Short-Term Outcomes of Transcatheter Aortic Valve Replacement in Low-Risk Patients With Pure Severe Aortic Regurgitation.

Transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for patients with pure severe aortic regurgitation (PSAR) who are contraindicated for surgery or have a high surgical risk. However, the therapeutic efficacy and safety of TAVR in low Society of Thoracic Surgeons (STS) score risk patients remain to be clarified. This study aimed to explore the feasibility of TAVR treatment in different STS-risk patients and to compare the adverse events between the groups. In this study, patients with PSAR who underwent TAVR at Zhongshan Hospital, Fudan University, China, during the inclusion period were included and categorized into 3 groups based on STS scores. The baseline data, imaging results, and follow-up data of the patients were documented. Therefore, of 75 TAVR patients, 38 (50.7%) were categorized as low risk (STS <4), and 37 (49.3%) patients were categorized as intermediate and high risk (STS ≥4). Compared with patients at intermediate and high risk, those in the low-risk group were younger, had a lower body mass index, had a lower prevalence of hypertension, chronic obstructive pulmonary disease, and previous percutaneous coronary intervention, and had better cardiac function (p all <0.05). In the hospital and at the 1-month follow-up, the degree of aortic regurgitation and cardiac function were significantly improved. No significant difference was found between the 2 groups in the hospital or during the 30-day follow-up. In conclusion, TAVR for PSAR in low-STS-risk patients is safe and efficient during 30 days of follow-up compared with intermediate- and high-STS-risk groups. TAVR for PSAR should not be limited to inoperable or STS-defined high-risk patients. Long-term follow-up is needed for further investigation.

Congenital disorder of glycosylation type Ia in a Chinese family: Function analysis of a novel PMM2 complex heterozygosis mutation.

Congenital disorder of glycosylation type Ia (CDG-Ia) is an autosomal recessive genetic disease caused by a mutation in the phosphomannomutase 2 (PMM2) gene. We have identified a 13-month-old boy who has been diagnosed with CDG-Ia. He displays several characteristic symptoms, including cerebellar hypoplasia, severe developmental retardation, hypothyroidism, impaired liver function, and abnormal serum ferritin levels. Through whole-exome sequencing, we discovered novel complex heterozygous mutations in the PMM2 gene, specifically the c.663C > G (p.F221L) mutation and loss of exon 2. Further analysis revealed that the enzymatic activity of the mutant PMM2 protein was significantly reduced by 44.97% (p < 0.05) compared to the wild-type protein.

Safety of SARS-CoV-2 vaccine in patients with autoimmune neurological conditions: A systematic review and meta-analysis.

Introduction: Risk of adverse effects and exacerbation in autoimmune neurological conditions (ANC)are frequently cited reasons for COVID-19 vaccine hesitancy. This study evaluates the ANC safety of COVID-19 vaccines in the real world. Methods: Electronic databases were searched to identify studies reporting the use of the COVID-19 vaccine in ANC. We selected studies that provided data on adverse effects and worsening conditions related to ANC after vaccination. The pooled incidence rates for various adverse effects, stratified for the disease category, dosage, and type of vaccine, were estimated. Results: Twenty-eight studies (31 vaccination cohorts) were included. The pooled incidence rate of general adverse events was 0.35 (95%CI, 0.27-0.43, I2 = 100 %). The pooled incidence rates of local injection reaction, fatigue, weakness, myalgia, fever, headache, and chills were 0.27 (0.18-0.36, I2 = 98 %), 0.16(0.11-0.21, I2 = 93 %), 0.15(0.00-0.31, I2 = 97 %), 0.13(0.08-0.19, I2 = 97 %), 0.11(0.07-0.15, I2 = 95 %), 0.11(0.07-0.16, I2 = 97 %), and 0.09 (0.03-0.16, I2 = 96 %), respectively. The pooled incidence rate of exacerbation adverse events was 0.05 (95%CI, 0.04-0.07, I2 = 84 %). Conclusion: According to available evidence, the administration of COVID-19 vaccines in individuals with autoimmune neurological disorders seems well-tolerated, with few reports of adverse events. Furthermore, exacerbation of autoimmune neurological conditions following vaccination appears to be infrequent.

Myasthenic crisis in thymoma-associated myasthenia gravis: a multicenter retrospective cohort study.

Thymoma-associated myasthenia gravis (TMG) had more severe symptoms and worse prognoses in comparison to non-thymoma-associated MG. Thymoma recurrence was frequently associated with transient worsening of MG and even acute respiratory failure, namely myasthenic crisis (MC). However, little is known about the clinical features and outcomes of MC in thymoma-associated MG patients. We performed a retrospective cohort study in MG patients recruited from 9 independent tertiary neuromuscular centers in China from Jan 2015, through Oct 2022. Overall, 156 MC from 149 MG patients with positive anti-acetylcholine receptor (AChR) antibodies were finally analyzed. Next, these patients were divided into two subgroups: the TMG group (n = 60 MCs, 58 patients) and the non-thymoma-associated MG group (n = 96 MCs, 91 patients). Compared with non-thymoma-associated MG, TMG patients had a significantly shorter disease duration from symptom onset to the crisis (17.95±40.9 vs 51.31±60.61 months, P<0.0001), a larger proportion of MGFA IVa as the initial onset clinical classification (6.67% vs 0, P = 0.0205), and a longer hospital stay (39.24±22.09 [6-111] vs. 33.2 ± 23.42 days [7-120]; P = 0.0317) during the crisis. Within the TMG group, the hospital stay was significantly longer in patients with unresected thymoma compared to that in postoperative myasthenic crisis (POMC) (47.68±24.9 [6-111] vs. 34.21±18.87 days [12-82]; P = 0.0257). Early identification of the MG categories may provide some hints in tailoring therapeutic strategies to improve the prognosis.

Potential Biomarker of Acute Anthracycline-induced Cardiotoxicity Among Children With Acute Lymphoblastic Leukemia: Cardiac Adriamycin-responsive Protein.

ABSTRACT: This study aimed to investigate whether serum cardiac adriamycin-responsive protein (CARP) can serve as a sensitive and specific biomarker of anthracyclines (ANT)-induced cardiotoxicity. Fifty-five children with acute lymphoblastic leukemia were recruited. Before and after the administration of ANT, serum levels of CARP, high-sensitivity troponin T, creatine kinase-MB, and electrocardiogram were measured. Postchemotherapeutic clinical manifestations of cardiotoxicity were also investigated. Adverse cardiac events (ACEs) were graded according to the Common Terminology Criteria for Adverse Events 4.0. Then, the CARP expression was statistically analyzed among different groups. The receiver operating characteristic curve was used to evaluate the efficacy of CARP in predicting acute ANT-induced cardiotoxicity. After ANT chemotherapy, the serum CARP concentration increased in the non-ACEs group but decreased in the ACEs group ( P < 0.05). In addition, not only the serum CARP levels (△CARP) was negatively correlated with the grade of ACEs (R=-0.754, P < 0.0001) but also the extent of QT interval corrected (QTc) prolongation (△QTc; R=-0.5592, P < 0.01). The area under the receiver operating characteristic curve of CARP was 90.94% ( P < 0.0001), and the sensitivity and specificity were 88.64% and 91.67%, respectively, all of which are superior to △high-sensitivity troponin T, △creatine kinase-MB, and △QTc. In conclusion, serum CARP could serve as a novel sensitive and specific biomarker of acute ANT-induced cardiotoxicity, which is negatively associated with ACE grade.

Landscape analysis of m6A modification regulators related biological functions and immune characteristics in myasthenia gravis.

BACKGROUND: N6-methyladenosine (m6A) modification has been recognized to play fundamental roles in the development of autoimmune diseases. However, the implication of m6A modification in myasthenia gravis (MG) remains largely unknown. Thus, we aimed to systematically explore the potential functions and related immune characteristics of m6A regulators in MG. METHODS: The GSE85452 dataset with MG and healthy samples was downloaded from Gene Expression Omnibus (GEO) database. m6A modification regulators were manually curated. The targets of m6A regulators were obtained from m6A2Target database. The differential expressed m6A regulators in GSE85452 dataset were identified by "limma" package and were validated by RT-PCR. Function enrichment analysis of dysregulated m6A regulators was performed using "clusterProfiler" package. Correlation analysis was applied for analyzing the relationships between m6A regulators and immune characteristics. Unsupervised clustering analysis was used to identify distinct m6A modification subtypes. The differences between subtypes were analyzed, including the expression level of all genes and the enrichment degree of immune characteristics. Weighted gene co-expression network analysis (WGCNA) was conducted to obtain modules associated with m6A modification subtypes. RESULTS: We found that CBLL1, RBM15 and YTHDF1 were upregulated in MG samples of GSE85452 dataset, and the results were verified by RT-PCR in blood samples from19 MG patients and 19 controls. The targeted genes common modified by CBLL1, RBM15, and YTHDF1 were mainly enriched in histone modification and Wnt signaling pathway. Correlation analysis showed that three dysregulated m6A regulators were closely associated with immune characteristics. Among them, RBM15 possessed the strongest correlation with immune characteristics, including CD56dim natural killer cell (r = 0.77, P = 0.0023), T follicular helper cell (r = - 0.86, P = 0.0002), Interferon Receptor (r = 0.78, P = 0.0017), and HLA-DOA (r = 0.64, P = 0.0200). Further two distinct m6A modification patterns mediated by three dysregulated m6A regulators was identified. Bioinformatics analysis found that there were 3029 differentially expressed genes and different immune characteristics between two m6A modification patterns. Finally, WGCNA analysis obtained a total of 12 modules and yellow module was the most positively correlated to subtype-2. CONCLUSION: Our findings suggested that m6A RNA modification had an important effect on immunity molecular mechanism of MG and provided a new perspective into understanding the pathogenesis of MG.

High indirect bilirubin levels as an independent predictor of postoperative myasthenic crisis: a single-center, retrospective study.

Background: Thymectomy is an efficient and standard treatment strategy for patients with myasthenia gravis (MG), postoperative myasthenic crisis (POMC) is the major complication related to thymectomy and has a strongly life-threatening effect. As a biomarker, whether the bilirubin level is a risk factor for MG progression remains unclear. This study aimed to investigate the association between the preoperative bilirubin level and postoperative myasthenic crisis (POMC). Methods: We analyzed 375 patients with MG who underwent thymectomy at Tangdu Hospital between January 2012 and September 2021. The primary outcome measurement was POMC. The association between POMC and bilirubin level was analyzed by restricted cubic spline (RCS). Indirect bilirubin (IBIL) was divided into two subgroups based on the normal upper limit of IBIL, 14 µmol/L. Results: Compared with non-POMC group, IBIL levels were significantly higher in patients with POMC. Elevated IBIL levels were closely associated with an increased risk of POMC (p for trend = 0.002). There was a dose-response curve relationship between IBIL levels and POMC incidence (p for non-linearity = 0.93). However, DBIL levels showed a U-shaped association with POMC incidence. High IBIL level (≥14 µmol/L) was an independent predictive factor for POMC [odds ratio = 3.47, 95% confidence interval (CI): 1.56-7.8, p = 0.002]. The addition of high IBIL levels improved the prediction model performance (net reclassification index = 0.186, 95% CI: 0.039-0.334; integrated discrimination improvement = 0.0345, 95% CI: 0.005-0.065). Conclusion: High preoperative IBIL levels, especially those exceeding the normal upper limit, could independently predict the incidence of POMC.

Clinical and genetic analysis of a pedigree with Wolfram syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical features and genetic background of autosomal recessive Wolfram syndrome caused by WFS1 gene mutation.METHODS: A pedigree with autosomal recessive Wolfram syndrome was studied by clinical examination, gene analysis and bioinformatics.RESULT: It was found that the proband and his brother had diabetes, color weakness and optic neuropathy. In addition, his brother had diabetes insipidus. Whole-exome sequencing(WES)analysis showed that there were two heterozygous variations in the WFS1 gene exon 8 of the two brothers: c.941G&#x0026;#x003E;A(p.W314X)and c.2309T&#x0026;#x003E;G(p.F770C), and were co-separated from the clinical phenotype in this family.CONCLUSION: The compound heterozygous mutation of WFS1 gene is associated with Wolfram syndrome in this pedigree. Among them, c.941G&#x0026;#x003E;A(p.W314X)has not been reported yet.

Perceived social support and coping style as mediators between resilience and health-related quality of life in women newly diagnosed with breast cancer: a cross-sectional study.

BACKGROUND: Breast cancer may impair health-related quality of life (HRQoL). We examined the mediating roles of perceived social support (PSS) and coping style (CS) in the relationship between resilience and HRQoL in newly diagnosed breast cancer patients. METHODS: Following a cross-sectional design, 431 patients completed a survey at two hospitals in Shaanxi Province, China. Four validated self-report measures assessed HRQoL, psychological resilience, PSS, and CS. A one-sample t-test analyzed differences between resilience, PSS, and CS in breast cancer patients and the corresponding norm. Multivariate linear regression analyzed the independent predictors of HRQoL. The mediating roles of PSS and CS between resilience and HRQoL were investigated using structural equation modeling (SEM). RESULTS: Participants had significantly lower scores for resilience and PSS, and higher scores for the avoidance and resignation CSs than their corresponding norm. SEM analysis showed resilience had significant direct effects on PSS (Bs: 0.59, 95% CI 0.49, 0.68, P = 0.003), CS (confrontation: 0.53 (0.44, 0.62), P = 0.001; resignation: - 0.66 (- 0.74, - 0.57), P = 0.002), and HRQoL (Bs range from 0.44 to 0.63, P < 0.05). Resilience had significant indirect effects (Bs range from 0.09 to 0.27), and PSS and CS had significant direct effects on HRQoL (P < 0.05). CONCLUSIONS: Newly diagnosed breast cancer patients had lower resilience and PSS, and higher negative CSs, suggesting that PSS and CS mediated the influence of resilience on HRQoL. A multimodal intervention program focusing on PSS and CS might improve the positive influences of resilience on HRQoL in breast cancer patients.

The mediator role of resilience between psychological predictors and health-related quality of life in breast cancer survivors: a cross-sectional study.

BACKGROUND: Although many psychological factors have been associated with health-related quality of life (HRQoL), the mediator role of resilience between psychological predictors (i.e., coping styles and perceived social support) and HRQoL has rarely been explored in breast cancer survivors (BCSs). METHODS: A total of 231 BCSs participated in this cross-sectional survey. Pearson correlation was performed to analyze the relationships among coping styles (confrontation, avoidance, and resignation), perceived social support, resilience, and HRQoL. A multivariate linear regression analysis was applied to identify the psychological predictors of HRQoL and resilience, respectively. A structural equation modeling (SEM) was employed to examine the mediating role of resilience between coping styles, perceived social support, and HRQoL. RESULTS: Perceived social support and resilience were positively associated with confrontation. Resilience was positively associated with perceived social support. HRQoL had positive correlations with confrontation/avoidance, perceived social support, and resilience. Resilience and resignation/avoidance were significant independent predictors of HRQoL, while resignation/confrontation and perceived social support were significant independent predictors of resilience. Confrontation/resignation, perceived social support, and resilience had significant direct effects on HRQoL; confrontation/resignation and perceived social support had significant direct effects on resilience; resilience had significant mediator roles between confrontation/resignation, perceived social support, and HRQoL. CONCLUSIONS: Resilience was a significant mediator between coping styles, perceived social support, and HRQoL. A resilience-oriented intervention is recommended to alleviate the detrimental influences of low resilience on HRQoL, providing a new strategy for improving the health status of BCSs.

Relationship between obesity indexes and body fat percentage in Naxi adults / 解剖学报

Objective To explore the relationship hetween obesity indexes and body fat rate in Naxi a d u l t s. Methods A total of 687 Naxi adults aged between 18 and 90 were selected from Yulong County, Lijiang City, Yunnan Province. Body weight, height, chest circumference, waist circumference, hip circumference, biceps skinfold, triceps skinfold, subscapular skinfold, suprailiac skinfold, anterior superior spine skinfold, body mass index (BMI), visceral fat index and body fat percentage were measured by anthropometry and bioelectrical impedance analysis. And the indexes and body fat percentage were statistically analyzed. Results The average body fat percentage of Naxi men was normal, while the women was obese. According to the criteria of visceral fat index, the average visceral fat index of Naxi men and women was within the normal range. According to the waist circumference, the waist circumference of Naxi men was within the normal range, while the waist circumference of women belonged to abdominal obesity. Correlation analysis showed that body weight, chest circumference, waist circumference, hip circumference, biceps skinfold, triceps skinfold, subscapular skinfold, suprailiac skinfold, anterior superior iliac spine skinfold, BMI, visceral fat index were positively correlated with body fat percentage among Naxi adults. There was the strongest correlation between visceral fat index and body fat percentage in Naxi men, followed by BMI; Naxi women' s chest circumference and body fat percentage, followed by waist circumference. Conclusion All the obesity indexes of Naxi adults are positively correlated with body fat percentage, and there are gender, regional and ethnic differences in the degree of correlation.

Three obesity indicators predicting central obesity in Naxi and Pumi ethnic groups in Yunnan Province and inter-ethnic comparison / 解剖学报

Objective To compare the predicted value of three different obesity indicators of on center obesity of Naxi and Pumi adult in Lijiang City, Yunnan Province; To calculate the best cut-off point of waist-to-height ratio(WHtR), body mass index(BMI) and abdominal volume index(AVT); And to compare the differences of BMI and WHtR between the Naxi, Pumi and North-South ethnic groups, so as to provide scientific reference for central obesity and related diseases. Methods By random sampling, 658 cases of Naxi adults (278 cases for men and 380 cases for women) and 496 cases of Pumi adults (2 1 6 cases for men and 280 cases for women) were selected as the subjects of the study, taking the internationally recognized visceral fat level (V F L) as the diagnostic criterion of central obesity, the relationship between WHtR, BMI, AVI and VFL was discussed by regression analysis, and the value of three obesity indicators was predicted by comparing the receiver operating characteristic (ROC) curve of the subjects. Using Excel 2019 to draw diagrams and SPSS 23. 0 to process data. Results The six indicators of age, weight, height, waist circumference, hip circumference and AVI of Naxi and Pumi men were statistically significant among different ethnic groups (P < 0 . 05); Naxi and Pumi women' s age, height, waist circumference, WHtR, BMI and abdominal volume index, the six indicators were statistically significant among different ethnic groups (P < 0 . 0 1) . Correlation analysis showed that the three indicators of WHtR, BMI and AVI were positively related to VFL (P< 0 . 0 1) . The ROC showed that the WHtR had the highest value for predicting central obesity in Naxi and Pumi men (P<0. 01), BMI had the highest value of predicting central obesity in Naxi and Pumi women (P<0. 0 1) . Cluster analysis showed that Naxi and Pumi males were similar to southern ethnic groups such as Lisu and Sui, Naxi females were similar to Zang and Jingpo, and Pumi females were similar to southern ethnic groups such as Lisu and Sui. Conclusion WHtR, BMI, AVI to determine central obesity are statistically significant, can be combined with BMI and AVI to determine Naxi, Pumi central obesity.

Normal tension glaucoma: reconsideration and reevaluation / 中华实验眼科杂志

Normal tension glaucoma (NTG) is almost the most difficult type of glaucoma to diagnose.The difficulty lies in the lack of specificity of the symptoms and signs of glaucomatous optic neuropathy (GON), so the reevaluation of NTG is a new understanding of GON.As a subtype of primary open-angle glaucoma (POAG), NTG is difficult to accurately conceptualize.One of the reasons is that the intraocular pressure (IOP) is closely linked to the occurrence of GON in POAG but not in NTG.GON seems to be secondary to a number of local or systemic disorders, including vascular dysfunction in the optic nerve head induced by compression (elevated IOP) or ischemia, hypoxia, migraine, Flammer syndrome, intracranial hypotension, low body mass index, low estrogen levels, nocturnal hypotension, obstructive sleep apnea-hypopnea syndrome, Alzheimer disease, Parkinson disease, and genetic background, which may influence the flow in the radial peripapillary capillaries (RPCs) and the underfilling of RPCs causing retinal ganglion cell damage.In some cases, GON does not progress with systemic diseases under control, and these systemic diseases are not risk factors for NTG but may be the cause of GON (or GON is one of the manifestations of these diseases). If these causes are not excluded and NTG is diagnosed only on the basis of GON, chamber angle opening, and normal IOP, it is easy to cause misdiagnosis, and the complete exclusion of these diseases is short of clinical significance in practice.In conclusion, the diagnosis of NTG may not be made before the other ocular or systemic disorders capable of presenting with GON are ruled out, and the concept and diagnostic criteria of NTG should be reconsidered.

Associations of body mass index and waist circumference with hospitalization risk of kidney stones in Chinese adults / 中华流行病学杂志

Objective: To evaluate the associations of body mass index (BMI) and waist circumference with hospitalization risk of kidney stones in Chinese adults. Methods: This study used long-term follow-up data from China Kadoorie Biobank. After excluding participants with chronic kidney disease, cancer, and extreme BMI or waist circumference values at baseline, 502 096 participants were included in the present analysis. Cox proportional hazards regression models were used to estimate the associations of BMI and waist circumference with hospitalization risk of kidney stones. Results: During an average follow-up period of (10.7±2.2) years, 12 396 participants were hospitalized for the first time with kidney stones. Using the participants with BMI (kg/m2) of 20.5-22.4 as reference, the multivariable-adjusted HR (95%CI) for those with BMI of <18.5, 18.5-20.4, 22.5-23.9, 24.0-25.9, 26.0-27.9, 28.0-29.9, and ≥30.0 were 0.96 (0.87-1.05), 0.94 (0.88-1.00), 1.11 (1.05-1.17), 1.25 (1.18-1.32), 1.29 (1.21-1.37), 1.39 (1.28-1.50), and 1.54 (1.40-1.71), respectively. For every 1 kg/m2 increase in BMI, the HR of kidney stones hospitalization increased by 4% (HR=1.04, 95%CI: 1.04-1.05). Using the participants with waist circumference (cm) of 75.0-79.9 as reference, the multivariable-adjusted HR (95%CI) for those with waist circumference of <65.0, 65.0-69.9, 70.0-74.9, 80.0-84.9, 85.0-89.9, 90.0-94.9, and ≥95.0 were 0.82 (0.74-0.91), 0.85 (0.80-0.92), 0.95 (0.89-1.00), 1.16 (1.09-1.22), 1.22 (1.15-1.30), 1.28 (1.19-1.38), and 1.46 (1.35-1.58), respectively. For every 5 cm increase in waist circumference, the HR of kidney stones hospitalization increased by 9% (HR=1.09, 95%CI: 1.08-1.10). After mutually adjusting for BMI and waist circumference in the above models, the association between BMI and hospitalization risk of kidney stones disappeared. In contrast, the association between waist circumference and hospitalization risk of kidney stones remained unchanged. Conclusions: BMI and waist circumference were positively associated with hospitalization risk of kidney stones. The increased waist circumference was an independent risk factor for kidney stones among Chinese adults.

Interaction between obesity/central obesity and hypertension / 预防医学

Objective@#To examine the effects of obesity and central obesity on hypertension, so as to provide insights into the prevention and control measures of hypertension.@*Methods@#From September to December 2018, residents at ages of 35 to 75 years were sampled using the multi-stage random sampling method in Baiyin District, Baiyin City, Gansu Province, and subjected to questionnaire surveys and physical examinations. The interaction between obesity/central obesity and hypertension was evaluated using logistic regression analysis. The synergy index ( SI ), relative excess risk due to interaction ( RERI ) and attributable proportion due to interaction ( AP ) were calculated using Excel compiled by Andersson et al.@*Results@#A total of 6 246 questionnaires were allocated and 6 169 valid questionnaires were recovered, with an effective recovery rate of 98.77%. The respondents included 3 038 men ( 49.25% ) and 3 131 women (50.75%), with a mean age of ( 52.05±8.78 ) years. There were 832 respondents with obesity ( 13.49% ) and 2 278 with central obesity ( 36.93% ). The crude and standardized prevalence rates of hypertension were 35.89% and 33.05%, respectively. Multivariable logistic regression analysis showed that obesity ( OR=2.020, 95%CI: 1.705-2.393 ) and central obesity ( OR=1.622, 95%CI: 1.433-1.836 ) were statistically associated with hypertension. There was no multiplicative interaction between obesity or central obesity and hypertension ( OR=1.011, 95%CI: 0.655-1.560 ), and no additive interaction was detected between obesity or central obesityand hypertension ( SI=1.405, 95%CI: 0.815-2.424; RERI=0.658, 95%CI: -0.298 to 1.614; AP=0.201, 95%CI: -0.075 to 0.476 ).@*Conclusions@#Obesity and central obesity increase the risk of hypertension; however, no interaction is detected between obesity or central obesity and hypertension.

Genetic analysis of a Chinese family with cataract-microcornea syndrome / 中华实验眼科杂志

Objective:To analyze the clinical and molecular genetic characteristics of a Chinese family with congenital cataract-microcornea syndrome.Methods:The method of pedigree investigation was adopted.A Chinese Han family with congenital cataract-microcornea syndrome was recruited in Xiamen Eye Center of Xiamen University.All the family members received detailed ophthalmologic examination including the best corrected visual acuity, intraocular pressure measurement by handheld applanation tonometry, slit lamp biomicroscopy, color fundus photography, B-scan ultrasonography, corneal diameter, anterior segment optical coherence tomography, ultrasound biomicroscopy, corneal endoscopy, and corneal topography.Genomic DNA was extracted from peripheral venous blood from some patients and unaffected family members.Targeted high-throughput DNA sequencing was performed on the proband.The sequencing chip contained 188 known pathogenic genes related to lens abnormalities.Suspected pathogenic genes were verified by Sanger sequencing in phenotypically normal family members to identify the co-segregation and the disease-causing gene.Bioinformatics analysis was performed to analyze the pathogenicity of variants by REVEL.Conserved protein domains were analyzed by InterPro.Physicochemical property of the mutant protein was analyzed by ProtParam.The deleteriousness of the protein was predicted by PolyPhen-2.Homology of the variants in pathogenic gene was analyzed by NCBI website to compare the conservation among various species.This study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.XMYKZX-LW-2009-003).Written informed consent was obtained from each subject prior to entering the study cohort.Results:There were 39 members of 4 generations in this family including 11 patients with an autosomal dominant inheritance pattern.Clinical features of the patients included congenital cataract and microcornea.No obvious abnormality was found in ophthalmic and general examination.A heterozygous mutation c. 61C>T in the CRYAA gene was found, resulting in the mutation of the amino acid from arginine to tryptophan (p.Arg21Trp) at position 21, consistent with co-segregation.The number of cationic cluster in the mutant protein decreased, and the hydrophilicity and stability were reduced.The variant was predicted to be deleterious and was highly conserved in multiple species. Conclusions:A novel heterozygous mutation c.61C>T p. Arg21Trp in CRYAA gene is considered as the causal gene of this family.It is the first time this variant has been reported in China.

Hepatic cystic echinococcosis complicated with tuberculous empyema misdiagnosed as hepatic and pulmonary cystic echinococcosis: one case report / 中国血吸虫病防治杂志

Hepatic cystic echinococcosis is a chronic parasitic disease caused by the infection with the larvae of Echinococcus granulosus in human or animal liver tissues. As a chronic active infectious disease, tuberculous empyema mainly invades the pleural space and then causes visceral and parietal pleura thickening. It is rare to present comorbidity for hepatic cystic echinococcosis and tuberculous empyema. This case report presents a case of hepatic cystic echinococcosis complicated with tuberculous empyema misdiagnosed as hepatic and pulmonary cystic echinococcosis, aiming to improve clinicians’ ability to distinguish this disorder.

Corrigendum: The 10-Repeat 3'-UTR VNTR Polymorphism in the SLC6A3 Gene May Confer Protection Against Parkinson's Disease: A Meta-Analysis.

[This corrects the article DOI: 10.3389/fgene.2021.757601.].

The 10-Repeat 3'-UTR VNTR Polymorphism in the SLC6A3 Gene May Confer Protection Against Parkinson's Disease: A Meta-analysis.

The dopamine transporter (DAT) is encoded by the SLC6A3 gene and plays an important role in the regulation of the neurotransmitter dopamine. The SLC6A3 gene contains several repetition alleles (3-11 repeats) of a 40-base pair variable number of tandem repeats (VNTR) in the 3'-untranslated region (3'-UTR), which may affect DAT expression levels. The 10-repeat (10R) allele could play a protective role against PD. However, inconsistent findings have been reported. Methods: A comprehensive meta-analysis was performed to accurately estimate the association between the 10R allele of the 3'-UTR VNTR in SLC6A3 and PD among four different genetic models. Results: This meta-analysis included a total of 3,142 patients and 3,496 controls. We observed a significant difference between patients and controls for the allele model (10R vs. all others: OR = 0.860, 95% CI: 0.771-0.958, P = 0.006), pseudodominant model (10R/10R + 10R/9R vs. all others: OR = 0.781, 95% CI: 0.641-0.952, P = 0.014) and pseudorecessive model (10R/10R vs. all others: OR = 0.858, 95% CI: 0.760-0.969, P = 0.013) using a fixed effects model. No significant differences were observed under the pseudocodominant model (10R/9R vs. all others: OR = 1.079, 95% CI: 0.945-1.233, P = 0.262). By subgroup analysis, the 10R, 10R/10R and 10R/9R genotypes were found to be significantly different from PD in Asian populations. Conclusion: Our findings suggest that the SLC6A3 10R may be a protective factor in susceptibility to PD.

Nucks1 gene polymorphism rs823114 is associated with the positive symptoms and neurocognitive function of patients with schizophrenia in parts of southern China.

Nuclear casein kinase and cyclin-dependent kinase substrate 1 (nucks1) are considered a potential susceptibility gene for certain neurological diseases, such as Parkinson's disease (PD). In our study, we genotyped three single nucleotide polymorphisms (SNPs) (rs4951261, rs823114 and rs951366) of the nucks1 gene in 774 schizophrenic patients and 819 healthy controls using the improved multiplex ligation detection reaction (imLDR) technique. Furthermore, we also studied the relationship between the above SNPs and the clinical psychiatric symptoms and neurocognitive function of the patients. Genotype distributions and allele frequencies of these SNPs showed no significant differences and were found between patients and healthy controls. However, in an analysis of the positive symptom score of rs823114 among male patients, we found that the score of the A/A genotype was lower than that of the G/A+G/G genotypes (P = 0.001, P(corr) = 0.003]. Additionally, we also found that among the female patients, G allele carriers with rs823114 had lower semantic fluency scores than subjects with the A/A genotype (P = 0.010, P(corr) = 0.030]. Our data show for the first time that rs823114 polymorphism of nucks1 may affect positive symptoms and neurocognitive function in patients with schizophrenia in parts of southern China.