Gestational diabetes mellitus and risk of long-term all-cause and cardiac mortality: a prospective cohort study.

BACKGROUND: To investigate the association between gestational diabetes mellitus (GDM) without subsequent overt diabetes and long-term all-cause and cardiac mortality. METHODS: This prospective cohort study included 10,327 women (weighted population: 132,332,187) with a pregnancy history from the National Health and Nutrition Examination Survey (2007 to 2018). Participants were divided into three groups (GDM alone, overt diabetes, and no diabetes). Mortality data was linked from the National Death Index up to December 31, 2019. Multivariable Cox regression analysis was performed to examine the association between GDM alone and overt diabetes with all-cause mortality and cardiac mortality. Data analysis was performed from October 2022 to April 2023. RESULTS: Among the participants, 510 (weighted 5.3%) had GDM alone and 1862 (weighted 14.1%) had overt diabetes. Over a median follow-up period of 6.7 years (69,063 person-years), there were 758 deaths. The GDM group did not show an increased risk of all-cause mortality (hazard ratio [HR] 0.67; 95% CI, 0.25-1.84), while the overt diabetes group had a significantly higher risk (HR 1.95; 95% CI, 1.62-2.35). Similarly, the GDM group did not exhibit an elevated risk of cardiac mortality (HR 1.48; 95% CI, 0.50-4.39), whereas the overt diabetes group had a significantly higher risk (HR 2.37; 95% CI, 1.69-3.32). Furthermore, sensitivity analysis focusing on women aged 50 or above showed that the HR of GDM history for all-cause mortality was 1.14 (95% CI, 0.33-3.95) and the HR for cardiac mortality was 1.74 (95% CI, 0.49-6.20). CONCLUSIONS: GDM alone was not associated with an increased risk of all-cause and cardiac mortality, while overt diabetes was significantly associated with both types of mortality.

High serum total bilirubin as a potential protective factor for gestational diabetes mellitus: A retrospective cohort study of 92,885 Chinese pregnant women.

AIMS: Identifying physiological factors that could reduce pregnant women's risk for developing gestational diabetes mellitus (GDM) is crucial for early prevention and intervention. We aimed to examine whether higher serum levels of total bilirubin (TBIL) were associated with a decreased risk of GDM. METHODS: We conducted a retrospective cohort study in a tertiary care hospital in Shanghai, China. A total of 92,885 pregnant women were included. Serum TBIL levels were determined during the first antenatal visit before 24 weeks of gestation and GDM was diagnosed with a 75-g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. RESULTS: A total of 13,037 GDM cases were identified, a prevalence of 14.0 % (13,037/92,885). These women had a higher median TBIL concentration 7.9 versus 7.6 mmol/l (P < 0.001). For the 91,051 women with TBIL within the physiologically normal range (≤ 17.1 µmol/l), a one interquartile range increase in TBIL (3.4 µmol/l) was associated with a decreased risk of GDM: adjusted odds ratio (OR)=0.89 [95 % CI 0.87;0.92]. For these women, the adjusted ORs for GDM across TBIL quartiles were: 0.92 [0.88;0.97] for the second, 0.85 [0.81;0.90] for the third, and 0.78 [0.74;0.83] for the fourth quartile in comparison with the first quartile. CONCLUSION: Our study demonstrated that elevated serum TBIL levels were associated with decreased risk of GDM and supported its potential role in the prevention and early intervention of GDM.

Novel LDLR variants affecting low density lipoprotein metabolism identified in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disease of lipid metabolism mainly caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Genetic detection of patients with FH help with precise diagnosis and treatment, thus reducing the risk of coronary heart disease (CHD) and other related diseases. The study aimed to identify the causative gene mutations in a Chinese FH family and reveal the pathogenicity and the mechanism of these mutations. METHODS AND RESULTS: Whole exome sequencing was performed in a patient with severe lipid metabolism dysfunction seeking fertility guidance from a Chinese FH family. Two LDLR variants c.1875 C > G (p.N625K; novel variant) and c.1448G > A (p.W483*) were identified in the family. Wildtype and mutant LDLR constructs were established by the site-direct mutagenesis technique. Functional studies were carried out by cell transfection to evaluate the impact of detected variants on LDLR activity. The two variants were proven to affect LDL uptake and binding, resulting in cholesterol clearance reduction to different degrees. According to The American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines, the W483* variant was classified as "Pathogenic", while the N625K variant as "VUS". CONCLUSIONS: Our results provide novel experimental evidence of functional alteration by LDLR variants identified in our study and expand the mutational spectrum of LDLR mutation induced FH.

Graphitic carbon nitride nanosheets mitigate cadmium toxicity in Glycine max L. by promoting cadmium retention in root and improving photosynthetic performance.

Cadmium (Cd) pollution poses a serious threat to plant growth and yield. Nanomaterials have shown great application potential for alleviation of Cd toxicity to plants. In this study, we applied graphitic carbon nitride nanosheets (g-C3N4 NSs) for alleviation of Cd-toxicity to soybean (Glycine max L.). The g-C3N4 NSs supplementation significantly improved plant growth and reduced oxidative damage in the Cd-toxicated soybean seedlings through hydroponic culture. Particularly, the g-C3N4 NSs dynamically regulated the root cell wall (RCW) components by increasing pectin content and modifying its demethylation via enhancing pectin methylesterase (PME) activity, therefore greatly enhanced stronger RCW-Cd retention (up to 82.8%) and reduced Cd migration to the shoot. Additionally, the g-C3N4 NSs reversed the Cd-induced chlorosis, increased photosynthetic efficiency because of enhancement in Fv/Fm ration, Y(II) and sugars content. These results provide new insights into the alleviation of Cd toxicity to plants by g-C3N4 NSs, and shed light on the application of low-cost and environmental-friendly carbon-based NMs for alleviating heavy metal toxicity to plants.

An exploration of immunohistochemistry-based prognostic markers in patients undergoing curative resections for colon cancer.

BACKGROUND: The immune system recognizes and destroys cancer cells. However, cancer cells develop mechanisms to avoid detection by expressing cell surface proteins. Specific tumour cell surface proteins (e.g. HLA-G, PD-L1, CDX2) either alone or in combination with the relative presence of immune cells (CD3 and CD8 positive T-cells) in the tumour tissue may describe the cancer cells' ability to escape eradication by the immune system. The aim was to investigate the prognostic value of immunohistochemical markers in patients with colon cancer. METHODS: We conducted a retrospective study including patients diagnosed with pT3 and pT4 colon cancers. Immunohistochemical staining with HLA-G, PD-L1, CDX2, CD3, and CD8 was performed on tissue samples with representation of the invasive margin. PD-L1 expression in tumour cells and immune cells was reported conjointly. The expression of CD3 and CD8 was reported as a merged score based on the expression of both markers in the invasive margin and the tumour centre. Subsequently, a combined marker score was established based on all of the markers. Each marker added one point to the score when unfavourable immunohistochemical features was present, and the score was categorized as low, intermediate or high depending on the number of unfavourable stains. Hazard ratios for recurrence, disease-free survival and mortality were calculated. RESULTS: We included 188 patients undergoing colon cancer resections in 2011-2012. The median follow-up was 41.7 months, during which 41 (21.8%) patients had recurrence and 74 (39.4%) died. In multivariable regression analysis positive HLA-G expression (HR = 3.37, 95%CI [1.64-6.93]) was associated with higher recurrence rates, while a preserved CDX2 expression (HR = 0.23, 95%CI [0.06-0.85]) was associated with a lower risk of recurrence. An intermediate or high combined marker score was associated with increased recurrence rates (HR = 20.53, 95%CI [2.68-157.32] and HR = 7.56, 95%CI [1.06-54.16], respectively). Neither high expression of PD-L1 nor high CD3-CD8 score was significantly associated with recurrence rates. Patients with a high CD3-CD8 score had a significantly longer DFS and OS. CONCLUSIONS: In tumour cells, expression of HLA-G and loss of CDX2 expression were associated with cancer recurrence. In addition, a combination of certain tumour tissue biomarkers was associated with colorectal cancer recurrence.

[Increasing incidence of colorectal cancer in young patients].

For the past decades, an increase in the incidence of colorectal cancer in young patients has been reported in several countries, including Denmark, and efforts need to be taken in order to halt this tendency. This review characterises the clinical and pathological attributes of young patients with early-onset colorectal cancer (EOCRC). Risk factors such as smoking and sedentary lifestyle have been found to be associated with EOCRC. Further studies are needed to evaluate, if the age of patients entering the Danish screening programme for bowel cancer should be lowered.

An Automated Rapid Iterative Negative Geotaxis Assay for Analyzing Adult Climbing Behavior in a Drosophila Model of Neurodegeneration.

Neurodegenerative diseases are frequently associated with a progressive loss of movement ability, reduced life span, and age-dependent neurodegeneration. To understand the mechanism of these cellular events, and their causal relationships with each other, Drosophila melanogaster, with its sophisticated genetic tools and diverse behavioral features, are used as disease models for assessing neurodegenerative phenotypes. Here we describe a high-throughput method to analyze Drosophila adult negative geotaxis behavior, as an indication for possible motor defects associated with neurodegeneration. An automated machine is designed and developed to drive fly synchronization using an initial electric impulse, later allowing the recording of negative geotaxis behavior over a course of secs to mins. Images from the digitally recorded video are then processed with the self-designed RflyDetection software for statistical data manipulation. Different from the manually controlled negative geotaxis assay based on single fly, this precise, fast, and high-throughput protocol allows data acquisition from more than hundreds of flies simultaneously, providing an efficient approach to advance our understanding in the underlying mechanism of locomotor deficits associated with neurodegeneration.