Publications by authors named "Xia Shen"

166 Publications

A Chinese host genetic study discovered IFNs and causality of laboratory traits on COVID-19 severity.

iScience 2021 Oct 30;24(10):103186. Epub 2021 Sep 30.

Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

The COVID-19 pandemic has caused over 220 million infections and 4.5 million deaths worldwide. Current risk factor cannot fully explain the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients' laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory traits and used Mendelian randomization (MR) analysis to further investigate the causality of traits on disease severity. Two causal traits, WBC counts and cholesterol levels, were identified based on MR study, and their functional genes are located at genes complex and , respectively. Our gene-based analysis and GSEA revealed four interferon pathways, including and . We hope that our work will contribute to studying the genetic mechanisms of disease and serve as a useful reference for COVID-19 diagnosis and treatment.
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http://dx.doi.org/10.1016/j.isci.2021.103186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481128PMC
October 2021

Development of a CAUTI risk factor evaluation index system for postoperative patients with gynecological malignant tumors.

J BUON 2021 Jul-Aug;26(4):1292-1297

The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.

Purpose: In this study, we developed a CAUTI risk factor evaluation index system for postoperative patients with gynecologic malignant tumors and provided scientific evidence for the prevention of catheter-related urinary tract infection (CAUTI).

Methods: A comprehensive method, including literature review, group discussion and Delphi method, was adopted to establish a CAUTI risk factor evaluation index system for postoperative patients with gynecologic malignant tumors.

Results: Two rounds of expert consultations resulted in effective response rates of 100%, with authority coefficients of 0.94, and coordination coefficients of 0.473 and 0.388 respectively (p<0.01). The risk factor indicator system consisted of 4 first-level indicators, 13 second-level indicators, and 56 third-level indicators.

Conclusion: The experts showed high enthusiasm, good authority, and coordination. The CAUTI risk factor evaluation index system for postoperative patients with gynecologic malignant tumors is comprehensive and scientific, and could serve as an important guide for assessment and prevention of CAUTI in patients with gynecologic malignant tumor postoperatively.
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September 2021

Improved Estimation of Phenotypic Correlations Using Summary Association Statistics.

Front Genet 2021 24;12:665252. Epub 2021 Aug 24.

Biostatistics Group, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Estimating the phenotypic correlations between complex traits and diseases based on their genome-wide association summary statistics has been a useful technique in genetic epidemiology and statistical genetics inference. Two state-of-the-art strategies, Z-score correlation across null-effect single nucleotide polymorphisms (SNPs) and LD score regression intercept, were widely applied to estimate phenotypic correlations. Here, we propose an improved Z-score correlation strategy based on SNPs with low minor allele frequencies (MAFs), and show how this simple strategy can correct the bias generated by the current methods. The low MAF estimator improves phenotypic correlation estimation, thus it is beneficial for methods and applications using phenotypic correlations inferred from summary association statistics.
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http://dx.doi.org/10.3389/fgene.2021.665252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421683PMC
August 2021

Targeted genetic screening in bacteria with a Cas12k-guided transposase.

Cell Rep 2021 Aug;36(9):109635

School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China; Guangzhou Laboratory, Guangzhou 510120, China. Electronic address:

Microbes employ sophisticated cellular networks encoded by complex genomes to rapidly adapt to changing environments. High-throughput genome engineering methods are valuable tools for functionally profiling genotype-phenotype relationships and understanding the complexity of cellular networks. However, current methods either rely on special homologous recombination systems and are thus applicable in only limited bacterial species or can generate only nonspecific mutations and thus require extensive subsequent screening. Here, we report a site-specific transposon-assisted genome engineering (STAGE) method that allows high-throughput Cas12k-guided mutagenesis in various microorganisms, such as Pseudomonas aeruginosa and Klebsiella pneumoniae. Exploiting the powerful STAGE technique, we construct a site-specific transposon mutant library that focuses on all possible transcription factors (TFs) in P. aeruginosa, enabling the comprehensive identification of essential genes and antibiotic-resistance-related factors. Given its broad host range activity and easy programmability, this method can be widely adapted to diverse microbial species for rapid genome engineering and strain evolution.
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http://dx.doi.org/10.1016/j.celrep.2021.109635DOI Listing
August 2021

Non-inferiority in cancer clinical trials was associated with more lenient margins and higher hypothesized outcome event rates.

J Clin Epidemiol 2021 Aug 23;139:214-221. Epub 2021 Aug 23.

Biostatistics Group, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China; Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Nansha District, Guangzhou, PR China. Electronic address:

Objective: To identify potential bias in non-inferiority design of published cancer trials, and to provide suggestions for future practice.

Study Design And Setting: We systematically searched MEDLINE, Embase and CENTRAL databases (until April 17, 2020) to obtain non-inferiority phase III cancer trials and protocols. Distribution of essential characteristics and study design parameters was compared between trials with and without concluding non-inferiority using multivariable logistic regression.

Results: A total of 291 eligible trials were included. We observed that increased odds of concluding non-inferiority was significantly associated with more lenient non-inferiority margins (OR = 1•94, 95% CI 1•02-3•69) and higher hypothesized event rate (OR = 1•24, 95% CI 1•06-1•47). Trials that established non-inferiority adopted margins that were more dispersedly distributed (dispersion OR = 2•90, 95% CI 1•88-4.48).

Conclusion: Although limited by the exploratory nature, our study demonstrated existence of possible distorted non-inferiority design which could incur excess non-inferiority in cancer clinical trials. Pre-registration and transparent reporting of detailed non-inferiority design is imperative for future research.
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http://dx.doi.org/10.1016/j.jclinepi.2021.08.020DOI Listing
August 2021

Esketamine may be an ideal substitute for ketamine during cochlear function measurement.

Braz J Med Biol Res 2021 20;54(11):e11503. Epub 2021 Aug 20.

Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, China.

The mixture of ketamine and xylazine is widely used for the auditory brainstem response (ABR) measurement. Esketamine is twice as potent as ketamine. Our objective was to assess the influence of esketamine in mice undergoing cochlear function measurement including ABR and distortion product otoacoustic emission (DPOAE) measurement. C57Bl/6J mice were treated with an equivalent dose of analgesia and received either a single intraperitoneal (ip) injection of 100 mg/kg ketamine and 25 mg/kg xylazine or 50 mg/kg esketamine and 25 mg/kg xylazine. Hearing thresholds, peak latencies of waves I and V, and DPOAE thresholds were recorded. Time to loss of righting and time to regain righting were also assessed. We found that hearing thresholds, the peak latencies of waves I and V, and DPOAE thresholds were similar between the two groups (all P>0.05). Time to regain righting was significantly shorter in the esketamine group (P<0.001) than in the ketamine group. We concluded that when using equivalent doses of analgesia, esketamine may be an ideal substitute for ketamine during cochlear function test.
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http://dx.doi.org/10.1590/1414-431X2021e11503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389612PMC
August 2021

Fructose-1,6-Bisphosphate Aldolase B Depletion Promotes Hepatocellular Carcinogenesis Through Activating Insulin Receptor Signaling and Lipogenesis.

Hepatology 2021 Jul 22. Epub 2021 Jul 22.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), University of the Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Shanghai, China.

Background And Aims: Insulin receptor (IR) transduces cell surface signal through phosphoinositide 3-kinase (PI3K)-AKT pathways or translocates to the nucleus and binds to the promoters to regulate genes associated with insulin actions, including de novo lipogenesis (DNL). Chronic activation of IR signaling drives malignant transformation, but the underlying mechanisms remain poorly defined. Down-regulation of fructose-1,6-bisphosphate aldolase (ALDO) B in hepatocellular carcinoma (HCC) is correlated with poor prognosis. We aim to study whether and how ALDOB is involved in IR signaling in HCC.

Approach And Results: Global or liver-specific ALDOB knockout (L-ALDOB ) mice were used in N-diethylnitrosamine (DEN)-induced HCC models, whereas restoration of ALDOB expression was achieved in L-ALDOB mice by adeno-associated virus (AAV). C -glucose was employed in metabolic flux analysis to track the de novo fatty acid synthesis from glucose, and nontargeted lipidomics and targeted fatty acid analysis using mass spectrometry were performed. We found that ALDOB physically interacts with IR and attenuates IR signaling through down-regulating PI3K-AKT pathways and suppressing IR nuclear translocation. ALDOB depletion or disruption of IR/ALDOB interaction in ALDOB mutants promotes DNL and tumorigenesis, which is significantly attenuated with ALDOB restoration in L-ALDOB mice. Notably, attenuated IR/ALDOB interaction in ALDOB-R46A mutant exhibits more significant tumorigenesis than releasing ALDOB/AKT interaction in ALDOB-R43A, whereas knockdown IR sufficiently diminishes tumor-promoting effects in both mutants. Furthermore, inhibiting phosphorylated AKT or fatty acid synthase significantly attenuates HCC in L-ALDOB mice. Consistently, ALDOB down-regulation is correlated with up-regulation of IR signaling and DNL in human HCC tumor tissues.

Conclusions: Our study reports a mechanism by which loss of ALDOB activates IR signaling primarily through releasing IR/ALDOB interaction to promote DNL and HCC, highlighting a potential therapeutic strategy in HCC.
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http://dx.doi.org/10.1002/hep.32064DOI Listing
July 2021

BoDV-1 infection induces neuroinflammation by activating the TLR4/MyD88/IRF5 signaling pathway, leading to learning and memory impairment in rats.

J Med Virol 2021 Nov 22;93(11):6163-6171. Epub 2021 Jul 22.

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Borna disease virus (BoDV-1) can infect the hippocampus and limbic lobes of newborn rodents, causing cognitive deficits and abnormal behavior. Studies have found that neuroinflammation caused by viral infection in early life can affect brain development and impair learning and memory function, revealing the important role of neuroinflammation in cognitive impairment caused by viral infection. However, there is no research to explore the pathogenic mechanism of BoDV-1 in cognition from the direction of neuroinflammation. We established a BoDV-1 infection model in rats, and tested the learning and memory impairment by Morris water maze (MWM) experiment. RNAseq was introduced to detect changes in the gene expression profile of BoDV-1 infection, focusing on inflammation factors and related signaling pathways. BoDV-1 infection impairs the learning and memory of Sprague-Dawley rats in the MWM test and increases the expression of inflammatory cytokines in the hippocampus. RNAseq analysis found 986 differentially expressed genes (DEGs), of which 845 genes were upregulated and 141 genes were downregulated, and 28 genes were found to be enriched in the toll-like receptor (TLR) pathway. The expression of TLR4, MyD88, and IRF5 in the hippocampus was significantly changed in the BoDV-1 group. Our results indicate that BoDV-1 infection stimulates TLR4/MyD88/IRF5 pathway activation, causing the release of downstream inflammatory factors, which leads to neuroinflammation in rats. Neuroinflammation may play a significant role in learning and memory impairment caused by BoDV-1 infection.
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http://dx.doi.org/10.1002/jmv.27212DOI Listing
November 2021

Cerebral Hemodynamic Responses to the Difficulty Level of Ambulatory Tasks in Patients With Parkinson's Disease: A Systematic Review and Meta-Analysis.

Neurorehabil Neural Repair 2021 Sep 25;35(9):755-768. Epub 2021 Jun 25.

12476Tongji University School of Medicine, Shanghai, China.

. Ambulatory tasks are the important components of balance training which effectively improve postural stability and functional activities in persons with Parkinson's disease (PD). The difficulty level of an ambulatory task is usually set in the form of attention, direction, speed, or amplitude requirement. . This study aimed to explore the neural mechanisms of cerebral hemodynamic responses to the difficulty level of ambulatory tasks in persons with PD. . We included ten studies that examined cerebral hemodynamic responses during ambulatory tasks at different difficulty levels in persons with PD. The change in hemodynamic responses was synthesized and meta-analyzed. . Patients during "ON" medication had higher relative change in oxygenated hemoglobin (ΔHBO) in the prefrontal cortex in response to difficulty levels of ambulatory tasks, which is comparable to that in healthy elderly individuals. However, patients during "OFF" medication did not show cortical activation in response to difficulty levels. During the lower-difficulty tasks, patients during "ON" medication demonstrated higher ΔHBO than healthy elderly participants and patients during "OFF" medication. Factors found to significantly contribute to the heterogeneity across studies included subjects' type and cognitive status, task duration, setting, and filter used for functional near-infrared spectroscopy (fNIRS) data pre-processing. . The findings suggest that ambulatory task at a higher difficulty level could be necessary to train the cortical capacity of PD persons, which should be conducted during "ON" medication; meanwhile, the contributing factors to the heterogeneity of studies would be useful as a reference when designing comparable fNIRS studies.
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http://dx.doi.org/10.1177/15459683211028548DOI Listing
September 2021

Postoperative Delirium is Not Associated with Long-Term Decline in Activities of Daily Living or Mortality After Laryngectomy.

Clin Interv Aging 2021 17;16:823-831. Epub 2021 May 17.

Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People's Republic of China.

Purpose: To determine the relationships between postoperative delirium (POD) and postoperative activities of daily living (ADL) and mortality in patients undergoing laryngectomy. We hypothesized that POD would reduce postoperative ADL and increase postoperative mortality.

Patients And Methods: The prospective study included older participants (age ≥65 y) undergoing total laryngectomy, partial laryngectomy, total laryngectomy plus neck dissection, or partial laryngectomy plus neck dissection under general anesthesia. The diagnosis of delirium was based on the Confusion Assessment Method algorithm, which was administered on postoperative days 1 through 6. ADL were evaluated using the Chinese version of the Index of ADL scale. Follow-up assessments of ADL and mortality were conducted 24 months after surgery.

Results: Of 127 participants (aged 70.3 ± 4.1 y), 19 (15.0%) developed POD. POD was not associated with a decrease in ADL after laryngectomy (p=0.599) nor with an increase in postoperative mortality [3/19 (15.8%) vs 12/108 (11.1%), p=0.560, Log rank test]. However, longer surgery duration was significantly associated with worse overall survival (OR, 3.262; 95% CI, 1.261-9.169, p=0.025).

Conclusion: POD was not associated with long-term ADL or mortality after laryngectomy. Prolonged surgery was the only factor associated with a higher postoperative mortality rate.
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http://dx.doi.org/10.2147/CIA.S303800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139736PMC
June 2021

Preoperative Psychological Burdens in Patients with Vestibular Schwannoma.

Ann Otol Rhinol Laryngol 2021 May 25:34894211018915. Epub 2021 May 25.

Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Objective: To assess preoperative psychological burden in patients with vestibular schwannoma (VS).

Methods: A total of 100 patients undergoing VS resection between September 2019 and June 2020 completed preoperative psychological screening. The Hospital Anxiety and Depression Scale (HADS) was applied the day before surgery, and a score >14 was considered clinically important. Univariate and multivariate logistic regression analyzes were used to identify risk factors associated with increased preoperative psychological stress.

Results: Of the 100 patients who underwent VS resection, 44% were male, with a mean age of 45.9 years. Twenty-two (22%) had HADS scores >14. For the univariate analysis, risk factors associated with elevated psychological burden included time since diagnosis, number of symptoms, headache, vertigo, and nausea and/or vomiting. In the regression analysis, the number of symptoms and greater time from diagnosis to treatment correlated with higher preoperative psychological stress.

Conclusion: Nearly 1 in 4 patients with VS experienced clinically significant emotional burden preoperatively. Number of symptoms and greater time from diagnosis to treatment contributed to this psychological burden.
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http://dx.doi.org/10.1177/00034894211018915DOI Listing
May 2021

Total genetic contribution assessment across the human genome.

Nat Commun 2021 05 14;12(1):2845. Epub 2021 May 14.

Biostatistics Group, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Quantifying the overall magnitude of every single locus' genetic effect on the widely measured human phenome is of great challenge. We introduce a unified modelling technique that can consistently provide a total genetic contribution assessment (TGCA) of a gene or genetic variant without thresholding genetic association signals. Genome-wide TGCA in five UK Biobank phenotype domains highlights loci such as the HLA locus for medical conditions, the bone mineral density locus WNT16 for physical measures, and the skin tanning locus MC1R and smoking behaviour locus CHRNA3 for lifestyle. Tissue-specificity investigation reveals several tissues associated with total genetic contributions, including the brain tissues for mental health. Such associations are driven by tissue-specific gene expressions, which share genetic basis with the total genetic contributions. TGCA can provide a genome-wide atlas for the overall genetic contributions in each particular domain of human complex traits.
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http://dx.doi.org/10.1038/s41467-021-23124-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121943PMC
May 2021

Changes in Plasma Metabolome Profiles Following Oral Glucose Challenge among Adult Chinese.

Nutrients 2021 Apr 27;13(5). Epub 2021 Apr 27.

Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Little is known about changes in plasma metabolome profiles during the oral glucose tolerance test (OGTT) in Chinese. We aimed to characterize plasma metabolomic profiles at 0 and 2 h of OGTT and their changes in individuals of different glycemic statuses. A total of 544 metabolites were detected at 0 and 2 h of OGTT by a nontarget strategy in subjects with normal glucose ( = 234), prediabetes ( = 281), and newly diagnosed type 2 diabetes (T2D) ( = 66). Regression model, mixed model, and partial least squares discrimination analysis were applied. Compared with subjects of normal glucose, T2D cases had significantly higher levels of glycerone at 0 h and 22 metabolites at 2 h of OGTT (false discovery rate (FDR) < 0.05, variable importance in projection (VIP) > 1). Seven of the twenty-two metabolites were also significantly higher in T2D than in prediabetes subjects at 2 h of OGTT (FDR < 0.05, VIP > 1). Two hours after glucose challenge, concentrations of 35 metabolites (normal: 18; prediabetes: 23; T2D: 13) significantly increased (FDR < 0.05, VIP > 1, fold change (FC) > 1.2), whereas those of 45 metabolites (normal: 36; prediabetes: 29; T2D: 18) significantly decreased (FDR < 0.05, VIP > 1, FC < 0.8). Distinct responses between cases and noncases were detected in metabolites including 4-imidazolone-5-acetate and 4-methylene-L-glutamine. More varieties of distinct metabolites across glycemic statuses were observed at 2 h of OGTT compared with fasting state. Whether the different patterns and responsiveness of certain metabolites in T2D reflect a poor resilience of specific metabolic pathways in regaining glucose homeostasis merits further study.
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http://dx.doi.org/10.3390/nu13051474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146292PMC
April 2021

Establishing content validity for a composite activities-specific risk of falls scale:linkage between fear of falling and physical activity.

BMC Geriatr 2021 04 26;21(1):275. Epub 2021 Apr 26.

Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai, 201619, China.

Background: Fear of falling (FoF) and physical activity (PA) are important psychological and behavioral factors associated with falls. No instrument quantifies the link between these two factors to evaluate the risk of falls. We aimed to design a scale linking FoF with PA (Composite Activities-specific Risk of Falls Scale, CARFS) for people with various disability levels.

Methods: First, we designed a questionnaire comprising 40 balance-related activities from the International Classification of Functioning, Disability, and Health (ICF) for a pilot survey. Second, participants were interviewed about their activities-specific FoF degree and PA frequency. The participants comprised 30 community-dwelling older adults, hospitalized patients with strokes, and those with spinal cord injuries, each with different disability levels. Third, the content validity of the items was evaluated twice by 12 experienced rehabilitation professionals: one based on experience and the other on the survey responses. Items with a higher than moderate relevance in both evaluations were included in the CARFS. The panel of professionals discussed and voted on the contribution of FoF and PA on the CARF score. Finally, the scale sensitivity in distinguishing disability levels was analyzed to evaluate the population suitability to the CARFS.

Results: The CARFS included 14 activities. A five-point Likert scale was used to quantify degree of FoF (A) and frequency of PA (B). The CARF score (C), which was determined using the eq. C = A+(4-B) + A × B/2, reflected sensitivity to disability levels in most items.

Conclusions: The CARFS has strong content validity for measuring risk of falls in relation to the FoF and PA of people with various disability levels. It has a potential to provide a guide for designing individualized exercise- and behavior-focused fall prevention programs and enable the precise trtrun 0acking of program effectiveness as a multidimensional outcome measure.
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http://dx.doi.org/10.1186/s12877-021-02211-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077745PMC
April 2021

Serum Metabolomics Identifies Dysregulated Pathways and Potential Metabolic Biomarkers for Hyperuricemia and Gout.

Arthritis Rheumatol 2021 09 6;73(9):1738-1748. Epub 2021 Aug 6.

ShanghaiTech University, Chinese Academy of Sciences Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China, and University of Chinese Academy of Sciences, Beijing, China.

Objective: To systematically profile metabolic alterations and dysregulated metabolic pathways in hyperuricemia and gout, and to identify potential metabolite biomarkers to discriminate gout from asymptomatic hyperuricemia.

Methods: Serum samples from 330 participants, including 109 with gout, 102 with asymptomatic hyperuricemia, and 119 normouricemic controls, were analyzed by high-resolution mass spectrometry-based metabolomics. Multivariate principal components analysis and orthogonal partial least squares discriminant analysis were performed to explore differential metabolites and pathways. A multivariate methods with Unbiased Variable selection in R (MUVR) algorithm was performed to identify potential biomarkers and build multivariate diagnostic models using 3 machine learning algorithms: random forest, support vector machine, and logistic regression.

Results: Univariate analysis demonstrated that there was a greater difference between the metabolic profiles of patients with gout and normouricemic controls than between the metabolic profiles of individuals with hyperuricemia and normouricemic controls, while gout and hyperuricemia showed clear metabolomic differences. Pathway enrichment analysis found diverse significantly dysregulated pathways in individuals with hyperuricemia and patients with gout compared to normouricemic controls, among which arginine metabolism appeared to play a critical role. The multivariate diagnostic model using MUVR found 13 metabolites as potential biomarkers to differentiate hyperuricemia and gout from normouricemia. Two-thirds of the samples were randomly selected as a training set, and the remainder were used as a validation set. Receiver operating characteristic analysis of 7 metabolites yielded an area under the curve of 0.83-0.87 in the training set and 0.78-0.84 in the validation set for distinguishing gout from asymptomatic hyperuricemia by 3 machine learning algorithms.

Conclusion: Gout and hyperuricemia have distinct serum metabolomic signatures. This diagnostic model has the potential to improve current gout care through early detection or prediction of progression to gout from hyperuricemia.
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http://dx.doi.org/10.1002/art.41733DOI Listing
September 2021

[Clinical application of nose ring drain technique combined with Ilizarov circular external fixation for Gustilo ⅢA Pilon fractures].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Feb;35(2):195-199

Department of Orthopaedics, the 920th Hospital of Joint Logistics Support Force, Kunming Yunnan, 650032, P.R.China.

Objective: To investigate the effectiveness of the nose ring drain (NRD) technique combined with Ilizarov circular external fixation in treatment of Gustilo ⅢA Pilon fracture.

Methods: Between March 2017 and December 2019, 17 patients with Gustilo ⅢA Pilon fractures were admitted and treated with NRD technique combined with Ilizarov circular external fixation. Among them, there were 11 males and 6 females; the age ranged from 24 to 63 years, with an average of 38.2 years. There were 3 cases of traffic accident injury, 13 cases of falling injury, and 1 case of penetrating injury. There were 13 cases of emergency admittance and 4 cases of wound infection after surgical treatment. Furthermore, there were 2 cases of fibula fractures and 3 cases of lateral malleolus fractures.

Results: All patients were followed up 8-12 months, with an average of 9.9 months. All wounds healed by first intention, and 4 patients with preoperative infection had no recurrence during the follow-up. The external fixator was removed after fracture healing in 17 patients at 3-7 months after operation (mean, 4.5 months). At last follow-up, the pain score of the ankle joint Kofoe score was 40-50, with an average of 44; the functional score was 17-27, with an average of 25; the mobility score was 8-18, with an average of 14; and the effectiveness was rated as excellent in 8 cases, good in 7 cases, and poor in 1 case.

Conclusion: For Gustilo ⅢA Pilon fractures, the NRD technique combined with Ilizarov circular external fixation has advantages of good fracture fixation and drainage effects, which greatly reduces the complications of traditional treatment options and the number of operations.
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http://dx.doi.org/10.7507/1002-1892.202009101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171683PMC
February 2021

Nontrivial Replication of Loci Detected by Multi-Trait Methods.

Front Genet 2021 3;12:627989. Epub 2021 Feb 3.

Biostatistics Group, School of Life Sciences and School of Ecology, Sun Yat-sen University, Guangzhou, China.

The ever-growing genome-wide association studies (GWAS) have revealed widespread pleiotropy. To exploit this, various methods that jointly consider associations of a genetic variant with multiple traits have been developed. Most efforts have been made concerning improving GWAS discovery power. However, how to replicate these discovered pleiotropic loci has yet to be discussed thoroughly. Unlike a single-trait scenario, multi-trait replication is not trivial considering the underlying genotype-multi-phenotype map of the associations. Here, we evaluate four methods for replicating multi-trait associations, corresponding to four levels of replication strength. Weak replication cannot justify pleiotropic genetic effects, whereas strong replication using our developed correlation methods can inform consistent pleiotropic genetic effects across the discovery and replication samples. We provide a protocol for replicating multi-trait genetic associations in practice. The described methods are implemented in the free and open-source R package MultiABEL.
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http://dx.doi.org/10.3389/fgene.2021.627989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886991PMC
February 2021

B cell lymphoma with IRF4 rearrangement: A clinicopathological study of 13 cases.

Pathol Int 2021 Mar 27;71(3):183-190. Epub 2021 Jan 27.

Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Interferon regulatory factor 4 (IRF4) rearrangement is commonly detected in patients with a range of lymphoproliferative malignancies, including myelomas, large B cell lymphomas and low-grade B cell neoplasms. However, IRF4 rearrangement is generally a relatively rare finding in these latter two cancer types. In the present article, we describe and summarize the clinicopathological and genetic features of 13 cases of B cell lymphoma with IRF4 rearrangement, including 12 cases of large B cell lymphoma and one case of low-grade lymphoma exhibiting such rearrangement. These cases were detected in six females and seven males between 14 and 71 years of age. From a morphological perspective, large B cell lymphoma tumors included in this analysis exhibited large neoplastic cells in diffuse or follicular patterns, while the case of low-grade lymphoma mainly composed of small lymphocytes. All analyzed cases exhibited a split in the IRF4 gene consistent with IRF4 translocation. Three of six analyzed large B cell lymphoma cases harbored IGLL5 mutations. Mutations in SAMHD1 were detected in the low-grade lymphoma with IRF4 rearrangement case. In summary, our results offer further insight into the morphological and molecular heterogeneity of cases of B cell lymphoma exhibiting IRF4 rearrangements.
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http://dx.doi.org/10.1111/pin.13067DOI Listing
March 2021

Muscovy duck reovirus promotes virus replication by inhibiting autophagy-lysosomal degradation pathway.

Vet Microbiol 2021 Feb 8;253:108945. Epub 2020 Dec 8.

College of Animal Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, People's Republic of China; Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health (Fujian Agricultural and Forestry University), Fuzhou, 350002, People's Republic of China. Electronic address:

Autophagy plays a momentous role in cellular responses against pathogens. However, the influence of the autophagy machinery on Muscovy duck reovirus (MDRV) infection is not yet confirmed. In this study, it was shown that MDRV infection significantly increased the number of autophagy-like vesicles in DF-1 cells under electron microscope and the LC3-I/LC3-II conversion, which was considered important indicators of autophagy. It was worth noting that the level of autophagy was positively correlated with MDRV replication. Further test results showed that MDRV-induced autophagy can promote virus replication in DF-1 cells, and both the envelope protein sigma A and non-structural protein sigma NS that play an important role in virus replication process can colocalize with the autophagosome marker molecule LC3-II by confocal immunofluorescence analysis. These results indicated that MDRV utilized the autophagosomes for replication. Through transfection of the dual fluorescent plasmid mcherry-EGFP-LC3 and fluorescence microscope observation, it was found that autophagosomes were more likely to fuse with lysosomes in MDRV-infected cells compared with the blank group. The phenomenon of pEGFP-LC3B fluorescent spot and LAMP1 co-localization appeared in MDRV infected cells, indicating that MDRV infection would promote the fusion of autophagosomes and the lysosomes. Conversely, accumulation of p62 was observed by immunoblotting, suggesting that autolysosomes does not exert effective degradation. MDRV infection triggered a incomplete autophagic response. Further studies found that the expression of LAMP1, a marker protein of late endosome/early lysosome, increased significantly in MDRV-infected cells, suggesting an increase in the number of immature lysosomes. In addition, the experiment detected the maturation of the lysosomal acid hydrolase Cathepsin D in the cells, and found that the expression of the 33 kDa mature form of Cathepsin D was significantly reduced after MDRV infection, indicating that MDRV inhibits the maturation of lysosomes. In general, MDRV infection induces autophagy of DF-1 cells, promotes the fusion of autophagosomes and lysosomes, inhibits autophagolysosome degradation, and promotes virus replication.
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http://dx.doi.org/10.1016/j.vetmic.2020.108945DOI Listing
February 2021

Genetic mechanisms of critical illness in COVID-19.

Nature 2021 03 11;591(7848):92-98. Epub 2020 Dec 11.

Intensive Care Unit, Royal Infirmary of Edinburgh, Edinburgh, UK.

Host-mediated lung inflammation is present, and drives mortality, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice.
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http://dx.doi.org/10.1038/s41586-020-03065-yDOI Listing
March 2021

Clostridium difficile toxin A and toxin B inhibit YAP in the colonic epithelial cells.

J Biochem Mol Toxicol 2021 Feb 30;35(2):e22652. Epub 2020 Nov 30.

Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Toxin A (TcdA) and toxin B (TcdB), the two exotoxins of Clostridium difficile, are main causal agents for the colonic epithelium damage in Clostridium difficile infection (CDI). The Hippo pathway is crucial for the control of tissue homeostasis and regeneration of intestines. However, the dysregulation of Hippo pathway in CDI is unclear. Here we show that YAP and TAZ, the transcriptional coactivators downstream of the Hippo pathway, are sequestered in the cytoplasm, degraded, and inactivated by treatment with TcdA and TcdB in colonic epithelial cells. The overexpression of YAP restores the messenger RNA expressions of YAP target genes, attenuates the disruption of cytoskeleton and cell rounding, and rescues the cell proliferation of colonic epithelial cells under exposure of the two toxins. Our results demonstrate that inhibition of YAP and TAZ is involved in the pathogenesis of CDI, implicating that increasing YAP activity could be a potential therapeutic strategy for the CDI treatment.
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http://dx.doi.org/10.1002/jbt.22652DOI Listing
February 2021

Money matters: a multicenter cross-sectional study of depressive symptoms among the caregivers of children on peritoneal dialysis in Mainland China.

BMC Nephrol 2020 11 10;21(1):472. Epub 2020 Nov 10.

Nephrology Department, Children's Hospital of Fudan University, Shanghai, 201102, China.

Background: The caregivers of children on peritoneal dialysis face heavy care burdens and may have a high risk of depression. This study aimed to describe the prevalence and severity of depression and identify its related demographic and socioeconomic factors in the caregivers of children on peritoneal dialysis in China.

Methods: A multicenter cross-sectional study was conducted in four pediatric dialysis centers in four tertiary children's hospitals in mainland China. Primary caregivers of children with end-stage kidney disease and currently on peritoneal dialysis were screened and recruited from December 2018 to July 2019. A self-developed questionnaire and the Self-Rating Depression Scale (SDS) were administered to the participants by a trained nurse in each center. The chi-square test or Fisher's exact test, one-way ANOVA, and the Mann-Whitney U test were used to compare the prevalence of depressive symptoms by demographic features. A multivariate logistic regression analysis was used to identify factors related to depressive symptoms in caregivers of children on peritoneal dialysis.

Results: One hundred twenty-one caregivers were included in the data analysis. The mean age of the caregivers was 40.1 ± 8.1 years. More than 75% of the participants were female, married, and unemployed. The overall prevalence of depressive symptoms was 59%. In total, 46 (38%), 20 (17%) and 5 (4%) caregivers reported mild, moderate, and severe depressive symptoms, respectively. In the univariate analysis, caregivers with an average household income per month under 4000 RMB and caregivers of children undergoing laparoscopic surgery had a higher prevalence of depressive symptoms. Characteristics such as treatment center, duration on PD, PD modalities, and history of peritonitis episodes showed no difference in terms of the prevalence of depressive symptoms. The multivariate logistic regression analysis demonstrated that an average household income per month under 4000 RMB was the associated factor for caregivers' depressive symptoms.

Conclusions: The caregivers of children on peritoneal dialysis in mainland China were socially vulnerable and experienced depression. Those who had a higher average household income were less vulnerable to depression.
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http://dx.doi.org/10.1186/s12882-020-02147-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653820PMC
November 2020

[Application of simple Ilizarov ring external fixation technique in treatment of tibial plateau fracture complicated with osteofascial compartment syndrome].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Oct;34(10):1248-1252

Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force, Kunming Yunnan, 650100, P.R.China.

Objective: To explore the effectiveness of simple Ilizarov ring external fixation technique in treatment of tibial plateau fractures complicated with osteofascial compartment syndrome.

Methods: Between September 2013 and March 2017, 30 patients with tibial plateau fractures complicated with osteofascial compartment syndrome were treated with simple Ilizarov ring external fixation technique. There were 23 males and 7 females, with an average age of 34.4 years (range, 23-43 years). The injuries were caused by traffic accident in 12 cases, by falling from height in 4 cases, by falling in 8 cases, and by a crashing object in 6 cases. The time from injury to admission was 1-12 hours (mean, 4.8 hours). According to the Schatzker classification, there was 1 case of type Ⅱ, 3 cases of type Ⅲ, 10 cases of type Ⅳ, 7 cases of type Ⅴ, and 9 cases of type Ⅵ. All patients underwent fasciotomy due to osteofascial compartment syndrome; the interval between fasciotomy and operation was 10-15 days (mean, 12.5 days). Knee Society Score (KSS) and Ilizarov Method Research and Application Association (ASAMI) protocol were used to evaluate knee function.

Results: The operation time was 110-155 minutes (mean, 123.1 minutes); the intraoperative blood loss was 100-500 mL (mean, 245 mL); the postoperative hospital stay was 3-5 days (mean, 3.8 days). All patients were followed up 20-24 weeks (mean, 22.7 weeks). Except for 2 patients with signs of needle tract infection, no other complication occurred. X-ray films showed that the fractures healed, and the healing time was 10-20 weeks (mean, 14.6 weeks). At last follow-up, the KSS clinical score was 70- 95 with an average of 87.5; the functional score was 70-90 with an average of 79.0. According to ASAMI protocol evaluation, the effectiveness was rated as excellent in 24 cases, good in 3 cases, fair in 2 cases, and poor in 1 case.

Conclusion: For tibial plateau fractures complicated with osteofascial compartment syndrome, simple Ilizarov ring external fixation technique can basically restore joint function and has fewer complications. It is a relatively safe and effective treatment method.
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http://dx.doi.org/10.7507/1002-1892.202003135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171881PMC
October 2020

Polyphenolic Proanthocyanidin-B2 suppresses proliferation of liver cancer cells and hepatocellular carcinogenesis through directly binding and inhibiting AKT activity.

Redox Biol 2020 10 25;37:101701. Epub 2020 Aug 25.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), Chinese Academy of Sciences (CAS), Shanghai, 200031, China; University of the Chinese Academy of Sciences, CAS, Beijing, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. Electronic address:

The well-documented anticarcinogenic properties of natural polyphenolic proanthocyanidins (OPC) have been primarily attributed to their antioxidant and anti-inflammatory potency. Emerging evidence suggests that OPC may target canonical oncogenic pathways, including PI3K/AKT; however, the underlying mechanism and therapeutic potential remain elusive. Here we identify that proanthocyanidin B2 (OPC-B2) directly binds and inhibits AKT activity and downstream signalling, thereby suppressing tumour cell proliferation and metabolism in vitro and in a xenograft and diethyl-nitrosamine (DEN)-induced hepatocellular carcinoma (HCC) mouse models. We further find that OPC-B2 binds to the catalytic and regulatory PH domains to lock the protein in a closed conformation, similar to the well-studied AKT allosteric inhibitor MK-2206. Molecular docking and dynamic simulation suggest that Lys297 and Arg86 are critical sites of OPC-B2 binding; mutation of Lys297 or Arg86 to alanine completely abolishes the antitumor effects of OPC-B2 but not MK-2206. Together, our study reveals that OPC-B2 is a novel allosteric AKT inhibitor with potent anti-tumour efficacy beyond its antioxidant and anti-inflammatory properties.
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http://dx.doi.org/10.1016/j.redox.2020.101701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472926PMC
October 2020

Determination of In-House Limit of Detection of Cell Number for PCR Based EGFR Mutations Detection in Small Biopsies of Non-Small Cell Lung Cancer.

Ann Clin Lab Sci 2020 Jul;50(4):551-556

Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Mutations in the EGFR gene are biomarkers that guide the targeted therapy of Non-Small Cell Lung Cancer (NSCLC). When the mutation assay was performed on small Formalin-Fixed, Paraffin-Embedded (FFPE) biopsies in which only a limited number of tumor cells were obtained, determining Limit of detection of cell number (LODCN) was helpful for quality control. An NCL-H1975 cell block was used to determine the range of LODCN for EGFR mutations. The in-house LODCN was set based on the results of 10 samples with known EGFR mutations. The other 35 samples were assayed to validate the LODCN value. The consistency of 35 clinical validated samples was 100% in samples with more than 70 tumor cells. LODCN could be a useful quality control parameter for mutation assays on small FFPE samples with a very limited number of tumor cells.
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July 2020

[Primarily application of Ilizarov microcirculation reconstruction technique for chronic wounds in post-traumatic ischemia limbs].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Aug;34(8):974-978

Department of Orthopaedic Surgery, Honghe State Hospital Affiliated to Kunming Medical University, Mengzi Yunnan, 661199, P.R.China.

Objective: To evaluate the treatment results of Ilizarov microcirculation reconstruction technique for chronic wounds in the post-traumatic ischemia limbs.

Methods: Between January 2016 and July 2019, 7 cases of chronic wounds in the post-traumatic ischemia limbs were treated. There were 5 males and 2 females, with an average age of 42.4 years (range, 29-66 years). The duration of the wound ranged from 1 month to 2 years (mean, 7.7 months). The wounds located in the leg (3 cases) or in the foot and ankle (4 cases). The wound sizes ranged from 4.0 cm×2.2 cm to 12.0 cm×7.1 cm. There were 1 case of tibial varus, 3 cases of equinovarus, 1 case of scleroderma, and 2 cases of Volkmann's ischemic contracture. After debridement, external fixators were used for tibial transverse transport, or correction of tibial varus and correction of equinovarus.

Results: All patients were followed up 8-20 months, with an average of 13 months. The infection of wound surface was all controlled in 7 cases and the granulation tissue grew well; the wound surface healed directly in 5 cases and healed after skin grafting in 2 cases, and the wound healing time was 1-3 months (mean, 1.7 months). During the follow-up, there was no recurrence of the wound. Six cases of limb deformity were corrected.

Conclusion: For the chronic wounds in the post-traumatic ischemia limbs, Ilizarov microcirculation reconstruction technique can effectively improve local circulation and facilitate the fresh granule growth and wound healing.
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http://dx.doi.org/10.7507/1002-1892.202003044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171910PMC
August 2020

Ribbon Synapses and Hearing Impairment in Mice After in utero Sevoflurane Exposure.

Drug Des Devel Ther 2020 8;14:2685-2693. Epub 2020 Jul 8.

Department of Anesthesiology, Shanghai Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai 200031, People's Republic of China.

Introduction: In utero, exposure to sevoflurane (a commonly used inhalation anesthetic) can lead to hearing impairment in offspring mice, but the underlying impairment mechanism is not known.

Materials And Methods: Day-15 pregnant mice were treated with 2.5% sevoflurane for 2 h to investigate sevoflurane ototoxicity. Cochleae from offspring mice were harvested for hair-cell and ribbon-synapse assessments. Hearing in offspring mice was assessed at postnatal day 30 using an auditory brainstem-response (ABR) test. Cochlear-explant cultures from offspring mice were exposed to 2.5% sevoflurane for 6 h. Immediately after treatment, explants were assessed for hair-cell morphology, mitochondrial oxidative stress, and autophagy.

Results: In utero, sevoflurane exposure impaired hearing in the offspring is demonstrated by a decrease in ABR wave I amplitudes, a marker for ribbon-synapse functionality. Sevoflurane exposure caused no obvious damage to hair cells, but cochlear ribbon synapses were reduced in postnatal day 15 offspring, and partially recovered by postnatal day 30. Sevoflurane treatment also increased mitochondrial reactive-oxygen species stress and decreased autophagy in the cochlear explants.

Conclusion: These results suggest that oxidative stress and reduced autophagy may underly ribbon-synapse involvement in sevoflurane-induced hearing loss.
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http://dx.doi.org/10.2147/DDDT.S253031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354911PMC
June 2021

High-definition likelihood inference of genetic correlations across human complex traits.

Nat Genet 2020 08 29;52(8):859-864. Epub 2020 Jun 29.

Biostatistics Group, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Genetic correlation is a central parameter for understanding shared genetic architecture between complex traits. By using summary statistics from genome-wide association studies (GWAS), linkage disequilibrium score regression (LDSC) was developed for unbiased estimation of genetic correlations. Although easy to use, LDSC only partially utilizes LD information. By fully accounting for LD across the genome, we develop a high-definition likelihood (HDL) method to improve precision in genetic correlation estimation. Compared to LDSC, HDL reduces the variance of genetic correlation estimates by about 60%, equivalent to a 2.5-fold increase in sample size. We apply HDL and LDSC to estimate 435 genetic correlations among 30 behavioral and disease-related phenotypes measured in the UK Biobank (UKBB). In addition to 154 significant genetic correlations observed for both methods, HDL identified another 57 significant genetic correlations, compared to only another 2 significant genetic correlations identified by LDSC. HDL brings more power to genomic analyses and better reveals the underlying connections across human complex traits.
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http://dx.doi.org/10.1038/s41588-020-0653-yDOI Listing
August 2020

Identification of potential candidate genes and pathways in atrioventricular nodal reentry tachycardia by whole-exome sequencing.

Clin Transl Med 2020 Jan;10(1):238-257

Department of Cardiology, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.

Background: Atrioventricular nodal reentry tachycardia (AVNRT) is the most common manifestation of paroxysmal supraventricular tachycardia (PSVT). Increasing data have indicated familial clustering and participation of genetic factors in AVNRT, and no pathogenic genes related to AVNRT have been reported.

Methods: Whole-exome sequencing (WES) was performed in 82 patients with AVNRT and 100 controls. Reference genes, genome-wide association analysis, gene-based collapsing, and pathway enrichment analysis were performed. A protein-protein interaction (PPI) network was then established; WES database in the UK Biobank and one only genetic study of AVNRT in Denmark were used for external data validation.

Results: Among 95 reference genes, 126 rare variants in 48 genes were identified in the cases (minor allele frequency < 0.001). Gene-based collapsing analysis and pathway enrichment analysis revealed six functional pathways related to AVNRT as with neuronal system/neurotransmitter release cycles and ion channel/cardiac conduction among the top 30 enriched pathways, and then 36 candidate pathogenic genes were selected. By combining with PPI analysis, 10 candidate genes were identified, including RYR2, NOS1, SCN1A, CFTR, EPHB4, ROBO1, PRKAG2, MMP2, ASPH, and ABCC8. From the UK Biobank database, 18 genes from candidate genes including SCN1A, PRKAG2, NOS1, and CFTR had rare variants in arrhythmias, and the rare variants in PIK3CB, GAD2, and HIP1R were in patients with PSVT. Moreover, one rare variant of RYR2 (c.4652A > G, p.Asn1551Ser) in our study was also detected in the Danish study. Considering the gene functional roles and external data validation, the most likely candidate genes were SCN1A, PRKAG2, RYR2, CFTR, NOS1, PIK3CB, GAD2, and HIP1R.

Conclusion: The preliminary results first revealed potential candidate genes such as SCN1A, PRKAG2, RYR2, CFTR, NOS1, PIK3CB, GAD2, and HIP1R, and the pathways mediated by these genes, including neuronal system/neurotransmitter release cycles or ion channels/cardiac conduction, might be involved in AVNRT.
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http://dx.doi.org/10.1002/ctm2.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240861PMC
January 2020
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