ObjectiveTo investigate the mechanism of topical treatment of allergic contact dermatitis （ACD） mice with Portulacae Herba based on the nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/nuclear factor-κB （NF-κB） signaling pathway. MethodsA total of 70 6-week-old specific pathogen free （SPF） female Kunming mice were adaptively fed for 1 week and randomly divided into blank group， model group， compound dexamethasone acetate cream group （2.075×10^-2 g·g^-1）， blank matrix cream group， low-dose Portulacae Herba cream group （0.1 g·g^-1）， high-dose Portulacae Herba cream group （0.2 g·g^-1）， and Portulacae Herba + inhibitor group （0.2 g·g^-1 + 30 mg·kg^-1 ML385）， with 10 mice in each group. One day before the experiment， the mice were shaved on the neck and back. Except for the blank group， the mice in the other groups were treated with 2，4-dinitrochlorobenzene （DNCB） to establish an ACD model. After respective administration， the skin lesion of the mice was scored， and the histopathological changes of the skin were stained with hematoxylin-eosin （HE）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， reactive oxygen species （ROS）， superoxide dismutase （SOD） activity， and malondialdehyde （MDA） in serum of mice. The expression of Nrf2/HO-1/NF-κB signaling pathway-related proteins in mouse skin tissue was detected by immunohistochemistry （IHC）， Western blot， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， the mice in the model group had an increased skin lesion score （P<0.01）， severe pathological damage to skin tissue， increased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and decreased content of SOD （P<0.01）. In addition， the mRNA and protein expression levels of Nrf2， HO-1， and nuclear factor-κB inhibitor α （IκBα） in skin tissue were up-regulated （P<0.01）， while the protein expression levels of phosphorylated （p）-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.01）. Compared with the model group and the blank matrix cream group， the mice treated with Portulacae Herba had a decreased skin lesion score （P<0.01）， reduced pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and increased content of SOD （P<0.01）. Additionally， the mRNA and protein expression levels of Nrf2， HO-1， and IκBα in skin tissue were down-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were up-regulated （P<0.05，P<0.01）. Compared with the Portulacae Herba + inhibitor group， the high-dose Portulacae Herba cream group had a decreased skin lesion score （P<0.01）， alleviated pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in the serum of mice （P<0.05，P<0.01）， and increased content of SOD （P<0.01）. The protein expression levels of Nrf2， HO-1， and IκBα and the mRNA expression of Nrf2 and HO-1 in skin tissue were up-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.05）. ConclusionPortulacae Herba can improve DNCB-induced ACD skin damage in mice by regulating the Nrf2/HO-1/NF-κB signaling pathway.

BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Objective: To analyze respiratory syncytial virus(RSV) outbreaks surveillance results and the epidemiological characteristics in kindergarten and school in Shenzhen during 2017-2023 , so as to provide a scientific reference for control and prevention of RSV. Methods: Epidemiological data and surveillance results of RSV outbreaks in kindergarten and school from 2017 to 2023 were collected for descriptive analyses. Results: A total of 31 RSV outbreaks were identified in kindergarten and school in 2017-2023 in Shenzhen, 346 cases were reported, the average incidence rate was 22.02%. The most annual RSV outbreaks were reported in 2020 with 14 outbreaks, followed by 8 outbreaks in 2023. A total of 64.52% of RSV outbreaks were identified in kindergarten with rest occurring in primary school or middle school. The greatest monthly count of outbreak was 18 (58.06%) in September, followed by 3 outbreaks (9.68%) in March and October. A total of 244 swab samples were collected, 169 samples were positive for respiratory viruses, the positive rate was 69.26%, 121 samples were positive for RSV,from 31 respiratory syncytical virus outbreaks 57 and samples were positive for other respiratory viruses(9 samples were positive for two respiratory viruses). A toral of 14(45.16%) outbreaks are caused by RSV alone, 17 outbreaks (54.84%) were caused by RSV and other respiratory viruses. Conclusions Most RSV outbreaks in kindergarten and school are reported after 2020 in Shenzhen, most RSV outbreaks occur in kindergarten, peak seasons of RSV outbreaks are autumn and spring.

OBJECTIVE To study the effects and mechanism of Portulaca oleracea cream on skin pruritus and barrier function in allergic contact dermatitis （ACD） mice. METHODS Low-concentration and high-concentration P. oleracea creams were prepared， with the P. oleracea extract solution （1 g/mL， calculated by crude drug） concentrations of 10% and 20%. Sixty BALB/c mice were randomly allocated into blank group， model group， Mometasone furoate cream group （positive control）， blank matrix cream group， P. oleracea low-concentration and high-concentration cream groups. Except for blank group， ACD model was induced in each group using 2，4-dinitrochlorobenzene solution. The blank group and model groups received normal saline， while the remaining groups were treated with their respective creams， once a day， at a dose of approximately 0.5 g per application， continuously for 14 days. At 24 h post-final administration， skin lesions of mice were observed and scored； pathological changes of skin tissue were observed； serum levels of immunoglobulin E（IgE） and tumor necrosis factor-α （TNF-α） were quantified. mRNA expression of MAS-related G protein-coupled receptors （including MrgprA3， MrgprC11， and MrgprD） in dorsal root ganglion （DRG） was assessed； while protein expressions of skin barrier function-related proteins Claudin-1 and Occludin in skin tissues were determined. RESULTS Compared with blank group， mice in the model group exhibited severe skin damage， characterized by loss of epidermal architecture， hyperkeratosis of the skin tissue， and the infiltration of a large number of inflammatory cells. The skin injury scores， as well as the serum levels of IgE and TNF-α， and the mRNA expression levels of MrgprA3， MrgprC11， and MrgprD in DRG， were all significantly elevated compared to the blank group （P＜0.05 or P＜0.01）； in contrast， the protein expression levels of Claudin-1 and Occludin in the skin tissue were markedly reduced （P＜0.05）. Compared with model group， mice in P. oleracea low-concentration and high- concentration cream groups demonstrated significant alleviation of skin damage， as evidenced by reduced epidermal hyperplasia， mitigated spongiosis in the dermis， and decreased infiltration of inflammatory cells； these quantitative indicators were almost significantly reversed （P＜0.05 or P＜0.01）. No significant differences were observed in the aforementioned skin injuries， pathological alterations， or quantitative indicators between the blank matrix cream group and the model group. CONCLUSIONS P. oleracea may ameliorate skin lesions and restore skin barrier function of ACD mice， the mechanism of which may be associated with downregulating mRNA expressions of MrgprA3， MrgprC11 and MrgprD in DRG， and up-regulating the protein expressions of Claudin-1 and Occludin in skin tissue.

Cytotoxicity, usually represented by cell viability, is a crucial parameter for evaluating drug safety in vitro. Accurate prediction of cell viability/cytotoxicity could accelerate drug development in the early stage. In this study, by integrating cellular transcriptome and cell viability data using four machine learning algorithms (support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM)) and two ensemble algorithms (voting and stacking), highly accurate prediction models of 50% and 80% cell viability were developed with area under the receiver operating characteristic curve (AUROC) of 0.90 and 0.84, respectively; these models also showed good performance when utilized for diverse cell lines. Concerning the characterization of the employed Feature Genes, the models were interpreted, and the mechanisms of bioactive compounds with a narrow therapeutic index (NTI) can also be analyzed. In summary, the models established in this research exhibit superior capacity to those of previous studies; these models enable accurate high-safety substance screening via cytotoxicity prediction across cell lines. Moreover, for the first time, Cytotoxicity Signature (CTS) genes were identified, which could provide additional clues for further study of mechanisms of action (MOA), especially for NTI compounds.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Objective To investigate the effect of health failure mode and effect analysis(HFMEA)in optimizing the management process of postoperative diabetes insipidus in children undergoing neurosurgery.Methods Based on HFMEA,a management flowchart for postoperative diabetes insipidus in children undergoing neurosurgery was created.Brainstorming was adopted to identify failure modes in the workflow,analyze risk factors,and develop improvement measures,thereby refining the management flowchart.The amelioration and prognosis of diabetes insipidus in these children before(October 2022 to November 2023)and after(January 2024 to February 2025)implementation of the management flowchart were compared.Results The HFMEA-based management process for postoperative diabetes insipidus in children undergoing neurosurgery alleviated the symptoms of diabetes insipidus regarding the number of diabetes insipidus in the pediatric intensive care unit(P=0.006),the average daily urine output in the pediatric intensive care unit(P=0.001),the proportion of electrolyte abnormalities at discharge/transfer(P=0.037),the duration of mechanical ventilation(P=0.007),and the length of stay in the intensive care unit(P=0.001).Conclusion The HFMEA-based management process for postoperative diabetes insipidus in children undergoing neurosurgery is beneficial to the optimization of the management process,the alleviation of postoperative diabetes insipidus,and the improvement of prognosis in these children.
Humans ; Diabetes Insipidus/etiology* ; Neurosurgical Procedures/adverse effects* ; Child ; Postoperative Complications/therapy* ; Healthcare Failure Mode and Effect Analysis ; Intensive Care Units, Pediatric ; Risk Factors

Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*