BACKGROUND: The benefits of ideal cardiovascular-health metrics (ICVHMs) in patients with renal insufficiency remain unclear. This study aimed to investigate the associations between ICVHM and prognosis in a renal insufficiency population. METHODS: The trial enrolled 29,682 participants from the US National Health and Nutrition Examination Survey (NHANES), 2007-2018, with mortality follow-up through December 31, 2019. Participants were divided into three groups based on estimated glomerular filtration rates. Cardiovascular health was assessed using new "Life's Essential 8" metrics. Cox regression analyses based on NHANES data were used to determine the associations between ICVHMs and cardiovascular mortality in patients with renal insufficiency. RESULTS: During a mean follow-up of 6.58 years, ideal cardiovascular health (hazard ratio [HR] = 0.42; 95% confidence interval [CI]; 0.25-0.70) and ideal health behavior (HR = 0.53; 95% CI; 0.39-0.73) reduced cardiovascular mortality in participants with renal insufficiency. For each one ICVHM increment, a 25% reduction in cardiovascular mortality was recorded (95% CI; 0.69-0.82). When compared with participants with normal renal function, for those with mild renal insufficiency, the HR for cardiovascular mortality gradually decreased from 1.47 (95% CI; 0.85-2.52) in those who had ≤1 ICVHMs to 0.30 (95% CI; 0.12-0.77) in participants who had >6 ICVHMs. CONCLUSIONS From an ICVHM perspective, enhanced cardiovascular benefits were observed in individuals with renal insufficiency, coupled with a reduced risk of all-cause mortality. Furthermore, when compared with individuals with normal renal function, increased ICVHMs can mitigate adverse risks associated with renal impairment.
Humans ; Male ; Female ; Nutrition Surveys ; Middle Aged ; Renal Insufficiency/physiopathology* ; Aged ; Prognosis ; Adult ; Cardiovascular Diseases/mortality* ; Glomerular Filtration Rate/physiology* ; Proportional Hazards Models

Tricellulin, a key tricellular tight junction (TJ) protein, is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands. This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren's syndrome (SS). Employing a multifaceted approach involving patient biopsies, non-obese diabetic (NOD) mice as a SS model, salivary gland acinar cell-specific tricellulin conditional knockout (Tric^CKO) mice, and IFN-γ-stimulated salivary gland epithelial cells, we investigated the role of tricellulin in SS-related hyposalivation. Our data revealed diminished levels of tricellulin in salivary glands of SS patients. Similarly, NOD mice displayed a reduction in tricellulin expression from the onset of the disease, concomitant with hyposecretion and an increase in salivary albumin content. Consistent with these findings, Tric^CKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals. Mechanistically, the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin. Treatment with AT1001, a TJ sealer, ameliorated epithelial barrier dysfunction, restored tricellulin expression, and consequently alleviated hyposalivation in NOD mice. Importantly, treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage. Collectively, we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS. Our findings highlight tricellulin as a potential therapeutic target for hyposecretion, particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
Sjogren's Syndrome/complications* ; Animals ; Xerostomia/etiology* ; Mice ; Mice, Inbred NOD ; MARVEL Domain Containing 2 Protein/metabolism* ; Humans ; Mice, Knockout ; Disease Models, Animal ; Interferon-gamma ; Salivary Glands/metabolism* ; Tight Junctions/metabolism* ; MicroRNAs/metabolism* ; Female

Objective:To explore the application effect of preoperative autologous blood localization method in laparoscopic resection of gastric stromal tumors in unfavorable areas of the stomach.Methods:A retrospective analysis was conducted on the case data of 40 patients with gastric stromal tumors in unfavorable locations admitted to Jinjiang Hospital from January 2019 to December 2022. The patients were divided into a control group (intraoperative endoscopic localization method) and an autologous blood localization group according to different intraoperative lesion localization methods, with 20 cases in each group. The surgical time, intraoperative blood loss, hospitalization time, postoperative exhaust time, and adverse reactions were compared between the two groups.Results:The surgery time of the autologous blood localization group was shorter than that of the control group [(92.30±8.80)min vs (108.20±14.87)min, P<0.05]. There was no statistically significant difference in intraoperative bleeding, hospitalization time, and postoperative exhaust time between the two groups (all P>0.05). Two groups of patients did not show an increase in inflammatory indicators such as white blood cells and C-reactive protein on the day after surgery. Both groups of patients did not experience adverse reactions such as fever, abdominal pain, or postoperative complications. Conclusions:The autologous blood injection localization method provides a safe, simple, and effective method for preoperative localization of gastric stromal tumors in unfavorable areas of the stomach under laparoscopy, and is worthy of clinical promotion and use.

BACKGROUND: Sjögren's syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. The treatment is still challenging. This study aimed to explore the therapeutic role and mechanism of exosomes obtained from the supernatant of stem cells derived from human exfoliated deciduous teeth (SHED-exos) in sialadenitis caused by SS. METHODS: SHED-exos were administered to the submandibular glands (SMGs) of 14-week-old non-obese diabetic (NOD) mice, an animal model of the clinical phase of SS, by local injection or intraductal infusion. The saliva flow rate was measured after pilocarpine intraperitoneal injection in 21-week-old NOD mice. Protein expression was examined by western blot analysis. Exosomal microRNA (miRNAs) were identified by microarray analysis. Paracellular permeability was evaluated by transepithelial electrical resistance measurement. RESULTS: SHED-exos were injected into the SMG of NOD mice and increased saliva secretion. The injected SHED-exos were taken up by glandular epithelial cells, and further increased paracellular permeability mediated by zonula occluden-1 (ZO-1). A total of 180 exosomal miRNAs were identified from SHED-exos, and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway might play an important role. SHED-exos treatment down-regulated phospho-Akt (p-Akt)/Akt, phospho-glycogen synthase kinase 3β (p-GSK-3β)/GSK-3β, and Slug expressions and up-regulated ZO-1 expression in SMGs and SMG-C6 cells. Both the increased ZO-1 expression and paracellular permeability induced by SHED-exos were abolished by insulin-like growth factor 1, a PI3K agonist. Slug bound to the ZO-1 promoter and suppressed its expression. For safer and more effective clinical application, SHED-exos were intraductally infused into the SMGs of NOD mice, and saliva secretion was increased and accompanied by decreased levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and Slug and increased ZO-1 expression. CONCLUSION Local application of SHED-exos in SMGs can ameliorate Sjögren syndrome-induced hyposalivation by increasing the paracellular permeability of glandular epithelial cells through Akt/GSK-3β/Slug pathway-mediated ZO-1 expression.
Mice ; Animals ; Humans ; Sjogren's Syndrome/therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Tight Junctions/metabolism* ; Glycogen Synthase Kinase 3 beta ; Mice, Inbred NOD ; Phosphatidylinositol 3-Kinases/metabolism* ; Exosomes/metabolism* ; Xerostomia ; Phosphatidylinositol 3-Kinase ; MicroRNAs/genetics*

Global developmental delay/intellectual disability (GDD/ID) is an enormous group of neurodevelopmental disorders with diverse clinical and genetic heterogeneity. The estimated prevalence of GDD/ID was 1%-3%, affecting about 150 million people. GDD/ID is one of the leading causes of disability in children worldwide. The causes of GDD/ID are complex, comprising genetic and environmental factors. It is often co-morbid with a variety of psychiatric behavioral disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder. Owing to the improvement of genetic technology, monogenic GDD/ID has been one of the hot-spot research in genomic era, and the relevant preventive measures deserve extensive attention. In this review, we summarized the advances in genetics and prevention of monogenic GDD/ID.

Objective:To summarize the prenatal diagnostic characteristics of monogenic global developmental delay/intellectual disability(GDD/ID) pedigrees.Methods:This study retrospectively collected the prenatal molecular diagnostic results of 43 pedigrees that were affected with monogenic GDD/ID in the genetic counseling clinic of Peking University First Hospital from January 2015 to June 2019. The results of prenatal molecular tests were validated after birth or pregnancy termination. Pregnancy outcomes and healthy condition of the offspring were followed up. All data were analyzed by descriptive statistical analysis.Results:Among the 43 pedigrees, 24 were affected with autosomal recessive inheritance (AR) GDD/ID, in which six (25%) fetuses were found to carry two pathogenic variants; 13 (55%) had only one pathogenic variant; five (20%) did not harbor any variant. GDD/ID inherited in an autosomal dominant inheritance (AD) pattern was found in 13 pedigrees, in which 11 fetuses carried no variants while the other two fetuses had the same variants as the proband had (in one pedigree, a low-level variant was detected in the peripheral blood sample of the father while absent in peripheral blood samples of parents in the other pedigree, so it was suspected that the variants of these two affected fetuses were inherited from parental mosaicism). In the other six pedigrees with X-linked inheritance (XL) of GDD/ID, one male fetus was found to harbor the pathogenic variant, while no variants were detected in the others. Maternal contamination was excluded in all prenatal samples using short tandem repeat for linkage analysis. Postnatal validations were consistent with the prenatal tests. All nine affected fetuses were terminated, and the other thirty-four children were delivered and in good health.Conclusions:Prenatal molecular diagnostic test is an effective method to detect pathogenic variants during the first and second trimesters for pedigrees affected by monogenic GDD/ID. For pedigrees affected with AD or XL patterns caused by de novo mutations, potential parental mosaicism should be noted and prenatal diagnostic tests are also recommended.

Conducting polymers have stable long-chain structure and good electrical conductivity. They have been used in various types of biosensors because of their excellent characteristics of the immobilization and electrical signal transmission. In recent years, researchers mainly study on improving its micro-nano structures and its signal conductivity to enhance its effect on the enzyme immobilization and signal conductive properties. This paper reviews firstly the application of conducting polymer on enzyme-immobilized glucose biosensor and the new technologies and methods in this field. This paper also points out the future application of conducting polymers in enzyme immobilization and biosensor preparation areas.
Biosensing Techniques ; methods ; trends ; Blood Glucose ; metabolism ; Electric Conductivity ; Enzymes, Immobilized ; Glucose Oxidase ; metabolism ; Nanostructures ; Polymers ; chemistry

To explore the effect of insulin therapy on serum level of insulin-like growth factor-I(IGF-I)in patients with type 2 diabetes mellitus.The results showed that serum IGF-I level increased[(126.70±51.91 vs 90.04±43.68)μg/L,P<0.01]and was positively correlated with insulin level in patients with type 2 diabetes mellitus after exogenous insulin therapy(r=0.298,P<0.05).

Objective To observe the expression of HER-2 and TOPO-Ⅱα in ovarian epithelial cancer,analyze the correlation between their expression and provide theoretical basis for clinical diagnosis,prognosis and treatment. Methods Expression levels of HER-2 and TOPO- Ⅱα in 10 normal ovarian tissues,20 benign tumors and 58 cases of ovarian epithelial cancers were detected by immunohistochemical method, and their correlations with pathological features were analyzed. Results The positive expression rate of HER-2 in normal ovarian and benign tumor tissues were significantly lower than ovarian epithelial cancers respectively ( 10. 0% , 15.0% VS 46. 6% ;P ＜ 0. 05 ). The positive expression rate of TOPO- Ⅱα in ovarian epithelial cancers was significantly higher than normal and benign epithelial ovarian tumor tissue (53.4% vs 10. 0%, and 15.0%,Ps ＜ 0. 05 ), but we did not find significant difference in the comparison between normal and benign epithelial ovarian tumor tissue ( Ps ＞ 0. 05 ). The expression of HER-2 and TOPO- Ⅱα were significantly correlated with clinical stages, histological differentiation of tumor cells (Ps ＜ 0. 05 ) ,but there were no correlations between the age or histological type. In ovarian cancer tissues, a positive correlation between the expression of HER-2 and TOPO- Ⅱα was observed ( r = 0. 324, P ＜ 0. 05 ) . Conclusion The overexpression of HER-2 and TOPO- Ⅱαplay an important role in ovarian carcinogenesis and development. The expression of HER-2 is positively correlated with TOPO- Ⅱα in ovarian epithelial cancers. Coexpression of the two moleculars may be involved in the development and progression of ovarian epithelial cancer, which should be further studied.

This is an experimental study in the realm of physiology inquiring about the effect of pulsatile fluid flow shear stress on the proliferation, differentiation and functions of osteoblasts;the objective is to validate the important effect of fluid flow shear stress on the mechanics adaptability of bone tissue. The osteoblasts derived from Wistar rat's calvaria were exposed to fluid shear stress 5, 10, 20 and 30 mN/cm2 for 3, 6, 9, 12, 24, 36h respectively in the flow chamber. The ability of proliferation, alkaline phosphatase (ALP) activity and extracellular calcium secretion of osteoblasts were assessed. The results showed that fluid flow shear stress at 5, and 10 mN/cm2 increased the proliferation, but at 20 and 30 N/cm2, the shear stress inhibited the proliferation. The shear stress at 5, 10, 20 mN/cm2 increased the ALP activity and extracellular calcium secretion of osteoblasts, and advanced the time of the peak value of ALP activity during the experiment period, but the shear stress at 30 mN/cm2 decreased ALP activity. So osteoblasts responded rapidly to shear stress; the proliferation, differentiation and mineralization of cells were regulated in the presence of some shear stress; and such regulation exhibited a pattern of dependence on the mN/cm2 level of shear stress.
Alkaline Phosphatase ; metabolism ; Animals ; Cell Proliferation ; Cells, Cultured ; Mechanotransduction, Cellular ; physiology ; Osteoblasts ; cytology ; enzymology ; Pulsatile Flow ; Rats ; Rats, Wistar ; Shear Strength ; Skull ; cytology ; Stress, Mechanical