedly increased in SS mice, but not in RES mice compared to controls. Furthermore, ubiquitination of NRG1 was increased in SS mice. Remarkably, overexpression of Nedd4l in mouse mPFC induced a decrease in NRG1 level and caused vulnerability to stress by subthreshold social defeat stress (SSDS), while downregulation of Nedd4l expression in the mPFC rescued the vulnerability to stress-induced social avoidance and anhedonia. Our data strongly indicate that the Nedd4l-mediated downregulation of NRG1 acts as a critical role in depression-like phenotypes of mice in CSDS.
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http://dx.doi.org/10.1038/s41398-020-00935-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378253PMC
July 2020

polysaccharide attenuates Aβ toxicity and cognitive defects in APP/PS1 mice.

Aging (Albany NY) 2020 07 11;12(13):13422-13436. Epub 2020 Jul 11.

Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Polysaccharides (CPPs), a traditional Chinese medicine used for thousands of years, is a potential neuroprotective polysaccharide via a relatively poorly understood mechanism. We previously reported that CPPs attenuated tau pathology in hTau transfected mice and therefore in the current work investigated the effect of CPPs on Aβ toxicity and cognitive defects in APP/PS1 mice model. It was found that one-month intragastric administration of CPPs significantly ameliorated cognitive defects in APP/PS1 mice. In addition, CPPs treatment mitigated the loss of the synaptic plasticity and increased the synaptic proteins including synaptotagmin and PSD95. The expression of Aβ42 and Aβ40 was remarkably decreased in the hippocampus of APP/PS1 mice after CPPs treatment. We also found that CPPs coincubation significantly reduced the amount of APPβ and Aβ42 expression in cells. Intriguingly, the activity of BACE1 was decreased following CPPs treatment in both the hippocampus of APP/PS1 mice and in vitro experiments. Collectively, these results indicated that CPPs attenuated Aβ pathology in APP/PS1 mice, and down-regulating BACE1 might be the underlaying mechanism which could be a therapeutic target for alleviating cognitive defects in AD pathology.
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http://dx.doi.org/10.18632/aging.103445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377903PMC
July 2020

LIG4 syndrome: clinical and molecular characterization in a Chinese cohort.

Orphanet J Rare Dis 2020 05 29;15(1):131. Epub 2020 May 29.

Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.

Background: DNA Ligase IV (LIG4) syndrome is a rare disease with few reports to date. Patients suffer from a broad spectrum of clinical features, including microcephaly, growth retardation, developmental delay, dysmorphic facial features, combined immunodeficiency, and malignancy predisposition. There may be a potential association between genotypes and phenotypes. We investigated the characteristics of LIG4 syndrome in a Chinese cohort.

Results: All seven patients had growth restriction. Most patients (6/7) had significant microcephaly (< - 3 SD). Recurrent bacterial infections of the lungs and intestines were the most common symptoms. One patient had myelodysplastic syndromes. One patient presented with an inflammatory bowel disease (IBD)-like phenotype. Patients presented with combined immunodeficiency. The proportions of naïve CD4+ and naïve CD8+ T cells decreased notably in five patients. All patients harbored compound heterozygous mutations in the LIG4 gene, which consisted of a missense mutation (c.833G > T, p.R278L) and a deletion shift mutation, primarily c.1271_1275delAAAGA (p.K424Rfs*20). Two other deletion mutations, c.1144_1145delCT and c.1277_1278delAA, were novel. Patients with p.K424Rfs*20/p.R278 may have milder dysmorphism but more significant IgA/IgM deficiency compared to the frequently reported genotype p.R814X/p.K424Rfs*20. One patient underwent umbilical cord blood stem cell transplantation (UCBSCT) but died.

Conclusions: The present study reported the clinical and molecular characteristics of a Chinese cohort with LIG4 syndrome, and the results further expand the phenotypic and genotypic spectrum and our understanding of genotype-to-phenotype correlations in LIG4 syndrome.
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http://dx.doi.org/10.1186/s13023-020-01411-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257218PMC
May 2020

Screening for primary immunodeficiency diseases by next-generation sequencing in early life.

Clin Transl Immunology 2020 May 17;9(5):e1138. Epub 2020 May 17.

Department of Neonatology Children's Hospital of Fudan University Shanghai China.

Objective: We aimed to use next-generation sequencing (NGS) for the early diagnosis of primary immunodeficiency diseases (PIDs) and define its effects on medical management for an infant cohort in early life.

Methods: A single-centre study was conducted from November 2015 to April 2018. Infants less than 3 months old with infections or abnormal white blood cell counts were enrolled in the study. Gene variants were analysed by NGS, and once a mutation was found in a PID-associated gene, the immune functions associated with this mutation were detected. The diagnosis rate of PIDs in the cohort was the main outcome. The patients received corresponding management and follow-up treatments.

Results: Among 2392 patients who were genetically tested with NGS, 51 infants were diagnosed with PIDs. Seven types of PIDs were detected, and the most common (25/51, 49%) were combined immunodeficiencies with associated or syndromic features. Thirty-five patients (68.6%) were cured or had improved outcomes after being diagnosed with PID. The NGS cost was US$280 per case.

Conclusions: This study not only highlighted the potential of NGS to rapidly deliver molecular diagnoses of PIDs but also indicated that the prevalence of PIDs is underestimated. With broader use, this approach has the potential to alter clinical strategies.
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http://dx.doi.org/10.1002/cti2.1138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231820PMC
May 2020
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