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.

The effect of serum calcium on the association of depression with infertility among U.S. women.

This study aimed to explored the association between depressive symptoms and infertility among U.S. women, and the effect of serum calcium on this association. We used data from the National Health and Nutrition Examination Survey (2013-2018), relating to women aged 20-45 years. Depressive symptoms were determined using the nine-item Patient Health Questionnaire (PHQ-9 scores ≥10), and interview data were used to identify self-reported infertility. Of 2708 women (mean age: 32.7 ± 7.5 years), 274 were depressed and 12.0 % self-reported being "ever-infertile." Depressive symptoms were associated with infertility in multivariable logistic regression (OR, 1.62; 95 % CI, 1.11-2.38). Depressive symptoms were associated with infertility among participants who were obese (OR, 1.68; 95 % CI, 1.03-2.74), had not received psychological counseling (OR, 1.60; 95 % CI, 1.03-2.50), were antidepressant users (OR 3.22; 95 % CI, 1.15-9.00), and had high serum calcium levels (OR, 2.05; 95 % CI, 1.25-3.35). A significant interaction between serum calcium and depression was observed for infertility (P = .038, interaction likelihood ratio test). In sensitivity analyses, the association between depressive symptoms and infertility remained after excluding women aged ≥35 years (OR, 1.87; 95 % CI, 1.08-3.23), lowering the cut-off for PHQ-9 scores (≥5) (OR, 1.48; 95 % CI, 1.12-1.96), excluding women with some gynecological diseases (OR, 1.63; 95 % CI, 1.07-2.49), and using inverse probability of treatment weighting (OR, 1.64; 95 % CI, 1.17-2.31). Conclusion: Our findings indicate that depression is associated with infertility among U.S. women and serum calcium may have an effect on the association. Interventions such as serum calcium reduction, weight management and psychosocial counseling for infertility treatment in individuals with depression may be integrated into routine clinical practice. Additionally, more caution could be exercised when using antidepressants.

Prevalence and genetic analysis of triplicated α-globin gene in Ganzhou region using high-throughput sequencing.

α-globin gene triplication carriers were not anemic in general, while some studies found that α-globin gene triplication coinherited with heterozygous ß-thalassemia may cause adverse clinical symptoms, which yet lacks sufficient evidence in large populations. In this study, we investigated the prevalence and distribution of α-globin gene triplication as well as the phenotypic characteristics of α-globin gene triplication coinherited with heterozygous ß-thalassemia in Ganzhou city, southern China. During 2021-2022, a total of 73,967 random individuals who received routine health examinations before marriage were genotyped for globin gene mutations by high-throughput sequencing. Among them, 1,443 were α-globin gene triplication carriers, with a carrier rate of 1.95%. The most prevalent mutation was αααanti3.7/αα (43.10%), followed by αααanti4.2/αα (38.12%). 42 individuals had coinherited α-globin gene triplication and heterozygous ß-thalassemia. However, they did not differ from the individuals with heterozygous ß-thalassemia and normal α-globin (αα/αα) in terms of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels. In addition, heterogenous clinical phenotypes were found in two individuals with the same genotype. Our study established a database of Ganzhou α-globin gene triplication and provided practical advice for the clinical diagnosis of α-globin gene triplication.

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.

Dietary zinc intake and body mass index as modifiers of the association between household pesticide exposure and infertility among US women: a population-level study.

Clinical studies on the relationship between pesticide exposure at home and infertility in the general population are scarce. Whether the antioxidant nutrients or other health-related factors affect the pesticide-infertility relationship remains unknown. This nationwide study screened 29,400 participants of the National Health and Nutrition Examination Surveys conducted between 2013 and 2018. The participants were subdivided according to dietary zinc intake based on the recommended dietary allowances as the low-zinc and high-zinc groups (< 8 and ≥ 8 mg/day, respectively), and according to body mass index (BMI; cut-off 28 kg/m2) as the low-BMI and high-BMI groups. Participants who were exposed to pesticides at home had an increased risk of infertility (odds ratio [OR] = 1.56, 95% confidence intervals [CI]: 1.06-2.29). The incidence of infertility differed in low-zinc and high-zinc groups (OR, 95% CI: 2.38, 1.40-4.06 vs. 0.98, 0.53-1.79, respectively), indicating an interaction between pesticide exposure and zinc intake in households (P = 0.047), which suggests that a zinc-rich diet may reduce the risk of pesticide-induced infertility. Similarly, the relationship between pesticide exposure and infertility risk differed in the low-BMI and high-BMI groups (OR, 95% CI: 0.90, 0.42-1.93 vs. 2.23, 1.39-3.58, respectively; P = 0.045), suggesting that high BMI may intensify the infertility risk caused by pesticide exposure. These new findings reveal the antagonistic and synergistic effect of zinc and obesity, respectively, in pesticide-induced infertility risk and suggest that individuals who are obese and on a low-zinc diet may be more susceptible to infertility induced by household pesticide exposure.

Dietary Magnesium Intake Ameliorates the Association Between Household Pesticide Exposure and Type 2 Diabetes: Data From NHANES, 2007-2018.

Aims/Hypothesis: This study aimed to explore whether household pesticide exposure in the general population increased the risk of developing type 2 diabetes and whether intake of dietary magnesium could lower type 2 diabetes from household pesticide exposure. Methods: For this cross-sectional study, we obtained the data of 9,187 United States adults from the National Health and Nutrition Examination Surveys, 2007-2018. Participants were subdivided into two groups based on the amount of daily dietary magnesium in the population: low group: <175 mg/day and high group: ≥175 mg/day. Using multivariable logistic regression analysis, we evaluated the relationship between pesticide exposure in the home and type 2 diabetes. Results: Compared to those unexposed at home, individuals who were exposed to pesticides in their households had a relatively higher odds ratio for type 2 diabetes (OR = 1.22, 95% CI: 1.04-1.44). The association of pesticide exposure in the home with the incidence of type 2 diabetes was different for low and high dietary magnesium groups, OR = 1.66, 95% Cl: 1.19-2.33 vs. OR = 1.1, 95% Cl: 0.92-1.32, respectively. An interaction (P = 0.035) between household pesticide exposure and magnesium intake, suggested that high dietary magnesium intake may reduce the risk of developing type 2 diabetes from pesticide exposure. Conclusions: Household pesticide exposure in the general population is associated with an elevated risk of type 2 diabetes. We report for the first time possible clinical relevance in that high magnesium intake may ameliorate the increased risk of type 2 diabetes from pesticide exposure.

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.

The efficacy and safety of Sacubitril/Valsartan in the treatment of chronic heart failure: a meta-analysis.

OBJECTIVE: A meta-analysis of the studies involving Sacubitril/Valsartan in chronic heart failure was performed to compare the efficacy and safety of Sacubitril/Valsartan with traditional drug therapy in chronic heart failure. METHODS: We searched databases from PubMed, EMBASE, the Cochrane Library, Web of Science, and clinicaltrials.gov for studies published between 2010 and 2020 that reported efficacy and safety following Sacubitril/Valsartan administration. RESULTS: Ten studies enrolling 1689 patients were included. Sacubitril/Valsartan outperformed traditional medicine (especially the Non-ARNI group) in terms of blood pressure, biomarkers and cardiac reverse remodeling indices, with striking changes in left ventricular ejection fraction, systolic blood pressure. Sacubitril/Valsartan showed significant benefit in renal function in patients with chronic heart failure. CONCLUSIONS: Compared with traditional drugs, Sacubitril/Valsartan significantly improved echocardiography, vital signs and biomarkers of patients with chronic heart failure, and reduced the incidence of hyperkalemia, renal dysfunction and other adverse reactions. Further large sample trials are needed in the future to determine the long-term effects of Sacubitril/Valsartan on efficacy and safety in patients with chronic heart failure.

Elevated Hb A2 is Not Always Indicative of ß-Thalassemia.

Hb A2 levels are usually high in carriers of ß-thalassemia (ß-thal). These levels also provide a sensitive marker for the identification of hemoglobin (Hb) variants. In this study, we aimed to examine two patients from two Chinese families who showed elevated Hb A2 levels but did not show any signs of ß-thal. The HBB variants were analyzed using direct sequencing of HBB and in silico prediction analysis. Moreover, the family's genetic history was investigated. We examined two probands from different Chinese families with elevated Hb A2 levels who were not afflicted with ß-thal, although several nucleotide changes were found at codon 81 (CTC>CTA) (HBB: c.246C>A) in Family 1 and a compound heterozygosity for codon 40 (AGG>AAG) (HBB: c.122G>A) and IVS-II-478 (C>A) (HBB: c.316-373C>A) in Family 2. After investigating the genetic history of both families including the ß-thal aspect, we found that these mutations were not responsible for the elevated Hb A2 levels. It is rarely reported that high Hb A2 level is not indicative of ß-thal. In contrast, low or normal Hb A2 level is always found with ß-thal due to other molecular defects that mask their ß-thal genotype. Our results highlight the importance of considering the genetic factors related and unrelated to ß-thal to improve the accuracy of future genetic counseling.

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.