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

In recent years，with the increase in environmental pollution，organisms are exposed to more internal and external oxidative stress factors than ever before.Nuclear factor erythroid 2-related factor 2（nuclear factor erythroid 2-related factor 2，NRF2），as a core transcription factor in response to oxidative stress，maintains cellular redox homeostasis by inducing the expression of various antioxidant factors.The nasal cavity，as the "gateway" of the respiratory tract，is often accompanied by oxidative stress（oxidative stress，OS）damage，leading to the occurrence of allergic rhinitis（allergic rhinitis，AR）.Recent studies have revealed some associations between the NRF2 signaling pathway and the mechanism of AR development.Activation of NRF2 provides a potential protective effect against AR，and some natural NRF2 activators have shown therapeutic potential in clinical experiments.Therefore，this article briefly reviews the relationship between NRF2 and AR，aiming to provide a new therapeutic target and perspective for the treatment of AR.
NF-E2-Related Factor 2/metabolism* ; Humans ; Rhinitis, Allergic/metabolism* ; Signal Transduction ; Oxidative Stress

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.

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

Diabetic nephropathy(DN),a severe complication of diabetes,is widely recognized as a primary contributor to end-stage renal disease.Recent studies indicate that the inflammation triggered by Toll-like receptor 4(TLR4)is of paramount importance in the onset and progression of DN.TLR4 can bind to various ligands,including exogenous ligands such as proteins and polysaccharides from bacteria or vi-ruses,as well as endogenous ligands such as biglycan,fibrinogen,and hyaluronan.In DN,the expression or release of TLR4-related ligands is significantly elevated,resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways.This process is closely associated with the progression of DN.Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases.Various types of natural compounds,including alkaloids,flavonoids,polyphenols,terpenoids,glycosides,and polysaccharides,have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway.In this review,we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway.We specifically highlight the potential of compounds such as curcumin,paclitaxel,berberine,and ursolic acid to inhibit the TLR4 signaling pathway,which provides an important direction of research for the treatment of DN.

A public hospital Party branch,in the establishment of the"Four Orientations"project(Leading groups work effectively,Party branches work with promising methods,Party building achieves a fame with brand,and each unit has its own model)and"Four Strengths"(strong political role,strong Party branch team,strong team of Party members,and strong per-formance)has combined its work with bold exploration at the intersection of party building and discipline development.The branch has refined a distinctive"Bridge Culture"concept,symbolizing its identity,and has implemented four key projects:"Building bridges""Consolidating bridges""Expanding bridges"and"Preserving bridges".Collectively,these initiatives have led to the development of a"Bridge Culture"brand.The branch's role,as a vanguard in discipline advancement and public health services,has been fully leveraged,aiming to drive high-quality development of discipline through the vehicle of ideological and political work.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To summarize the clinical and prognostic features of children with opsoclonus-myoclonus-ataxia syndrome (OMAS).Methods:A total of 46 patients who met the diagnostic criteria of OMAS in the Department of Neurology, Beijing Children′s Hospital from June 2015 to June 2023 were retrospectively analyzed. Centralized online consultations or telephone visits were conducted between June and August 2023. The data of the children during hospitalization and follow-up were collected, including clinical manifestations, assistant examination, treatment and prognosis. According to the presence or absence of tumor, the patients were divided into two groups. The chi-square test or Mann-Whitney U test was used to compare the differences between the two groups. Univariate Logistic regression was used to analyze the factors related to OMAS recurrence and prognosis. Results:There were 46 patients, with 25 males and the onset age of 1.5 (1.2, 2.4) years. Twenty-six (57%) patients were diagnosed with neuroblastoma during the course of the disease, and no patients were categorized into the high-risk group. A total of 36 patients (78%) were followed up for≥6 months, and all of them were treated with first-line therapy with glucocorticoids, gammaglobulin and (or) adrenocorticotrophic hormone. Among the 36 patients, 9 patients (25%) were treated with second-line therapy for ≥3 months, including rituximab or cyclophosphamide, and 17 patients (47%) received chemotherapy related to neuroblastoma. At the follow-up time of 4.2 (2.2, 5.5) years, 10 patients (28%) had relapsed of OMAS. The Mitchell and Pike OMS rating scale score at the final follow-up was 0.5 (0, 2.0). Seven patients (19%) were mildly cognitively behind their peers and 6 patients (17%) were severely behind. Only 1 patient had tumor recurrence during follow-up. The history of vaccination or infection before onset was more common in the non-tumor group than in the tumor group (55%(11/20) vs. 23%(6/26), χ2=4.95, P=0.026). Myoclonus occurred more frequently in the non-tumor group (40%(8/20) vs. 4%(1/26), χ2=7.23, P=0.007) as the onset symptom. Univariate Logistic regression analysis showed that the tumor group had less recurrence ( OR=0.19 (0.04-0.93), P=0.041). The use of second-line therapy or chemotherapy within 6 months of the disease course had a better prognosis ( OR=11.64 (1.27-106.72), P=0.030). Conclusions:OMAS in children mostly starts in early childhood, and about half are combined with neuroblastoma. Neuroblastoma in combination with OMAS usually has a low risk classification and good prognosis. When comparing patients with OMAS with and without tumors, the latter have a more common infection or vaccination triggers, and myoclonus, as the onset symptom, is more common. Early addition of second-line therapy is associated with better prognosis in OMAS.