BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

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

Traditionally, platelets, which are anucleate cell fragments derived from blood cells, have been primarily associated with their pivotal functions in hemostasis and thrombosis. However, recent research has elucidated their significant role in immune regulation, highlighting their expression of various immune receptors, involvement in numerous immune-related signaling pathways, and activation of diverse effector functions. This paper elaborates on the fundamental biological characteristics and immune functions of platelets, the involvement of activated platelets in immune regulation, and their prospective applications in clinical therapy. Furthermore, the paper discusses future directions in platelet immune research, as well as the prospects and developmental trends in immunotherapy, aiming to furnish a thorough reference for the investigation and clinical utilization of platelets within the domain of immune regulation.

Objective To explore the active monitoring strategies for hypoglycemia in hospitalized dia-betic patients,as well as their clinical symptom characteristics and influencing factors.Methods A retrospec-tive search was conducted on all inpatients in a tertiary hospital in 2023.The hospital's electronic medical re-cord system was manually retrieved through the inpatient numbers of the patients.Adult inpatients with dia-betes who experienced hypoglycemia were included as the research subjects,and the general conditions and possible hypoglycemia-related risk factors were collected.Embed the hypoglycemic electronic trigger program in China Hospital Pharmacovigilance System(CHPS),reviewed the original medical records of patients with positive trigger triggering,and calculated the positive predictive value(PPV).Searched for the number of hy-poglycemic adverse reaction cases voluntarily reported by this hospital during the same period from National Adverse Reaction Monitoring System and compared with the actual number of hypoglycemic cases discovered.Patients with suspected drug-induced hypoglycemia were divided into the symptomatic group and the asymp-tomatic group based on whether they presented hypoglycemia-related symptoms.Multivariate logistic regres-sion analysis was applied to analyze the influencing factors.Results A total of 1 001 adult hospitalized diabet-ic patients with hypoglycemia were included in the study.Among them,725 cases were suspected of drug-in-duced hypoglycemia,and 495 cases were suspected of hypoglycemia caused by drug interactions.After manual review,131 cases of drug-induced hypoglycemia patients had clinical symptoms,and hypoglycemic adverse re-action events should be reported,PPV of this trigger for symptomatic hypoglycemia was 18.1%(131/725).However,the number of hypoglycemic adverse reactions spontaneously reported through National Adverse Reaction Monitoring System by this hospital during the same period was 4 cases,and the reporting rate was only 3.1%(4/131).Multivariate logistic regression analysis showed that aging and grade 2 hypoglycemia were risk factors for the occurrence of related symptoms in patients with suspected drug-induced hypoglycemia(P<0.05),while surgery,type 2 glucosuria,unclassified diabetes,and the use of insulin secretagogues were protective factors(P<0.05).Conclusion Drug-induced hypoglycemia dominates among hospitalized diabetic patients,and age,hypoglycemia grade,inpatient department using insulin secretagogues,diabetes diagnosis and classification are closely related to the occurrence of clinical hypoglycemia-related symptoms.Active monito-ring through CHPS can effectively increase the detection rate and reporting rate of hypoglycemic adverse e-vents in hospitalized diabetic patients.

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
Animals ; Dentate Gyrus/metabolism* ; Mice ; Morphogenesis/physiology* ; Neurons/pathology* ; Cell Movement ; Mice, Inbred C57BL ; Autism Spectrum Disorder/pathology* ; Mice, Knockout ; Neural Stem Cells ; Male ; Neurogenesis ; Autistic Disorder/genetics*

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene