Despite half-century old, but comprehensive national and international guidance, evidence of clinical effectiveness and widespread agreement on management of risk factors along with sophisticated measures for primary ...Despite half-century old, but comprehensive national and international guidance, evidence of clinical effectiveness and widespread agreement on management of risk factors along with sophisticated measures for primary and secondary prevention of major cardiovascular events, cardiovascular disease remains the dominant cause of death and disability world-wide. Life style changes at population-level (e.g., lower salt and saturated fat consumption or reduced/banned amount of industrially-produced trans fatty acids in specific products, etc.) or changes at individual level (e.g., targeting modifiable risk factors/life style changes affecting smoking/tobacco use, poor diet, high blood cholesterol, high blood pressure, insufficient physical activity, overweight/obesity) have reduced coronary heart disease mortality to variable extent in different countries (mostly so reported in Finland, Iceland and Sweden) at the beginning of the new century. Overall, however, cardiovascular mortality is estimated to increase in the next coming years until 2030 at a cost exceeding US $1044 billion. Several decades of status quo are also noted in the therapeutic spectrum of cardiovascular disease, mainly consisting of variations to LDL-C lowering agents, antihypertensives, anticoagulants, antiplatelets and fibrinolytics. Most of the therapeutic interventions are “tertiary” in nature (probably some 60%), meaning that treatment is instituted once the individual has developed a pathologic condition;“secondary prevention” may cover some 25%?-?30% (meant to prevent re-occurrence of the condition or occurrence of complications) while “primary prevention” is left with 10%?-?15% share (most commonly implying life style changes at individual level and rarely pharmacological intervention). For almost three decades, the so-called inflammatory hypothesis has been promoted as a reasonable pathogenetic theory behind initiation and growth of atherosclerotic plaque (Alexander RW, 1994;Ross R, 1999). With the discovery of molecular and cellular pathways that promote atherosclerosis and the role of cytokines as inflammatory messengers, the concept as such—inflammation, has received a primordial role?in atherogenesis. The present review paper aims at ascertaining the role of inflammation as a common pathogenetic denominator of cardiovascular disease in patients primarily treated for their psoriasis and/or psoriatic arthritis.展开更多
Dear Editor,Psoriasis is increasingly recognized as a systemic inflammatory disease associated with several comorbidities,including metabolic syndrome,depression,and malignancies[1].Colorectal cancer(CRC)is the third ...Dear Editor,Psoriasis is increasingly recognized as a systemic inflammatory disease associated with several comorbidities,including metabolic syndrome,depression,and malignancies[1].Colorectal cancer(CRC)is the third most common cancer worldwide and ranks second in mortality among all malignancies.Currently,it has become one of the most severe challenges faced by healthcare systems in many countries[2].A previous study has found that patients with psoriasis have a significantly increased risk of developing CRC[3].展开更多
Objective To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization(MR)study.Methods A two-sample MR study was performed using summarized statistics from the g...Objective To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization(MR)study.Methods A two-sample MR study was performed using summarized statistics from the genome-wide association studies(GWAS)conducted in reproductive traits,as well as GWAS data on overall psoriasis,psoriatic arthritis(PsA),and psoriasis vulgaris(PV).Besides univariable MR(UVMR),multivariable MR and two-step MR was used to calculate the independent effects and quantify the proportion mediated by education or body mass index(BMI).Results Genetically predicted early age at first sexual intercourse(AFS)led to an increased risk of overall psoriasis[odds ratio(OR)UVMR:0.54];36.13%of this effect was mediated through BMI and 47.79%through educational attainment.The direct negative casual association between age at first birth(AFB)-PsA was dominant(ORUVMR:0.76),with 49.61%proportion of the mediation due to BMI.The mediating effect was found for BMI on the AFS-PV relationship,which accounted for 26.27%of the proportion.AFS was inversely associated with the risk of overall psoriasis and PV,with considerable mediation by BMI and educational attainment.Conclusion Early AFB may cause a higher risk of PsA,while the AFS-PsA association was fully mediated by BMI.展开更多
BACKGROUND Mild cognitive impairment(MCI)is common in atrial fibrillation(AF)patients and may develop earlier in those with multiple cardiovascular comorbidities,potentially impairing self-management and treatment adh...BACKGROUND Mild cognitive impairment(MCI)is common in atrial fibrillation(AF)patients and may develop earlier in those with multiple cardiovascular comorbidities,potentially impairing self-management and treatment adherence.This study aimed to characterize the prevalence and profile of MCI in AF patients,examine its associations with cardiovascular comorbidities,and assess how these comorbidities influence specific cognitive domains.METHODS This cross-sectional study analyzed data from AF patients who underwent cognitive assessment between 2017 and 2021.Cognitive status was categorized as MCI or non-MCI based on the Montreal Cognitive Assessment.Associations between comorbidities and MCI were assessed by logistic regression,and cognitive domains were compared using the Mann-Whitney U test.RESULTS Of 4136 AF patients(mean age:64.7±9.4 years,64.7%male),33.5%of patients had MCI.Among the AF patients,31.2%of patients had coronary artery disease,20.1%of patients had heart failure,and 18.1%of patients had hypertension.88.7%of patients had left atrial enlargement,and 11.0%of patients had reduced left ventricular ejection fraction.Independent factors associated with higher MCI prevalence included older age(OR=1.04,95%CI:1.03-1.05,P<0.001),lower education level(OR=1.51,95%CI:1.31-1.73,P<0.001),hypertension(OR=1.28,95%CI:1.07-1.52,P=0.001),heart failure(OR=1.24,95%CI:1.04-1.48,P=0.020),and lower left ventricular ejection fraction(OR=1.43,95%CI:1.04-1.98,P=0.028).A higher CHA_(2)DS_(2)-VASc score(OR=1.27,95%CI:1.22-1.33,P<0.001;≥2 points vs.<2 points),and greater atherosclerotic cardiovascular disease burden(OR=1.45,95%CI:1.02-2.08,P=0.040;2 types vs.0 type)were linked to increased MCI risk.These above factors influenced various cognitive domains.CONCLUSIONS MCI is common in AF and closely associated with cardiovascular multimorbidity.Patients with multiple comorbidities are at higher risk,highlighting the importance of routine cognitive assessment to support self-management and integrated care.展开更多
There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,...There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.展开更多
Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in...Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in psoriasis.Methods:An imiquimod(IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters,TMAO levels,and liver flavin monooxygenase 3(FMO3)mRNA expression.Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles.To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model,exogenous TMAO,choline,or 3,3-dimethyl-1-butanol(DMB)were administered via intraperitoneal injections or diet in IMQ-treated mice.Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results:IMQ-induced psoriatic mice exhibited abnormal glucose,insulin,and lipid levels.IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2(Glut2)and silence information regulator 1(Sirt1),while upregulating glucose transporter 4(Glut4)and peroxisome proliferator-activated receptor gamma(PPARγ).Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice.Additionally,liver FMO3 mRNA expression was increased in the psoriatic mouse model.In patients,TMAO levels positively correlated with Psoriasis Area and Severity Index(PASI)scores,serum triglyceride(TG),and total cholesterol(TC)levels.The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice.A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice,whereas DMB treatment alleviated these effects.RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122(miR-122),which may suppress the expression of gremlin 2(GREM2),thus contributing to lipid metabolism disorder.Conclusion:TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.展开更多
Background: Erythrodermic psoriasis (EP) is a rare, severe variant of psoriasis characterized by widespread erythema, scaling, and systemic complications. Despite advances in systemic treatments, the management of EP ...Background: Erythrodermic psoriasis (EP) is a rare, severe variant of psoriasis characterized by widespread erythema, scaling, and systemic complications. Despite advances in systemic treatments, the management of EP remains challenging, particularly in patients with comorbidities or contraindications to standard therapies. Objectives: To evaluate the effectiveness of ozonated water as an adjunctive treatment for EP, delivered using a patented robotic therapy system designed for hygiene and infection prevention in non-self-sufficient patients. Methods: We report the case of a 90-year-old male patient with acute EP who received daily skin treatments with ozonated water in conjunction with supportive care, including rehydration and antibiotics. The intervention was facilitated by the robotic system “COPERNICO Surveillance & Prevention,” which ensured standardized hygiene practices and clinical documentation. Results: Within one week of treatment, the patient showed complete desquamation of necrotic skin, resolution of erythema, and significant metabolic recovery. Fever subsided, renal function improved, and the patient was discharged in stable condition. Follow-up confirmed sustained clinical improvement, and no adverse events were reported. Conclusions: Ozonated water demonstrated efficacy in alleviating the dermatological and systemic manifestations of EP in a high-risk elderly patient. This case highlights the potential of ozone therapy as a safe, cost-effective adjunctive treatment for EP and underscores the utility of robotic systems in managing complex dermatological conditions. Further research is warranted to validate these findings in larger cohorts.展开更多
Objective: To explore the effect of Health Action Process Approach (HAPA) theory in patients with type D personality psoriasis. Methods: A total of 66 patients with type D personality psoriasis admitted to the dermato...Objective: To explore the effect of Health Action Process Approach (HAPA) theory in patients with type D personality psoriasis. Methods: A total of 66 patients with type D personality psoriasis admitted to the dermatology department of a top-three hospital in Jingzhou City from November 2022 to July 2023 were selected and divided into control group and test group with 33 cases in each group by random number table method. The control group received routine health education, and the experimental group received health education based on the HAPA theory. Chronic disease self-efficacy scale, hospital anxiety and depression scale and skin disease quality of life scale were used to evaluate the effect of intervention. Results: After 3 months of intervention, the scores of self-efficacy in experimental group were higher than those in control group (P P Conclusion: Health education based on the theory of HAPA can enhance the self-efficacy of patients with type D personality psoriasis, relieve negative emotions and improve their quality of life.展开更多
Psoriasis is a chronic inflammatory skin disease,which seriously affects the physical and mental health of patients.The progression of psoriasis is influenced by the excessive production of reactive oxygen species(ROS...Psoriasis is a chronic inflammatory skin disease,which seriously affects the physical and mental health of patients.The progression of psoriasis is influenced by the excessive production of reactive oxygen species(ROS)and inflammatory responses.In this paper,novel celastrol(Ce)-loaded metal-phenolic nanozymes(tannic acid-Fe^(3+))(TA-Fe)integrated microneedles(Ce@TA-Fe/MNs)were constructed to achieve the combined oxidative stress alleviation and anti-inflammatory therapy of psoriasis.Molecular dynamics simulations and structural characterization confirmed the successful fabrication of nanozymes.The Ce@TA-Fe/MNs system,characterized by its rapid dissolution kinetics and superior mechanical strength,enabled minimally invasive skin penetration for efficient nanozymes delivery.Nanozymes possessed superoxide dismutase and catalase mimetic enzyme activities,effectively eliminating excessive ROS in psoriatic skin lesions.Additionally,the release of Ce from Ce@TA-Fe provided strong antioxidant and anti-inflammatory effects.Based on these characteristics,Ce@TA-Fe/MNs could effectively alleviate the symptoms in psoriasis mice models.These findings demonstrated that the integration of Ce-equipped nanozymes within MNs holds great promise as a therapeutic strategy for the clinical management of psoriasis.展开更多
BACKGROUND Erythrodermic psoriasis(EP)is a rare and life-threatening form of psoriasis associated with significant morbidity and mortality.Systemic immunosuppre-ssive therapies are often required but may predispose to...BACKGROUND Erythrodermic psoriasis(EP)is a rare and life-threatening form of psoriasis associated with significant morbidity and mortality.Systemic immunosuppre-ssive therapies are often required but may predispose to opportunistic infections.Disseminated herpes simplex virus type-1(HSV-1)is an unusual complication in otherwise immunocompetent patients and has not been reported in association with ixekizumab therapy for EP.CASE SUMMARY We describe a 49-year-old man with longstanding severe plaque psoriasis,liver cirrhosis,and bipolar disorder who developed EP involving>90%of body surface area[Psoriasis Area and Severity Index(PASI)45].Following initial stabil-ization,he was admitted to the intensive care unit(ICU)with hemodynamic instability,leukocytosis with eosinophilia,and diffuse desquamation.Ixekizumab was initiated with high-dose topical clobetasol.During his ICU stay,he developed recurrent bacteremias and neurologic decline(Glasgow Coma Scale 7/15),fo-llowed by the appearance of widespread vesicles and hemorrhagic crusts.HSV-1 infection was confirmed by polymerase chain reaction(PCR).Immunosuppressive therapy was withheld,and intravenous acyclovir was started,leading to progre-ssive improvement.After ten days,ixekizumab was reintroduced with careful monitoring,resulting in marked clinical improvement(PASI 9.7 at six weeks).The patient remained stable on long-term follow-up with oral acyclovir prophylaxis.CONCLUSION This case highlights the diagnostic and therapeutic challenges of managing EP in the setting of biologic therapy.Disseminated cutaneous HSV-1 should be considered in immunosuppressed patients presenting with new vesicular eruptions,and prompt PCR testing with early antiviral therapy is essential.A multidisciplinary approach is critical to balance immunosuppression for disease control with infection risk.展开更多
BACKGROUND Psoriasis is a chronic inflammatory condition related to an increased athero-sclerotic cardiovascular disease(ASCVD)risk.AIM To investigate whether lipoprotein(a)[Lp(a)]levels are increased in patients with...BACKGROUND Psoriasis is a chronic inflammatory condition related to an increased athero-sclerotic cardiovascular disease(ASCVD)risk.AIM To investigate whether lipoprotein(a)[Lp(a)]levels are increased in patients with psoriasis.METHODS A comprehensive literature search up to January 30,2025 was conducted utilizing PubMed and Cochrane Library databases.A qualitative synthesis and a meta-analysis on Lp(a)mean differences(MD)between psoriasis cases and healthy controls(HC)was performed.The protocol of this meta-analysis has been re-gistered to PROSPERO(No.CRD420250652465).RESULTS Eighteen studies with 1650 psoriasis patients and 1621 HC were eligible for qua-litative synthesis.Pooled analysis from 16 studies(1401 psoriasis patients and 1320 HC)demonstrated that psoriasis patients had significantly higher Lp(a)levels compared with the HC group(MD:6.72 mg/dL,95%CI:4.32-9.12,P<0.00001,I2=71%).Sensitivity analyses according to the region of origin was also performed.The pooled analysis of the European sub-population showed a pronounced increase in Lp(a)levels in 189 patients with psoriasis vs 178 HC(MD:15.86 mg/dL,95%CI:5.79-25.92,P<0.002,I2=79%),while the pooled analysis on the Asian sub-population demonstrated a smaller but still significant difference in Lp(a)levels between 1177 psoriasis patients and 1127 HC(MD:4.95 mg/dL,95%CI:2.99-6.92,P<0.00001,I2=58%).CONCLUSION Our findings suggest that Lp(a)levels are significantly elevated in psoriasis patients,further adding to their ASCVD risk.展开更多
This research aimed to identify and validate ferroptosis-related signature genes associated with psoriasis through a comprehensive bioinformatics approach,while also predicting potential traditional Chinese medicines(...This research aimed to identify and validate ferroptosis-related signature genes associated with psoriasis through a comprehensive bioinformatics approach,while also predicting potential traditional Chinese medicines(TCMs)targeting these genes.The findings might offer a foundation for understanding ferroptosis mechanisms in psoriasis and exploring TCM-based therapeutic strategies.To begin,we retrieved gene expression profile data from psoriasis patients and healthy controls from the Gene Expression Omnibus(GEO)database,followed by data normalization.Ferroptosis-associated differentially expressed genes(Fer-DEGs)were identified using the FerrDb database.Subsequent GO and KEGG enrichment analyses provided insights into the biological functions and signaling pathways of these Fer-DEGs.Core Fer-DEGs were identified using machine learning algorithms,and their expression levels were further validated with an external dataset to evaluate diagnostic potential.Additionally,the symMap database facilitated the reverse prediction of TCMs targeting these key signature genes.The analysis identified 265 significant Fer-DEGs.GO enrichment indicated their involvement in diverse biological processes,while KEGG analysis highlighted their roles in various pathways,including ferroptosis,autophagy,cancer,infection,and metabolism,as well as PI3K-Akt,FoxO,mTOR,and HIF-1 signaling pathways.Machine learning pinpointed nine core psoriasis-related Fer-DEGs:PRKAA2,ANO6,POR,PTEN,MAPK8,ZFAS1,ADAM23,TMBIM4,and PARP14,all demonstrating strong diagnostic performance.Predicted TCMs primarily included those with heat-clearing,detoxifying,blood-activating,stasis-resolving,and phlegm-resolving properties.In conclusion,our study suggested that PRKAA2,ANO6,POR,PTEN,MAPK8,ZFAS1,ADAM23,TMBIM4,and PARP14 were key players in the ferroptosis pathway in psoriasis.TCMs with properties such as heat-clearing,blood activation,and phlegm resolution might hold promise for anti-ferroptosis interventions in psoriasis treatment.展开更多
BACKGROUND Psoriasis is often first recognized by patients through online image searches.However,search engine algorithms influenced by geographic location may still produce results that predominantly feature lighter ...BACKGROUND Psoriasis is often first recognized by patients through online image searches.However,search engine algorithms influenced by geographic location may still produce results that predominantly feature lighter skin tones,regardless of the region’s majority skin type.This underrepresentation may limit recognition and delay care for people of color.AIM To examine whether search algorithms tailor region-specific results in terms of skin color for psoriasis imagery.METHODS This observational study recruited 66 participants from 18 countries who conducted image searches for“psoriasis”across various web browsers.During the meeting,a Google form was posted to record observations,and participants reported the diversity of skin tones in the first three rows of search results using a reference image depicting Fitzpatrick types.RESULTS Results showed a global bias toward lighter skin tones,with 94%of participants identifying light skin predominance in the first row and minimal representation of medium or darker skin tones in subsequent results,verified via χ^(2) analysis.Participants who observed darker or mixed skin tones typically found them further down their results.CONCLUSION There remains a significant gap in global representation of psoriasis imagery.This paper deepens the current understanding of bias in online media and pushes for further exploration of more inclusive dermatologic imagery.展开更多
This review explores the emerging connection between psoriasis and atrial fibrillation(AF),focusing on shared inflammatory mechanisms,clinical implications,and research gaps.Psoriasis,characterized by chronic systemic...This review explores the emerging connection between psoriasis and atrial fibrillation(AF),focusing on shared inflammatory mechanisms,clinical implications,and research gaps.Psoriasis,characterized by chronic systemic inflammation,has been associated with increased AF risk,driven by elevated pro-inflammatory cytokines such as interleukin(IL)-6,IL-17,and tumor necrosis factor-alpha.These inflammatory mediators contribute to atrial remodeling,fibrosis,and conduction abnormalities,evidenced by prolonged P-wave dispersion and atrial electromechanical delay in psoriasis patients.Severe psoriasis further exacerbates atrial dysfunction,increasing susceptibility to AF.This review synthesizes existing epidemiological and biological data,highlighting the need for interdisciplinary management of psoriasis patients to mitigate cardiovascular risks.However,the reliance on observational studies limits definitive conclusions about causality.We emphasize the necessity for large-scale,multicenter research to validate these findings,investigate genetic predispositions,and evaluate lifestyle factors and AF burden.Future research should aim to delineate the pathophysiological link between psoriasis and AF.By examining the interplay of systemic inflammation,electrophysiological changes,and clinical outcomes,this review aims to advance understanding of the psoriasis-AF link and guide strategies for early detection,prevention,and management of AF in psoriasis patients.Comprehensive care integrating dermatology and cardiology is essential for improving patient outcomes.展开更多
Objective:To assess the efficiency of a Sophora flavescens Ait(S.flavescens,Ku Shen)-soluble microneedle(SFA-MN)for improving skin lesion symptoms in mice with psoriasis.Methods:SFA-MNs were prepared using a two-mold ...Objective:To assess the efficiency of a Sophora flavescens Ait(S.flavescens,Ku Shen)-soluble microneedle(SFA-MN)for improving skin lesion symptoms in mice with psoriasis.Methods:SFA-MNs were prepared using a two-mold molding process with 20%w/v poly-vinylpyrrolidone and 15%w/v polyvinyl alcohol.The SFA-MNs were assessed for morphology,mechanical properties,in vitro dissolution,identification of components,and skin lesion improvement in imiquimod-induced psoriasis mice.Results:The SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis,facilitating efficient drug delivery.Furthermore,they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differ-entiation 3 and tumor necrosis factor-a.In addition,this system alleviated skin inflammation,splenic swelling,and thymic atrophy in the psoriasis-like mouse model.Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios(m/z)of the secondary fragments N-methylcytisine,5a,9a-dihydroxymatrine,sophoramine,matrine,oxysophocarpine,oxymatrine,and kushenol O.Conclusion:The drug delivery strategy combining traditional herbal S.flavescens with soluble micro-needle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models,enabling enhanced therapeutic effects compared with the control group.展开更多
BACKGROUND A significant association between increased age and an increased risk of metachronous gastric cancer(MGC)following curative endoscopic submucosal dissection(ESD)has previously been reported.AIM To determine...BACKGROUND A significant association between increased age and an increased risk of metachronous gastric cancer(MGC)following curative endoscopic submucosal dissection(ESD)has previously been reported.AIM To determine risk factors for the metachronous occurrence of early gastric cancer(EGC)in elderly individuals.METHODS This retrospective cohort study comprised 653 elderly patients(aged≥65 years)who underwent curative ESD for EGC between January 2014 and June 2020 at Nanjing Drum Tower Hospital.Comprehensive analyses were conducted to compare lifestyle habits,comorbidities,and Helicobacter pylori(H.pylori)infections as potential indicators.RESULTS During a median follow-up of 38 months,46 patients(7.0%,20.46/1000 person-years)developed MGC in the elderly cohort.The cumulative incidences of MGC at 2,3,and 5 years were 3.3%,5.3%,and 11.5%,respectively.In multivariate Cox regression analyses,the independent risk factors for MGC included metabolic dysfunctionassociated steatotic liver disease(MASLD)[hazard ratio(HR)=2.44,95%confidence interval(CI):1.15-5.17],persistent H.pylori infection(HR=10.38,95%CI:3.36-32.07),severe mucosal atrophy(HR=2.71,95%CI:1.45-5.08),and pathological differentiation of EGC(well/moderately differentiated vs poorly differentiated:HR=10.18,95%CI:1.30-79.65).Based on these risk factors,a risk stratification system was developed to categorize individuals into low(0-1 point),intermediate(2-3 points),and high(4-8 points)risk categories for MGC,with cumulative incidence rates of 12.3%,21.6%,and 45%,respectively.CONCLUSION Among elderly individuals,MASLD,persistent H.pylori infection,severe mucosal atrophy,and well/moderately differentiated EGC were associated with an increased risk of MGC.Elderly patients are recommended to adopt healthy lifestyle practices,and undergo regular endoscopic screening and H.pylori testing after curative ESD for EGC.展开更多
Psoriasis is a common and chronic immune-mediated disorder that severely impacts the life quality of patients.Phosphodiesterase-4(PDE4)inhibitors have attracted significant interests in the psoriasis treatment due to ...Psoriasis is a common and chronic immune-mediated disorder that severely impacts the life quality of patients.Phosphodiesterase-4(PDE4)inhibitors have attracted significant interests in the psoriasis treatment due to their ability to suppress the inflammatory cascades.In this study,extensive screening of an in-house library of 1200 Chinese medicinal plant extracts identified Platycladus orientalis(L.)Franco(P.orientalis)as a potent PDE4 inhibitor,exhibiting 42.7%inhibition at 0.2μg/m L.Subsequent bioassayguided isolation revealed flavonoids,particularly amentoflavone(AMF),as the principal component responsible for PDE4 inhibition.To enrich the effective ingredients,a purification protocol using microporous resin was developed,yielding a flavonoid-rich extract(FLDs)that efficiently increased AMF content from 6.2%to 72.3%and improved PDE4 inhibitory activity to 74.2%at 0.2μg/mL.Notably,P.orientalis with favorable safety profiles demonstrated superior in vitro and in vivo anti-psoriasis effects to both AMF and the approved PDE4 inhibitor apremilast.These findings highlight the potential of P.orientalis as a novel therapeutic agent for psoriasis and provide valuable insights for its development in psoriasis treatment.展开更多
Psoriasis is a prevalent inflammatory disease that shares chronic inflammation pathways with the pathophysiology of metabolic syndrome(MetS),type-2 diabetes mellitus and atherosclerosis.A high prevalence of steatosis ...Psoriasis is a prevalent inflammatory disease that shares chronic inflammation pathways with the pathophysiology of metabolic syndrome(MetS),type-2 diabetes mellitus and atherosclerosis.A high prevalence of steatosis and advanced liver fibrosis has been described in psoriasis.The influence of MetS and its compounds,patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 gene polymorphisms and the cumulative dose of methotrexate(MTX)in the progression of steatotic disease are still under debate.A suitable new classification for psoriasis-related liver disease,under the umbrella of steatotic liver disease(SLD),might be evaluated due to the potential impact of MTX on liver steatosis.Considering the interplay between the MetS,steatosis and MTX,a new definition for this complex disease might be discussed since it is not entirely addressed under the umbrella of SLD and metabolic-dysfunction associated SLD.Hence,shortly,a discussion could be raised on the feasible term“Met-Drug SLD”,metabolic and drug-induced SLD,which comprises both metabolic dysfunction and drug-related SLD.This review aims to report the best evidence to accurately classify liver disease in psoriasis,considering the new definition of SLD,allowing appropriate management once it is carefully defined.展开更多
OBJECTIVE:To explore the therapeutic mechanisms of Xiaoyin Anshen Yin( 消银安神饮, XYAS) in treating psoriasis associated with sleep focusing on melatonin and the regulation of the nuclear factor kappa-B(NF-κB) pathw...OBJECTIVE:To explore the therapeutic mechanisms of Xiaoyin Anshen Yin( 消银安神饮, XYAS) in treating psoriasis associated with sleep focusing on melatonin and the regulation of the nuclear factor kappa-B(NF-κB) pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into four groups, and administered distilled water, XYAS and its two different disassembly prescriptions by gavage respectively. Four types of drug-containing serums corresponding to the four groups were then prepared. Tumor necrosis factor(TNF)-α stimulated Ha Ca T was used to establish a psoriasis cell model, and the serums and the retinoid related orphan receptor alpha(RORα) inverse agonist were used respectively to intervene in the model. Enzyme-linked immunosorbent assay was used to detect the levels of interleukin(IL)-6 and melatonin in each group;flow cytometry was used to detect the levels of reactive oxygen species(ROS), mitochondrial membrane potential, and apoptosis;Western blot was used to evaluate the levels of superoxide dismutase 2(SOD2), cytochrome-c(Cyt-c), inhibitor of kappa-B alpha(IκBα), p65 and phosphorylated p65. RESULTS:XYAS and its disassembly prescriptions inhibited the secretion of inflammatory factors such as IL-6, reduced the ROS content and Cyt-c expression, increased the mitochondrial membrane potential and SOD2 content, promoted the apoptosis in Ha Ca T cells and inhibited the activation of the NF-κB pathway. XYAS was also found increase the melatonin content. The above effects are beneficial in the treatment of psoriasis combined with sleep disorders. Meanwhile, XYAS no longer had a significant ameliorative effect after applying the RORα inverse agonist, suggesting that the therapeutic effect of XYAS is related to RORα. CONCLUSIONS:The results of this study confirm that XYAS can be utilized for the treatment of psoriasis combined with sleep disorders via inhibiting the NF-κB pathway, anti-inflammatory, antioxidant and proapoptotic, which is in part related to the regulatory role of melatonin and its receptor RORα.展开更多
BACKGROUND Neurodevelopmental delays encompass a wide range of conditions that impair cognitive,motor,and social functioning,often increasing the risk of psychiatric comorbidities.Children with these delays frequently...BACKGROUND Neurodevelopmental delays encompass a wide range of conditions that impair cognitive,motor,and social functioning,often increasing the risk of psychiatric comorbidities.Children with these delays frequently present with disorders such as attention-deficit/hyperactivity disorder(ADHD),anxiety,and behavioral disturbances,which can significantly affect development and quality of life.While genetic predisposition has been linked to these comorbidities,growing evidence highlights the role of environmental factors,including prenatal and early-life stressors.However,the interaction between genetic susceptibility and environmental influences remains poorly understood.Identifying specific genetic variants,environmental risks,and their interactions is essential for early detection and targeted interventions.AIM To investigate the combined effects of genetic and environmental factors on psychiatric comorbidities in children with neurodevelopmental delays,elucidate underlying mechanisms,and inform clinical management strategies.METHODS This retrospective cohort study included 80 children with confirmed neurodevelopmental delays and 40 age-and sex-matched typically developing controls.Comprehensive clinical and psychiatric evaluations,genetic testing(chromosomal microarray analysis and targeted next-generation sequencing),and environmental exposure assessments were conducted.Statistical analyses explored associations between genetic variants and psychiatric comorbidities,environmental risk factors,and gene-environment interactions.RESULTS Children with neurodevelopmental delays exhibited significantly higher rates of psychiatric comorbidities(70.0%)compared to controls(15.0%),with ADHD(42.5%),anxiety disorders(28.8%),and behavioral disorders(23.8%)being the most common.Pathogenic genetic variants were identified in specific pathways associated with distinct psychiatric presentations:Glutamatergic signaling variants were linked to anxiety disorders(odds ratio=3.8),dopaminergic system variants to ADHD(odds ratio=4.2),and synaptic function variants to both behavioral and anxiety disorders.Environmental factors,particularly prenatal maternal stress,early childhood adversity,and family dysfunction were strong predictors of psychiatric outcomes(β=0.42).Significant gene-environment interactions were identified,indicating that environmental exposure can moderate the effects of genetic risks on psychiatric outcomes.CONCLUSION Psychiatric comorbidities in children with neurodevelopmental delays are significantly influenced by both genetic and environmental factors,with complex interactions between the two.These findings underscore the need for integrated assessments and targeted interventions addressing both biological and environmental contributors to improve outcomes in this vulnerable population.展开更多
文摘Despite half-century old, but comprehensive national and international guidance, evidence of clinical effectiveness and widespread agreement on management of risk factors along with sophisticated measures for primary and secondary prevention of major cardiovascular events, cardiovascular disease remains the dominant cause of death and disability world-wide. Life style changes at population-level (e.g., lower salt and saturated fat consumption or reduced/banned amount of industrially-produced trans fatty acids in specific products, etc.) or changes at individual level (e.g., targeting modifiable risk factors/life style changes affecting smoking/tobacco use, poor diet, high blood cholesterol, high blood pressure, insufficient physical activity, overweight/obesity) have reduced coronary heart disease mortality to variable extent in different countries (mostly so reported in Finland, Iceland and Sweden) at the beginning of the new century. Overall, however, cardiovascular mortality is estimated to increase in the next coming years until 2030 at a cost exceeding US $1044 billion. Several decades of status quo are also noted in the therapeutic spectrum of cardiovascular disease, mainly consisting of variations to LDL-C lowering agents, antihypertensives, anticoagulants, antiplatelets and fibrinolytics. Most of the therapeutic interventions are “tertiary” in nature (probably some 60%), meaning that treatment is instituted once the individual has developed a pathologic condition;“secondary prevention” may cover some 25%?-?30% (meant to prevent re-occurrence of the condition or occurrence of complications) while “primary prevention” is left with 10%?-?15% share (most commonly implying life style changes at individual level and rarely pharmacological intervention). For almost three decades, the so-called inflammatory hypothesis has been promoted as a reasonable pathogenetic theory behind initiation and growth of atherosclerotic plaque (Alexander RW, 1994;Ross R, 1999). With the discovery of molecular and cellular pathways that promote atherosclerosis and the role of cytokines as inflammatory messengers, the concept as such—inflammation, has received a primordial role?in atherogenesis. The present review paper aims at ascertaining the role of inflammation as a common pathogenetic denominator of cardiovascular disease in patients primarily treated for their psoriasis and/or psoriatic arthritis.
基金supported by the National Natural Science Foundation of China(Grant No.82373475).
文摘Dear Editor,Psoriasis is increasingly recognized as a systemic inflammatory disease associated with several comorbidities,including metabolic syndrome,depression,and malignancies[1].Colorectal cancer(CRC)is the third most common cancer worldwide and ranks second in mortality among all malignancies.Currently,it has become one of the most severe challenges faced by healthcare systems in many countries[2].A previous study has found that patients with psoriasis have a significantly increased risk of developing CRC[3].
基金supported by the National Key R&D Program of China(No,2019YFA0112100)the National Natural Science Foundation of China(No.81472073)the Fundamental Research Funds for the Central Universities of Central South University(Grant Number:2022ZZTS0824).
文摘Objective To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization(MR)study.Methods A two-sample MR study was performed using summarized statistics from the genome-wide association studies(GWAS)conducted in reproductive traits,as well as GWAS data on overall psoriasis,psoriatic arthritis(PsA),and psoriasis vulgaris(PV).Besides univariable MR(UVMR),multivariable MR and two-step MR was used to calculate the independent effects and quantify the proportion mediated by education or body mass index(BMI).Results Genetically predicted early age at first sexual intercourse(AFS)led to an increased risk of overall psoriasis[odds ratio(OR)UVMR:0.54];36.13%of this effect was mediated through BMI and 47.79%through educational attainment.The direct negative casual association between age at first birth(AFB)-PsA was dominant(ORUVMR:0.76),with 49.61%proportion of the mediation due to BMI.The mediating effect was found for BMI on the AFS-PV relationship,which accounted for 26.27%of the proportion.AFS was inversely associated with the risk of overall psoriasis and PV,with considerable mediation by BMI and educational attainment.Conclusion Early AFB may cause a higher risk of PsA,while the AFS-PsA association was fully mediated by BMI.
基金supported by the National Natural Science Foundation of China(No.82270316)the Beijing Municipal Commission of Science and Technology(Z24-1100007724008).
文摘BACKGROUND Mild cognitive impairment(MCI)is common in atrial fibrillation(AF)patients and may develop earlier in those with multiple cardiovascular comorbidities,potentially impairing self-management and treatment adherence.This study aimed to characterize the prevalence and profile of MCI in AF patients,examine its associations with cardiovascular comorbidities,and assess how these comorbidities influence specific cognitive domains.METHODS This cross-sectional study analyzed data from AF patients who underwent cognitive assessment between 2017 and 2021.Cognitive status was categorized as MCI or non-MCI based on the Montreal Cognitive Assessment.Associations between comorbidities and MCI were assessed by logistic regression,and cognitive domains were compared using the Mann-Whitney U test.RESULTS Of 4136 AF patients(mean age:64.7±9.4 years,64.7%male),33.5%of patients had MCI.Among the AF patients,31.2%of patients had coronary artery disease,20.1%of patients had heart failure,and 18.1%of patients had hypertension.88.7%of patients had left atrial enlargement,and 11.0%of patients had reduced left ventricular ejection fraction.Independent factors associated with higher MCI prevalence included older age(OR=1.04,95%CI:1.03-1.05,P<0.001),lower education level(OR=1.51,95%CI:1.31-1.73,P<0.001),hypertension(OR=1.28,95%CI:1.07-1.52,P=0.001),heart failure(OR=1.24,95%CI:1.04-1.48,P=0.020),and lower left ventricular ejection fraction(OR=1.43,95%CI:1.04-1.98,P=0.028).A higher CHA_(2)DS_(2)-VASc score(OR=1.27,95%CI:1.22-1.33,P<0.001;≥2 points vs.<2 points),and greater atherosclerotic cardiovascular disease burden(OR=1.45,95%CI:1.02-2.08,P=0.040;2 types vs.0 type)were linked to increased MCI risk.These above factors influenced various cognitive domains.CONCLUSIONS MCI is common in AF and closely associated with cardiovascular multimorbidity.Patients with multiple comorbidities are at higher risk,highlighting the importance of routine cognitive assessment to support self-management and integrated care.
文摘There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.
基金supported by the National Natural Science Foundation(82173426)the Natural Science Foundation of Hunan Province(2023JJ30984),China。
文摘Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in psoriasis.Methods:An imiquimod(IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters,TMAO levels,and liver flavin monooxygenase 3(FMO3)mRNA expression.Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles.To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model,exogenous TMAO,choline,or 3,3-dimethyl-1-butanol(DMB)were administered via intraperitoneal injections or diet in IMQ-treated mice.Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results:IMQ-induced psoriatic mice exhibited abnormal glucose,insulin,and lipid levels.IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2(Glut2)and silence information regulator 1(Sirt1),while upregulating glucose transporter 4(Glut4)and peroxisome proliferator-activated receptor gamma(PPARγ).Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice.Additionally,liver FMO3 mRNA expression was increased in the psoriatic mouse model.In patients,TMAO levels positively correlated with Psoriasis Area and Severity Index(PASI)scores,serum triglyceride(TG),and total cholesterol(TC)levels.The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice.A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice,whereas DMB treatment alleviated these effects.RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122(miR-122),which may suppress the expression of gremlin 2(GREM2),thus contributing to lipid metabolism disorder.Conclusion:TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
文摘Background: Erythrodermic psoriasis (EP) is a rare, severe variant of psoriasis characterized by widespread erythema, scaling, and systemic complications. Despite advances in systemic treatments, the management of EP remains challenging, particularly in patients with comorbidities or contraindications to standard therapies. Objectives: To evaluate the effectiveness of ozonated water as an adjunctive treatment for EP, delivered using a patented robotic therapy system designed for hygiene and infection prevention in non-self-sufficient patients. Methods: We report the case of a 90-year-old male patient with acute EP who received daily skin treatments with ozonated water in conjunction with supportive care, including rehydration and antibiotics. The intervention was facilitated by the robotic system “COPERNICO Surveillance & Prevention,” which ensured standardized hygiene practices and clinical documentation. Results: Within one week of treatment, the patient showed complete desquamation of necrotic skin, resolution of erythema, and significant metabolic recovery. Fever subsided, renal function improved, and the patient was discharged in stable condition. Follow-up confirmed sustained clinical improvement, and no adverse events were reported. Conclusions: Ozonated water demonstrated efficacy in alleviating the dermatological and systemic manifestations of EP in a high-risk elderly patient. This case highlights the potential of ozone therapy as a safe, cost-effective adjunctive treatment for EP and underscores the utility of robotic systems in managing complex dermatological conditions. Further research is warranted to validate these findings in larger cohorts.
文摘Objective: To explore the effect of Health Action Process Approach (HAPA) theory in patients with type D personality psoriasis. Methods: A total of 66 patients with type D personality psoriasis admitted to the dermatology department of a top-three hospital in Jingzhou City from November 2022 to July 2023 were selected and divided into control group and test group with 33 cases in each group by random number table method. The control group received routine health education, and the experimental group received health education based on the HAPA theory. Chronic disease self-efficacy scale, hospital anxiety and depression scale and skin disease quality of life scale were used to evaluate the effect of intervention. Results: After 3 months of intervention, the scores of self-efficacy in experimental group were higher than those in control group (P P Conclusion: Health education based on the theory of HAPA can enhance the self-efficacy of patients with type D personality psoriasis, relieve negative emotions and improve their quality of life.
基金supported by Key Research Project of the Educational Department of Liaoning Province,China(JYTZD2023139).
文摘Psoriasis is a chronic inflammatory skin disease,which seriously affects the physical and mental health of patients.The progression of psoriasis is influenced by the excessive production of reactive oxygen species(ROS)and inflammatory responses.In this paper,novel celastrol(Ce)-loaded metal-phenolic nanozymes(tannic acid-Fe^(3+))(TA-Fe)integrated microneedles(Ce@TA-Fe/MNs)were constructed to achieve the combined oxidative stress alleviation and anti-inflammatory therapy of psoriasis.Molecular dynamics simulations and structural characterization confirmed the successful fabrication of nanozymes.The Ce@TA-Fe/MNs system,characterized by its rapid dissolution kinetics and superior mechanical strength,enabled minimally invasive skin penetration for efficient nanozymes delivery.Nanozymes possessed superoxide dismutase and catalase mimetic enzyme activities,effectively eliminating excessive ROS in psoriatic skin lesions.Additionally,the release of Ce from Ce@TA-Fe provided strong antioxidant and anti-inflammatory effects.Based on these characteristics,Ce@TA-Fe/MNs could effectively alleviate the symptoms in psoriasis mice models.These findings demonstrated that the integration of Ce-equipped nanozymes within MNs holds great promise as a therapeutic strategy for the clinical management of psoriasis.
文摘BACKGROUND Erythrodermic psoriasis(EP)is a rare and life-threatening form of psoriasis associated with significant morbidity and mortality.Systemic immunosuppre-ssive therapies are often required but may predispose to opportunistic infections.Disseminated herpes simplex virus type-1(HSV-1)is an unusual complication in otherwise immunocompetent patients and has not been reported in association with ixekizumab therapy for EP.CASE SUMMARY We describe a 49-year-old man with longstanding severe plaque psoriasis,liver cirrhosis,and bipolar disorder who developed EP involving>90%of body surface area[Psoriasis Area and Severity Index(PASI)45].Following initial stabil-ization,he was admitted to the intensive care unit(ICU)with hemodynamic instability,leukocytosis with eosinophilia,and diffuse desquamation.Ixekizumab was initiated with high-dose topical clobetasol.During his ICU stay,he developed recurrent bacteremias and neurologic decline(Glasgow Coma Scale 7/15),fo-llowed by the appearance of widespread vesicles and hemorrhagic crusts.HSV-1 infection was confirmed by polymerase chain reaction(PCR).Immunosuppressive therapy was withheld,and intravenous acyclovir was started,leading to progre-ssive improvement.After ten days,ixekizumab was reintroduced with careful monitoring,resulting in marked clinical improvement(PASI 9.7 at six weeks).The patient remained stable on long-term follow-up with oral acyclovir prophylaxis.CONCLUSION This case highlights the diagnostic and therapeutic challenges of managing EP in the setting of biologic therapy.Disseminated cutaneous HSV-1 should be considered in immunosuppressed patients presenting with new vesicular eruptions,and prompt PCR testing with early antiviral therapy is essential.A multidisciplinary approach is critical to balance immunosuppression for disease control with infection risk.
文摘BACKGROUND Psoriasis is a chronic inflammatory condition related to an increased athero-sclerotic cardiovascular disease(ASCVD)risk.AIM To investigate whether lipoprotein(a)[Lp(a)]levels are increased in patients with psoriasis.METHODS A comprehensive literature search up to January 30,2025 was conducted utilizing PubMed and Cochrane Library databases.A qualitative synthesis and a meta-analysis on Lp(a)mean differences(MD)between psoriasis cases and healthy controls(HC)was performed.The protocol of this meta-analysis has been re-gistered to PROSPERO(No.CRD420250652465).RESULTS Eighteen studies with 1650 psoriasis patients and 1621 HC were eligible for qua-litative synthesis.Pooled analysis from 16 studies(1401 psoriasis patients and 1320 HC)demonstrated that psoriasis patients had significantly higher Lp(a)levels compared with the HC group(MD:6.72 mg/dL,95%CI:4.32-9.12,P<0.00001,I2=71%).Sensitivity analyses according to the region of origin was also performed.The pooled analysis of the European sub-population showed a pronounced increase in Lp(a)levels in 189 patients with psoriasis vs 178 HC(MD:15.86 mg/dL,95%CI:5.79-25.92,P<0.002,I2=79%),while the pooled analysis on the Asian sub-population demonstrated a smaller but still significant difference in Lp(a)levels between 1177 psoriasis patients and 1127 HC(MD:4.95 mg/dL,95%CI:2.99-6.92,P<0.00001,I2=58%).CONCLUSION Our findings suggest that Lp(a)levels are significantly elevated in psoriasis patients,further adding to their ASCVD risk.
基金Yunnan Provincial Excellent Clinical Talents Training Project(the First Batch)(Yunnan Financial Society(2024)No.103).
文摘This research aimed to identify and validate ferroptosis-related signature genes associated with psoriasis through a comprehensive bioinformatics approach,while also predicting potential traditional Chinese medicines(TCMs)targeting these genes.The findings might offer a foundation for understanding ferroptosis mechanisms in psoriasis and exploring TCM-based therapeutic strategies.To begin,we retrieved gene expression profile data from psoriasis patients and healthy controls from the Gene Expression Omnibus(GEO)database,followed by data normalization.Ferroptosis-associated differentially expressed genes(Fer-DEGs)were identified using the FerrDb database.Subsequent GO and KEGG enrichment analyses provided insights into the biological functions and signaling pathways of these Fer-DEGs.Core Fer-DEGs were identified using machine learning algorithms,and their expression levels were further validated with an external dataset to evaluate diagnostic potential.Additionally,the symMap database facilitated the reverse prediction of TCMs targeting these key signature genes.The analysis identified 265 significant Fer-DEGs.GO enrichment indicated their involvement in diverse biological processes,while KEGG analysis highlighted their roles in various pathways,including ferroptosis,autophagy,cancer,infection,and metabolism,as well as PI3K-Akt,FoxO,mTOR,and HIF-1 signaling pathways.Machine learning pinpointed nine core psoriasis-related Fer-DEGs:PRKAA2,ANO6,POR,PTEN,MAPK8,ZFAS1,ADAM23,TMBIM4,and PARP14,all demonstrating strong diagnostic performance.Predicted TCMs primarily included those with heat-clearing,detoxifying,blood-activating,stasis-resolving,and phlegm-resolving properties.In conclusion,our study suggested that PRKAA2,ANO6,POR,PTEN,MAPK8,ZFAS1,ADAM23,TMBIM4,and PARP14 were key players in the ferroptosis pathway in psoriasis.TCMs with properties such as heat-clearing,blood activation,and phlegm resolution might hold promise for anti-ferroptosis interventions in psoriasis treatment.
文摘BACKGROUND Psoriasis is often first recognized by patients through online image searches.However,search engine algorithms influenced by geographic location may still produce results that predominantly feature lighter skin tones,regardless of the region’s majority skin type.This underrepresentation may limit recognition and delay care for people of color.AIM To examine whether search algorithms tailor region-specific results in terms of skin color for psoriasis imagery.METHODS This observational study recruited 66 participants from 18 countries who conducted image searches for“psoriasis”across various web browsers.During the meeting,a Google form was posted to record observations,and participants reported the diversity of skin tones in the first three rows of search results using a reference image depicting Fitzpatrick types.RESULTS Results showed a global bias toward lighter skin tones,with 94%of participants identifying light skin predominance in the first row and minimal representation of medium or darker skin tones in subsequent results,verified via χ^(2) analysis.Participants who observed darker or mixed skin tones typically found them further down their results.CONCLUSION There remains a significant gap in global representation of psoriasis imagery.This paper deepens the current understanding of bias in online media and pushes for further exploration of more inclusive dermatologic imagery.
文摘This review explores the emerging connection between psoriasis and atrial fibrillation(AF),focusing on shared inflammatory mechanisms,clinical implications,and research gaps.Psoriasis,characterized by chronic systemic inflammation,has been associated with increased AF risk,driven by elevated pro-inflammatory cytokines such as interleukin(IL)-6,IL-17,and tumor necrosis factor-alpha.These inflammatory mediators contribute to atrial remodeling,fibrosis,and conduction abnormalities,evidenced by prolonged P-wave dispersion and atrial electromechanical delay in psoriasis patients.Severe psoriasis further exacerbates atrial dysfunction,increasing susceptibility to AF.This review synthesizes existing epidemiological and biological data,highlighting the need for interdisciplinary management of psoriasis patients to mitigate cardiovascular risks.However,the reliance on observational studies limits definitive conclusions about causality.We emphasize the necessity for large-scale,multicenter research to validate these findings,investigate genetic predispositions,and evaluate lifestyle factors and AF burden.Future research should aim to delineate the pathophysiological link between psoriasis and AF.By examining the interplay of systemic inflammation,electrophysiological changes,and clinical outcomes,this review aims to advance understanding of the psoriasis-AF link and guide strategies for early detection,prevention,and management of AF in psoriasis patients.Comprehensive care integrating dermatology and cardiology is essential for improving patient outcomes.
基金supported by the National Natural Science Foundation of China(82274225)NATCM's Project of High-level Construction of Key TCM Disciplines-Beijing University of Chinese Medicine-Life Science from the Perspective of Chinese Medicine(zyyzdxk-2023263).
文摘Objective:To assess the efficiency of a Sophora flavescens Ait(S.flavescens,Ku Shen)-soluble microneedle(SFA-MN)for improving skin lesion symptoms in mice with psoriasis.Methods:SFA-MNs were prepared using a two-mold molding process with 20%w/v poly-vinylpyrrolidone and 15%w/v polyvinyl alcohol.The SFA-MNs were assessed for morphology,mechanical properties,in vitro dissolution,identification of components,and skin lesion improvement in imiquimod-induced psoriasis mice.Results:The SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis,facilitating efficient drug delivery.Furthermore,they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differ-entiation 3 and tumor necrosis factor-a.In addition,this system alleviated skin inflammation,splenic swelling,and thymic atrophy in the psoriasis-like mouse model.Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios(m/z)of the secondary fragments N-methylcytisine,5a,9a-dihydroxymatrine,sophoramine,matrine,oxysophocarpine,oxymatrine,and kushenol O.Conclusion:The drug delivery strategy combining traditional herbal S.flavescens with soluble micro-needle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models,enabling enhanced therapeutic effects compared with the control group.
基金Supported by the National Natural Science Foundation of China,No.81572338 and No.82170548C-class-sponsored research project of the Jiangsu Provincial Six Talent Peaks,No.WSN-078+2 种基金Jiangsu Province“333 High-level Talents Training Project”,No.2016-III-0126the Jiangsu Provincial Key Research and Development Program,No.BE2021601the Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.SJCX24_1037.
文摘BACKGROUND A significant association between increased age and an increased risk of metachronous gastric cancer(MGC)following curative endoscopic submucosal dissection(ESD)has previously been reported.AIM To determine risk factors for the metachronous occurrence of early gastric cancer(EGC)in elderly individuals.METHODS This retrospective cohort study comprised 653 elderly patients(aged≥65 years)who underwent curative ESD for EGC between January 2014 and June 2020 at Nanjing Drum Tower Hospital.Comprehensive analyses were conducted to compare lifestyle habits,comorbidities,and Helicobacter pylori(H.pylori)infections as potential indicators.RESULTS During a median follow-up of 38 months,46 patients(7.0%,20.46/1000 person-years)developed MGC in the elderly cohort.The cumulative incidences of MGC at 2,3,and 5 years were 3.3%,5.3%,and 11.5%,respectively.In multivariate Cox regression analyses,the independent risk factors for MGC included metabolic dysfunctionassociated steatotic liver disease(MASLD)[hazard ratio(HR)=2.44,95%confidence interval(CI):1.15-5.17],persistent H.pylori infection(HR=10.38,95%CI:3.36-32.07),severe mucosal atrophy(HR=2.71,95%CI:1.45-5.08),and pathological differentiation of EGC(well/moderately differentiated vs poorly differentiated:HR=10.18,95%CI:1.30-79.65).Based on these risk factors,a risk stratification system was developed to categorize individuals into low(0-1 point),intermediate(2-3 points),and high(4-8 points)risk categories for MGC,with cumulative incidence rates of 12.3%,21.6%,and 45%,respectively.CONCLUSION Among elderly individuals,MASLD,persistent H.pylori infection,severe mucosal atrophy,and well/moderately differentiated EGC were associated with an increased risk of MGC.Elderly patients are recommended to adopt healthy lifestyle practices,and undergo regular endoscopic screening and H.pylori testing after curative ESD for EGC.
基金supported by the National Key R&D Program of China(No.2023YFF1205102)National Natural Science Foundation of China(Nos.22277019,22307031,22377023 and 22077143)+2 种基金the Fundamental Research Funds for Hainan University(Nos.RZ2200001094,KYQD(ZR)-21031,and KYQD(ZR)-21108)Collaborative Innovation Center Funds for Hainan University(No.XTCX2022JKA01)the Science Foundation of Hainan Province(Nos.KJRC2023B10 and 824YXQN420)。
文摘Psoriasis is a common and chronic immune-mediated disorder that severely impacts the life quality of patients.Phosphodiesterase-4(PDE4)inhibitors have attracted significant interests in the psoriasis treatment due to their ability to suppress the inflammatory cascades.In this study,extensive screening of an in-house library of 1200 Chinese medicinal plant extracts identified Platycladus orientalis(L.)Franco(P.orientalis)as a potent PDE4 inhibitor,exhibiting 42.7%inhibition at 0.2μg/m L.Subsequent bioassayguided isolation revealed flavonoids,particularly amentoflavone(AMF),as the principal component responsible for PDE4 inhibition.To enrich the effective ingredients,a purification protocol using microporous resin was developed,yielding a flavonoid-rich extract(FLDs)that efficiently increased AMF content from 6.2%to 72.3%and improved PDE4 inhibitory activity to 74.2%at 0.2μg/mL.Notably,P.orientalis with favorable safety profiles demonstrated superior in vitro and in vivo anti-psoriasis effects to both AMF and the approved PDE4 inhibitor apremilast.These findings highlight the potential of P.orientalis as a novel therapeutic agent for psoriasis and provide valuable insights for its development in psoriasis treatment.
文摘Psoriasis is a prevalent inflammatory disease that shares chronic inflammation pathways with the pathophysiology of metabolic syndrome(MetS),type-2 diabetes mellitus and atherosclerosis.A high prevalence of steatosis and advanced liver fibrosis has been described in psoriasis.The influence of MetS and its compounds,patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 gene polymorphisms and the cumulative dose of methotrexate(MTX)in the progression of steatotic disease are still under debate.A suitable new classification for psoriasis-related liver disease,under the umbrella of steatotic liver disease(SLD),might be evaluated due to the potential impact of MTX on liver steatosis.Considering the interplay between the MetS,steatosis and MTX,a new definition for this complex disease might be discussed since it is not entirely addressed under the umbrella of SLD and metabolic-dysfunction associated SLD.Hence,shortly,a discussion could be raised on the feasible term“Met-Drug SLD”,metabolic and drug-induced SLD,which comprises both metabolic dysfunction and drug-related SLD.This review aims to report the best evidence to accurately classify liver disease in psoriasis,considering the new definition of SLD,allowing appropriate management once it is carefully defined.
基金National Natural Science Foundation of China:Study on the Mechanism of Cooling Blood and Tranquilizing Mind in the Treatment of Psoriasis with Sleep Disorder based on the Regulation of Oxidative Stress by Melatonin (No. 82074436)。
文摘OBJECTIVE:To explore the therapeutic mechanisms of Xiaoyin Anshen Yin( 消银安神饮, XYAS) in treating psoriasis associated with sleep focusing on melatonin and the regulation of the nuclear factor kappa-B(NF-κB) pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into four groups, and administered distilled water, XYAS and its two different disassembly prescriptions by gavage respectively. Four types of drug-containing serums corresponding to the four groups were then prepared. Tumor necrosis factor(TNF)-α stimulated Ha Ca T was used to establish a psoriasis cell model, and the serums and the retinoid related orphan receptor alpha(RORα) inverse agonist were used respectively to intervene in the model. Enzyme-linked immunosorbent assay was used to detect the levels of interleukin(IL)-6 and melatonin in each group;flow cytometry was used to detect the levels of reactive oxygen species(ROS), mitochondrial membrane potential, and apoptosis;Western blot was used to evaluate the levels of superoxide dismutase 2(SOD2), cytochrome-c(Cyt-c), inhibitor of kappa-B alpha(IκBα), p65 and phosphorylated p65. RESULTS:XYAS and its disassembly prescriptions inhibited the secretion of inflammatory factors such as IL-6, reduced the ROS content and Cyt-c expression, increased the mitochondrial membrane potential and SOD2 content, promoted the apoptosis in Ha Ca T cells and inhibited the activation of the NF-κB pathway. XYAS was also found increase the melatonin content. The above effects are beneficial in the treatment of psoriasis combined with sleep disorders. Meanwhile, XYAS no longer had a significant ameliorative effect after applying the RORα inverse agonist, suggesting that the therapeutic effect of XYAS is related to RORα. CONCLUSIONS:The results of this study confirm that XYAS can be utilized for the treatment of psoriasis combined with sleep disorders via inhibiting the NF-κB pathway, anti-inflammatory, antioxidant and proapoptotic, which is in part related to the regulatory role of melatonin and its receptor RORα.
文摘BACKGROUND Neurodevelopmental delays encompass a wide range of conditions that impair cognitive,motor,and social functioning,often increasing the risk of psychiatric comorbidities.Children with these delays frequently present with disorders such as attention-deficit/hyperactivity disorder(ADHD),anxiety,and behavioral disturbances,which can significantly affect development and quality of life.While genetic predisposition has been linked to these comorbidities,growing evidence highlights the role of environmental factors,including prenatal and early-life stressors.However,the interaction between genetic susceptibility and environmental influences remains poorly understood.Identifying specific genetic variants,environmental risks,and their interactions is essential for early detection and targeted interventions.AIM To investigate the combined effects of genetic and environmental factors on psychiatric comorbidities in children with neurodevelopmental delays,elucidate underlying mechanisms,and inform clinical management strategies.METHODS This retrospective cohort study included 80 children with confirmed neurodevelopmental delays and 40 age-and sex-matched typically developing controls.Comprehensive clinical and psychiatric evaluations,genetic testing(chromosomal microarray analysis and targeted next-generation sequencing),and environmental exposure assessments were conducted.Statistical analyses explored associations between genetic variants and psychiatric comorbidities,environmental risk factors,and gene-environment interactions.RESULTS Children with neurodevelopmental delays exhibited significantly higher rates of psychiatric comorbidities(70.0%)compared to controls(15.0%),with ADHD(42.5%),anxiety disorders(28.8%),and behavioral disorders(23.8%)being the most common.Pathogenic genetic variants were identified in specific pathways associated with distinct psychiatric presentations:Glutamatergic signaling variants were linked to anxiety disorders(odds ratio=3.8),dopaminergic system variants to ADHD(odds ratio=4.2),and synaptic function variants to both behavioral and anxiety disorders.Environmental factors,particularly prenatal maternal stress,early childhood adversity,and family dysfunction were strong predictors of psychiatric outcomes(β=0.42).Significant gene-environment interactions were identified,indicating that environmental exposure can moderate the effects of genetic risks on psychiatric outcomes.CONCLUSION Psychiatric comorbidities in children with neurodevelopmental delays are significantly influenced by both genetic and environmental factors,with complex interactions between the two.These findings underscore the need for integrated assessments and targeted interventions addressing both biological and environmental contributors to improve outcomes in this vulnerable population.
