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.

The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

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

As a major category of occupational hazards in China, physical factors are widely distributed in various industries and affect a large number of workers. The list and diagnostic criteria of occupational diseases caused by physical factors are important basis for occupational disease diagnosis and protection of occupational health rights and interests for occupational populations. This article compares the differences in the list of occupational diseases caused by physical factors at home and abroad, analyzes the problems in the current list of occupational diseases caused by physical factors and related diagnostic standards in China, and puts forward relevant suggestions for further adjusting the list of occupational diseases caused by physical factors, formulating and revising relevant diagnostic standards for occupational diseases, providing reference for improving the classification and catalogue of occupational diseases in China in the future.

Objective:To analyze factors influencing the melasma severity, and to evaluate the efficacy of different treatment modalities.Methods:A retrospective analysis was conducted on clinical data from patients diagnosed with melasma at the Pigmentary Disorders Specialty Clinic in the Department of Dermatology, Huashan Hospital, Fudan University from July 2018 to December 2023. Patients' Fitzpatrick skin types, lesion color, locations and subtypes were evaluated by dermatologists, the melasma area and severity index (MASI) scores were calculated, and ΔMASI scores (baseline MASI scores - post-treatment MASI scores) were used for efficacy evaluation. The t test and one-way analysis of variance were used to analyze factors influencing the severity of melasma, the paired t test was used to analyze the differences in MASI scores before and after treatment, and a multivariate linear regression model was established to analyze factors influencing the efficacy in the treatment of melasma. Results:A total of 254 patients (including 249 females, 98.0%) with melasma were included, with ages of 40.8 ± 6.1 years. The Fitzpatrick skin type was Ⅲ in 213 (83.9%) patients, and Ⅳ in 41 (16.1%) patients; 180 (70.9%) patients lacked the habit of using sunscreens regularly. According to the location of pigment deposition, 166 cases (65.4%) were classified as epidermal type, and 88 (34.6%) as mixed type. Pigmented lesions were located on the cheek (174 cases, 68.5%), midface (26 cases, 10.2%), or lower jaw (54 cases, 21.3%), with periorbital involvement observed in 127 cases (50.0%). Before treatment, baseline MASI scores were significantly higher in the skin type Ⅳ group (19.75 ± 5.08) than in the skin type Ⅲ group (14.47 ± 4.18, P < 0.001), in the non-sunscreen users (16.45 ± 4.61) than in the sunscreen users (12.59 ± 3.91, P < 0.001), in the epidermal type group (15.99 ± 4.82) than in the mixed type group (14.07 ± 4.35, P < 0.001), in the mandibular type group (18.37 ± 5.14) than in the midfacial type group (14.23 ± 3.46, P < 0.001) and malar type group (14.54 ± 4.40, P < 0.001), as well as in the patients with periorbital involvement (16.54 ± 4.90) than in those without (14.10 ± 4.26, P < 0.001). According to the main treatment regimens, the patients were divided into the topical 2% hydroquinone group (109 cases, topically treated with 2% hydroquinone cream nightly), topical non-hydroquinone skin-lightening agents group (36 cases, topically treated with non-hydroquinone skin-lightening or exfoliating agents), oral tranexamic acid group (50 cases, treated with oral tranexamic acid 250 mg twice daily), and alpha hydroxy acid (AHA) chemical peeling group (30 cases, receiving AHA chemical peeling treatment monthly with the AHA concentration escalating from 20% to 50%). After treatment, MASI scores were significantly reduced from baseline in all the 4 groups (all P < 0.001), and the ΔMASI values significantly differed among the topical 2% hydroquinone group, topical non-hydroquinone skin-lightening agents group, oral tranexamic acid group, and AHA chemical peeling group (1.65 ± 2.19, 1.40 ± 2.16, 4.58 ± 3.09, 3.39 ± 3.61, respectively, F = 17.40, P < 0.001). The oral tranexamic acid group and AHA chemical peeling group showed significantly superior efficacy compared to the topical 2% hydroquinone group and topical non-hydroquinone skin-lightening agents group (all P < 0.05), while there was no significant difference in the efficacy between the oral tranexamic acid group and the AHA chemical peeling group ( P > 0.05). After adjustment for potential confounders in the multivariate linear regression model, the oral tranexamic acid group (β = 2.64) and AHA chemical peeling group (β = 1.55) still showed significantly superior efficacy compared to the topical 2% hydroquinone group (both P < 0.05) ; the skin type Ⅳ group exhibited significantly superior efficacy compared to the skin type Ⅲ group (β = 1.87, P < 0.001) . Conclusions:Dark skin color, lack of sun protection habits, epidermal melasma, and mandibular-type melasma, and periorbital involvement were associated factors for the severity of melasma. Oral tranexamic acid and AHA chemical peeling appeared to exhibit superior efficacy compared to topical 2% hydroquinone cream and topical non-hydroquinone skin-lightening agents.

Objective:To explore the effect of Danggui Shaoyao Powder(DGSYP)on the Toll-like receptor 4(TLR4)/Myeloid differen-tiation factor 88(MyD88)/Nuclear factor-κB(NF-κB)signaling pathway in ulcerative colitis(UC)rats.Methods:Forty-eight male SD rats were randomly divided into 6 groups:normal group,model group,DGSYP low-dose group(11.61 g/kg),medium-dose group(23.22 g/kg),high-dose group(46.44 g/kg)and salazosulapyridine group(0.36 g/kg).There were 8 rats in each group.In addition to the normal group,the rats in other groups were induced by 5%sodium trinitrobenzene sulfonate(TNBS)to establish a UC rat model.After successful modeling,each drug treatment group continued to administer the intervention for 14 days.At the same time,the rats in the normal group and the model group were given equal volume of nor-mal saline.The disease activity index(DAI)score was calculated.hematoxylin-eosin(HE)staining was used to observe the histo-pathological changes in the colon of rats.The levels of interleukin-6(IL-6),IL-1β,and tumor necrosis factor α(TNF-α)in colon tissue were measured by enzyme-linked immunosorbent assay(ELISA).Real-time fluorescence quantitative polymerase chain re-action(RT-qPCR)was used to detect the mRNA expression levels of TLR4,MyD88 and NF-κB p65 in colon tissues.The expression levels of TLR4,MyD88 and NF-κB in colon tissues were detected by Western blot(WB).Results:Compared with the normal group,the DAI score of the model group was increased,the colon was shortened,the histopathological changeswere obvious.The levels of in-flammatory factors IL-6,IL-1β and TNF-α in colon tissue of model group were significantly increased(P<0.01),the mRNA and pro-tein expressions of TLR4,MyD88 and NF-κB p65 were also significantly increased(P<0.05,P<0.01).Compared with the model group,the above disease-related conditions of rats in each treatment group of DGSYP were improved to varying degrees,DAI fraction decreased significantly(P<0.05),colon growth,no obvious edema or edema degree decreased,the histopathological changes of colon were improved to varying degrees.The levels of inflammatory factors IL-6,IL-1β and TNF-α in colon tissues were significantly de-creased(P<0.01),and the mRNA and protein expressions of TLR4,MyD88 and NF-κB p65 were significantly decreased(P<0.05,P<0.01).Conclusion:DGSYP can regulate the TLR4/MyD88/NF-κB signaling pathway,thereby reducing the release of inflammatory fac-tors,and then alleviating the degree of inflammatory damage in the colon of UC rats.

BACKGROUND:Individuals with chronic ankle instability are prone to inversion ankle sprains during landing.Moderately increasing the foot toe-out angle during landing may reduce the occurrence of inversion ankle sprains,but no studies have directly demonstrated this effect. OBJECTIVE:To explore the effect of increased toe-out angle during landing on the peak inversion angle,peak angular velocity,and the time to peak inversion among individuals with and without chronic ankle instability. METHODS:A total of 60 participants were recruited for this study,including 30 individuals with chronic ankle instability and 30 without chronic ankle instability.The study utilized a simulated sprain apparatus for drop-landing tests,featuring a platform that could tilt forward by 24° and inward by 15°,thus simulating the foot position during an ankle inversion sprain.Participants were required to perform drop-landing tests under two landing conditions:natural landing and toe-out landing,with the latter involving a greater foot toe-out angle,over 150%more than the former.Kinematic data of participants were recorded using a 12-camera three-dimensional motion capture system.Data analysis was conducted using two-way repeated measures analysis of variance and Spearman correlation analysis. RESULTS AND CONCLUSION:(1)Significant main effects of condition were found for peak inversion angle during drop-landing(P<0.001,η2 p=0.270),peak inversion velocity(P=0.015,η2 p=0.098),and peak inversion time(P<0.001,η2 p=0.260);a significant main effect of group was found for peak inversion velocity(P=0.029,η2 p=0.080).(2)There were significant negative correlations between the foot toe-out angle at landing and the peak ankle inversion angle(P=0.021,r=-0.310;P=0.042,r=-0.278)as well as the peak inversion time(P=0.018,r=-0.312;P=0.021,r=-0.309)in both chronic ankle instability and non-chronic ankle instability groups.Moreover,a significant negative correlation was also found between the foot toe-out angle and peak inversion velocity in the chronic ankle instability group(P=0.021,r=-0.312).(3)It is indicated that increasing the foot toe-out angle at landing can reduce the peak inversion angle,peak inversion velocity,and the peak inversion time during landing in patients with chronic ankle instability and non-chronic ankle instability,thereby decreasing the risk of ankle inversion sprains.

In 1861, the missionary William Lockhart founded the Peking Hospital in Beijing. From 1861 to 1863, William Lockhart not only cured a large number of patients in the Peking Hospital but also introduced western surgical techniques, hygiene and disinfection concepts, and medical record management systems. During its operation, the Peking Hospital's unique value can be seen in its sources and modes of financing, scope of services, number of patients treated, and missionary functions. The Peking Hospital served as a vital bridge for the exchange of medical knowledge between the East and the West, and it played a pivotal role in transforming China's modern medical system and modern health concepts, exerting a profound influence on the development of modern medicine.