The long-term effects of blood urea nitrogen levels on cardiovascular disease and all-cause mortality in diabetes: a prospective cohort study.

BACKGROUND: The long-term effects of blood urea nitrogen(BUN) in patients with diabetes remain unknown. Current studies reporting the target BUN level in patients with diabetes are also limited. Hence, this prospective study aimed to explore the relationship of BUN with all-cause and cardiovascular mortalities in patients with diabetes. METHODS: In total, 10,507 participants with diabetes from the National Health and Nutrition Examination Survey (1999-2018) were enrolled. The causes and numbers of deaths were determined based on the National Death Index mortality data from the date of NHANES interview until follow-up (December 31, 2019). Multivariate Cox proportional hazard regression models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs) of mortality. RESULTS: Of the adult participants with diabetes, 4963 (47.2%) were female. The median (interquartile range) BUN level of participants was 5 (3.93-6.43) mmol/L. After 86,601 person-years of follow-up, 2,441 deaths were documented. After adjusting for variables, the HRs of cardiovascular disease (CVD) and all-cause mortality in the highest BUN level group were 1.52 and 1.35, respectively, compared with those in the lowest BUN level group. With a one-unit increment in BUN levels, the HRs of all-cause and CVD mortality rates were 1.07 and 1.08, respectively. The results remained robust when several sensitivity and stratified analyses were performed. Moreover, BUN showed a nonlinear association with all-cause and CVD mortality. Their curves all showed that the inflection points were close to the BUN level of 5 mmol/L. CONCLUSION: BUN had a nonlinear association with all-cause and CVD mortality in patients with diabetes. The inflection point was at 5 mmol/L.

Lack of association between XRCC1 SNPs and acute radiation­induced injury or prognosis in patients with nasopharyngeal carcinoma.

The response to radiation therapy (RT) is closely associated with DNA damage repair. X-ray repair cross-complementing group-1 (XRCC1) is a key gene in the DNA damage repair pathway, and SNPs in this gene alter the expression and activity of its effector protein, which may in turn affect sensitivity to RT. Therefore, the course of tumor treatment and local control rate can be influenced. In the present study, a group of 158 patients with nasopharyngeal carcinoma (NPC) who received intensity-modulated RT at Fujian Cancer Hospital (Fuzhou, China) between July 2012 and October 2013 were included in retrospective chart review and followed up. Plasma was collected before treatment for genotype analysis of the three SNPs of XRCC1, namely Arg194Trp, Arg280His and Arg399Gln. Acute radiation-induced injuries sustained during treatment was graded according to the Radiation Therapy Oncology Group scoring criteria. Post-treatment follow-up was performed until August 2020. In the 158 cases of NPC, no statistically significant association was observed between the three SNPs of the XRCC1 gene and the severity of acute radiation-induced injury or prognosis. However, the AA genotype of XRCC1-Arg399Gln tended to be associated with worse progression-free survival (PFS) compared with the GA + GG genotype, although this was not significant (P=0.069). In addition, multivariate logistic analysis showed that nodal stage was significantly associated with the occurrence of acute severe radiation-induced oral mucositis (P=0.018), and there was also a trend towards an association between nodal stage and the incidence of acute severe radiation-induced pharyngitis; however, this was not statistically significant (P=0.061). Furthermore, multivariate Cox regression analysis showed that older age, distant metastasis and higher clinical stage were independent risk factors for PFS in patients with NPC. In conclusion, relying solely on the aforementioned SNPs of the XRCC1 gene may not provide a robust enough basis to predict the response to RT or prognosis in patients with NPC.

Vitamin D Intake Attenuated the Association between Pesticides Exposure and Female Infertility.

BACKGROUND: Only a few epidemiological studies have illuminated the association between pesticide exposure and female infertility. However, evidence of the available data is restricted and also controversial. Vitamin D supplement was considered as having a beneficial effect on fertility. So, the purpose of our study is to assess the effect of dietary vitamin D consumption on the relationship between pesticide exposure in home and female infertility. METHODS: There were a total of 2,968 subjects from the National Health and Nutrition Examination Survey (NHANES), 2011 - 2018. The daily vitamin D intake was divided into two groups high intake (≥ 6 µg/d) and low intake (< 6 µg/d). Multi-variable logistic regression analysis was used to assess the relationship among vitamin D intake, pesticide exposure, and female infertility. RESULTS: We found a significant association between household pesticide exposure and infertility on a basis of a fully-adjusted model (OR 1.61; 95% CI 1.1 - 2.37). Furthermore, the relationship between pesticide exposure and in-fertility differed from low vitamin D intake group (OR 3.96; 95% CI 1.77 - 8.86) and high intake group (OR 1.36, 95% CI: 0.86 - 2.16), and p for interaction is 0.043 stratified by vitamin D intake. CONCLUSIONS: A significant association of female infertility with pesticide exposure in home is modified by dietary vitamin D consumption. This was the first study to demonstrate that dietary vitamin D may alter associations of human female infertility with pesticide exposure in home.

Nonlinearity association of serum calcium with the risk of anaemia in US adults.

BACKGROUND: Calcium plays a key role in many bio-homeostasis functions. Previous studies indicated that serum calcium is associated with diseases such as anaemia. However, the evidence on the association between serum calcium levels and anaemia risk is limited. Thus, the purpose of our study is to investigate the relationship between serum calcium and anaemia in US adults. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) including 15,519 participants, aged ≥18 years. The analyses were performed using multivariate logistic regression and a generalized additive model (GAM). Subgroup analysis, stratified by gender and age, was also performed. RESULTS: Among the sample of 15,519 individuals, 1565 (10.8%) had been diagnosed with anaemia. Both the univariate logistic regression model and multivariate logistic regression model showed a reverse relationship between serum calcium and anaemia risk. Moreover, a non-linear association between serum calcium and anaemia risk was observed using GAM and smooth curve fitting. The inflection point of serum calcium was at 2.3 mmol/L. GAM with penalized splines suggested a reverse association between serum calcium and the prevalence of anaemia when the concentration of serum calcium was below 2.3 mmol/L. In contrast, we found no statistically significant difference when serum calcium concentration was higher than the inflection point (2.3 mmol/L). CONCLUSION: Lower serum calcium levels were associated with increased risk of anaemia risk. Moreover, we observed non-linear associations between serum calcium and anaemia risk. Our results need to be confirmed in future prospective studies.

Elevated Blood Selenium Level has a Non-Linear Association with Risk of Anemia in U.S.A. Adults: Data from the NHANES 2011-2016.

BACKGROUND: Only a few epidemiological studies have reported the association between blood selenium and the prevalence of anemia. To date, the evidence is limited and inconsistent. METHODS: We enrolled 9,335 participants (≥ 20 years) who participated in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016 to assess the link between blood selenium and the risk of anemia. Multivariate logistic regression analysis and a generalized additive model (GAM) was applied to assess the relationship between blood selenium and anemia risk. RESULTS: We found a significant adverse association between blood selenium and the prevalence of anemia after adjusting for all potential covariates (OR = 0.98, 95% CI: 0.97, 0.98, p < 0.001). After a sequence of sensitive analyses, the conclusion remains stable (p for trend < 0.001). However, a non-linear relationship was detected based on GAM. We calculated a turning point of 205.89 µg/L using a two-piecewise linear regression model. CONCLUSIONS: When blood selenium level is lower than 205.89 µg/L, blood selenium level is inversely associated with the risk of anemia. Our results provide a new strategy to reduce the risk of anemia.

Association between magnesium intake and the risk of anemia among adults in the United States.

Background: Magnesium deficiency is related to an increased risk of anemia, but epidemiological evidence supporting this association remains scarce. The purpose of the present survey was to evaluate the relationship between dietary magnesium intake and the risk of anemia. Methods: In total, 13,423 participants aged 20-80 years were enrolled using data from the National Health and Nutrition Examination Survey 2011-2016. Magnesium consumption was evaluated using 24 h dietary recalls. Multivariable generalized linear models were developed to demonstrate the association between dietary magnesium intake and the prevalence of anemia. Results: An inverse association between dietary magnesium intake and the risk of anemia was detected based on a full adjustment model. We evaluated magnesium intake as a categorical variable (five quartiles). Compared with the lowest value, the highest multivariate adjusted odds ratio (95% confidence interval) for anemia was 0.64 (0.46-0.89). Stratified analyses revealed a reverse relationship between magnesium intake and anemia in women. However, no significant association was observed in men (p for trend = 0.376). A similar reverse association was found among the older group (aged ≥60 years). Conclusion: Magnesium deficiency is closely related to a higher rate of anemia occurrence, especially among women and older Americans. Further larger-scale prospective studies are required to confirm these conclusions.

Characterization of a novel HBB:c.194dup variant of the ß-globin gene combined with six alpha genes.

ß-thalassemia (ß-thal) is one of the most prevalent inherited blood disorders in Ganzhou, south China. Next-generation sequencing was used to screen for thalassemia carriers in the general population. During the screening, we identified a novel ß-thal variant in a 46-year-old Chinese man, which was validated by Sanger sequencing. Based on the patient's clinical data, this novel mutation was classified as severe ß0. However, the patient was mildly anemic (hemoglobin, 89 g/L), which was inconsistent with typical ß0 carrier characteristics. On further evaluation, quantitative PCR indicated the presence of six α genes, while molecular analysis and pedigree analysis revealed the coexistence of αααanti3.7 and αααanti4.2. Therefore, we report a novel ß-thal variant combined with six α genes. We describe the patient's clinical phenotype and the process of molecular diagnosis. This case extends the spectrum of thalassemia variants.

A novel ß-thalassemia variant at HBB:c.14delC (Codon 4, -C) identified via next-generation sequencing.

OBJECTIVES: ß-Thalassemia (ß-thal) is a genetic disease of the blood caused by mutations in the ß-globin gene. Conventional methods for detecting thalassemia variants often miss rare and novel variants. Identifying the rare and novel ß-thal variants, especially in the high prevalence regions, would enable better disease prevention. METHODS: A Chinese family who had joined the Thalassemia Prevention Program was recruited in this study. The ß-thal carrier screening was performed using next-generation sequencing (NGS), and the results were validated through direct DNA sequencing. Hematological parameters were analyzed, and hemoglobin electrophoresis was performed. Additionally, the presence of thalassemia-associated deletions was determined using gap-polymerase chain reaction. RESULTS: A novel frameshift variant of ß-thal, HBB:c.14delC(Codon 4, -C), was identified in a 31-year-old Chinese man. Subsequent genetic investigation showed that his mother also carried this novel variant. Hematological analysis and clinical evaluation suggested that this variant was present in the heterozygous state and might belong to a severe phenotype of ß-thal. CONCLUSIONS: We identified a novel frameshift variant of ß-thal. NGS has the potential for identifying rare and novel thalassemia variants and broadening the spectrum of thalassemia screening and thus may contribute to effective prevention of thalassemia.

A child with a novel DDX3X variant mimicking cerebral palsy: a case report.

BACKGROUND: Cerebral palsy (CP) is a non-progressive disorder of movement and posture due to a static insult to the brain. In CP, the depth of investigation is guided by the patients' medical history and their clinical examination. Magnetic resonance imaging (MRI) has a high yield and is widely used for investigation in CP. CASE PRESENTATION: In this paper, we report a novel DDX3X variant in a girl afflicted with the X-linked mental retardation-102 (MRX102). The girl had been misdiagnosed with CP in her early life based on a comprehensive clinical evaluation and associated clinical features, such as developmental delay, reduced activities of the arms and legs, and abnormal brain MRI. Subsequently, whole-exome sequencing was applied to better distinguish between CP and actual MRX102 with similar characteristics. CONCLUSIONS: We report on a de novo heterozygous DDX3X variant mimicking cerebral palsy and suggest a thorough and conscientious review during diagnosis of CP.

A 47,XXY Pregnant Woman without the SRY Gene.

Individuals with a 47,XXY karyotype usually present with a male phenotype due to the additional Y chromosome. In this paper, we describe a 47,XXY female who was pregnant with a fetus of the same karyotype based on chromosome analysis of amniotic fluid cells. Further analysis of her Y chromosome indicated that the additional Y chromosome contains no SRY gene on the short arm but carries the azoospermia factor region on the long arm, including azoospermia factor a, b and c (AZFa, AZFb, AZFc). This region may influence her female phenotype. Fertile females with a 47,XXY karyotype and loss of SRY are extremely rare. This paper is the first report of a 47,XXY pregnant woman with a normal phenotype and may enrich our knowledge on 47,XXY individuals.

A Novel ß-Thalassemia Mutation in a Chinese family: IVS-II-203-205 (TCT>CC) (HBB: c.315+203TCT>CC).

ß-Thalassemia (ß-thal) is one of the most common inherited disorders in southern China. More than 300 ß-globin gene mutations around the world have been reported in the HbVar database. In this study, a novel mutation in a 30-year-old Chinese woman [IVS-II-203-205 (TCT>CC), HBB: c.315+203TCT>CC] was first found by direct sequencing. Subsequently, investigation of her parents' genetic codes was completed, and the results showed that her father also carried this mutation. Based on the features observed in clinical practice, this novel mutation was regarded as a mild phenotype of ß-thal.

Diagnostic Value of Serum Epstein-Barr Virus Capsid Antigen-IgA for Nasopharyngeal Carcinoma: a Meta-Analysis Based on 21 Studies.

BACKGROUND: Epstein-Barr virus capsid antigen immunoglobulin A (EBV VCA-IgA) exerts an important role in the diagnosis of nasopharyngeal carcinoma (NPC). This meta-analysis aimed to evaluate the pooled diagnostic performance of VCA-IgA for NPC. METHODS: Literature fulfilling the criteria was searched in PubMed and Embase databases. The quality of the studies was assessed in terms of the Quality Assessment of Diagnosis Accuracy Studies (QUADAS) criteria. The pooled diagnostic parameters were generated using a bivariate meta-analysis model. Statistical analysis was performed based on the platforms of Meta-Disc 1.4 and Stata 12.0 software. The trim and fill adjustment method was applied to further assess the possible effects of publication bias. RESULT: Twenty one studies comprising 2986 NPC patients and 3507 controls were included in this meta-analysis. The overall pooled sensitivity and specificity of serum VCA-IgA for NPC were 0.83 (95%CI: 0.82 - 0.84) and 0.88 (95% CI: 0.87 - 0.89), respectively, accompanied by a pooled diagnostic odds ratio (DOR) of 49.87 and area under curve (AUC) of 0.9390. Moreover, our stratified analyses suggested that combinations of multiple EBV antigens (sensitivity, specificity, DOR, and AUC of 0.93, 0.95, 331.8, and 0.9850, respectively) yielded higher accuracy than single VCA-IgA test (sensitivity, specificity, DOR and AUC of 0.83, 0.88, 49.87, and 0.9393, respectively). Additionally, the immunoenzyme assay (IEA) seemed to be a better alternative for the analysis of serum VCA-IgA level, with a sensitivity of 0.92, specificity of 0.94, and AUC of 0.9644. CONCLUSIONS: Serum VCA-IgA hallmarks promising accuracy in the management of NPC and that parallel tests of multiple EBV antigens may be more suitable for NPC serodiagnosis than single VCA-IgA assay. .151122)