Combined exposure to multiple essential elements and cadmium at early pregnancy on gestational diabetes mellitus: a prospective cohort study.

Background: Minerals and trace elements were involved in the pathogenesis and progression of diabetes. However, the association of mixed exposure to essential elements and toxic elements with gestational diabetes mellitus (GDM) is poorly understood. Objective: This study aims to examine the associations between serum calcium (Ca), iron (Fe), zinc (Zn), copper (Cu), magnesium (Mg), and cadmium (Cd) concentrations in early pregnancy and GDM risk in Chinese pregnant women. Method: A total of 1,168 pregnant women were included in this prospective cohort study. The concentrations of serum elements were measured using the polarography method before 14 gestational weeks and an oral glucose tolerance test was conducted at 24-28 gestational weeks to diagnose GDM. Binary logistic regression analysis and restricted cubic spline were applied to evaluate the association between serum individual element and GDM. Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression were used to assess the associations between mixed essential elements and Cd exposure and GDM risk. Results: The mean concentrations of Zn (124.65 vs. 120.12 µmol/L), Fe (135.26 vs. 132.21 µmol/L) and Cu (23.33 vs. 23.03 µmol/L) in the GDM group were significantly higher than those in the control group. Single-element modeling results suggested that second and fourth-quartile maternal Zn and Fe concentration, third and fourth-quartile Cu concentration and fourth-quartile Ca concentration were associated with an increased risk of GDM compared to first-quartile values. Restricted cubic spline analysis showed U-shaped and non-linear relationships between Cd and GDM. According to the BKMR models and WQS analyses, a six-element mixture was significantly and positively associated with the risk of GDM. Additionally, Cd, Zn, and Cu contributed the most strongly to the association. Conclusion: Serum Zn, Cu, Fe, and Ca exposure during early pregnancy showed a positive association with GDM in the individual evaluation. The multiple-evaluation showed that high levels of elements mixture, particularly Cd, Zn, and Cu, may promote the development of GDM.

Sarcopenia and mild kidney dysfunction and risk of all-cause and cause-specific mortality in older adults.

BACKGROUND: Sarcopenia has been identified as a risk factor for increased mortality in individuals with CKD. However, when considering individuals with mild kidney dysfunction prior to CKD, the impact of sarcopenia on adverse outcomes, particularly mortality, remains uncertain. METHODS: This study included 323 801 participants from the UK Biobank. Mild kidney dysfunction was defined as eGFR between 60 and 89.9 mL/min/1.73 m2, and sarcopenia was defined according to the criteria of the 2019 European Working Group of Sarcopenia in Older People. Cox proportional hazard models with inverse probability weighting and competing risk models were used for analysis. RESULTS: During a median follow-up of 11.8 years, 20 146 participants died from all causes. Compared with participants with normal kidney function and without sarcopenia, those with mild kidney dysfunction or sarcopenia had significantly increased risks of all-cause mortality [hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.12 to 1.19; HR: 1.29, 95% CI: 1.20 to 1.37]; those with both mild kidney dysfunction and sarcopenia had an even higher risk of all-cause mortality (HR: 1.61, 95% CI: 1.52 to 1.71), with a significant overall additive interaction (relative risk due to interaction 0.17, 95% CI: 0.05 to 0.29). Further subgroup analyses revealed that the associations of probable sarcopenia with all-cause and cause-specific mortality (non-accidental cause, non-communicable diseases, and cancer) were stronger among participants with mild kidney dysfunction than those with normal kidney function. CONCLUSIONS: The study indicates that sarcopenia and mild kidney dysfunction synergistically increase the risk of all-cause and cause-specific mortality. Early recognition and improvement of mild kidney function or sarcopenia in older people may reduce mortality risk but would require more prospective confirmation.

Meta-analysis of efficacy of Chinese medicine compound combined with concurrent radiotherapy and chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma is a prevalent malignant tumor in clinical practice, with the highest incidence rate among otorhinolaryngological malignant tumors. OBJECTIVES: This study aims to comprehensively evaluate the clinical efficacy and safety of traditional Chinese medicine compound (CMC) combined with concurrent radiotherapy and chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: Relevant essays published before November 20, 2021, were retrieved from China National Knowledge Internet (CNKI), China Science and Technology Journal Database (CQVIP), Wanfang database, PubMed, and Web of Science databases. Randomized controlled trials regarding the clinical efficacy of CMC combined with concurrent radiotherapy and chemotherapy in the treatment of LA-NPC were included. RESULTS: A total of 15 publications involving 1324 patients were included in this study, including 665 in the experimental group and 659 in the control group. Meta-analyses revealed that compared with radiotherapy or chemotherapy only, CMC combined with concurrent radiotherapy and chemotherapy for LA-NPC significantly improved the efficacy [risk ratio (RR)=1.15, 95% confidence interval (95% CI) (1.09, 1.20), P<0.00001], the quality of life [RR=1.35, 95% CI (1.13, 1.62), P=0.0009], immune function indices CD4+ levels [RR=6.2, 95% CI (3.64, 8.76), P<0.00001], CD4+/CD8+ [RR=0.33, 95% CI (0.14, 0.53), P=0.0009], and alleviated the decrease in white blood cell counts [RR=0.67, 95% CI (0.52, 0.86), P=0.002]. CONCLUSION: CMC combined with concurrent radiotherapy and chemotherapy for the treatment of LA-NPC can significantly improve the efficacy and reduce severe adverse reactions caused by conventional radiotherapy and chemotherapy. However, due to limitations in the quantity and quality of the included studies, more high-quality, multi-center, and large sample-size studies are needed to provide high-level and high-quality medical evidence for systematic evaluation.

Meta-analysis of risk factors associated with pharyngocutaneous fistulas following total laryngectomy.

BACKGROUND: To investigate the risk factors for pharyngocutaneous fistulas following total laryngectomy. METHODS: PubMed, Web of Science, CNKI, Medline and Wanfang database were utilized to conduct a systematic literature research. Further, sensitivity and publication bias were analyzed to comprehensively estimate the risk factors associated with pharyngocutaneous fistulas following total laryngectomy. RESULTS: Of the 112 studies identified, 25 were included in this analysis. The results showed that age (OR = 0.21, 95% CI 0.11-0.39, P<0.00001), smoking (OR = 3, 95% CI 1.54-5.84, P<0.00001), T-stage (OR = 0.3, 95% CI 0.22-0.4, P<0.00001), previous radiotherapy (OR = 0.31, 95% CI 0.23-0.44, P<0.000001) and preoperative albumin (OR = 0.28, 95% CI 0.16-0.47, P<0.00001) were risk factors associated with pharyngocutaneous fistulas. CONCLUSIONS: This review is a comprehensive analysis of the risk factors associated with pharyngocutaneous fistulas following total laryngectomy. Age, smoking, T-stage, previous radiotherapy and preoperative albumin were found to be the risk factors.

Gut microbial DL-endopeptidase alleviates Crohn's disease via the NOD2 pathway.

The pattern-recognition receptor NOD2 senses bacterial muropeptides to regulate host immunity and maintain homeostasis. Loss-of-function mutations in NOD2 are associated with Crohn's disease (CD), but how the variations in microbial factors influence NOD2 signaling and host pathology is elusive. We demonstrate that the Firmicutes peptidoglycan remodeling enzyme, DL-endopeptidase, increased the NOD2 ligand level in the gut and impacted colitis outcomes. Metagenomic analyses of global cohorts (n = 857) revealed that DL-endopeptidase gene abundance decreased globally in CD patients and negatively correlated with colitis. Fecal microbiota from CD patients with low DL-endopeptidase activity predisposed mice to colitis. Administering DL-endopeptidase, but not an active site mutant, alleviated colitis via the NOD2 pathway. Therapeutically restoring NOD2 ligands with a DL-endopeptidase-producing Lactobacillus salivarius strain or mifamurtide, a clinical analog of muramyl dipeptide, exerted potent anti-colitis effects. Our study suggests that the depletion of DL-endopeptidase contributes to CD pathogenesis through NOD2 signaling, providing a therapeutically modifiable target.

A pilot study: effect of erythrocyte lifespan determined by a modified carbon monoxide breath test on glycosylated hemoglobin interpretation.

Glycosylated hemoglobin (HbA1c) is an important criterion for the diagnosis of diabetes and an indicator of the blood glucose level. The red blood cell (RBC) lifespan heterogeneity is sufficient to influence the HbA1c interpretation. In this study, we recruited 120 patients with diabetes mellitus and 85 nondiabetic controls. The HbA1c and the RBC lifespan were detected by high-performance liquid chromatography and the advanced carbon monoxide breath detection method, respectively. Potential correlations of gender and age with HbA1c were analyzed and a receiver operator characteristic curve was generated to get the HbA1c cut-off for every RBC lifespan group. It was confirmed that HbA1c has no correlation with gender or age. The correlation formula between the HbA1c diagnostic criteria and RBC lifespan was derived to correct the HbA1c diagnostic criteria using the least-square method. The RBC-lifespan-corrected HbA1c diagnostic criteria provided 100% sensitivity and specificity for the diagnosis of diabetes in the experimental set and was not refuted in the validated set. The diagnostic value of HbA1c is positively correlated with the RBC lifespan, and four patients with hyperglycemia, whose HbA1c values were lower than the general diagnosis criterion of 6.5%, were still considered to be diabetic according to this formula; that is, the application of this formula may help us to eliminate the 2.2% misdiagnosis rate of the current diagnostic criteria. To provide more accurate detection results, the effect of the RBC lifespan needs to be taken into account when HbA1c is used as a clinical indicator.

Relationship between glycated haemoglobin concentration and erythrocyte survival in type 2 diabetes mellitus determined by a modified carbon monoxide breath test.

In clinical practice, an unexplained discordance between percentage haemoglobin A1c (HbA1c) and the progression of diabetes and its complication is observed. HbA1c is determined by the blood glucose level and the red blood cell (RBC) lifespan. Whether the RBC lifespan changes in diabetic patients remains undefined because of the lack of a convenient and accurate measurement method. In the present study, we aim to observe the RBC lifespan in type 2 diabetic patients with poor blood glucose control by an endogenous carbon monoxide (CO) measurement using a rapid and simplified CO breath test machine. The RBC lifespan, age, RBC count, haemoglobin, haematocrit, fasting blood glucose (FBG) level, HbA1c, blood lipids and the liver and kidney function were compared between 38 diabetic patients and 40 healthy individuals. Compared with the control group, in the diabetic patients, the RBC lifespan was significantly decreased by 17.52 ± 4.58 (86.08 ± 18.13 d versus 103.6 ± 22.02 d, p = 0.00). Although a univariate linear correlation analysis showed that the RBC lifespan was negatively correlated with the FBG level (r = -0.386, p = 0.000), haemoglobin A1c (r = -0.346, p = 0.002) and age (r = -0.291, p = 0.010), a stepwise multiple linear regression analysis showed that the RBC lifespan was most affected by the FBG level (t = -3.554, p = 0.001), but not by HbA1c or age, while HbA1c was most affected by the FBG level (t = 13.989, p = 0.000), but not the RBC lifespan. The RBC lifespan in diabetic patients with poor glycaemic control was reduced. The decrease in the RBC lifespan caused by hyperglycaemia was not associated with HbA1c. Thus, a decrease in the RBC lifespan will lead to an underestimation of the actual level of hyperglycaemia and the progression of disease by HbA1c in type 2 diabetic patients if we do not adjust the RBC lifespan.

Forkhead Protein FoxO1 Acts as a Repressor to Inhibit Cell Differentiation in Human Fetal Pancreatic Progenitor Cells.

Our colleagues have reported previously that human pancreatic progenitor cells can readily differentiate into insulin-containing cells. Particularly, transplantation of these cell clusters upon in vitro induction for 3-4 w partially restores hyperglycemia in diabetic nude mice. In this study, we used human fetal pancreatic progenitor cells to identify the forkhead protein FoxO1 as the key regulator for cell differentiation. Thus, induction of human fetal pancreatic progenitor cells for 1 week led to increase of the pancreatic ß cell markers such as Ngn3, but decrease of stem cell markers including Oct4, Nanog, and CK19. Of note, FoxO1 knockdown or FoxO1 inhibitor significantly upregulated Ngn3 and insulin as well as the markers such as Glut2, Kir6.2, SUR1, and VDCC, which are designated for mature ß cells. On the contrary, overexpression of FoxO1 suppressed the induction and reduced expression of these ß cell markers. Taken together, these results suggest that FoxO1 may act as a repressor to inhibit cell differentiation in human fetal pancreatic progenitor cells.

Dihydroartemisinin inhibits cell proliferation by induced G1 arrest and apoptosis in human nasopharyngealcarcinoma cells.

CONTEXT: Dihydroartemisinin (DHA) exhibits anticancer activity in a number of human cancer cells. However, it is still unknown whether DHA has anticancer effect on nasopharyngeal cancer (NPC) cells. AIMS: To investigate the anticancer activity of DHA on CNE-2 cells. MATERIALS AND METHODS: Cell cycleand invasion assay were used to detect the effect of DHA on CNE-2 cells. Protein molecular differences were examined by Western blot. RESULTS: DHA strongly inhibited cell proliferation by induced cell cycle G1 arrest and apoptosis in CNE-2 cells. In addition, cell motility, invasion, and colony formation were suppressed by DHA. CONCLUSIONS: DHA shows significant anticancer effects on human NPC cells, and may be a preventive and therapeutic agent against NPC.

Go is required for the release of IL-8 and TNF-α, but not degranulation in human mast cells.

Mast cells activated by IgE-dependent and -independent mechanisms play important roles in innate and acquired immune responses. Activation of pertussis toxin (PTX)-sensitive Gi/o proteins is the key step in mast cell degranulation and release of de novo synthesized inflammatory mediators through IgE-independent mechanism. However, the roles of Gi and Go proteins in mast cells activation have not yet been differentiated. In the current study, the functional roles of Go proteins in the activities of LAD2 cells, a human mast cell line, are identified. Knockdown of Gαo expression significantly inhibited the synthesis of IL-8 and TNF-α from substance P activated LAD2 cells but demonstrated no effect on degranulation. This effect was associated with the activation of Erk and JNK/MAPKs signaling, whereas PI3K-Akt, calcium mobilization and NFAT translocation remained unchanged. These results suggest that Gi and Go proteins differentially regulate human mast cells activities through activating distinct signaling cascades.

[Apoptosis of nasopharyngeal carcinoma cells line CNE-2 induced by dihydroartemisinin and its possible mechanism].

OBJECTIVE: Dihydroartemisinin is a traditional anti-malarial drug, a derivative of the artemisinin, it has anti-tumor activity of a variety of tumor cells. This study investigated the effect of growth inhibition of nasopharyngeal carcinoma cells line CNE-2 induced by dihydroartemisinin and its possible mechanism. METHOD: The effect of DHA on the cell proliferation of CNE-2 was detected by CCK-8 assay with different concentrations and time. The effects of DHA on the cell apoptosis of CNE-2 were detected by Annexin V-FITC assay through flow cytometry and caspase-3 activity assay. RESULT: CCK-8 experimental results show that CNE-2 cell proliferation was suppressed with DHA treatment, as compared with the control group. DHA could induce marked apoptosis in CNE-2 by apoptosis assay, as compared with the control group, The percentages of apoptotic cells increased along with the increase of DHA concentrations in CNE-2; The activity of caspase-3 was increased following DHA treatment in a dose-dependent manner. CONCLUSION: DHA could effectively inhibit proliferation and induce apoptosis of human nasopharyngeal carcinoma cells line CNE-2, the possible mechanism DHA induce apoptosis of CNE-2 cells by upregulating the expression of caspase-3.

[The effect of smoking on resting energy expenditure in patients with early diabetic kidney disease].

OBJECTIVE: To study the effect of smoking on resting energy expenditure (REE) and the relationships among REE, smoking, inflammation and oxidative stress in patients with diabetic kidney disease. METHODS: A case control study of 31 smokers and 40 non-smokers with early stage of diabetic kidney disease (stage III) were performed to evaluate the chronic effect of smoking on REE. REE/fat free mass (FFM), biomarkers of oxidative stress malondialdehyde (MDA), superoxide dismutase (SOD) and inflammation high-sensitivity C-reactive protein (hs-CRP), adiponectin, TNFα were also measured in these subjects. Data were analyzed by Pearson correlation analysis. RESULTS: Compared with non-smokers, REE/FFM in smokers group was significantly increased by 15.96% (P = 0.001). Pearson analysis showed that smoking was significantly correlated with REE/FFM (t = 0.395, P = 0.001). There were significantly different between smokers and non-smokers in MDA, SOD and hs-CRP (P < 0.05). But no difference between two groups in adiponectin and TNFα (P > 0.05). No significant relationships between REE/FFM and MDA, SOD, hs-CRP, adiponectin, TNFα was found (P > 0.05). CONCLUSION: Chronic smoking can lead to increased REE, arouse oxidative stress and inflammatory in patients with early stage of diabetic kidney disease. However, there is no relationship between increased REE due to smoking and oxidative stress and inflammatory.