Cellular senescence, stable cell cycle arrest that can be triggered in normal cells in response to various intrinsic and extrinsic stressors, has been highlighted as one of the most important mechanisms involved in kidney diseases. It not only serves as a fundamental biological process promoting normal organogenesis and successful wound repair but also contributes to organ dysfunction, tissue fibrosis, and the generalized aging phenotype. Moreover, senescent cells exhibit reduced regenerative capacity, which impairs renal function recovery from injuries. Importantly, senescent cells are involved in immune regulation via secreting a diverse array of proinflammatory and profibrotic factors known as senescence-associated secretory phenotype (SASP) with autocrine, paracrine, and endocrine activities. Thus, eliminating detrimental senescent cells or inhibiting SASP production holds great promise for developing innovative therapeutic strategies for kidney diseases. In this review, we summarize the current knowledge of the intricate mechanisms and hallmarks of cellular senescence in kidney diseases and emphasize novel therapeutic targets, including epigenetic regulators, G protein-coupled receptors, and lysosome-related proteins. Particularly, we highlight the recently identified senotherapeutics, which provide new therapeutic strategies for treating kidney diseases.
Humans ; Cellular Senescence/genetics* ; Kidney Diseases/pathology* ; Senescence-Associated Secretory Phenotype/physiology* ; Animals ; Epigenesis, Genetic/physiology*

Ten novel xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), along with sixteen known analogs (9-24), were isolated from Garcinia pedunculata and G. nujiangensis. Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 exhibited significant anti-inflammatory activity with IC₅₀ values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L^-1, respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b, 19, and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L^-1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
Xanthones/therapeutic use* ; Garcinia ; Anti-Inflammatory Agents/therapeutic use* ; Plant Preparations/therapeutic use* ; Structure-Activity Relationship ; Nitric Oxide/metabolism* ; RAW 264.7 Cells ; Animals ; Mice ; Enzyme-Linked Immunosorbent Assay ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Circular Dichroism

【Objective】 To investigate the differential diagnosis of 1 anti-C, e alloantibodies combined with anti-e, Jk^b mimicking alloantibodies by absorption-elution test and titer integral method. 【Methods】 ABO, Rh and Kidd blood group antigens were identified by tube method. Two sets of panel cells were used for antibody screening and antibody specificity identification by saline method, polyamine method and microcolumn gel method.The antibody was further confirmed by multiple absorption-elution tests and titer integral method. RHCE and JK gene were sequenced by multiple PCR. 【Results】 Serological gene sequencing analysis showed that the ABO blood group of the patient was A type with Rh subtype ccDEE and was positive for direct antiglobulin test (DAT). Multiple absorption-elution tests and titer integral method demonstrated that the serum of the patient contained anti-C, e alloantibodies along with anti-e, Jk^b mimicking autoantibodies and there were anti-e, Jk^b mimicking autoantibodies on red blood cells(RBCs). According to gene sequencing analysis, there was G>C at exon 676 of the RHCE gene, and the remaining exons were not mutated, suggesting that the RHCE phenotype was ccEE. The 838 G/A heterozygote of exon 9 in JK gene, Jk blood group phenotype was Jk (a+ b+ ). Cross matched type A ccDEE and Jk(a+ b-) RBCs were transfused, and no adverse reactions occurred. 【Conclusion】 Serology combined with molecular biology to identify the phenotype of the patient′s RBCs, absorption-elution test and titer integral method to identify the antibody of the patient′s serum can detect the alloantibody type, thus providing strategies for targeted blood transfusion.

Objective: To analyze the global epidemiology of renal cell carcinoma (RCC) in 2020. Methods: The incidence and mortality data of RCC in the cooperative database GLOBOCAN 2020 of International Agency for Research on Cancer of WHO and the human development index (HDI) published by the United Nations Development Programme in 2020 were collated. The crude incidence rate (CIR), age-standardized incidence rate (ASIR), crude mortality rate (CMR), age-standardized mortality rate (ASMR) and mortality/incidence ratio (M/I) of RCC were calculated. Kruskale-Wallis test was used to analyze the differences in ASIR or ASMR among HDI countries. Results: In 2020, the global ASIR of RCC was 4.6/100 000, of which 6.1/100 000 for males and 3.2/100 000 for females and ASIR was higher in very high and high HDI countries than that in medium and low HDI countries. With the rapid increase of age after the age of 20, the growth rate of ASIR in males was faster than that in females, and slowed down at the age of 70 to 75. The truncation incidence rate of 35-64 years old was 7.5/100 000 and the cumulative incidence risk of 0-74 years old was 0.52%. The global ASMR of RCC was 1.8/100 000, 2.5/100 000 for males and 1.2/100 000 for females. The ASMR of males in very high and high HDI countries (2.4/100 000-3.7/100 000) was about twice that of males (1.1/100 000-1.4/100 000) in medium and low HDI countries, while the ASMR of female (0.6/100 000-1.5/100 000) did not show significant difference. ASMR continued to increase rapidly with age after the age of 40, and the growth rate of males was faster than that of females. The truncation mortality rate of 35-64 years old was 2.1/100 000, and the cumulative mortality risk of 0-74 years old was 0.20%. M/I decreases with the increase of HDI, with M/I as 0.58 in China, which was higher than the global average of 0.39 and the United States' 0.17. Conclusion: The ASIR and ASMR of RCC presented significant regional and gender disparities globally, and the heaviest burden was in very high HDI countries.
Male ; Humans ; Female ; Adult ; Middle Aged ; Infant, Newborn ; Infant ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Aged ; Carcinoma, Renal Cell/epidemiology* ; Incidence ; Databases, Factual ; China ; Kidney Neoplasms/epidemiology* ; Global Health

The impact of plateau environment on cerebral venous thrombosis (CVT) is more complex and diverse than in plain areas. This article reviews the epidemiological characteristics, affected sites, and especially the pathogenesis of CVT in plateau areas.

This review aims to interpret the interventions to improve physical function for children and young people with cerebral palsy, thus providing relevant suggestions.Relevant literatures published before November 2018 were systematically searched in Cochrane library, CINAHL, and Embase MEDLINE using the Grading of Recommendations Assessment, Development and Evaluation method.Consult with international experts and patients to assess evidence and recommend it.Based on 3 systematic reviews, 30 randomized clinical trials, and 5 pre-and post-treatment studies, a total of 13 recommendations were given.The guidelines recommend that, in order to achieve functional stan-dards, intervention measures should include, patient-selected goals, full-task practice in real-life settings, support for family empowerment, and a team approach.The age, ability, and child/family preferences were all needed to be considered.In order to improve walking ability, ground walking and treadmill training can be carried out.Various methods can promote the realization of hand use goals hand use, including the two-hand exercise training, constraint-induced moverment therapy, goal-oriented training and cognitive therapy.In terms of patient self-care, the guideline proposed that, the combination of full-task practice and auxiliary equipment can improve the independence of self-care and reduce the burden of care givers.Leisure goals could be achieved by the combination of the practice of the entire task with strategies to address environmental, personal, and social barriers.The intervention of children and adolescents with cerebral palsy should take into consideration of patient selection and the goal of full-task practice.The child/family preference, age and ability should be considered when clinical workers selecting specific interventions.

Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation, high drug-loading efficiency, and excellent therapeutic efficacy. Herein, MnAs-ICG nanospike was generated by self-assembly of indocyanine green (ICG), manganese ions (Mn²⁺), and arsenate (AsO₄ ^3-) based on electrostatic and coordination interactions, effectively integrating the bimodal imaging ability of magnetic resonance imaging (MRI) and fluorescence (FL) imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an "all-in-one" theranostic nano-platform. The as-prepared MnAs-ICG nanospike had a uniform size, well-defined nanospike morphology, and impressive loading capacities. The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability, enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components. In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect, prolonged blood circulation and increased tumor accumulation compared to their individual components, effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect. Taken together, this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.

Objective:To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation.Methods:Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD.Results:A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95% CI: 0.49-0.55) and 0.76 (95% CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD ( rA=0.10, 95% CI:0.02-0.17). Conclusion:In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

Objective:To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation.Methods:Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD.Results:A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95% CI: 0.49-0.55) and 0.76 (95% CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD ( rA=0.10, 95% CI:0.02-0.17). Conclusion:In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

The First Affiliated Hospital of Xi'an Jiaotong University has established pediatric MOOCs courses, including the formation of excellent MOOC teachers, the curriculum planning and design of MOOCs, making MOOCs videos, and using MOOCs for teaching activities. The MOOCs for teaching is intuitive, the courses are interesting, and the learning time is flexible. Besides, it is open and resources-sharing, and it also can increase the educational equity. At the same time, it can reduce teachers' burden, improve teaching ability, and improve learning ability of students. Most students and teachers agree that MOOCs are worthy of promotion and application.