Risk factors of pancreatitis after endoscopic retrograde cholangiopancreatography in patients with biliary tract diseases.

BACKGROUND: To investigate the risk factors of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in patients with biliary tract diseases. METHODS: We retrospectively analyzed the clinical data of 480 patients who underwent ERCP for biliary tract diseases at the Affiliated Zhongshan Hospital of Dalian University from October 2011 to October 2016. The patients were divided into a study group (n = 75, with PEP) and a control group (n = 405, without PEP) based on whether they developed post-ERCP pancreatitis (PEP), and their clinical baseline data and intraoperative conditions were retrieved and compared. Then, factors associated with PEP were analyzed using logistic regression model, based on which a nomogram prediction model was constructed. The receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the performance of the prediction model. RESULTS: Significant differences in age, sex, history of pancreatitis, history of choledocholithiasis, pancreatic duct imaging, pancreatic sphincterotomy, difficult cannulation, multiple cannulation attempts and juxtapapillary duodenal diverticula were observed between the two groups. Multivariate logistic regression analysis showed that age less than 60 years (OR, 0.477; 95% CI, 0.26-0.855), female sex (OR, 2.162; 95% CI, 1.220-3.831), history of pancreatitis (OR, 2.567; 95% CI, 1.218-5.410), history of choledocholithiasis (OR, 2.062; 95% CI, 1.162-3.658), pancreatic sphincterotomy (OR, 2.387; 95% CI, 1.298-4.390), pancreatic duct imaging (OR, 4.429; 95% CI, 1.481-13.242), multiple cannulation attempts (OR, 2.327; 95% CI, 1.205-4.493), difficult cannulation (OR, 2.421; 95% CI, 1.143-5.128), and JPD (OR, 2.002; 95% CI, 1.125-3.564) were independent risk factors for PEP. The nomogram for predicting the occurrence of PEP demonstrated an area under the ROC curve (AUC) of 0.787, and the calibration curves of the model showed good consistency between the predicted and actual probability of PEP. CONCLUSION: Our results showed that age less than 60 years, female sex, history of pancreatitis, history of choledocholithiasis, pancreatic sphincterotomy, pancreatic duct imaging, multiple cannulation attempts, difficult cannulation and juxtapapillary duodenal diverticula were independent risk factors for PEP. In addition, the established nomogram demonstrated promising clinical efficacy in predicting PEP risk in patients who underwent ERCP for biliary tract diseases.

Nance-Horan syndrome pedigree due to a novel microdeletion and skewed X chromosome inactivation.

BACKGROUND: Nance-Horan syndrome (NHS) is a rare and often overlooked X-linked dominant disorder characterized by dense congenital cataracts, dental abnormalities, and mental retardation. The majority of NHS variations include frameshift mutations, nonsense mutations, microdeletions, and insertions. METHODS: Copy number variation sequencing was performed to determine the microdeletion. The expression of NHS was detected by RT-PCR. Four family members were tested for X chromosome inactivation. RESULTS: In this study, all members were examined for systemic examinations and genetic testing of four members and two affected subjects are observed. We identified a heterozygous microdeletion of -0.52 Mb at Xp22.13 in a female proband presenting NHS phenotypically. The microdeletion contains the REPS2 and NHS genes and was inherited from a phenotypically normal mother. Of interest, the expression NHS of proband was reduced and the skewed X chromosome inactivation rate reached more than 85% compared with her mother and the control. It was concluded that the haploinsufficiency of the NHS gene may account for the majority of clinical symptoms in the affected subjects. The variability among female carriers presumably results from nonrandom X chromosome inactivation. CONCLUSION: Our findings broaden the spectrum of NHS mutations and provide molecular insight into NHS clinical prenatal genetic diagnosis.

Nonpharmacological interventions for subthreshold depression in adults: A systematic review and network meta-analysis.

Subthreshold depression (StD) is very common, with an estimated global incidence of 25%, and is associated with other clinical conditions. Nonpharmacological interventions have been demonstrated to be effective, but which one is best should be further investigated. This study aims to compare and rank the efficacy of nonpharmacological interventions in adults with StD. Ten databases were searched, and comparisons were made using a random-effects network meta-analysis using the frequentist framework. The assumption of local consistency was assessed by using the node-splitting method. The surface under the cumulative ranking curve (SUCRA) was used to separately rank each intervention. A total of 32 randomized controlled trials (RCTs) were included. The results showed that psychotherapy, as an intervention class, had significantly positive effects compared to control groups (SMD = -0.78, 95% CI: -1.06, -0.49) and had the highest rank (SUCRA, 79.0%; mean rank, 1.6). Cognitive behavioral therapy (CBT), as an individual intervention, had significantly positive effects relative to all control groups and had the highest rank (SUCRA, 82.5%; mean rank, 3.1). We speculate that psychotherapy, especially CBT, may be the most effective nonpharmacological intervention to improve StD in adults. More RCTs examining the efficacy of different nonpharmacological interventions are needed.

Genetic Analysis of 28 Chinese Families With Tyrosinase-Positive Oculocutaneous Albinism.

BACKGROUND: Tyrosinase-positive oculocutaneous albinism (OCA, type II, OCA2) is an autosomal recessive genetic disease in which the biosynthesis of melanin decreases in the skin, hair, and eyes. OCA2 disease is caused by mutations in OCA2 gene. The gene product plays a role in regulating the pH of melanosomes. Up to now, hundreds of OCA2 mutations have been reported and novel variants are still being discovered. METHODS: In this study, we reviewed the records of OCA2 patients who had conducted albinism genetic testing, and then analyzed the clinical and genetic information of 28 OCA2 patients who had been genetically diagnosed by using Sanger sequencing and next-generation sequencing. RESULTS: In this study, we reported 31 variants screened from 28 Chinese OCA2 families, and characterized the detailed molecular and clinical presentations. There were 12 novel variants among all detected variants, including 3 missense variants (p.G393V, p.T482A, and p.R720P), 4 frameshift variants (p.R53Gfs∗49, p.N279Kfs∗17, p.I469Lfs∗4, p.I655Nfs∗12), 2 splicing variants (c.1637-2A > G, c.1951 + 1G > C), 2 stopgain variants (p.L278X, p.W652X) and 1 insertion variants (p.P315LinsT). One potential cluster of missense variants was implicated indicating the important roles of the underlying domains in OCA2 pathogenesis. CONCLUSION: Our results were beneficial for diagnosis and precision clinical management for OCA2-related disorder, and this study expanded the mutation spectrum of oculocutaneous albinism.

Biallelic loss-of-function variants in NEMF cause central nervous system impairment and axonal polyneuropathy.

We aimed to detect the causative gene in five unrelated families with recessive inheritance pattern neurological disorders involving the central nervous system, and the potential function of the NEMF gene in the central nervous system. Exome sequencing (ES) was applied to all families and linkage analysis was performed on family 1. A minigene assay was used to validate the splicing effect of the relevant discovered variants. Immunofluorescence (IF) experiment was performed to investigate the role of the causative gene in neuron development. The large consanguineous family confirms the phenotype-causative relationship with homozygous frameshift variant (NM_004713.6:c.2618del) as revealed by ES. Linkage analysis of the family showed a significant single-point LOD of 4.5 locus. Through collaboration in GeneMatcher, four additional unrelated families' likely pathogenic NEMF variants for a spectrum of central neurological disorders, two homozygous splice-site variants (NM_004713.6:c.574+1G>T and NM_004713.6:c.807-2A>C) and a homozygous frameshift variant (NM_004713.6: c.1234_1235insC) were subsequently identified and segregated with all affected individuals. We further revealed that knockdown (KD) of Nemf leads to impairment of axonal outgrowth and synapse development in cultured mouse primary cortical neurons. Our study demonstrates that disease-causing biallelic NEMF variants result in central nervous system impairment and other variable features. NEMF is an important player in mammalian neuron development.

POGZ de novo missense variants in neuropsychiatric disorders.

BACKGROUND: De novo likely gene-disrupting variants of POGZ cause autism spectrum disorder (ASD) and intellectual disability. However, de novo missense variants of this gene were not well explored in neuropsychiatric disorders. METHODS: The single-molecule molecular inversion probes-based targeted sequencing method was performed on the proband. Variant was validated using Sanger sequencing in both proband and parents. Immunoblot analysis was performed to examine the expression of POGZ in patient-derived peripheral blood lymphocytes. Published POGZ de novo missense variants in neuropsychiatric disorders were reviewed. RESULTS: We detected a novel de novo missense variant in POGZ (c.1534C>A, p.H512N, NM_015100.4) in an individual with ASD. Immunoblot analysis revealed a dramatic reduction in POGZ protein in patient-derived peripheral blood lymphocytes suggesting a loss-of-function mechanism of this de novo missense variant. In addition, we collected and annotated additional eight POGZ de novo missense variants identified in neuropsychiatric disorders from literatures. CONCLUSION: Our findings will be beneficial to the functional analysis of POGZ in ASD pathogenesis, and for genetic counseling and clinical diagnosis of patients with POGZ de novo missense variants.