Diabetic kidney disease(DKD)is one of the most prevalent complications of diabetes mellitus,with progressive proteinuriaas the main clinical manifestation.Podocytes,a key structural component of the renal filtration barrier,age faster in diabetic state.Theirand morphologies gradually change,mainly in the form of multinucleation,widening of the peduncle,podocyte detachment and increased secretion of senescence-related secretory phenotypes.Various essential signaling pathways in senescent podocytes are altered in the high glucose environment,which results in mitochondrial dysfunction,increased oxidative stress and increased secretion of inflammatory factors.The removal of senescent podocyte,targeting and modulating senescence-related signaling pathways and blocking the secretionofsenescence associated secretory phenotypes may slow down the progression of DKD due to podocyte senescence.This article reviews the research progress on the mechanism of podocyte aging in DKD.

Obesity is a global health problem,and traditional weight loss therapies are often limited in their effectiveness and prone to accompanying adverse reactions In recent years,it has been found that the use of small interfering RNA(siRNA)technology to target regulation of obesity-related genes can effectively reduce body weight,opening up a new path for weight loss treatment.This review summarizes the mechanisms of action,delivery systems,and clinical progress of novel siRNA-based drugs,focusing on targeting genes such as transforming growth factor/cyclooxygenase,inhibin subunit beta E,and activin receptor-like kinase 7,which achieve precise targeting and enhanced therapeutic efficacy through their respective delivery systems.Meanwhile,this review also points out the drawbacks of existing drugs,including low delivery efficiency,risk of immune activation,and off-target effects.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Obesity is a global health problem,and traditional weight loss therapies are often limited in their effectiveness and prone to accompanying adverse reactions In recent years,it has been found that the use of small interfering RNA(siRNA)technology to target regulation of obesity-related genes can effectively reduce body weight,opening up a new path for weight loss treatment.This review summarizes the mechanisms of action,delivery systems,and clinical progress of novel siRNA-based drugs,focusing on targeting genes such as transforming growth factor/cyclooxygenase,inhibin subunit beta E,and activin receptor-like kinase 7,which achieve precise targeting and enhanced therapeutic efficacy through their respective delivery systems.Meanwhile,this review also points out the drawbacks of existing drugs,including low delivery efficiency,risk of immune activation,and off-target effects.

Diabetic kidney disease(DKD)is one of the most prevalent complications of diabetes mellitus,with progressive proteinuriaas the main clinical manifestation.Podocytes,a key structural component of the renal filtration barrier,age faster in diabetic state.Theirand morphologies gradually change,mainly in the form of multinucleation,widening of the peduncle,podocyte detachment and increased secretion of senescence-related secretory phenotypes.Various essential signaling pathways in senescent podocytes are altered in the high glucose environment,which results in mitochondrial dysfunction,increased oxidative stress and increased secretion of inflammatory factors.The removal of senescent podocyte,targeting and modulating senescence-related signaling pathways and blocking the secretionofsenescence associated secretory phenotypes may slow down the progression of DKD due to podocyte senescence.This article reviews the research progress on the mechanism of podocyte aging in DKD.

As cell aggregates in three-dimensional culture derived from primary tissues or stem cells, organoids possess the ability to self-organize into organotypic structures, mimic the cellular microenvironment, and represent tissue physiology. The thyroid′s follicular tissue plays a crucial role in thyroid hormone biosynthesis. Despite prolonged in vitro expansion of thyroid follicles from adult tissues and pluripotent stem cells have been expanded for a long time, the development of thyroid organoid technology still encounters numerous challenges. Establishing a comprehensive thyroid organoid that closely mimics the human body′s actual conditions remains a research challenge. This article reviews the development process of thyroid, the related applications of existing thyroid organoid models and the methods employed in the construction.

Diabetes mellitus(DM)is a chronic metabolic disease characterized by sustained elevation of blood glucosedue toin sulin resistance and islet β cell damage.Rheb1 regulates cell growth and metabolism,promotes islet β cell growth,proliferation and insulin secretion through the mTORC1 pathway,affects the function of vascular endothelial cells,macrophages and glomerular podocytes,and participates in the occurrence and development of atherosclerosis and diabetic kidney disease.This article reviews the research progress on the role of Rheb1 in DM and its complications.