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BackgroundObesity and dyslipidemia, major global health concerns, have been linked to psoriasis, but previous studies faced methodological limitations and their shared genetic basis remains unclear. This study examines various obesity-related and lipidemic traits as potential contributors to psoriasis development, aiming to clarify their genetic associations and potential causal links.MethodsSummary statistics from genome-wide association studies (GWAS) conducted for obesity-related traits (body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for the body mass index (WHRadjBMI)) and lipidemic traits (high-density lipoprotein (HDL), LDL, triglyceride (TG), total Cholesterol (TC), apolipoprotein A1 (apoA1), apolipoprotein B (apoB), and apolipoprotein E (apoE)) and psoriasis, all in populations of European ancestry, were used. We quantified genetic correlations, identified shared loci and explored causal relationship across traits.ResultsWe found positive genetic correlation between BMI and psoriasis (rg=0.22, p=2.44×10-18), and between WHR and psoriasis (rg=0.19, p=1.41×10-12). We further found the positive genetic correlation between psoriasis and WHRadjBMI(rg=0.07, p=1.81×10-2) the genetic correlation, in while the effect of BMI was controlled for. We identified 14 shared loci underlying psoriasis and obesity-related traits and 43 shared loci between psoriasis and lipidemic traits via cross-trait meta-analysis. Mendelian randomization (MR) supported the causal roles of BMI (IVW OR=1.483, 95%CI=1.333-1.649), WHR (IVW OR=1.393, 95%CI=1.207-1.608) and WHRadjBMI (IVW OR=1.18, 95%CI=1.047-1.329) in psoriasis, but not observe any significant association between lipidemic traits and the risk of psoriasis. Genetic predisposition to psoriasis did not appear to affect the risk of obesity and lipidemic traits.ConclusionsAn intrinsic link between obesity-related traits and psoriasis has been demonstrated. The genetic correlation and causal role of obesity-related traits in psoriasis highlight the significance of weight management in both the prevention and treatment of this condition.

ObjectiveTo explore the influence of serum metabolites on the risk of psoriasis.MethodsIn the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance Weighted method and Wald Ratio’s odds ratios, and 95% confidence intervals. False Discovery Rate was used for multiple comparison corrections. Sensitivity analyses were conducted using Cochran’s Q Test, MR-PRESSO. MR-Steiger Test was employed to check for reverse causality. In the validation stage, we sought other sources of psoriasis GWAS data to verify the initial results and used meta-analysis to combine the effect sizes to obtain robust causal relationships. In addition, we also conducted metabolic pathway enrichment analysis on known metabolites that have a causal relationship with the risk of psoriasis in both stages.ResultsIn the initial stage, we identified 112 metabolites causally associated with psoriasis, including 32 metabolite ratios and 80 metabolites (69 known and 11 unknown). In the validation stage, 24 metabolites (16 known, 1 unknown, and 7 metabolite ratios) were confirmed to have a causal relationship with psoriasis onset. Meta-analysis results showed that the overall effect of combined metabolites was consistent with the main analysis in direction and robust in the causal relationship with psoriasis onset. Of the 16 known metabolites, most were attributed to lipid metabolism, with 5 as risk factors and 8 as protective factors for psoriasis. Peptidic metabolite Gamma-glutamylvaline levels had a negative causal relationship with psoriasis, while exogenous metabolite Catechol sulfate levels and amino acid 3-methylglutaconate levels had a positive causal relationship with the disease onset. The metabolites associated with psoriasis risk in the two stages are mainly enriched in the following metabolic pathways: Glutathione metabolism, Alpha Linolenic Acid and Linoleic Acid Metabolism, Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism, Glycerophospholipid metabolism.ConclusionCirculating metabolites may have a potential causal relationship with psoriasis risk, and targeting specific metabolites may benefit psoriasis diagnosis, disease assessment, and treatment.

Alternative polyadenylation (APA) is a widespread mechanism of gene regulation that generates mRNA isoforms with alternative 3' untranslated regions (3' UTRs). Our previous study has revealed the global 3' UTR shortening of host mRNAs through APA upon viral infection. However, how the dynamic changes in the APA landscape occur upon viral infection remains largely unknown. Here we further found that, the reduced protein abundance of CPSF6, one of the core 3' processing factors, promotes the usage of proximal poly(A) sites (pPASs) of many immune related genes in macrophages and fibroblasts upon viral infection. Shortening of the 3' UTR of these transcripts may improve their mRNA stability and translation efficiency, leading to the promotion of type I IFN (IFN-I) signalling-based antiviral immune responses. In addition, dysregulated expression of CPSF6 is also observed in many immune related physiological and pathological conditions, especially in various infections and cancers. Thus, the global APA dynamics of immune genes regulated by CPSF6, can fine-tune the antiviral response as well as the responses to other cellular stresses to maintain the tissue homeostasis, which may represent a novel regulatory mechanism for antiviral immunity.

Background: Psoriasis, a chronic skin condition characterized by systemic inflammation and altered gut microbiota, has been a target of Traditional Chinese Medicine (TCM) for centuries. Shenling Baizhu Powder (SLBZP), a TCM formulation, holds promise for treating inflammatory diseases, but its specific role in psoriasis and impact on gut microbiota is not fully understood.Objective: This study aims to elucidate the mechanism of SLBZP in treating psoriasis, integrating component analysis, network pharmacology, and experimental validation in mice models.Methods: We commenced with a detailed component analysis of SLBZP using liquid chromatograph and mass spectrometer (LC-MS). Network pharmacology analysis was used to predict the potential action targets and pathways of SLBZP in psoriasis. An in vivo experiment was conducted with psoriasis mice models, treated with SLBZP. Therapeutic effects were assessed via symptomatology, histopathology, and immunohistochemical analysis. Gut microbiota composition was analyzed using 16S rRNA gene sequencing.Results: A total of 42 main components and quality markers were identified, primarily from licorice and ginseng, including flavonoids, saponins and other markers. PPI topology analysis showed that TNF, IL-6, IL-1β, TP53 and JUN were the core DEPs. 168 signaling pathways including lipid and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway and Th17 cell differentiation were enriched by KEGG. SLBZP demonstrated significant therapeutic effects on psoriasis in mice, with alterations in skin pathology and biomarkers. Additionally, notable changes in gut microbiota composition were observed post-treatment, indicating a possible gut-skin axis involvement.Conclusion: This research has pinpointed lipid metabolism as a key pathway in the treatment of psoriasis with SLBZP. It explores how SLBZP’s modulation of gut microbiota and lipid metabolism can alleviate psoriasis, suggesting that balancing gut microbiota may reduce inflammation mediators and offer therapeutic benefits. This underscores lipid metabolism modulation as a potential new strategy in psoriasis treatment.

Psoriasis vulgaris is a chronic dermatological disease with a high global prevalence. It significantly reduces patients' quality of life and is associated with a substantial economic burden. Conventional therapies for mild-to-moderate psoriasis are often associated with insufficient long-term symptomatic relief and side effects. Chinese herbal medicine (CHM) is commonly used for psoriasis management. A CHM formula, namely Fu zheng he fu zhi yang (FZHFZY), has shown promising treatment effects in clinical practice when used as a bath therapy. However, its efficacy and safety has not been evaluated by a rigorous randomized controlled trial (RCT). Therefore, we designed a double-blinded pilot RCT embedded with a qualitative study on CHM formula FZHFZY plus topical urea for mild-to-moderate psoriasis vulgaris to advance the evidence development and practice of CHM external application for psoriasis. This will be a mixed-method design consisting of a pilot RCT and a qualitative study. The pilot RCT is a two-arm, parallel, placebo-controlled, double-blinded trial. Sixty eligible participants will be randomized at a 1:1 ratio to receive eight weeks' treatment of either FZHFZY plus 10% urea cream, or placebo plus 10% urea cream, with 12-week follow-up visits after the treatment phase. The CHM or placebo will be administered externally as a bath therapy. Outcome measures include trial feasibility, efficacy and safety. The primary efficacy outcome will be Psoriasis Area Severity Index (PASI). Secondary efficacy outcomes include Physician Global Assessment, PASI-75, PASI-50, Body Surface Area, Dermatology Life Quality Index, Skindex-16, itch visual analogue scale and relapse. The qualitative study will be conducted to collect participants' feedback on CHM external application and their experience with the pilot RCT. This study will advance the evidence-based clinical practice of using CHM for psoriasis vulgaris and then to support translation of findings into clinical practice in the future. Trial registration number: ChiCTR2200064092.

Background Psoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical treatment. However, the exact mechanism by which this treatment regimen relieves psoriasis is unknown. Method We assembled a cohort of 65 psoriasis patients and divided post-treatment cohort into responder group and non-responder group according to the Psoriasis Area Severity Index (PASI) score after 12-week treatment. We measured the expression levels of proteins in collected 130 serum samples using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the responder group and constructed a proteomics landscape of psoriasis pathogenesis response to treatment. We then validated the biomarkers of disease severity in an independent cohort of 88 samples using an enzyme-linked immunosorbent assay. Results We first identified 174 differentially expressed proteins (DEPs) for comparative analysis of proteins between responders and non-responders at baseline (p

Background and objectives: Safe and effective management of cancer-related pain is a worldwide challenge. In the search for treatment options, natural products used in Chinese herbal medicines (CHMs) have received attention in clinical studies for their effects on cancer-related pain. The objective of this systematic review is to evaluate the clinical evidence for topically applied CHMs as adjunctive treatments for cancer pain management. Methods: Nine biomedical databases and 4 clinical trial registries were searched for randomized-controlled trials (RCTs) that reported measures of pain and/or quality of life. Risk of bias was assessed using the Cochrane tool. Meta-analysis employed mean difference (MD) with 95% confidence intervals (random effects). Results: Twenty (20) RCTs (1636 participants) met the inclusion criteria. Meta-analyses were grouped based on the comparisons and outcome measures. For pain intensity, there was a greater reduction in the topical CHM group versus placebo (MD −0.72 [−1.04, −0.40]), no difference when compared to tramadol (MD −0.15 [−0.38, 0.08]), and a greater reduction when topical CHMs were combined with conventional analgesic medications (MD −0.67 [−0.93, −0.40]). Analgesic onset time was reduced in the CHM group compared to tramadol (MD −26.02 [−27.57, −24.47] minutes), and for CHMs combined with conventional medications (MD −19.17 [−21.83, −16.52] minutes). When CHMs were combined with analgesic medications, improvements were found for duration of analgesia (MD 1.65 [0.78, 2.51] hours), analgesic maintenance dose (MD −31.72 [−50.43, −13.01] milligrams/day), and quality of life. Conclusion: Addition of topical CHMs to conventional analgesic medications was associated with improved outcomes for pain intensity, some other pain-related outcomes, and measures of quality of life. Limitations included methodological issues in some studies and considerable heterogeneity in some pooled results.

Objectives: This study aimed to examine the effect of acupuncture on symptoms and health-related quality of life in patients with endometriosis. Methods: Nine biomedical databases were searched to April 2022 to identify randomized controlled trials of acupuncture and/or moxibustion used alone or as adjunct to guideline-recommended pharmacotherapy for the treatment of endometriosis. One reviewer extracted data and another verified the data. A random effects model was used to calculate mean differences. Results: Fifteen trials involving 1018 patients met the inclusion criteria, but diversity in comparisons and outcome measures prevented meta-analysis. Compared to sham acupuncture, manual acupuncture was more effective at reducing dysmenorrhea VAS pain score (mean difference [MD] − 2.40, 95 % CI [− 2.80, − 2.00]; moderate certainty evidence), pelvic pain VAS score (MD − 2.65, 95 % CI [− 3.40, − 1.90]; high certainty evidence) and dyspareunia VAS scores (MD − 2.88, [− 3.83, − 1.93]), lessened the size of ovarian cyst (MD − 3.88, 95 % CI [− 7.06, − 0.70]), and improved quality of life. Compared to conventional therapy, manual acupuncture plus conventional therapy and warm needle alone resulted in greater improvements in quality of life than conventional therapy. Among the six studies that reported safety, fewer adverse events were reported in participants who received acupuncture or moxibustion. Conclusions: Low to moderate certainty evidence from single studies showed that manual acupuncture may improve pain-related symptoms and quality of life; however, there is insufficient evidence on the overall effectiveness of acupuncture and moxibustion for endometriosis.

Background: Psoriasis vulgaris (PV) is a longstanding, inflammatory, immune-responsive skin condition. Chinese herbal medicine injections (CHMIs) have been utilized for treating PV in Asian countries. This study aims to conduct a thorough systematic review and meta-analysis to comprehensively appraise the efficacy of CHMIs in treating PV.Methods: Seven databases were searched for randomized controlled trials that evaluated the effect of CHMIs in treating PV, ranging from 2004 to June 2022. The meta-analysis was undertaken based on outcome measures, treatment options, and treatment durations using Review Manager 5.4. The primary outcome measure of this study was a 60% or higher reduction in the Psoriasis Area and Severity Index score (PASI 60). A descriptive analysis was performed for the assessment of adverse events.Results: This systematic review incorporated 33 studies, comprising 3,059 participants. The main findings indicated significant differences based on the PASI 60 (RR = 1.30, 95% CI: 1.24 to 1.37, Z = 10.72, p < 0.00001), PASI 30 (RR = 1.25, 95% CI: 1.13 to 1.38, Z = 4.48, p < 0.00001), and PASI 20 (RR = 1.28, 95% CI: 1.13 to 1.45, Z = 3.82, p = 0.0001) outcome measures. Evaluating the treatment options, CHMIs in combination with monotherapies like narrowband ultraviolet B (NB-UVB) and the acitretin capsule (AC) showed a greater reduction in PASI 60 (RR = 1.33, 95% CI: 1.25 to 1.43, Z = 8.32, p < 0.00001). In terms of treatment duration, no significant difference was observed when the duration extended beyond 56 days. Furthermore, the results suggested that CHMIs might reduce the incidence of adverse events in the treatment of PV.Conclusion: This systematic review revealed preliminary clinical evidence supporting the use of CHMIs for treating PV, considering outcome measures, treatment options, and treatment durations. However, due to the low methodological quality and limited sample size of the included studies, there is an urgent need for high-quality, multi-center and larger-scale studies of CHMIs for PV to provide robust evidence for their clinical application.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=326531], identifier [CRD42022326531].

Hyperplasia of epidermal keratinocytes that depend on glycolysis is a new hallmark of psoriasis pathogenesis. Our previous studies demonstrated that PSORI-CM02 could halt the pathological progression of psoriasis by targeting inflammatory response and angiogenesis, but its effect(s) and mechanism(s) on proliferating keratinocytes remained unclear. In this study, we aim to identify components of PSORI-CM02 that are absorbed into the blood and to determine the effect(s) of PSORI-CM02 on keratinocyte proliferation and its molecular mechanism(s). We used the immortalized human epidermal keratinocyte cell line, HaCaT, as an in vitro model of proliferating keratinocytes and the imiquimod-induced psoriasis mouse (IMQ) as an in vivo model. Metabolite profiles of vehicle pharmaceutic serum (VPS), PSORI-CM02 pharmaceutic serum (PPS), and water extraction (PWE) were compared, and 23 components of PSORI-CM02 were identified that were absorbed into the blood of mice. Both PPS and PWE inhibited the proliferation of HaCaT cells and consequently reduced the expression of the proliferation marker ki67. Additionally, PPS and PWE reduced phosphorylation levels of mTOR pathway kinases. Seahorse experiments demonstrated that PPS significantly inhibited glycolysis, glycolytic capacity, and mitochondrial respiration, thus reducing ATP production in HaCaT cells. Upon treatments of PPS or PWE, hexokinase 2 (HK2) expression was significantly decreased, as observed from the set of glycolytic genes we screened. Finally, in the IMQ model, we observed that treatment with PSORI-CM02 or BPTES, an inhibitor of mTOR signaling, reduced hyperproliferation of epidermal keratinocytes, inhibited the expression of p-S6 and reduced the number of proliferating cell nuclear antigen (PCNA)-positive cells in lesioned skin. Taken together, we demonstrate that PSORI-CM02 has an anti-proliferative effect on psoriatic keratinocytes, at least in part, by inhibiting the mTOR/HK2/glycolysis axis.

Introduction: Psoriasis is an inflammatory autoimmune skin disease that is hard to cure and prone to relapse. Currently available global immunosuppressive agents for psoriasis may cause severe side effects, thus it is crucial to identify new therapeutic reagents and druggable signaling pathways for psoriasis.Methods: To check the effects of SOCE inhibitors on psoriasis, we used animal models, biochemical approaches, together with various imaging techniques, including calcium, confocal and FRET imaging.Results and discussion: Store operated calcium (Ca2+) entry (SOCE), mediated by STIM1 and Orai1, is crucial for the function of keratinocytes and immune cells, the two major players in psoriasis. Here we showed that a natural compound celastrol is a novel SOCE inhibitor, and it ameliorated the skin lesion and reduced PASI scores in imiquimod-induced psoriasis-like mice. Celastrol dose- and time-dependently inhibited SOCE in HEK cells and HaCaT cells, a keratinocyte cell line. Mechanistically, celastrol inhibited SOCE via its actions both on STIM1 and Orai1. It inhibited Ca2+ entry through constitutively-active Orai1 mutants independent of STIM1. Rather than blocking the conformational switch and oligomerization of STIM1 during SOCE activation, celastrol diminished the transition from oligomerized STIM1 into aggregates, thus locking STIM1 in a partially active state. As a result, it abolished the functional coupling between STIM1 and Orai1, diminishing SOCE signals. Overall, our findings identified a new SOCE inhibitor celastrol that suppresses psoriasis, suggesting that SOCE pathway may serve as a new druggable target for treating psoriasis.

This systematic review and meta-analysis aims to: assess the effectiveness and safety of orally administered Chinese herbal medicines (CHMs) as adjuncts to the post-surgical management of chronic rhinosinusitis (CRS); inform clinicians of the current evidence; identify the best available evidence; and suggest directions for further research. Randomised controlled trials (RCTs) were identified from searches of nine databases plus clinical trial registries. Participants were adults and/or children diagnosed with sinusitis or rhinosinusitis, with or without nasal polyps, who had received surgery. Interventions were CHMs used orally following surgery for CRS as additions to conventional post-surgical management. Controls received conventional post-surgical management without CHMs. Studies reported results for Sino-Nasal Outcome Test (SNOT), visual analogue scales (VAS), Lund-Mackay computed tomography score (LM), Lund-Kennedy endoscopic score (LK), mucociliary transport time (MTT), mucociliary transport rate (MTR), mucociliary clearance (MC) or quality of life (QoL). Twenty-one RCTs were included. All used oral CHMs following functional endoscopic sinus surgery (FESS). The pooled results showed no significant difference between groups for SNOT-20 at the end of treatment (EoT) but there was a significant difference at follow up (FU) in favour of additional CHMs. The VAS for total nasal symptoms (VAS-TNS) showed greater improvements in the CHM groups at EoT and FU. Only FU data were reported for LM which showed greater improvement in the CHM groups. LK showed greater improvements at EoT and FU. The measures of mucociliary transport (MTT, MTR, and MC) each showed significantly greater improvement at EoT in the group that received additional CHMs. No study reported QoL. Adverse events were not serious, but reporting was incomplete. The meta-analyses suggested the addition of oral CHMs to conventional management following FESS may improve recovery. However, most studies were not blinded, and substantial heterogeneity was evident in some meta-analyses. Blinded studies are required to further investigate the roles of oral CHMs in post-surgical recovery. Systematic review registration number: The protocol was registered in PROSPERO (CRD42019119586).

Abstract Objectives The precise pathogenesis of psoriasis remains incompletely explored. We aimed to better understand the underlying mechanisms of psoriasis, using a systems biology approach based on transcriptomics and microbiome profiling. Methods We collected the skin tissue biopsies and swabs in both lesional and non‐lesional skin of 13 patients with psoriasis, 15 patients with psoriatic arthritis and healthy skin from 12 patients with ankylosing spondylitis. To study the similarities and differences in the molecular profiles between these three conditions, and the associations between the host defence and microbiota composition, we performed high‐throughput RNA‐sequencing to quantify the gene expression profile in tissues. The metagenomic composition of 16S on local skin sites was quantified by clustering amplicon sequences and counted into operational taxonomic units. We further analysed associations between the transcriptome and microbiome profiling. Results We found that lesional and non‐lesional samples were remarkably different in terms of their transcriptome profiles. The functional annotation of differentially expressed genes showed a major enrichment in neutrophil activation. By using co‐expression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we found a ‘core’ set of genes that was functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria. Skin microbiome analysis revealed that the abundances of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the genes in core network. Conclusions We identified a core gene network that associated with local disease severity and microbiome composition, involved in the inflammation and hyperkeratinization in psoriatic skin.

Psoriasis is an immune-mediated, persistent inflammatory disease with a genetic predisposition, and the involvement of multiple organs in psoriasis remains indicative of systemic disease. Atherosclerosis (AS) is a common complication of patients with severe or prolonged psoriasis. The specific pathogenesis of psoriasis is still unclear. Current studies suggest that psoriasis is a polygenic genetic disease with the interaction of multiple factors such as heredity and environment. Keratinocytes are proliferated through immune-mediated inflammatory pathway, which leads to cell activation, infiltration of dermis cells and release of inflammatory factors. Activation of inflammatory cells and pro-inflammatory factors play an important role in the progression of psoriasis and atherosclerosis. Studies have found that there is a close relationship between psoriasis and atherosclerosis, and systemic inflammation may be the common feature of psoriasis and AS. This paper attempts to explore the possibility of the relationship between psoriasis and atherosclerotic comorbidities from the aspects of potential epidemiology and immune mechanism, in order to provide some reference for the subsequent scientific research.

Background: Treatment effect of current pharmacotherapies for migraine is unsatisfying. Discovering new anti-migraine natural products and nutraceuticals from large collections of Chinese medicine classical literature may assist to address this gap.Methods: We conducted a comprehensive search in the Encyclopedia of Traditional Chinese Medicine (version 5.0) to obtain migraine-related citations, then screened and scored these citations to identify clinical management of migraine using oral herbal medicine in history. Information of formulae, herbs and symptoms were further extracted. After standardisation, these data were analysed using frequency analysis and the Apriori algorithm. Anti-migraine effects and mechanisms of actions of the main herbs and formula were summarised.Results: Among 614 eligible citations, the most frequently used formula was chuan xiong cha tiao san (CXCTS), and the most frequently used herb was chuan xiong. Dietary medicinal herbs including gan cao, bai zhi, bo he, tian ma and sheng jiang were identified. Strong associations were constructed among the herb ingredients of CXCTS formula. Symptoms of chronic duration and unilateral headache were closely related with herbs of chuan xiong, gan cao, fang feng, qiang huo and cha. Symptoms of vomiting and nausea were specifically related to herbs of sheng jiang and ban xia.Conclusion: The herb ingredients of CXCTS which presented anti-migraine effects with reliable evidence of anti-migraine actions can be selected as potential drug discovery candidates, while dietary medicinal herbs including sheng jiang, bo he, cha, bai zhi, tian ma, and gan cao can be further explored as nutraceuticals for migraine.

Metabolic status and gut microecology are implicated in psoriasis. Methotrexate (MTX) is usually the first-line treatment for this disease. However, the relationship between MTX and host metabolic status and the gut microbiota is unclear. This study aimed to characterize the features of blood metabolome and gut microbiome in patients with psoriasis after treatment with MTX. Serum and stool samples were collected from 15 patients with psoriasis. Untargeted liquid chromatography–mass spectrometry and metagenomics sequencing were applied to profile the blood metabolome and gut microbiome, respectively. We found that the response to MTX varied according to metabolomic and metagenomic features at baseline; for example, patients who had high levels of serum nutrient molecular and more enriched gut microbiota had a poor response. After 16 weeks of MTX, we observed a reduction in microbial activity pathways, and patients with a good response showed more microbial activity and less biosynthesis of serum fatty acid. We also found an association between the serum metabolome and the gut microbiome before intervention with MTX. Carbohydrate metabolism, transporter systems, and protein synthesis within microbes were associated with host metabolic clusters of lipids, benzenoids, and organic acids. These findings suggest that the metabolic status of the blood and the gut microbiome is involved in the effectiveness of MTX in psoriasis, and that inhibition of symbiotic intestinal microbiota may be one of the mechanisms of action of MTX. Prospective studies in larger sample sizes are needed to confirm these findings.

Psoriasis is a chronic inflammatory skin disorder. Although it has been studied extensively, the molecular mechanisms driving the disease remain unclear. In this study, we utilized a tree-based machine learning approach to explore the gene regulatory networks underlying psoriasis. We then validated the regulators and their networks in an independent cohort. We identified some key regulators of psoriasis, which are candidates to serve as potential drug targets and disease severity biomarkers. According to the gene regulatory network that we identified, we suggest that interferon signaling represents a key pathway of psoriatic inflammation.

Abstract Background Seborrheic dermatitis (SD) is a common, chronic, inflammatory skin disorder, yet few studies have reported its clinical characteristics, or addressed its effect on quality of life (QoL). This study assesses the clinical characteristics and QoL of SD patients in China. It also identifies the clinical, demographic and environmental factors that may influence QoL. Methods Three hundred twelve SD outpatients from 9 hospitals completed a survey. QoL was measured with the dermatology-specific instrument Skindex-29. We collected social demographic characteristics and disease severity, and conducted logistic regression to determine the factors associated with QoL impairment. Results 67.3% of the patients were females. The mean Skindex-29 overall score was 33.97 (SD = 20.55). The breakdown was 40.79 (SD = 24.24) for emotions, 32.83 (SD = 19.84) for symptoms and 28.3 (SD = 23.24) for functioning. 48.1% had severe emotional problems. Logistic regression analysis showed that BMI less than 25 (OR = 0.223; 95% CI: 0.072–0.692; P = 0.009), skin disease-related hospitalization (OR = 6.882; 95% CI:1.767–26.795; P = 0.005), environmental PM 10 levels above 120 μg/m3 (OR = 3.386; 95% CI: 1.253–9.15; P = 0.016) and severe disease conditions (OR = 4.438; 95% CI:1.26–15.626; P = 0.02) were risk factors for severe emotional impairment. Moreover, skin disease-related hospitalization (OR = 6.057; 95% CI:1.351–27.149; P = 0.019), environmental PM 10 levels between 70 and 120 μg/m3 (OR = 6.317; 94% CI: 1.704–23.42; P = 0.006), moderate (OR = 2.388; 95% CI: 1.272–4.487; P = 0.007) and severe disease conditions (OR = 5.732; 95% CI: 1.838–17.88; P = 0.003) were each risk factors for overall severe impairment. Conclusion In China, nearly half of SD patients had severely emotional problems. Disease severity, BMI, dermatologic hospitalization, and ambient PM 10 levels are each risk factors for QoL impairment in SD patients. These implications are alarming, and warrant public health attention in SD disease management.

Abstract Background Many previous studies have reported factors that contribute to health-related quality of life (HRQoL) for a single skin disease. However, little is known about generalized factors associated with HRQoL across skin diseases. The objective of this study was to investigate overall HRQoL, and to identify factors related to severely impaired HRQoL among patients with 16 different skin diseases. Methods A cross-sectional study of 9845 patients with skin disease was conducted in 9 hospitals in China. HRQoL was assessed with the Chinese version of the Skindex-29 which measures dermatology-specific health along three domains (symptoms, emotions and functioning). With the published Skindex-29 cut-off scores for severely impaired HRQoL, logistic regression models assessed the relationship between severely impaired HRQoL and demographic/clinical characteristics, with adjustments for different skin diseases. To guarantee the models’ convergence, 16 skin diseases with frequencies of at least 100 were included, and the sample size was 8789. Results Emotions was the most impaired aspect of HRQoL. Co-existing chronic diseases, 3 years or longer duration, and more severity were identified as associated factors for severely impaired HRQoL for each Skindex-29 domain, and for the aggregate. Being female, under 45 years old, and consuming alcohol were associated with a severely impaired emotion domain; Lack of exercise and smoking were associated with severely impaired symptoms and function domains, respectively. Conclusions Skin diseases can affect many facets of HRQoL, but the emotional impairment deserves more attention. In addition to skin disease severity, this study shows that other chronic diseases and long duration are correlated with severely impaired HRQoL for patients with 16 clinical common skin diseases. This suggests the need for increased awareness in treating skin disease as a chronic disease. It also suggests that disease management decisions should consider HRQoL improvement, especially emotional conditions, when making management decisions.

Abstract Background To analyze the expression of miRNA (microRNA) in peripheral blood mononuclear cells in patients with Psoriasis vulgaris with different TCM syndromes by miRNA chip. It further revealed the micromaterial basis of different syndrome types of psoriasis at the miRNA level. Methods Peripheral blood monocytes were collected and prepared from 30 patients with Psoriasis vulgaris (including 9 patients of blood heat syndrome, 8 patients of blood stasis syndrome, and 13 patients of blood dry syndrome) and 9 healthy controls. The miRNA expression profile of peripheral blood monocytes was detected by Agilent Hum miRNA chip. Results Compared to the healthy control group, 156 upregulated and 242 downregulated miRNAs were detected in all psoriasis patients. Compared to the healthy control group, 40 miRNAs were upregulated and 44 were downregulated in the blood heat syndrome group. Furthermore, there were 49 upregulated miRNAs and 44 downregulated miRNAs in the dry syndrome group as compared to the healthy control group. Also, 67 miRNAs were upregulated and 154 miRNAs were downregulated in the blood stasis syndrome group as compared to the healthy control group. Conclusions There are common different miRNAs and pathways, as well as specific miRNAs between the psoriasis and the healthy control groups. Trial registration ChiCTR-TRC-14005185 registered on August 8, 2014.

BackgroundPoria cocos (Schw.) Wolf or Fuling is one of the top 10 most frequently prescribed herbs in China for the treatment of type 2 diabetes mellitus (T2DM).ObjectiveThe purpose of this systematic review is to determine the additional benefit of Fuling formulae use in addition to hypoglycaemic agents for T2DM in randomised clinical trials.MethodsEnglish (5) and Chinese (4) medical databases were searched from their inception to August 2021. RCTs that included Fuling in herbal formulae for T2DM were included. Risk of bias were assessed using the Cochrane Collaboration's procedures. Stata software (13.0) was used for data analysis.ResultsSeventy-three RCTs (6,489 participants) with herbal formulae containing Fuling were included. Most studies were at risk of bias and strength of the evidence were low to moderate. Meta-analysis findings showed that the addition of formulae containing Fuling to hypoglycaemic agent-treatments could benefit people with T2DM by reducing fasting blood glucose (MD -0.82 [-0.93, -0.71]; I2 = 79.6%, P = 0.00), 2-hour postprandial blood glucose (MD-1.15 [-1.31, -0.98], I2 = 80%, P = 0.00) and haemoglobin A1c (MD-0.64 [-0.75, -0.53], I2 = 84.7%, P = 0.00). Adverse events were also significantly lower in the integrative group than in the hypoglycaemic alone group (RR 0.99 [0.93, 1.06], P = 0.87).ConclusionEvidence from this study supports the use of Fuling formulae combined with hypoglycaemic agents for T2DM. The combined therapies appear to be well tolerated.Trail registrationThis review is registered with the PROSPERO international prospective register of systematic reviews (CRD42020214635).

This systematic review aims to assess the effects and safety of Chinese herbal medicines (CHMs) in the management of rhinosinusitis (RS); inform clinicians of the current state of the evidence; identify the best available evidence; and suggest further directions for research. Five English and four Chinese language databases, and four clinical trial registries were searched. Eligible studies were randomised controlled trials (RCTs). Participants were diagnosed with RS based on established criteria. Test interventions were CHMs administered orally and/or nasally, excluding injections and displacement techniques. Control interventions included placebos, no additional treatment, and conventional non-invasive treatments including pharmacotherapies and/or nasal irrigation, and/or inhalations. Polyposis and post-surgical recovery were excluded. Outcomes were Sino-Nasal Outcome Test (SNOT), visual analogue scales (VAS), Lund-Mackay computed tomography score (LM), Lund-Kennedy Endoscopic score (LK), Mucociliary transport time (MTT), Mucociliary transport rate (MTR), quality of life and adverse events (AEs). Risk of bias used the Cochrane tool. Meta-analysis in Review Manager 5.4.1 used random effects for mean difference (MD) or risk ratio (RR) with 95% confidence intervals. Heterogeneity was assessed as I2. Thirty-four RCTs were included, 30 of chronic RS (CRS) and four of acute RS (ARS). These enrolled 3,752 participants. Five RCTs blinded participants. For CRS, comparisons with placebo showed greater improvements in the CHM groups for SNOT-20 and VAS-TNS (total nasal symptoms). Blinded comparisons with pharmacotherapies showed no differences between groups in the degree of improvement for SNOT-20, VAS-TNS, and LM, suggesting these CHMs had similar effects, at least in the short term. In ARS, pooled results found improved scores on VAS-TNS and LK suggesting a benefit for combining these CHMs with pharmacotherapies. Limitations included inadequacies in study design and methodological reporting, and insufficient reporting of AEs. Heterogeneity in some pooled results precluded strong conclusions. Further well-designed studies are needed to test whether the results are replicable. Systematic review registration number: PROSPERO (CRD42019119586).

Psoriasis is chronic skin disease and an important health concern. Traditional Chinese Medicine (TCM) has shown great promise in the treatment of psoriasis. However, the correlation between TCM Syndromes and genomics of psoriasis has not been evaluated. Here, we analyzed gene expression profiling of monocytes from psoriasis vulgaris patients with different TCM syndrome types to reveal the molecular basis of different psoriasis syndromes. Of the 62 cases of psoriasis vulgaris recruited, 16, 23, and 23 cases were of blood-heat syndrome, blood stasis syndrome, and blood-dryness syndrome, respectively; 10 healthy controls were recruited as controls. Affymertix’s Gene Chip ®clariom D gene chip was used to detect the gene expression profile of peripheral blood monocytes collected from recruited individuals. Compared with the healthy control group, 1570 genes were up-regulated and 977 genes were down-regulated in the psoriasis vulgaris patients group; 798 genes and 108 genes were up- and down-regulated in the blood-heat syndrome group respectively; 319 and 433 genes were up- and down-regulated in the blood-dryness syndrome group, respectively; and 502 and 179 genes were up-and down-regulated in the blood-stasis syndrome group. Our analyses indicated not only common differential genes and pathways between psoriasis syndrome groups and healthy controls, but also syndrome-specific genes and pathways. The results of this study link the three syndromes at the gene level and will be useful for clarifying the molecular basis of TCM syndromes of psoriasis.Clinical Trial Registration: (http://www.chictr.org.cn/showproj.aspx?proj=4390), identifier (ChiCTR-TRC-14005185).

Psoriasis is a chronic and inflammatory skin disorder characterized by inflammation and epidermal hyperplasia. Punicalagin (PUN) is a main active ingredient of pomegranate (Punica granatum L.) peel with multiple biological activities, such as antibacterial, antioxidant and anti-tumor effects. However, the potential effect of PUN on psoriasis remains unknown. In this study, we want to investigate the pharmacological effect of PUN on psoriasis by using imiquimod (IMQ)-induced psoriatic mice model in vivo and tumor necrosis factor a (TNF-α) and interleukin-17A (IL-17A)-stimulated HaCaT cells in vitro. Our results showed that PUN can effectively alleviate the severity of psoriasis-like symptoms. Mechanistically, PUN potently suppresses the aberrant upregulation of interleukin-1β (IL-1β) and subsequent IL-1β-mediated inflammatory cascade in keratinocytes by inhibiting the nuclear factor kappa B (NF-κB) activation and cleaved caspase-1 expression in vitro and in vivo. Taken together, our findings indicate that PUN can relieve psoriasis by repressing NF-κB-mediated IL-1β transcription and caspase-1-regulated IL-1β secretion, which provide evidence that PUN might represent a novel and promising candidate for the treatment of psoriasis.

Psoriasis is a chronic and refractory inflammatory and autoimmune-mediated cutaneous disease affecting approximately 2%–3% of the global population. Most of the current therapies could relieve symptoms rapidly, while the side effects cannot be negligible. Hence, it is urgent to explore much safer and more effective treatments. In the current work, we evaluated the potential beneficial effect of Punica granatum peel polysaccharides (PPPs) in an imiquimod-elicited psoriasis-like mouse model and unraveled their mechanism of action. Firstly, PPPs were isolated from P. granatum peels, and then the molecular weight was determined and monosaccharide analysis was performed. The results revealed that PPPs significantly ameliorated psoriasis-like skin lesions and reduced the Psoriasis Area and Severity Index (PASI) scores and transepidermal water loss (TEWL). PPPs also attenuated the expressions of CD3 and Ki67 in psoriasis-like mouse skin and suppressed the serum or skin levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-1β, IL-8, IL-17, and IL-23. Moreover, PPPs were able to upregulate the mRNA and protein expressions of aquaporin-3 (AQP3) and filaggrin (FLG) in the skin of mice. In addition, PPPs inhibited the NF-κB and STAT3 signaling pathways. Overall, these results indicated that PPPs ameliorated the symptoms of psoriasis through inhibition of the inflammatory cytokines by suppressing the NF-κB and STAT3 signaling pathways and improved skin barrier protection via enhancing AQP3 and FLG. These observations potentially contribute to providing theoretical and experimental evidence for the clinical application of PPPs for psoriasis.

Background: psoriasis is a chronic inflammatory skin disease. The accumulation of IL-17 cytokines in the lesions leads to epidermis proliferation. Traditional Chinese medicine has a significant effect on psoriasis treatment. Among them, Tuhuaiyin is a representative prescription, which has an outstanding curative effect in acute and remission stage. Methods: To reveal the target and molecular mechanism of Tuhuaiyin, systematic pharmacology platform and database screening were used to construct the Tuhuaiyin interaction network with compounds, targets and diseases. The intervention of Tuhuaiyin on keratinocyte proliferation and inflammation was verified in the model of psoriasis-like lesions induced by imiquimod. The effect on the number and function of IL-17-producing cells was detected, and the regulatory effect of Tuhuaiyin on gut microbial was explored. Results: 32 selected active molecules in Tuhuaiyin acted on psoriasis biological processes. Tuhuaiyin significantly alleviates erythema and scales in the psoriasis like mouse model induced by imiquimod. Excessive proliferation of keratinocytes and infiltration of inflammatory cells were restrained in the dermis by using Tuhuaiyin. The expression of IL-17 was down-regulated in skin and peripheral blood. The proportion of IL-17-producing cells was decreased in immune organs. And phosphorylation of JNK inhibited in skin lesions. At the same time, the change of gut microbial diversity in the psoriasis-like model was improved. Conclusion: our study predicted and verified the molecular immunological mechanism of Tuhuaiyin, alleviated the abnormal proliferation of keratinocytes by inhibiting the proportion of IL-17-producing cells and the expression of IL-17 cytokines. Taken together, our data identify the therapeutic potential of Tuhuaiyin for psoriasis.

Psoriasis is a chronic proliferative skin disorder characterised by abnormal epidermal differentiation. The Fuzhenghefuzhiyang (FZHFZY) formula created by Chuanjian Lu, a master of Chinese medicine in dermatology, has been external used in the Guangdong Provincial Hospital of Chinese Medicine for the treatment of psoriasis, but its mechanisms of action against psoriasis remain poorly understood. This study involved an exploration of the effects of FZHFZY on epidermal differentiation and its underlying mechanisms in interleukin (IL)-17A/IL-22/interferon (IFN)-γ/tumour necrosis factor (TNF)-α–stimulated HaCaT cells and in a mouse model of imiquimod (IMQ)-induced psoriasis. Cell viability was assessed by MTT assay. Epidermal differentiation was detected by reverse-transcription polymerase chain reaction and western blotting. Histological evaluation of the skin tissue was performed via haematoxylin and eosin staining, and the Akt/mTORC1/S6K1 pathway was analysed by western blotting. FZHFZY inhibited proliferation and improved epidermal differentiation in IL-17A/IL-22/IFN-γ/TNF-α–induced HaCaT cells. FZHFZY ameliorated symptoms of psoriasis, regulated epidermal differentiation and inhibited phosphorylation of the Akt/mTORC1/S6K1 pathway in the skin of mice with imiquimod-induced psoriasis. Our results suggest that FZHFZY may exhibit therapeutic action against psoriasis by regulating epidermal differentiation via inhibition of the Akt/mTORC1/S6K1 pathway.

Abstract Introduction Psoriasis vulgaris is a common skin disease characterized by persistent localized erythematous scaly plaques, typically on the elbows, knees, and scalp. It is an immune-abnormal disease that progresses slowly over a long period with frequent symptom recurrence. Current studies have shown that acupuncture is an effective therapy for psoriasis. However, the scientific evidence of the efficacy of auricular acupressure treatment for patients with psoriasis is still insufficient. Therefore, we designed a randomized controlled clinical trial to investigate the effect, safety, and cost-effectiveness of auricular acupressure in addition to medication in patients with psoriasis. Methods and analysis This on-going study is a two-arm parallel, assessor-blinded, randomized controlled trial in which 180 participants with psoriasis will be recruited and then randomly allocated into two groups in a 1:1 ratio. Equal randomization will be conducted using a computer-generated random allocation sequence. Participants in the intervention group will receive auricular acupressure treatment once per week for 4 weeks, and calcipotriol betamethasone ointment for topical use once daily for 4 weeks. Participants in the control group will receive only calcipotriol betamethasone ointment treatment once daily for 4 weeks. All patients will be followed up for 12 weeks. The primary outcome is relapse rate. The secondary outcomes include time to relapse, rebound rate, time to new onset, Psoriasis Area and Severity Index score improvement rate, body surface area affected, a visual analogue scale, and Dermatology Life Quality Index. Cost-effectiveness analysis will be carried out from a health and community care provider perspective. Discussion This multicenter randomized controlled trial will provide important clinical evidence for the effect and safety of auricular acupressure as a complementary therapy in patients with psoriasis. Trial registration Chinese Clinical Trial Registry, ChiCTR-TRC-14004916. Registered on 20 May 2014. This protocol is version 3.0 which was updated on 24 September 2016.

Psoriasis is a chronic proliferative autoimmune dermatologic disease characterised by abnormal angiogenesis. Thus, regulating angiogenesis in the skin is an important treatment strategy for psoriasis. PSORI-CM02, an empirical Chinese medicine formula optimised from Yin Xie Ling, was created by the Chinese medicine specialist, Guo-Wei Xuan. Clinical studies have shown that PSORI-CM02 is safe and effective for the treatment of psoriasis. However, its anti-psoriatic mechanisms remain to be further explored. In this study, we investigated the effects of PSORI-CM02 on angiogenesis in the skin and the underlying mechanisms in IL-17A-stimulated human umbilical vein endothelial cells (HUVECs) and a murine model of imiquimod (IMQ)-induced psoriasis. In vitro, PSORI-CM02 significantly inhibited the proliferation and migration of IL-17A-stimulated HUVECs in a dose-dependent manner. Further, it markedly regulated the antioxidative/oxidative status and inflammation; suppressed the expression of VEGF, VEGFR1, VEGFR2, ANG1, and HIF-1α; and reduced the phosphorylation of MAPK signalling pathway components in IL-17A-stimulated HUVECs. In vivo studies showed that PSORI-CM02 markedly reduced angiogenesis in the skin of mice with IMQ-induced psoriasis, while significantly rebalancing antioxidant/oxidant levels; inhibiting the production of IL-6, TNF-α, IL-17A, and IL-17F; and repressing the synthesis of angiogenic mediators. In addition, PSORI-CM02 markedly reduced the activation of the MAPK signalling pathway in psoriatic skin tissue. Taken together, our results demonstrated that PSORI-CM02 inhibited psoriatic angiogenesis by reducing the oxidative status and inflammation, suppressing the expression of angiogenesis-related molecules, and inhibiting the activation of the MAPK signalling pathway in vitro and in vivo.

N6-methyladenosine (m6A) modification, the addition of a methylation decoration at the position of N6 of adenosine, is one of the most prevalent modifications among the over 100 known chemical modifications of RNA. Numerous studies have recently characterized that RNA m6A modification functions as a critical post-transcriptional regulator of gene expression through modulating various aspects of RNA metabolism. In this review, we will illustrate the current perspectives on the biological process of m6A methylation. Then we will further summarize the vital modulatory effects of m6A modification on immunity, viral infection, and autoinflammatory disorders. Recent studies suggest that m6A decoration plays an important role in immunity, viral infection, and autoimmune diseases, thereby providing promising biomarkers and therapeutic targets for viral infection and autoimmune disorders.

Psoriasis is a chronic inflammatory skin disease that is associated with multiple coexisting conditions. Extensive literature suggests that psoriasis is a T-cell-mediated condition, and its pathogenesis is related to dysfunction of the immune system. Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that have suppressive effects on T cells. MDSCs are present at very low levels in healthy individuals but can substantially expand in tumours or inflammatory conditions. PSORI-CM02, a Chinese medical formula designed based on the Chinese medicine theory (Blood Stasis), has been prescribed extensively for psoriasis therapy and shows a stable clinical effect and safety. This study discusses the mechanisms of MDSCs involved in disease development and therapeutic progress. Our data provides evidence that monocytic myeloid-derived suppressor cells (M-MDSCs) play a role in IMQ-induced psoriatic dermatitis. Functional characterization and correlation analysis indicated that MDSCs are positively correlated with Th17 cells. PSORI-CM02 alleviated IMQ-induced psoriatic dermatitis and suppressed the proliferation of Th17 cells via M-MDSC-induced Arg1 upregulation, suggesting M-MDSCs could be a novel therapeutic target for psoriasis, and PSORI-CM02 exerted its effects via the perturbation of M-MDSCs and Th17 cell crosstalk.

BackgroundChinese medicine has been used to treat diabetes symptoms for thousands of years. Dioscoreae rhizome or Shanyao is a Chinese medicinal herb that is routinely used in the treatment of diabetes mellitus (DM).ObjectiveThe purpose of this study is to evaluate the evidence of the added benefits and safety of herbal formulae containing Shanyao in clinical studies and the possible mechanisms of Shanyao in the prevention and treatment of DM in experimental studies.MethodsWe searched nine databases for randomized controlled trials (RCTs) that included Shanyao in the formulae in the treatment of type 2 DM. Furthermore, experimental studies on the prevention and treatment of DM by Shanyao in English- and Chinese-language databases were identified.ResultsFifty-three moderate quality RCTs with herbal formulae containing Shanyao were identified. Results from meta-analysis indicated that Shanyao alone or formulae containing Shanyao in addition to conventional treatments could benefit people with type 2 DM in lowering blood glucose, blood lipids and reducing insulin resistance. Moreover, adverse events were significantly lower in the CHM plus conventional group than those in the conventional group. Shanyao may exert the benefit through various mechanisms including inhibition of α-glucosidase and DPP-IV activity, increase of endogenous GLP-1 and immune regulating activities.ConclusionEvidence from this review suggested that there appeared to be added clinical benefits associated with the use of Shanyao for DM, whether as a food supplement or as a CHM combined with hypoglycemic agents with a good safety profile.

The beneficial effect of quercetin in rheumatic diseases is unclear. Studies have already confirmed that human umbilical cord mesenchymal stem cells (hUCMSCs) alleviate some symptoms of rheumatoid arthritis (RA) by their immunosuppressive capacities. This study explored whether there are additive effects of quercetin and hUCMSCs on peripheral blood mononuclear cells (PBMCs) under simulated rheumatic conditions. hUCMSCs were pretreated with quercetin (10 μM) before coculture with TNF-α/IFN-γ-stimulated PBMCs at a ratio of 1:1 for 3 days. PBMC proliferation was inhibited, and the proportion of Th17 cells was shifted. These effects may be related to the effect of quercetin on functional molecules in hUCMSCs, including nitric oxide (NO), indoleamine 2,3-dioxygenase (IDO), interleukin 6 (IL-6) and Toll-like receptor-3 (TLR-3) and the Akt/IκB pathways. These results suggest that quercetin effectively promoted the immunoregulatory effect of hUCMSCs by inhibiting the Akt/IκB pathway, activating the Toll-like receptor-3 pathway, and regulating downstream cytokines.

Psoriasis is a T cells mediated chronic skin inflammation in which helper T (Th) cells play in critical roles in its pathogenesis. Taxifolin (TXL) has been discovered to exert various pharmacological activities. In this study, we wished to observe whether TXL had potential activities on psoriasis, and how it works. We found that TXL can inhibit LPS-induced abnormal proliferation in Hacat cell line, ant also significantly alleviate the IMQ-induced psoriasis in BALB/c mice, comparing with the control group. Although TXL has no significant effects on the ratio of total T cells in skin draining lymph nodes (SDLN), it decreases the ratio of pro-inflammatory Th1 and Th17 cells, both in skin lesions and SDLN. Our results also disclosed that TXL may regulate Th cells differentiation by inhibiting the transcript factors, including T-bet, GATA-3 and RORγt. Further data show that TXL can inhibit Notch1 and Jak2/Stat3 signal pathways. In summary, TXL may be able to treat psoriasis by regulating Th cells differentiation via inhibiting Notch1 and Jak2/Stat3 pathways.

Psoriasis is recognized as an autoimmune and inflammatory dermatosis, which is estimated to affect 2-3% of the population worldwide. 18β-Glycyrrhetinic acid (GA), one of the main ingredients of Licorice (Glycyrrhiza glabra L.), has been shown to have numerous pharmacological effects such as antioxidative, antitumor, and anti-inflammatory activities. However, it remains to be explored whether GA has antipsoriatic effect on psoriasis. In this study, we evaluated the protective effect of GA on psoriasis and its mechanisms of action in imiquimod-induced psoriasis-like mouse model. Results indicated that GA dramatically improved psoriatic lesions and reduced psoriasis area and severity index scores. GA also suppressed the mRNA levels of IL-6, TNF-α, IL-17, IL-23, and IL-1β in the skin and increased the proportion of CD4+ Foxp3+ regulatory T cells (Tregs) in both lymph nodes and spleens. Its anti-inflammatory and immunomodulatory activities may be related to its suppression of the STAT3 and mTOR signaling. In conclusion, GA ameliorated the symptoms of psoriasis, at least in part, through inhibition of inflammatory cytokines and STAT3/mTOR signaling and activation of Tregs in both lymph nodes and spleens. These effects are expected to be beneficial in the treatment and prevention of psoriasis.

Abstract The gasdermins, family of pore‐forming proteins, are emerging key regulators of infection, autoinflammation and antitumor immunity. Multiple studies have recently characterised their crucial roles in driving pyroptosis, a lytic pro‐inflammatory type of cell death. Additionally, gasdermins also act as key effectors of NETosis, secondary necrosis and apoptosis. In this review, we will address current understanding of the mechanisms of gasdermin activation and further describe the protective and detrimental roles of gasdermins in host defence and autoinflammatory diseases. These data suggest that gasdermins play a prominent role in innate immunity and autoinflammatory disorders, thereby providing potential new therapeutic avenues for the treatment of infection and autoimmune disease.

Abstract Background This study aimed to develop the clinical practice guidelines applicability evaluation (CPGAE-V1.0) scale and to evaluate its validity and reliability. Methods One hundred fifty assessors were invited to rate two rounds of importance scoring of the applicability indicators by using the 5-point Likert scale. Approved indicators formed the CPGAE-V1.0 scale, consisting of 19 items, arranged into 4 domains. We enrolled eligible clinicians from 8 institutions to evaluate 9 clinical practice guidelines using the CPGAE-V1.0 scale. Content validity, construct validity, internal reliability, intra-rater reliability, and responsiveness were analyzed. Results A total of 220 clinicians participated, and the response rate was 98.6% (217/220). The CPGAE-V1.0 scale had favorable content validity. The four-factor model produced acceptable fit indices. The scale had an excellent internal consistency and item discrimination. It could identify the degree of applicability of the different dimensions between different guidelines. In all domains, 77.8% (7/9) of CPGs in the minimum-scoring domain were concentrated in the “coordination of support” domain. Conclusions The CPGAE-V1.0 scale is a valid and reliable instrument for measuring the applicability of CPG.

Abstract Background Chinese herbal medicine formula Yu ping feng san (YPFS) is commonly used for allergic rhinitis (AR). Previous review had summarized the effectiveness and safety of YPFS, however without any subgroup analysis performed to provide detailed evidence for guiding clinical practice. YPFS was recommended for the management of AR by Chinese medicine clinical practice guideline, but the treatment duration of YPFS was also not specified. The aim of this study is to evaluate the effectiveness and safety of YPFS in treating adult AR with the most recent evidence, and attempt to specify the duration of utilisation through subgroup meta-analyses. Methods Seven databases were searched from their inceptions to September 2017. Randomized controlled trials (RCTs) evaluating YPFS for adult AR were included. Methodological quality of studies was assessed using the Cochrane risk of bias tool. Meta-analysis and subgroup meta-analyses were conducted for evaluating the effectiveness of YPFS. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence. Results Twenty-two RCTs involving 23 comparisons were included in this review. YPFS was compared to placebo, pharmacotherapy, and used as an add-on treatment compared to pharmacotherapy. Meta-analyses were feasible for the outcomes of four individual nasal symptom scores and “effective rate”. Four individual nasal symptom scores decreased after YPFS’ combination treatment: itchy nose (MD-0.46, 95% CI[−0.50, −0.42]), sneezing (MD-0.41, 95% CI[−0.47, −0.35]), blocked nose (MD-0.46, 95% CI[−0.54, −0.39]) and runny nose (MD-0.42, 95% CI[−0.58, −0.26]). Based on “effective rate”, meta-analysis showed that YPFS did not achieve better effect than pharmacotherapy (RR1.07, 95%CI [0.94, 1.22), but its combination with pharmacotherapy seemed more effective than pharmacotherapy alone (RR1.27, 95%CI [1.19, 1.34]) (low quality). Subgroup analysis suggested that YPFS was not superior to the second-generation antihistamine (RR1.04, 95%CI [0.90, 1.19]) (low quality). Further, YPFS’ combination treatment seemed more beneficial when it was used for more than three weeks (RR1.15, 95%CI [1.01, 1.32]). In addition, YPFS was well-tolerated for treating adult AR. Conclusion Chinese herbal medicine formula YPFS seems beneficial for adult AR. This potential benefit need to be further evaluated by more rigorous RCTs.

The objective of this study was to examine the psychometric properties of the Chinese version of the Dermatology Life Quality Index (DLQI) and to assess the invariance of its items with respect to several patient parameters via Rasch analysis. Data were aggregated from 9,845 patients with various skin diseases across 9 hospitals in different regions of China. The response structure, local independence, and reliability of the DLQI scale were analysed in a partial credit model, and differential item functioning (DIF) across region, disease, sex, and age were assessed with a Mantel-Haenszel procedure. Although acceptable scale reliability (Person Separation Index=2.3) was obtained, several problems were revealed, including disordered response thresholds, misfitting items, DIF by geogra­phical region and disease, and mis-targeting patients with mild impairment regarding health-related quality of life (HRQL). In conclusion, the DLQI provides inadequate information on patients’ impairments in HRQL, and the application of the DLQI in Chinese patients with skin disease is limited.

Abstract Retinoic acid inducible‐gene I (RIG‐I) functions as one of the major sensors of RNA viruses. DDX58, which encodes the RIG‐I protein, has been newly identified as a susceptibility gene in psoriasis. Here, we show that the activation of RIG‐I by 5′ppp‐dsRNA, its synthetic ligand, directly causes the production of IL‐23 and triggers psoriasis‐like skin disease in mice. Repeated injections of IL‐23 to the ears failed to induce IL‐23 production and a full psoriasis‐like skin phenotype, in either germ‐free or RIG‐I‐deficient mice. RIG‐I is also critical for a full development of skin inflammation in imiquimod (IMQ)‐induced psoriasis‐like mouse model. Furthermore, RIG‐I‐mediated endogenous IL‐23 production was mainly confined to the CD11c+ dendritic cells (DCs) via nuclear factor‐kappa B (NF‐κB) signaling, and stimulated RIG‐I expression in an auto‐regulatory feedback loop. Thus, our data suggest that the dysregulation in the antiviral immune responses of hosts through the innate pattern recognition receptors may trigger the skin inflammatory conditions in the pathophysiology of psoriasis.

Background: Treatment for post-stroke spasticity (PSS) remains a major challenge in clinical practice. Chinese herbal medicine (CHM) is often administered to assist in routine care (RC) in the treatment of PSS, with increasing numbers of clinical research and preclinical studies suggesting that it has potential benefits. Therefore, we conducted a systematic review and meta-analysis to evaluate the add-on effects and safety of CHM for PSS.Methods: Five English and four Chinese databases were searched from their respective inception to 28 February 2018. We included randomized controlled trials that evaluated the add-on effects of CHM for PSS, based on changes in the scores of the (Modified) Ashworth Scale (AS or MAS), Fugl-Meyer Assessment of Sensorimotor Recovery (FMA), and Barthel Index (BI).Results: Thirty-five trials involving 2,457 patients were included. For upper-limb AS or MAS, the estimated add-on effects of CHM to RC were significantly better when using oral (SMD −1.79, 95% CI: −3.00 to −0.57) or topical CHM (SMD −1.06, 95% CI: −1.40 to −0.72). For lower-limb AS or MAS, significant add-on benefits to RC were also detected (SMD −1.01, 95% CI: −1.43 to −0.59 and SMD −1.16, 95% CI: −1.83 to −0.49) using oral and topical CHM, respectively. For FMA and BI, better results were detected when adding CHM to RC, except for the subgroup of oral CHM for upper-limb FMA. Ten of the 35 included studies reported safety information, with two of them mentioning two mild adverse events.Conclusions: Noting the quality concerns of the included trials, this review suggests that CHM appears to be a well-tolerated therapy for patients with PSS, and the potential add-on effects of CHM in reducing spasticity and improving the daily activities of patients with PSS require further rigorous assessment.

Background: Shoulder-hand syndrome (SHS) is prevalent in hemiplegic patients after stroke. Potential benefits of acupuncture were shown in recent clinical trials. This systematic review aimed to comprehensively evaluate the safety and efficacy of acupuncture for SHS in stroke patients.Methods: Five English databases (PubMed, Embase, CINAHL, CENTRAL, and AMED) and four Chinese databases (CBM, CNKI, CQVIP, and Wanfang) were searched from their inceptions to January 2019. Randomized, controlled trials that evaluated the add-on effects of acupuncture to rehabilitation for post-stroke SHS were identified.Results: Thirty-eight studies involving 3,184 participants fulfilled the eligible criteria and were included in the review. The overall meta-analysis showed that acupuncture combined with rehabilitation significantly improved motor function (upper-limb Fugl-Meyer Assessment (FMA): 34 studies, mean difference (MD) 8.01, 95% confidence interval (CI) [6.69,9.33]), and reduced pain (visual analog scale (VAS): 25 studies, MD −1.59, 95%CI [−1.86,−1.32]). It also improved activities of daily living (ADL) when compared with rehabilitation alone (ADL: 11 studies, MD 9.99, 95%CI [5.91,14.06]). However, the certainty of evidence of all these outcomes was assessed as “low.” Subgroup analyses of acupuncture stimulation types and treatment duration all showed significant add-on effects comparing with rehabilitation alone. The safety of acupuncture was unclear because there is a lack of detailed reporting of adverse events in most of the included studies.Conclusions: Acupuncture therapy seems effective for motor function, pain relief and activities of daily living in stroke patients with mild SHS, when it is used in combination with rehabilitation. The low certainty of evidence downgrades our confidence in making recommendations to clinical practice.

Objectives: To assess the clinical evidence for integrative herbal medicine therapy in the management of chemotherapy-induced peripheral neuropathy (CIPN) and hand-foot syndrome (HFS) resulting from treatments for colorectal cancer (CRC). Design: Randomized controlled trials (RCTs) were identified from major English and Chinese databases. Participants had been diagnosed with CRC by pathology and had received or were undergoing chemotherapy. Interventions included herbal medicines administered orally or topically. Controls were placebo, supportive care or conventional chemotherapy for CRC. Methods followed the Cochrane handbook. Meta-analyses were grouped by study design, outcome measure, severity, and chemotherapy. Random-effects models with 95% confidence intervals were used. Heterogeneity was assessed as I 2 . Results: Sixty-three RCTs (4286 participants) were included. Five used a placebo in the control groups. Fifty-eight studies tested oral herbal medicine, and 5 tested topical herbal medicine. Data were available for CIPN (60 studies) and HFS (12 studies). Fifty-seven studies combined orally administered herbal medicine with chemotherapy compared with the same chemotherapy. For CIPN, 33 studies used World Health Organization (WHO) criteria, 7 used Levi’s criteria, and 10 used the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). These were analyzed separately. For grades III + IV CIPN, there was a significant reduction in the integrative groups for WHO (relative risk [RR] 0.42 [0.23, 0.77], I 2 = 0%) and Levi’s (RR 0.28 [0.11, 0.69], I 2 = 0%) but not NCI-CTCAE (RR 0.65 [0.37, 1.13], I 2 = 26.4%). Hand and foot baths showed no differences for Levi’s grades III + IV CIPN but a significant reduction in all grades (RR 0.69 [0.50, 0.95], I 2 = 68.8%). For HFS (all grades) there was a significant reduction in the integrative groups for WHO (RR 0.62 [0.41, 0.96], I 2 = 22%) but not for NCI-CTCAE (RR 0.93 [0.55, 1.55], I 2 = 75.7%). Sensitivity analyses explored sources of heterogeneity. Conclusions: Integrative herbal therapy appeared to reduce CIPN and HFS in people receiving chemotherapy for CRC. However, the strength of the evidence was limited by lack of blinding in most studies, potential for bias, and relatively short study durations.

Psoriasis is an autoimmune and inflammatory skin disease affecting around 2–3% of the world's population. Patients with psoriasis need extensive treatments with global immunosuppressive agents that may cause severe side effects. Esculetin, a type of coumarins, is an active ingredient extracted mainly from the bark of Fraxinus rhynchophylla, which has been used to treat inflammatory and autoimmune diseases in China. However, the antipsoriatic effects of esculetin have not been reported. In this study, we aimed to investigate the effects of esculetin on psoriatic skin inflammation in a mouse model and explored the potential molecular mechanisms underlying its action. We found that esculetin ameliorated the skin lesion and reduced PASI scores as well as weight loss in imiquimod-induced psoriasis-like mice, accompanied with weakened proliferation and differentiation of keratinocytes and T cell infiltration in esculetin-treated psoriatic mice. In addition, esculetin reduced the frequency of CD8+CD44highCD62Llow effector T cells in psoriatic mice. In contrast, it increased the frequency of CD4+Foxp3+ Tregs in both lymph nodes and spleens of the psoriatic mice while promoting the differentiation of CD4+CD25− T cells into CD4+Foxp3+ Tregs in vitro. Interestingly, depleting CD4+Foxp3+ Tregs largely reversed esculetin-mediated reduction in PASI scores, indicating that esculetin attenuates murine psoriasis mainly by inducing CD4+Foxp3+ Tregs. Furthermore, the mRNA levels of proinflammatory cytokines in the psoriatic mouse skin, including IL-6, IL-17A, IL-22, IL-23, TNF-α, and IFN-γ, were dramatically decreased by the treatment with esculetin. Finally, we found that esculetin inhibited the phosphorylation of IKKα and P65 in the psoriatic skin, suggesting that it inhibits the activation of NF-κB signaling. Thus, we have demonstrated that esculetin attenuates psoriasis-like skin lesion in mice and may be a potential therapeutic candidate for the treatment of psoriasis in clinic.

A recipient usually rejects a transplanted organ and thus needs immunosuppressive treatments to prevent rejection. Achieving long-term allograft survival without continuous global immunosuppression is highly desirable in transplantation as long-term immunosuppression causes various side effects. Therefore, it is necessary to search for medicine with potentially less side effects. Traditional Chinese medicine PSORI-CM01 (Yin Xie Ling), a formula with seven natural herbs, has been used to treat patients with psoriasis. Here, we investigated a “sharpened” formula, PSORI-CM02 consisting of only five herbs from PSORI-CM01: Curcumae rhizoma, Radix paeoniae rubra, Rhizoma smilacis glabrae, Mume fructus, and Sarcandrae herba. We examined whether or not PSORI-CM02 would suppress alloimmunity and found that PSORI-CM02 significantly inhibited murine skin allograft rejection and reduced graft-infiltration of CD3+ T cells. Interestingly, omitting any single herbal component rendered the whole formula ineffective in suppression, indicating that these herbal components exert their effects cooperatively as a whole. Moreover, PSORI-CM02 increased CD8+CD122+PD-1+ Treg frequency with CD4+FoxP3+ Tregs remaining unchanged in recipient mice, whereas CsA reduced CD4+FoxP3+ Treg frequency. PSORI-CM02 also hindered CD11c+ DC maturation posttransplantation. Importantly, PSORI-CM02-induced CD8+CD122+PD-1+ Tregs were more potent in suppression of allograft rejection in Rag-/- mice than control Tregs. On the other hand, PSORI-CM02 suppressed T cell proliferation in vitro and reduced their phosphorylation of P70S6K and P50/P65, suggesting that it inhibits both mTOR and NFκB signaling pathways. It also increased IL-10 production while reducing IFNγ level in the supernatant of activated T cells co-cultured with CD8+CD122+PD-1+ Tregs. Furthermore, HPLC fingerprinting ruled out that PSORI-CM02 contained CsA or rapamycin. PSORI-CM02 also did not cause any illness and toxic injury in recipient mice. Thus, we demonstrate that PSORI-CM02 formula suppresses allograft rejection without toxicity.

Psoriasis is an autoimmune and inflammatory disease, which is estimated to affect 2–3% of the population in the world. PSORI-CM02 is an empirical formula of Chinese medicine optimized from Yin Xie Ling, which is widely used to treat psoriasis in China for decades. However, its antipsoriatic mechanisms are still not well understood. Here, we explored the therapeutic effects of PSORI-CM02 on psoriasis and its mechanisms of action in imiquimod-induced psoriasis-like mouse models and human HaCaT cells. In experiments in vitro, PSORI-CM02 significantly inhibited HaCaT cell proliferation in dose-dependent and time-dependent manners. Furthermore, it hindered the progression of HaCaT cell cycle and arrested HaCaT cells at G1 phase. On the other hand, our in vivo studies demonstrated that PSORI-CM02 dramatically reduced psoriasis area and severity index scores and lesion temperature in imiquimod-induced psoriatic mice. The antioxidative activities of glutathione, catalase, and superoxide dismutase were increased while oxidative activity of malonaldehyde was markedly decreased after treatments with PSORI-CM02. PSORI-CM02 also suppressed the mRNA expression of proinflammatory cytokines, including TNF-α, IL-6, and IL-17, and lowered their protein levels in the serum as well. In addition, PSORI-CM02 could reduce the expression of IKKα and NF-κB in psoriatic skin tissue. It also upregulated the proportion of CD4+ Foxp3+ regulatory T cells (Tregs) in both lymph nodes and spleens and promoted CD4+ CD25+ Treg proliferation in vitro. Taken together, our research demonstrated that PSORI-CM02 inhibited HaCaT cell proliferation by arresting them at G1 phase and alleviated systemic inflammation and psoriasis in mice via altering the oxidative/anti-oxidative status, tipping the balance between Th17 responsiveness and CD4+ Foxp3+ Treg generation, and suppressing the expression of proinflammatory cytokines as well as NF-κB signaling.

This systematic review evaluated the effects of Chinese herbal medicine (CHM) plus routine pharmacotherapy (RP) on the objective outcome measures BODE index, 6-minute walk test (6MWT), and 6-minute walk distance (6MWD) in individuals with stable chronic obstructive pulmonary disease (COPD). Searches were conducted of six English and Chinese databases (PubMed, EMBASE, CENTRAL, CINAHL, CNKI and CQVIP) from their inceptions until 18th November 2013 for randomized controlled trials involving oral administration of CHM plus RP compared to the same RP, with BODE Index and/or 6MWT/D as outcomes. Twenty-five studies were identified. BODE Index was used in nine studies and 6MWT/D was used in 22 studies. Methodological quality was assessed using the Cochrane Risk of Bias tool. Weaknesses were identified in most studies. Six studies were judged as 'low' risk of bias for randomisation sequence generation. Twenty-two studies involving 1,834 participants were included in the meta-analyses. The main meta-analysis results showed relative benefits for BODE Index in nine studies (mean difference [MD] -0.71, 95% confidence interval [CI] -0.94, -0.47) and 6MWT/D in 17 studies (MD 54.61 meters, 95%CI 33.30, 75.92) in favour of the CHM plus RP groups. The principal plants used were Astragalus membranaceus, Panax ginseng and Cordyceps sinensis. A. membranaceus was used in combination with other herbs in 18 formulae in 16 studies. Detailed sub-group and sensitivity analyses were conducted. Clinically meaningful benefits for BODE Index and 6MWT were found in multiple studies. These therapeutic effects were promising but need to be interpreted with caution due to variations in the CHMs and RPs used and methodological weakness in the studies. These issues should be addressed in future trials.