AIM To investigate the effects of Wenyang Jiedu Tongluo Recipe(WYJDTLR)on macrophage recruitment and polarization function in a mouse model of diabetic kidney disease(DKD).METHODS 50 db/db mice were randomly divided into the model group,the valsartan group(10.29 mg/kg)and the high-dose,medium-dose and low-dose WYJDTLR groups(26.52,13.26 and 6.63 g/kg),with 10 mice in each group,in contrast to another 10 db/m mice of the blank group.After 8 weeks of administration,the mice had their levels of fasting blood glucose,24-hour urinary protein quantity(24h-UTP),serum creatinine(Scr)and blood urea nitrogen(BUN)observed;their morphological changes of renal tissues observed by HE staining;their degree of renal glycogen deposition observed by PAS staining;their degree of renal fibrosis observed by Masson staining;their levels of MCP-1 and MCF-1 in serum and TNF-α and IL-1 β in renal tissue detected by ELISA;their renal protein expressions of VCAM-1 and ICAM-1 detected by IHC and Western blot;and their renal expressions of CD86 and CD206 detected by IF.RESULTS Compared with the model group,the WYJDTLR groups displayed decreased levels of fasting blood glucose,24h-UTP,Scr and BUN(P＜0.05,P＜0.01);improved degree of glomerular hypertrophy,mild proliferation of mesangial cells,dilatation of renal tubular,vacuolar degeneration of renal tubular epithelial cells,deposition of glomerular glycogen,and fibrosis of renal tissues(P＜0.01);decreased levels of MCP-1 and MCF-1 in serum and TNF-α and IL-1β in renal tissue(P＜0.05,P＜0.01);decreased renal protein expressions of VCAM-1 and ICAM-1(P＜0.05,P＜0.01),thus reduced the recruitment of macrophages to the kidney;decreased renal CD86 protein expression(P＜0.01);and increased CD206 protein expression(P＜0.01),thus inhibited M1-type polarization of macrophages and promoted M2-type polarization of macrophages.CONCLUSION WYJDTLR can delay the DKD progression in mice by reducing the occurrence of inflammatory reactions through reducing the level of macrophage recruitment factor,inhibiting the M1-type polarization,and promoting the M2-type polarization.

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

A 42-year-old female patient received toremifene 60 mg orally once daily for 5 years after breast cancer surgery. She had a regular menstrual cycle and no history of abnormal bleeding. For more than 1 month, she experienced irregular vaginal bleeding, which worsened for 3 days. The transvaginal color doppler ultrasound revealed endometrial thickening, and laboratory tests showed red blood cell count 1.8×10 12/L and hemoglobin 35 g/L. The clinical diagnosis was abnormal uterine bleeding, endometrial thickening, and severe anemia. Symptomatic and supportive treatments, such as hemocoagulase, human erythropoietin, oxytocin, cefuroxime, and blood transfusion were given immediately. Civen the suspicion that toremifene-induced endometrial hyperplasia was the cause of abnormal uterine bleeding, toremifene was discontinued the following day. The symptomatic treatments (including blood transfusion) were continued, and iron supplementation was given. On the third day after discontinuation of toremifene, the patient underwent diagnostic hysteroscopic curettage. The postoperative pathological examination showed endometrial hyperplasia. The next day, the patient had no significant vaginal bleeding, with red blood cell count 3.6×10 12/L and hemoglobin 93 g/L. Reexamination at 4 weeks revealed red blood cell count 4.3×10 12/L and hemoglobin 135 g/L.

Cannabidiol(CBD),a natural,non-toxic,non-psy-choactive cannabinoid extracted from Cannabis sativa L,has a wide range of pharmacological activities,including anti-inflam-matory,antioxidant,immunomodulatory,analgesic,anti-tumor,anti-convulsant,anxiolytic effects.Recent studies have indica-ted that CBD may have potential neuroprotective effects in vari-ous models of central nervous system diseases.This paper re-views the experimental research progress of CBD in central nerv-ous system diseases and its possible neuroprotective mecha-nisms,aiming to provide references for its clinical application and new drug development.

Objective: To understand the status and related factors of knowledge, attitude and practice (KAP) on vision health among young children s parents in Bao an District, Shenzhen, so as to provide reference for further controlling myopia and promoting children s visual health. Methods: From May 16th to 26th, 2024, a stratified cluster random sampling method was used to conduct an online questionnaire survey on 7 666 parents of kindergarten children across 41 kindergartens in a street of Bao an District, Shenzhen. The t-test, variance analysis and multiple linear regression analysis were used to analyze the related factors of KAP on vision health among children s parents. Results: The pass rates of parental vision KAP and overall assessment were 25.10%, 98.49 %, 71.18% and 58.26%, respectively. The results of the multiple linear regression analysis showed that only fathers with myopia, only mothers with myopia, both parents with myopia, children in the bottom classes, middle classes, senior classes, and pre school had higher standardized scores for KAP on vision health among parents ( β=0.08, 0.11, 0.16, 0.17, 0.16, 0.16, 0.05, P <0.05), compared to both parents without myopia and children in daycare classes. Parents of young children with myopia, and who didn t know their children s visual acuity and their own visual acuity had a lower KAP standardized scores ( β=-0.02, -0.04, -0.05 , P< 0.05). Conclusions Young children s parents in Bao an District hold a positive attitude towards vision health, but are lack of knowledge and practice. It is imperative to transmit accurate information and concepts about children s vision health to parents in a targeted manner. In particular, knowledge and guidance should be strengthened for children s parents.

Objective To develop and validate a fast Monte Carlo(MC)-based patient-specific quality assurance(PSQA)tool using the treatment log files that is suitable to be used in the online adaptive radiotherapy for pencil beam scanning proton therapy(PBSPT-ART).Methods The proposed tool first used the delivery log file of a PBSPT plan to reversely reconstruct the PBSPT(rPBSPT)plan,and then used an in-house developed graphic processing unit(GPU)-accelerated virtual particle MC(VPMC)dose engine to calculate the dose distribution of the rPBSPT plan.The rPBSPT dose calculated by VPMC was then compared to the rPBSPT dose calculated by another independent MC dose engine(MCsquare),using 3D gamma analysis to verify the accuracy of VPMC calculation.As a demonstration of the feasibility of developed log file-based PSQA,the VPMC calculated dose of the rPBSPT plan was compared to the pre-delivery second check dose of the corresponding PBSPT plan calculated by MCsquare,using 3D gamma analysis.3D gamma analysis employes a criterion of 2 mm/2%/10%.Twenty patients with different disease sites were representatively selected to validate the efficiency and accuracy of the tool.Results The average calculation time of a rPBSPT plan by VPMC was(5.88±4.00)s in the accuracy verification.Compared to MCsquare,the passing rate of the 3D gamma analysis was 99.47%±0.72%.In the proposed PSQA tool demonstration,the passing rate of comparing the VPMC calculated rPBSPT dose to MCsquare calculated second check dose of the corresponding PBSPT plan was 98.91%±0.92%.Conclusion The accuracy and efficiency of the tool can meet the requirements of PSQA in the online PBSPT-ART workflow.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,with a high mortality rate.Sirtuin 3,a deacetylase within mitochondria,plays an important regulatory role in cellular metabolism,oxidative stress,and inflammatory responses.In recent years,significant progress has been made in the study of the function and regulatory role of sirtuin 3 in sepsis-related diseases.Research has shown that sirtuin 3 can alleviate organ damage caused by sepsis by regulating mitochondrial function,reducing oxidative stress,and inhibiting inflammatory responses.The specific mechanisms include the regulation of mitochondrial bioenergetics,activation of antioxidant enzyme systems,and inhibition of inflammatory mediator expression.In addition,sirtuin 3 plays a protective role in the pathological process of sepsis by interacting with multiple signaling pathways.This article summarizes the functions and regulatory mechanisms of sirtuin 3 in various sepsis-related diseases,aiming to provide new targets and strategies for the prevention and treatment of sepsis in the future.
Sepsis/metabolism* ; Sirtuin 3/physiology* ; Humans ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Signal Transduction

A primary hallmark of pathological cardiac hypertrophy is excess protein synthesis due to enhanced translational activity. However, regulatory mechanisms at the translational level under cardiac stress remain poorly understood. Here we examined the translational regulations in a mouse cardiac hypertrophy model induced by transaortic constriction (TAC) and explored the conservative networks versus the translatome pattern in human dilated cardiomyopathy (DCM). The results showed that the heart weight to body weight ratio was significantly elevated, and the ejection fraction and fractional shortening significantly decreased 8 weeks after TAC. Puromycin incorporation assay showed that TAC significantly increased protein synthesis rate in the left ventricle. RNA-seq revealed 1,632 differentially expressed genes showing functional enrichment in pathways including extracellular matrix remodeling, metabolic processes, and signaling cascades associated with pathological cardiomyocyte growth. When combined with ribosome profiling analysis, we revealed that translation efficiency (TE) of 1,495 genes was enhanced, while the TE of 933 genes was inhibited following TAC. In DCM patients, 1,354 genes were upregulated versus 1,213 genes were downregulated at the translation level. Although the majority of the genes were not shared between mouse and human, we identified 93 genes, including Nos3, Kcnj8, Adcy4, Itpr1, Fasn, Scd1, etc., with highly conserved translational regulations. These genes were remarkably associated with myocardial function, signal transduction, and energy metabolism, particularly related to cGMP-PKG signaling and fatty acid metabolism. Motif analysis revealed enriched regulatory elements in the 5' untranslated regions (5'UTRs) of transcripts with differential TE, which exhibited strong cross-species sequence conservation. Our study revealed novel regulatory mechanisms at the translational level in cardiac hypertrophy and identified conserved translation-sensitive targets with potential applications to treat cardiac hypertrophy and heart failure in the clinic.
Animals ; Humans ; Cardiomegaly/physiopathology* ; Ribosomes/physiology* ; Protein Biosynthesis/physiology* ; Mice ; Cardiomyopathy, Dilated/genetics* ; Ribosome Profiling

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C

Recent studies have shown that an imbalance in iron metabolism can affect the composition and microstructural changes of bone, disrupting bone homeostasis and leading to osteoporosis(OP). The imbalance in iron metabolism, along with its induced local abnormal microenvironment and cellular iron death, has become a new focal point in OP research, drawing increasing attention from the academic community regarding the regulation of iron metabolism to prevent and manage OP. From the perspective of traditional Chinese medicine(TCM), iron metabolism imbalance has potential connections to TCM theories regarding internal organs, as well as treatments aimed at tonifying the kidney, strengthening the spleen, and activating blood circulation. Evidence is continually emerging that TCMs and effective components that tonify the kidney, strengthen the spleen, and activate blood circulation can prevent and manage OP by regulating iron metabolism. This article analyzes the relationship between iron and bone, as well as the effects of TCM formulations on improving iron metabolism and influencing bone metabolism, from the perspectives of iron metabolism mechanisms and TCM interventions, aiming to broaden existing clinical strategies for prevention and treatment and inject new momentum into the field of OP as it moves into a new era.
Osteoporosis/drug therapy* ; Humans ; Iron/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Medicine, Chinese Traditional ; Bone and Bones/drug effects*