MMP2hi Fibroblasts Regulate CD8+ T Cell Residency and Inflammation via CD100 in Psoriasis.

BACKGROUND: Psoriasis, a T cell-mediated chronic inflammatory skin condition, is characterized by the interaction of T cells with various cell types, forming an inflammatory microenvironment that sustains psoriatic inflammation. The homeostasis of these tissue-resident T cells are supported by fibroblasts, the primary structural cells in the dermis. In psoriasis, there is an increased expression of matrix metalloproteinase 2 (MMP2), mediating the structural alterations of skin tissues and the modulation of inflammation. Additionally, the CD100-PLXNB2 axis is known to enhance psoriasis inflammation via keratinocytes, and CD103 levels are associated with the severity of psoriasis upon relapse. OBJECTIVE: To elucidate the role of fibroblasts and the MMP2/CD100 axis in modulating psoriasis inflammation. METHODS: CD100 expression and function in psoriasis were assessed using immunofluorescence, ELISA, single-cell transcriptome sequencing, cellular interaction analyses, and qRT-PCR. CD8+ T cells from psoriasis patients were isolated using magnetic beads to investigate the regulatory effect of MMP2 on CD100 expression on their membranes. Single-cell transcriptome sequencing, spatial transcriptome sequencing, mimetic timing analysis, immunofluorescence, and flow cytometry were utilized to determine the origin of MMP2 and its impact on CD103+CD8+ T cells. The hypotheses were further validated in vivo using MMP2 and CD100 inhibitors. RESULTS: Soluble CD100 (sCD100) was significantly upregulated in both psoriatic lesions and peripheral blood, amplifying psoriasis inflammation by promoting the production of inflammatory cytokines by keratinocytes, fibroblasts, and endothelial cells through the sCD100-PLXNB2 axis. Fibroblasts with high MMP2 expression (MMP2hi) exacerbate psoriasis symptoms by facilitating CD100 shedding from CD8+ T cell membranes. Additionally, it was demonstrated that fibroblasts enhance the upregulation of the CD8+ T cell residency factor CD103 in co-cultures with CD8+ T cells. Inhibitors targeting MMP2 and CD100 proved effective in reducing inflammation in a model of imiquimod-induced psoriasis. CONCLUSION: Our findings underscore the pivotal role of MMP2hi fibroblasts in the amplification and recurrence of inflammatory responses in psoriasis. These fibroblasts augment psoriasis inflammation through the CD100-PLXNB2 axis by facilitating CD100 shedding on CD8+ T cell membranes and by upregulating CD103, thereby enhancing CD8+ T cell residency.

The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis.

Psoriasis is a common immune-mediated inflammatory skin disease. Although biological agents have achieved good clinical efficacy in the treatment of moderate-to-severe psoriasis, the phenomenon of secondary non-response (SNR) has been gradually recognized. SNR refers to the gradual decline of efficacy after the patient achieves clinical remission with biological agents such as TNF-α biologics. Acitretin, as an immunomodulatory systemic drug for psoriasis, can improve the SNR to biological agents with good tolerance, but there are still individual differences in efficacy. Single-nucleotide polymorphisms (SNPs) of many related inflammatory cytokines have been shown to be important factors of individual differences in drug response in psoriasis, but there have been few reports on the use of pharmacogenomics to alleviate the SNR to biological agents. This study recruited 43 patients with psoriasis and 24 normal controls to investigate whether SNPs of inflammatory cytokines could be used as biomarkers for acitretin to alleviate SNR to TNF-α biologics in psoriasis, including rs1800795 (IL-6), rs6887695 (IL-12b), rs3212227 (IL-12b), rs10484879 (IL-17a), rs4819554 (IL-17ra), rs763780 (IL-17F), rs11209032 (IL23R), rs11209026 (IL23R), and rs2201841 (IL23R). The study also analyzed the correlation between the abovementioned SNPs and the efficacy of acitretin-only patients so as to understand whether the improvement is attributable to the intervention of acitretin on SNR or a simple response of acitretin. We found that in patients with homozygous AA (χ2 = 6.577, p = 0.02) at the SNP rs112009032 (IL-23R), acitretin could improve the SNR to TNFα monoclonal antibody. Patients with the genotype of TG (χ2 = 6.124, p = 0.035) at rs3212227 (IL-12B) were more sensitive to using acitretin in the treatment of psoriasis. Rs3212227 (χ2 = 7.664, p = 0.022) was also associated with the susceptibility to psoriasis. The study might provide a clinical decision reference for personalized treatment of secondary loss of response to psoriasis biologics.

LncRNA AGXT2L1-2:2 facilitates keratinocytes proliferation and inhibits apoptosis by interacting with estrogen-related receptor alpha in psoriasis.

Our previous studies have revealed that long noncoding RNA (lncRNA) AGXT2L1-2:2 was highly expressed in keratinocytes of psoriasis. However, the functions of lnc-AGXT2L1-2:2 in keratinocytes remain unknown. Meanwhile, co-expression network analysis indicated lnc-AGXT2L1-2:2 could interact with estrogen-related receptor alpha (ERRα). In this study, interleukin (IL)-17A could stimulate the production of lnc-AGXT2L1-2:2 in keratinocytes, thus establishing an in vitro cellular model of psoriasis. Lnc-AGXT2L1-2:2 was overexpressed using lentiviral-vector and ERRα was downregulated with small interfering RNA. Then the effects of lnc-AGXT2L1-2:2 and ERRα on viability, apoptosis, and cell cycle in IL-17A-stimulated keratinocytes were assessed by CCK-8, EdU assay, and flow cytometry. We found that lnc-AGXT2L1-2:2 and ERRα both resulted in higher proliferation ability, lower apoptosis rates, and reduction of G0/G1 phase proportion. Furthermore, lnc-AGXT2L1-2:2 could promote the expression of ERRα and siERRα antagonized the effects of lnc-AGXT2L1-2:2 on the phenotypes above in IL-17A-induced keratinocytes. In conclusion, lnc-AGXT2L1-2:2 was found to promote keratinocytes proliferation, inhibit cell apoptosis and the effects of lnc-AGXT2L1-2:2 on keratinocytes are dependent on ERRα.

Prevalence of Metabolic Syndrome in Chinese Patients With Erythrodermic Psoriasis: A Case-Control Study.

Erythroderma psoriasis (EP) is a rare and severe form of psoriasis, which is a chronic inflammatory skin disease that usually occurs simultaneously with cardiovascular disease (CVD). Metabolic syndrome (MetS) is a significant precursor of CVD. This study was to investigate the association between EP and MetS in the Chinese population. We conducted a retrospective study on 86 consecutive patients with EP and 100 healthy controls from Huashan Hospital between 2013 and 2018. Demographic, biochemical parameters for MetS, and other relevant data including the severity of EP, family history of EP, age of onset, and treatment history involved in those individuals were recorded. The prevalence of MetS in erythrodermic psoriatic patients was 88.37%, which was significantly higher than that of controls (P < 0.0001). Erythrodermic psoriatic patients also had a higher prevalence of MetS components, including abdominal obesity, dyslipidemia and hypertension, whereas hyperglycemia was similar. Adjusted for confounding factors, MetS, abdominal obesity, hypertension, smoking and alcohol use were positive independent predictors of EP (odds ratio > 1, P < 0.05). The area under the receiver operating characteristic curve calculated from determined risk factors for predicting the EP's incidence was 0.934 (95% CI 0.902-0.966). There was no correlation between the severity of EP and the prevalence of MetS. Compared with patients with mild EP, patients with moderate-to-severe EP had higher body mass index, waist circumstance and blood pressure (P < 0.05). We concluded that the prevalence of MetS and its components was higher in patients with EP. MetS an independent predictor of EP, which can favor CVD and should be encouraged to correct these cardiovascular risk factors aggressively for managing EP.

Relationship between Different Psoriasis Types and Thyroid Dysfunction: A Retrospective Analysis.

OBJECTIVE: The aim of this study was to investigate the relationship between different psoriasis types and thyroid dysfunction. METHODS: The data of patients diagnosed with psoriasis between January 2013 and October 2018 who underwent thyroid function tests were collected. Free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroid-stimulating hormone (TSH), thyroglobulin antibody (TGAb), and thyroid peroxidase antibody (TPOAb) were measured. The thyroid function of patients with psoriasis vulgaris, pustular psoriasis, erythrodermic psoriasis, and psoriatic arthritis was evaluated, and the differences in hormone levels and antibodies in the pituitary-thyroid axis with psoriasis type were analyzed. RESULTS: The data of a total of 468 patients were analyzed in this study. The proportion of normal hormone levels was higher among vulgaris patients (P < 0.001), while the erythrodermic patients were more likely to have decreased FT3 or FT4 but normal TSH (P < 0.001). FT3 levels were lower in pustular patients (P < 0.05), FT4 levels were lower in erythrodermic patients (P < 0.05), and TSH levels were higher in patients with psoriatic arthritis (P < 0.05). TPOAb levels were higher than normal in all patients, but there was no significant difference in the levels of TPOAb and TGAb among 4 types of the patients. CONCLUSION: Psoriasis is related to thyroid dysfunction, especially in patients with atypical psoriasis types. The possibility of complications should be considered in erythrodermic patients.

The long non-coding RNA and mRNA expression profiles in keratinocytes from patients with psoriasis vulgaris.

BACKGROUND: Psoriasis is a chronic inflammatory dermatosis. The hyperproliferation and hyperkeratosis of keratinocytes is a key step in the pathogenesis of psoriasis. Long non-coding RNAs (lncRNAs) and mRNAs regulate gene expression in various biological process, including the function of keratinocytes. This research investigated the expression profile of lncRNAs and mRNAs in keratinocytes of patients with psoriasis vulgaris. METHODS: The expression of lncRNAs and mRNAs in keratinocytes from patients with psoriasis vulgaris and healthy patients was examined and compared using microarrays. Quantitative polymerase chain reaction (qPCR) and bioinformatic analysis was also performed. DAVID and KEGG were used to analyze the gene function. The competing endogenous RNA (ceRNA) network was also constructed. RESULTS: A total of 48 lncRNAs and 17 mRNAs were differentially expressed in keratinocytes of psoriasis vulgaris. Quantitative PCR data showed that the expression of lnc-AGXT2L1-2:2 (P=0.009) and NR_027032 (P=0.033) was up-regulated in psoriasis vulgaris. The lncRNA-miRNA-mRNA interaction network was established. The mRNA showing the most connections with the lncRNAs and miRNAs was CEP104. The miRNA showing the most connections with the lncRNAs and mRNAs was miR-484. The lncRNA showing the most connections with miRNAs and mRNAs was ENST00000494887. CONCLUSIONS: The identification of the differentially expressed lncRNAs and mRNAs in psoriasis vulgaris provides significant insights into the pathogenesis of the disease.

Psychological effects of traditional Chinese mind-body exercises for low back pain: A protocol for meta-analysis.

INTRODUCTION: Several studies reported that traditional Chinese mind-body exercises showed beneficial effects on improving anxiety and depression of patients with low back pain (LBP) in recent years. However, the effects of traditional Chinese mind-body exercises on improving psychological disorders of patients with LBP remain controversial. Most previous reviews only focused on the effects of traditional Chinese mind-body exercises for LBP on pain and dysfunction. Therefore, the present systematic review and meta-analysis will be conducted to evaluate the evidence on psychological effects of traditional Chinese mind-body exercises for LBP. METHODS AND ANALYSIS: The electronic databases (PubMed, Embase, MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, China Knowledge Resource Integrated Database, and Wanfang Data) will be searched. The search will include all documents from their inception to February 2021. The Physiotherapy Evidence Database scale will be used for quality assessment of eligible studies. Risk of bias of eligible studies will also be assessed by Cochrane tool. The meta-analysis will be conducted using the Review Manager Version 5.3 software. The Higgins I2 statistic will be performed to examine for heterogeneity. The subgroup analysis will be conducted based on different types of traditional Chinese mind-body exercises, different intervention time, and different outcomes. Quality of evidence will be assessed using the Grades of Recommendation, Assessment, Development and Evaluation. ETHICS AND DISSEMINATION: No ethical statement will be required for the performance of this review and meta-analysis. The results of this review will be published in an international peer-reviewed journal. INPLASY REGISTRATION NUMBER: INPLASY202130075.

The effects of acupuncture for patients with psoriasis: Study protocol for a randomized controlled trial.

INTRODUCTION: Psoriasis is a common chronic relapsing inflammatory skin disease, which may have considerable detrimental effects on the quality of life. Considering high costs and side effects associated with the use of conventional medications, acupuncture, as one of complementary and alternative nonpharmacological therapies, is commonly used in the management of psoriasis for reducing itching, repairing the skin lesions, etc. However, the effects of acupuncture in the management of psoriasis are still inconsistent, especially in psychosocial abnormality due to psoriasis. Therefore, we designed a randomized controlled trials (RCT) involving a placebo control to ensure participants' blinding to investigate the effects of acupuncture for psoriasis in improving typical clinical symptoms and psychosocial abnormality. METHODS: A singlecenter RCT was designed. 220 participants who meet the eligibility criteria will be randomly allocated into manual acupuncture group or sham acupuncture group in a 1:1 ratio. Participants will respectively receive 15 minutes manual acupuncture or sham acupuncture per session, 3 sessions per week, totally 12 weeks. Psoriasis Area and Severity Index scores, body surface area (BSA), Medical Outcomes Study 36-Item Short-Form Health Survey, Montgomery-Asberg Depression Rating Scale, and Depression, Anxiety, and Stress Scale-21 will be evaluated by blinded operators at baseline and 12 weeks. All analyses will be based on an intention-to-treat principle. The results will be published in an international peer-reviewed journal. DISCUSSION: The results of this study are expected to clarify the effects of acupuncture on improving typical clinical symptoms and psychosocial abnormality of patients with psoriasis. It will contribute to clinical practice of acupuncture in the management of psoriasis. TRIAL REGISTRATION: Chinese Clinical Trail Registry: ChiCTR2100045481. Registration date: April 17, 2021.

Platelet distribution width as a novel indicator of disease activity in systemic lupus erythematosus.

BACKGROUND: Significance of platelet distribution width (PDW) and mean platelet volume (MPV) in assessing disease activity of systemic lupus erythematosus (SLE) remains unclear. This study was aimed to evaluate PDW and MPV as potential disease activity markers in adult SLE patients. MATERIALS AND METHODS: A total of 204 study participants, including 91 SLE patients and 113 age- and gender-matched healthy controls, were selected in this cross-sectional study. They were classified into three groups: control group (n = 113), active SLE group (n = 54), and inactive SLE group (n = 37). Demographic, clinical, and laboratory data were analyzed. RESULTS: In patient group, PDW was statistically higher than that in control group (13.54 ± 2.67 vs. 12.65 ± 2.34, P = 0.012), and in active group, PDW was significantly increased compared to inactive group (14.31 ± 2.90 vs. 12.25 ± 1.55, P < 0.001). However, MPV was significantly lower in SLE group than in control group (10.74 ± 0.94 vs. 11.09 ± 1.14, P = 0.016). PDW was positively correlated with SLE disease activity index (P < 0.001, r = 0.529) and erythrocyte sedimentation rate (P = 0.002, r = 0.321) and negatively correlated with C3 (P < 0.001, r = -0.419). However, there was no significant association between MPV and these study variables. A PDW level of 11.85% was determined as a predictive cutoff value of SLE diagnosis (sensitivity 76.9%, specificity 42.5%) and 13.65% as cutoff of active stage (sensitivity 52.6%, specificity 85.3%). CONCLUSION: This study first associates a higher PDW level with an increased SLE activity, suggesting PDW as a novel indicator to monitor the activity of SLE.

Comparison between photodynamic therapy with topical application of 5-aminolevulinic acid and CO2 laser therapy in the treatment of cervical condylomata acuminate: a randomized controlled trial.

The present study aimed to evaluate the efficacy of photodynamic therapy with topical applied 5-aminolevulinic acid (ALA-PDT) for the treatment of cervical condylomata accuminate (CA). 161 Patients with cervical CA were randomly divided into ALA-PDT group and CO2 laser (control) group. Patients (n=89) in the ALA-PDT group were treated with topical 5% ALA under occlusive dressing for 3 h followed by irradiation with semiconductor laser at a dose of 1000 J/cm(-2) and a power of 100 mW. Patients were treated 2 weeks later if necessary. Patients (n=72) in the control group were treated with CO2 laser. The treatment was repeated at 1-week interval when necessary. No response rate, complete response rate (CR) and recurrence rate of wart lesions as well as rate of eradication of HPVs were analyzed. The CR rate was 90.2% in the ALA-PDT group and 96.2% in the control group. The eradication rate was 90.2% in the ALA-PDT group and 65.8% in the control group after 3 months of follow-up. Both the eradication rate and recurrence rate in the ALA-PDT group were significantly lower than those in the control group (P<0.001). The adverse event in patients receiving ALA-PDT was mainly mild bleeding. ALA-PDT is a more effective and well-tolerated treatment for cervical CA compared with conventional CO2 laser therapy.

Evaluation of photodynamic therapy using topical aminolevulinic acid hydrochloride in the treatment of condylomata acuminate.

OBJECTIVES: To investigate the efficacy and safety of topical application of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) for the treatment of condylomata acuminata (CA) in larger population. METHODS: Patients with CA were given a treatment of ALA-PDT once a week for 3 weeks and followed up at 4, 8, 12 and 24 weeks after the treatment finished. RESULTS: In 531 patients, a clearance rate was observed 95.27%. The rates rouse with PDT cycles. The clearance rate of three PDT cycles was significant higher than one PDT cycles (P < 0.001) and two PDT cycles (P < 0.001). The clearance rate (88.73%) of small lesions (diameter small than 5mm) was significant higher than that (97.74%) of larger lesions (P < 0.001). The clearance rate varied with the location of the lesions. The clearance rate of urethral meatus was highest and that of perianal was lowest. Follow-up for patients with complete response lasted for 24 weeks. The recurrence rate was 5.65%, 11.30%, 15.07%, 15.44% and 16.20% after 1, 4, 8, 12 and 24 weeks. The recurrence rate varied with the location of the lesions. The recurrence rate of perianal was highest and that of labium was lowest. The side effects mainly included flare, pain, erosion, ulcer, and hyperpigmentation. The adverse reaction rate was 7.72%, 8.10%, 2.26%, 0.94% and 0.19%. Sexual dysfunction and urethral malformations were not observed during the 24 weeds visit. CONCLUSION: Topical application of ALA-PDT is a simple and as effective therapy with a lower incidence of adverse effects in the treatment of condylomata acuminata.

Occupational toxic epidermal necrolysis associated with dalbergia cochinchinensis: a retrospective comparative study of eight cases in China.

BACKGROUND: Occupational toxic epidermal necrolysis (TEN) related to Dalbergia cochinchinensis has seldom been reported in the past. Its clinical characteristic needs to be investigated. This study reports eight cases of such disease in China. METHODS: Eight patients with occupational TEN admitted from 2003 to 2012 were retrospectively analyzed and compared with 15 patients admitted with TEN caused by drugs as controls. Patients all received combination therapy of corticosteroid and intravenous immunoglobulin. The times for bullous ceasing, tapering of corticosteroid, and total hospitalization were compared between the two groups of patients. SCORTEN, a severity-of-illness scoring system for TEN prognosis, was applied to evaluate clinical outcome. RESULTS: The three time measurements in occupational TEN were longer than those in control, and the differences were statistically significant (P = 0.0023, 0.026, 0.0017), which means the total dose of corticosteroid needed in occupational TEN was higher than that in the control. There were no deaths in the two groups, although expected deaths were 0.612 and 0.836, respectively. DISCUSSION: Occupational TEN has a longer progression than TEN caused by drugs, and there is more difficulty in its treatment. Clinicians should pay attention to this disease. However, its mechanism and target therapy remain unclear.

Motivations for sexual risk behaviors among older men in Shanghai, China: a qualitative study.

BACKGROUND: China's population is quickly aging and this trend is expected to continue. Thus it is important to develop HIV interventions to help protect older Chinese from infection. Limited information exists regarding sexual risk behaviors and associated personal motivations among persons aged 50 and over in China. METHODS: In-depth interviews were conducted with 12 HIV-infected and 14 uninfected men aged 50 and over in Shanghai, China. RESULTS: More than 71% of heterosexual participants had engaged in commercial sex, 37.5% either had engaged in casual sex or had a steady extramarital partner. All gay/bisexual participants had engaged in casual sex with men, and 16.7% had engaged in commercial sex. Personal motivations associated with sexual risk behaviors included sexual desire and interest in sex remaining high at an older age, unfulfilled sexual desires within marriage, homosexual or bisexual orientation, need to socialize with others, peer influence, personal choice of "hobby", and financial freedom. CONCLUSIONS: This study sheds light on the sexual needs of older people. Our findings underscore the need for both greater education in order to reshape societal perceptions of sexuality among older adults and prevention strategies to help the older male population maintain a healthy sexual life.

In vitro and in vivo anticancer activity of aconitine on melanoma cell line B16.

The anti-tumor effect of aconitine in melanoma cell line B16 has been studied in this paper. We found that B16 cells showed significantly reduced growth rates and increased apoptotic effects in the presence of aconitine. Furthermore, aconitine inhibited the PI3K/AKT and MAPK/ERK1/2 signaling pathways, thus regulating the levels of protein and mRNA of PCNA and apoptotic related signaling molecules. Above all, we found that aconitine showed an anti-melanoma effect in suppressing tumor growth in vivo. In conclusion, we show that aconitine may be a useful anticancer drug in the future.

Transcriptional regulatory network for psoriasis.

Psoriasis is a common, chronic, intractable skin disease that affects approximately 2% of the world's population. Transcriptional regulation is one of the most fundamental processes in psoriasis. However, high-throughput functional analysis of multiple transcription factors and their target genes in psoriasis is still rare. Thus, the objective of our study was to interpret the mechanisms of psoriasis through the regulation network construction using the GSE14905 microarray data. The results showed E2F transcription factor 1 (E2F1), jun proto-oncogene (JUN), nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NF-κB1), signal transducer and activator of transcription 1 (STAT1), STAT3 and SP3 were hinge points in our transcriptome network. Importantly, JUN may regulate activating transcription factor 3 expression to involve cell proliferation process; STAT1 and STAT3 can inhibit tissue inhibitor of metalloproteinases-3 expression to modulate the cell adhesion molecule pathway; NF-κB and E2F1 can downregulate cyclin D1, but upregulate proliferating cell nuclear antigen expression to promote the cell cycle pathway. In addition, the regulation network between transcription factors and pathways revealed that NF-κB1 could promote the Toll-like receptor signaling pathway and that SP3 may inhibit the steroid hormone biosynthesis pathway in psoriasis. This transcriptional regulation analysis may provide a better understanding of molecular mechanism and some potential therapeutic targets in the treatment of human psoriasis.