IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a major cause of chronic kidney disease and kidney failure. IgAN exhibits marked heterogeneity in clinical presentation, histopathology, and pathogenic mechanisms, contributing to variable treatment responses and prognosisamong patients. Precise risk assessment and individualized intervention are therefore of critical importance. This review systematically traces the evolution of IgAN management from traditional risk stratification toward biomarker-driven precision medicine. We first review the clinical utility and limitations of established risk stratification tools, including the KDIGO guidelines, the Oxford MEST-C classification, and the International IgAN Prediction Tool. We then discuss emerging biomarkers closely linked to disease pathogenesis, including galactose-deficient IgA1 (Gd-IgA1), anti-Gd-IgA1 autoantibodies, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), and complement components, as well as the targeted therapies they have informed. In addition, urinary biomarkers and multi-omics approaches show promise for dynamic disease monitoring and individualized risk stratification.

Aim To investigate the therapeutic effects of corylifol A(CYA)on Lewis lung carcinoma(LLC)cachexia mice and its ameliorating effects on myotube atrophy induced by LLC cell-conditioned medium(LLC CM)in vitro,and to explore the mechanisms.Methods The cancer cachexia was induced by subcu-taneous inoculation of LLC cells to C57BL/6J mice.The effects of CYA(10,20 mg·kg-1·d-1,i.p.)on the cachexia symptoms and survival time of cachexia mice were observed.The effects of 2.5 or 5 μmol·L-1 CYA on myotube atrophy of C2C12 induced by LLC CM were observed.The effects of CYA on its pos-sible target the serine/threonine-protein kinase TAO1(TAOK1)and downstream signaling pathways were detected using Western blot.The influence of TAOK1 knockout on the ameliorating effects of CYA on myo-tube atrophy was observed.Results CYA could sig-nificantly prolong the survival time of tumor-bearing mice and ameliorate the muscle atrophy associated with LLC.The effects of CYA on myotube atrophy are relat-ed to its regulation of TAOK1.The effects of CYA could be reduced by knockout of TAOK1.Conclusions CYA improves the survival of LLC cachexia mice and ameliorates the related skeletal muscle atrophy.The mechanism of CYA is related to its inhibition on TAOK1 and downstream signaling pathways.

Aim To investigate the therapeutic effects of corylifol A(CYA)on Lewis lung carcinoma(LLC)cachexia mice and its ameliorating effects on myotube atrophy induced by LLC cell-conditioned medium(LLC CM)in vitro,and to explore the mechanisms.Methods The cancer cachexia was induced by subcu-taneous inoculation of LLC cells to C57BL/6J mice.The effects of CYA(10,20 mg·kg-1·d-1,i.p.)on the cachexia symptoms and survival time of cachexia mice were observed.The effects of 2.5 or 5 μmol·L-1 CYA on myotube atrophy of C2C12 induced by LLC CM were observed.The effects of CYA on its pos-sible target the serine/threonine-protein kinase TAO1(TAOK1)and downstream signaling pathways were detected using Western blot.The influence of TAOK1 knockout on the ameliorating effects of CYA on myo-tube atrophy was observed.Results CYA could sig-nificantly prolong the survival time of tumor-bearing mice and ameliorate the muscle atrophy associated with LLC.The effects of CYA on myotube atrophy are relat-ed to its regulation of TAOK1.The effects of CYA could be reduced by knockout of TAOK1.Conclusions CYA improves the survival of LLC cachexia mice and ameliorates the related skeletal muscle atrophy.The mechanism of CYA is related to its inhibition on TAOK1 and downstream signaling pathways.

Endothelial-to-mesenchymal transition(End MT)re-fers to the process in which endothelial cells undergo morpholog-ical and functional changes under certain conditions and are transformed into cells with mesenchymal characteristics.EndMT has been found to be involved in the pathological development of cardiovascular diseases,fibrotic diseases of various tissues and tumors.This article reviews the recent progress in research of EndMT,focusing on its important roles in cardiovascular diseases and related pathological mechanisms.

Background Obstructive sleep apnea (OSA) is a sleep disorder characterized by recurrent episodes of obstruction of the upper airway during sleep. Given the substantial number of OSA patients, it is urgently in need to address the burden on society. Current available evidence linking outdoor light at night (LAN) to OSA is scarce. Objective To explore the relationships regarding outdoor LAN and OSA among residents in Southern China. Methods A total of 3925 hospitalized patients in Guangdong Provincial People's Hospital Sleep Center were recruited between January 1, 2005 and December 31, 2015. The severity of OSA was determined by apnea-hypopnea index (AHI) using polysomnography or home sleep test. The annual Suomi National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (NPP-VIIRS)-like LAN data with a 500 m spatial resolution were used to evaluate outdoor LAN levels of the participants 1, 3, and 5 years before undergoing sleep monitoring. Generalized linear regression models were utilized to examine the associations of outdoor LAN with OSA. Results The ORs (95%CIs) of OSA, mild OSA, and moderate OSA were 1.175 (1.021, 1.351), 1.215 (1.038, 1.421), and 1.195 (1.003, 1.425) respectively for per interquartile range (IQR) increment in three-year average outdoor LAN. The results of stratified analyses showed a higher OR of 1.933 (95%CI: 1.424, 2.637) in female than male participants (P _interaction < 0.001). Additionally, the ORs of OSA did not substantially change using one-year/ five-year instead of three-year average outdoor LAN. Conclusion Our findings demonstrate that an elevated outdoor LAN is significantly associated with higher odds of OSA (especially mild and moderate OSA) in Southern China, especially in females. An effective outdoor LAN management and policy-making framework has been suggested as potential preventive measures to reduce burden of OSA.

BACKGROUND: Enzalutamide, a second-generation androgen receptor (AR) pathway inhibitor, is widely used in the treatment of castration-resistant prostate cancer. However, after a period of enzalutamide treatment, patients inevitably develop drug resistance. In this study, we characterized leucine-rich repeated G-protein-coupled receptor 5 (LGR5) and explored its potential therapeutic value in prostate cancer. METHODS: A total of 142 pairs of tumor and adjacent formalin-fixed paraf-fin-embedded tissue samples from patients with prostate cancer were collected from the Pathology Department at Sun Yat-sen Memorial Hos-pital. LGR5 was screened by sequencing data of enzalutamide-resistant cell lines combined with sequencing data of lesions with different Gleason scores from the same patients. The biological function of LGR5 and its effect on enzalutamide resistance were investigated in vitro and in vivo . Glutathione-S-transferase (GST) pull-down, coimmunoprecipitation, Western blotting, and immunofluorescence assays were used to explore the specific binding mechanism of LGR5 and related pathway changes. RESULTS: LGR5 was significantly upregulated in prostate cancer and negatively correlated with poor patient prognosis. Overexpression of LGR5 promoted the malignant progression of prostate cancer and reduced sensitivity to enzalutamide in vitro and in vivo . LGR5 promoted the phosphorylation of glycogen synthase kinase-3β (GSK-3β) by binding heat shock protein 90,000 alpha B1 (HSP90AB1) and mediated the activation of the Wingless/integrated (WNT)/β-catenin signaling pathway. The increased β-catenin in the cytoplasm entered the nucleus and bound to the nuclear AR, promoting the transcription level of AR, which led to the enhanced tolerance of prostate cancer to enzalutamide. Reducing HSP90AB1 binding to LGR5 significantly enhanced sensitivity to enzalutamide. CONCLUSIONS LGR5 directly binds to HSP90AB1 and mediates GSK-3β phosphorylation, promoting AR expression by regulating the WNT/β-catenin signaling pathway, thereby conferring resistance to enzalutamide treatment in prostate cancer.
Male ; Humans ; Phenylthiohydantoin/pharmacology* ; Benzamides ; Receptors, G-Protein-Coupled/genetics* ; Nitriles ; Cell Line, Tumor ; HSP90 Heat-Shock Proteins/metabolism* ; Drug Resistance, Neoplasm/genetics* ; Prostatic Neoplasms/drug therapy* ; beta Catenin/metabolism* ; Receptors, Androgen/genetics* ; Animals ; Mice ; Wnt Signaling Pathway/physiology*

Endothelial-to-mesenchymal transition(End MT)re-fers to the process in which endothelial cells undergo morpholog-ical and functional changes under certain conditions and are transformed into cells with mesenchymal characteristics.EndMT has been found to be involved in the pathological development of cardiovascular diseases,fibrotic diseases of various tissues and tumors.This article reviews the recent progress in research of EndMT,focusing on its important roles in cardiovascular diseases and related pathological mechanisms.

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal

Preterm birth and its complications are the leading cause of neonatal death, and also a perinatal problem that contributes to the global burden of disease. Recently, the association between maternal heat exposure and elevated risk of preterm birth has been found in lots of studies. But the potential mechanisms of how heat exposure increase the incidence of preterm birth are still unclear. Thus, we reviewed maternal vulnerability factors and territorial moderators associated with preterm birth due to heat exposure during pregnancy, and summarized potential mechanisms between heat exposure and risk of preterm birth based on previous studies. We found that heat exposure during pregnancy may involve various mechanisms to increase the risk of preterm birth, such as oxidative stress, inflammation, reproductive and urinary infections, neuroendocrine changes, and complications during pregnancy. Prospective cohort studies and animal experiments should be conducted to clarify the adverse health effects of heat exposure on different types of preterm birth from three facets of "exposure-mechanism-effect", aiming to provide a scientific basis for the protection of maternal and infant health through conducing clinical preventive interventions against preterm birth in scorching weather.

Background Preterm birth-related complications are the leading cause of death in newborns and children under the age of 5 years. Maternal heat exposure has been associated with both sleep status during pregnancy and the increased risk of preterm birth. However, whether sleep status could mediate the association between heat exposure and preterm birth remains unclear. Objective To evaluate the association between maternal heat exposure in early pregnancy and preterm birth, and to further explore potential mediation effect of sleep status on the association between heat exposure and preterm birth. Methods A birth cohort was established in Guangzhou Panyu Maternal Child Health Hospital (Guangzhou Panyu District He Xian Memorial Hospital) from 2017 until now. Pregnant women (with gestational age between 8 and 13 weeks) were included in this study when they presented to the hospital for their first prenatal care visit and signed an informed consent. Then they were followed up until delivery. A total of 3 268 pregnant women were included for the final analysis. Questionnaires were distributed to collect the demographic characteristics, lifestyles, and sleep status of pregnant women. Daily meteorological data during the study period were collected from meteorological monitoring stations in Guangzhou and the average ambient mean temperature of four weeks before the survey was calculated and assigned for each pregnancy. The 75th, 80th, 85th, 90th, and 95th percentiles (P₇₅, P₈₀, P₈₅, P₉₀, and P₉₅) of the average ambient temperature of all pregnant women were used as the thresholds to define heat exposure. Logistic regression was used to evaluate the effects of heat exposure in different definitions on preterm birth and sleep status (sleep duration, night sleep timing, and wake up timing). The mediation effects of sleep status on the relationship between heat exposure and preterm birth were also analyzed. Results Among all the included participants, 165 newborns were preterm births with an incidence rate of 5.0%. Heat exposures with thresholds of P₉₀ and P₉₅ increased the risk of preterm birth, with ORs (95%CIs) of 1.66 (1.04-2.57) and 1.90 (1.03-3.33), respectively (P<0.05). Heat exposures with thresholds of P₇₅, P₈₀, P₈₅, P₉₀, and P₉₅ decreased the sleep duration (<9 h vs. ≥9 h, control group: ≥9 h), and the ORs (95%CIs) were 1.51 (1.25-1.83), 1.44 (1.17-1.77), 1.35 (1.08-1.70), 1.43 (1.09-1.87), and 1.45 (1.00-2.13), respectively. Heat exposures with P₇₅ and P₈₀ thresholds resulted in earlier wake up timing (<8: 00 vs. ≥8: 00, control group: <8: 00), with ORs (95%CIs) of 0.77 (0.63-0.93) and 0.76(0.61-0.93), respectively. No significant association was observed between heat exposure and night sleep timing. The mediation analyses showed that under heat exposure with P₉₀ threshold, a statistically significant mediation effect was observed for sleep duration, and the proportion mediated was 6.07% (95%CI: 0.17%-25.00%) (P<0.05). No significant mediation effect was observed for night sleep timing and wake up timing. Conclusion An elevated risk of preterm birth after heat exposure in early pregnancy may be partly mediated through reducing sleep duration.