Investigation of vascular risk factor control and secondary prevention medication compliance in acute ischemic stroke.

Objectives: This study aimed to investigate the management of vascular risk factors, with a specific focus on understanding the various factors affecting risk factor control through an in-depth analysis of clinical data and a longitudinal follow-up of patients who have experienced ischemic strokes. Methods: A total of 1,572 participants were included in the analysis. We assessed thresholds for blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and glycated hemoglobin (HbA1c) levels to uncover the contextual conditions and factors affecting vascular risk factor control. Moreover, the study also scrutinized medication compliance at intervals of 3, 6, and 12 months post-onset. Logistic regression was used to adjust for confounding factors. Results: At 3, 6, and 12 months, BP,LDL, hemoglobin control targets were achieved in 50.7, 51.8, and 50.6%; 51.5, 59.4, and 50.6%; 48.1, 44.0, and 48.4%,respectively. Notably, age was associated with the achievement of BP control (odds ratio [OR], 0.96; 95% confidence intervals [CI], 0.94-0.98; p < 0.0001). Ethnic minorities (OR, 4.23; 95% CI, 1.19-15.09; p = 0.02) and individuals with coronary heart disease (OR, 0.5; 95% CI, 0.3-1.0; p = 0.05) experienced decreased BP control ratios. A previous history of stroke (OR, 1.7; 95% CI, 1.0-2.8; p = 0.03) and unrestricted alcohol consumption (OR, 3.3; 95% CI, 1.0-11.1; p = 0.05) was significantly associated with the achievement of lipid control. Furthermore, lifestyle modifications were significantly correlated with the achievement of BP control (OR, 0.19; 95% CI, 0.12-0.30; p < 0.01), blood glucose control (OR, 0.03; 95% CI, 0.01-0.08; p < 0.01), and blood lipid control (OR, 0.26; 95% CI, 0.16-0.42; p < 0.01). The absence of regular physical activity was associated with lower rates of glycemic (OR, 0.14; 95% CI, 0.06-0.36; p < 0.01) and lipid controls (OR, 0.55; 95% CI, 0.33-0.90; p = 0.01). Over time, overall medication compliance declined. Conclusion: Within the cohort of patients under medication, the compliance rate concerning vascular risk factors remains unsatisfactory. Attention should be paid to compliance with secondary prevention medications and enhance the control of vascular risk factors, as compliance emerges as the key to effective prevention.

Silencing DOCK2 Attenuates Cardiac Fibrosis Following Myocardial Infarction in Mice Via Targeting PI3K/Akt and Wnt/ß-Catenin Pathways.

Cardiac fibrosis following myocardial infarction (MI) seriously affects the prognosis and survival rate of patients. This study aimed to determine the effect and regulation mechanism of the dedicator of cytokinesis 2 (DOCK2) during this process. Experiments were carried out in mice in vivo, and in Ang II treated cardiac fibroblasts (CFs) in vitro. DOCK2 was increased in mouse myocardial tissues after MI and Ang II-treated CFs. In MI mice, DOCK2 silencing improved cardiac function, and ameliorated cardiac fibrosis. DOCK2 knockdown suppressed the activation of CFs and decreased the expression of α-SMA, collagen I, and collagen III. Suppression of DOCK2 mitigated Ang II induced migration of CFs. DOCK2 inhibition reduced the activity of the PI3K/Akt and Wnt/ß-catenin pathways, while this change could be reversed by the pathway activators, SC79 and SKL2001. In summary, DOCK2 suppression improves cardiac dysfunction and attenuates cardiac fibrosis after MI via attenuating PI3K/Akt and Wnt/ß-catenin pathways.

Retracing from Outcomes to Causes: NRF2-Driven GSTA4 Transcriptional Regulation Controls Chronic Inflammation and Oxidative Stress in Atopic Dermatitis Recurrence.

Atopic dermatitis (AD), a chronic and recurrent inflammatory skin disorder, presents a high incidence and imposes a substantial economic burden. Preventing its recurrence remains a significant challenge in dermatological therapy owing to poorly understood underlying mechanisms. In our study, we adopted a strategy of tracing the mechanisms of recurrence from clinical outcomes. We developed a mouse model of recurrent AD and applied clinically validated treatment regimens. Transcriptomic analyses revealed a pronounced enrichment in the glutathione metabolic pathway in the treated group. Through integrated bioinformatics and in vivo validation, we identified glutathione S-transferase alpha 4 (GSTA4) as a pivotal mediator in AD recurrence. Immunohistochemical analysis demonstrated decreased GSTA4 expression in lesions from patients with AD. Functionally, in vitro overexpression of GSTA4 significantly curtailed AD-like inflammatory responses and ROS production. Moreover, we discovered that NRF2 transcriptional activity regulates GSTA4 expression and function. Our treatment notably augmented NRF2-mediated GSTA4 transcription, yielding pronounced anti-inflammatory and ROS-neutralizing effects. Conclusively, our findings implicate GSTA4 as a critical factor in the recurrence of AD, particularly in the context of oxidative stress and chronic inflammation. Targeting the NRF2-GSTA4 axis emerges as a promising anti-inflammatory and antioxidative strategy for preventing AD recurrence.

Hyperbaric oxygen therapy improves the efficacy of conventional supportive treatment for late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

OBJECTIVE: This study aims to investigate the efficacy and safety of hyperbaric oxygen therapy (HBOT) in the treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. METHODS: This retrospective analysis included 16 patients with late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation between 2016 and 2022. Among them, 8 patients received HBOT in addition to conventional treatment, while the other 8 received only conventional treatment. The clinical efficacy and safety of HBOT were evaluated by comparing the Numeric Rating Scale pain scores and clinical grades of hematuria before and after treatment, reflecting the patients' urinary pain and hematuria status. RESULTS: The patients were divided into two groups based on whether they received HBOT. The group that received HBOT (n = 8) had a shorter duration of illness compared to the non-HBOT group (n = 8) (p < 0.05). The time for the NRS to decrease to below 2 was also shorter in the HBOT group. Furthermore, the patients who received HBOT did not experience any significant adverse reactions. CONCLUSION: The combination of conventional treatment and hyperbaric oxygen therapy (HBOT) has been shown to improve symptoms such as urinary pain, frequency, urgency, and hematuria in patients with late-onset hemorrhagic cystitis after transplantation. This approach has been proven to be safe and effective.

Epidemiology of malignant tumors in patients with pemphigus: an analysis of trends from 1955 to 2021.

BACKGROUND: The incidence of malignant tumors has increased in patients with non-paraneoplastic pemphigus, although there has been no systematic analysis of global epidemiology. OBJECTIVE: To explore the epidemiology of various types of non-paraneoplastic pemphigus associated with malignant tumors. METHODS: Five databases from establishment through October 20, 2023, were searched. STATA SE 17 was used for the data analysis. Subgroup, meta-regression, and sensitivity analyses were used to evaluate the heterogeneity of pooled studies. RESULTS: A total of 6679 participants were included in our meta-analysis from 16 studies. The aggregated prevalence of tumors in patients diagnosed with pemphigus was 8%. The prevalence was 7% in patients with pemphigus vulgaris, 10% in those with pemphigus foliaceus, and 12% in individuals diagnosed with other types of pemphigus. The prevalence was 8% in Asia, 11% in Europe, and 8% in North America. From a country-specific perspective, patients with pemphigus from Israel, Greece, and Germany exhibited a higher prevalence of tumors at 11%. Furthermore, when categorized by the duration of the study period, the highest prevalence was observed in studies spanning 10 to 20 years, at 11%. CONCLUSION: These findings demonstrate the incidence and prevalence of malignant tumors in patients with non-paraneoplastic pemphigus, which may achieve early detection and intervention, and then reduce mortality rates.

Formation and clinical effects of anti-drug antibodies against biologics in psoriasis treatment: An analysis of current evidence.

BACKGROUND: Formation of anti-drug antibodies (ADAs) against biologics is an important cause of psoriasis treatment failure. OBJECTIVE: This study aimed to summarize the characteristics of ADAs formation under different biological therapies and the influence of ADAs on the clinical effects and safety of biologics in patients with psoriasis. METHODS: PubMed, Embase, and Web of Science databases were searched from their inception to August 2022. Studies on biologics that assessed ADA levels in patients with psoriasis were included. The Cochrane risk-of-bias tool was used to assess the quality of randomized controlled trials (RCTs), the Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control and cohort studies, and the Joanna Briggs Institute (JBI) critical appraisal checklist for single-arm studies. We calculated the pooled incidence with a random-effects model using R software. Subgroup analyses revealed that differences in patient characteristics, disease conditions, study design, and immunoassays may influence ADA generation and detection. RESULTS: The analysis included 86 studies, with a total population of 42,280 individuals. The pooled ADA rates were 0.49%, 2.20%, 2.38%, 4.08%, 7.38%, 7.94%, 14.29%, 21.93%, 29.70%, 31.76%, and 39.58% for secukinumab, etanercept, brodalumab, ustekinumab, tildrakizumab, guselkumab, ixekizumab, risankizumab, infliximab, adalimumab, and bimekizumab, respectively. >70% (95% CI, 0.71-0.81) of ADAs against adalimumab were neutralizing antibodies, and over 70% of ADAs against secukinumab and brodalumab were transient. Concomitant methotrexate therapy with tumor necrosis factor-α (TNF-α) inhibitors decreased ADA levels. Lower infliximab doses and intermittent therapy with interleukin (IL)-23 p19 inhibitors increased ADA formation. Additionally, ADA formation under treatment using TNF-α inhibitors and IL-12/23 p40 inhibitors was associated with lower response rates or serum drug levels, but only high ADA titers reduced the clinical effects of IL-17 inhibitors. The occurrence of IL-23 p19 and TNF-α inhibitors has been linked to injection-site reactions. CONCLUSIONS: Among the 11 biologics, secukinumab, etanercept, and brodalumab resulted in the lowest ADA formation rates. Immunogenicity contributes to lower biological efficacy and a higher likelihood of injection-site reactions. Low doses, intermittent treatment may increase ADA formation. An appropriate biologic should be selected based on the ADA formation rate and course of treatment.

Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial.

BACKGROUND: Acute gouty arthritis (AGA) is an inflammatory joint disease with a high prevalence. Typical medical interventions, including nonsteroidal anti-inflammatory drugs, colchicine and glucocorticoids, can have serious adverse reactions. Huzhang Granule (HZG), a compound Chinese herbal medicine, has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions. However, the efficacy and safety of HZG in AGA patients remains unknown. OBJECTIVE: The present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The current study was conducted as a noninferiority, randomized controlled clinical trial on 180 eligible enrolled participants. Participants were randomly assigned into the HZG and etoricoxib groups. Treatments were administered for 5 d, during which the HZG group received HZG and placebo etoricoxib, while the etoricoxib group received etoricoxib and placebo HZG in the same ratio (1:1). MAIN OUTCOME MEASURES: The primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window. The pain level was measured via a visual analogue scale, ranging from 0 mm to 100 mm. The secondary outcomes comprised joint tenderness and swelling, reduction of inflammatory biomarkers, and the patient's and investigator's global evaluations of therapeutic response. RESULTS: The mean reduction in pain was -51.22 mm (95% confidence interval [CI], [-53.42, -49.03] mm) for the HZG and -52.00 mm (95% CI, [-54.06, -49.94] mm) for the etoricoxib groups. The mean difference between the two groups was 0.78 mm (95% CI, [-2.25, 3.81] mm). All additional efficacy endpoints, covering decreased inflammation and pain relief, yielded compelling proof of noninferiority. Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group (4.44% vs 13.33%; P ≤ 0.05). CONCLUSION: HZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness. The safety and efficacy of HZG indicates that it can be used as a potential therapeutic option for treating AGA. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000036970). Please cite this article as: Wang H, Chen ST, Ding XJ, Kuai L, Hua L, Li X, Wang YF, Zhang M, Li B, Wang RP, Zhou M. Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial. J Integr Med. 2024; 22(3): 270-278.

Calycosin enhances Treg differentiation for alleviating skin inflammation in atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder that poses a significant global health challenge. There is a lack of safe and effective medications to treat AD. Astragalus membranaceous is a traditional Chinese medicine widely used in clinical treatment of skin diseases. Calycosin (CA), derived from the root of Astragalus membranaceous, exhibits dual attributes of anti-inflammatory and antioxidant properties, suggesting its promise for addressing cutaneous inflammation. Nonetheless, the precise mechanisms underlying CA's therapeutic actions in AD remain elusive. AIM OF THE STUDY: This study aimed to evaluate the efficacy and safety of CA in treating AD while also delving into the mechanistic underpinnings of CA's action in AD. MATERIALS AND METHODS: The cell viability and anti-inflammatory impacts of CA in vitro were first gauged using CCK-8 and RT-qPCR. The potential mechanisms of CA were then probed using modular pharmacology. Flow cytometry was employed to ascertain the differentiation of Treg and Th17 cells derived from naïve T cells, as well as the proportions and mean fluorescence intensity (MFI) of human iTreg cells. The expressions of IL-10 and TGF-ß1 were measured and Treg suppression assay was performed. The in vivo therapeutic efficacy of topical CA application was assessed using a calcipotriol (MC903)-induced AD mouse model. The expression metrics of inflammatory cytokines, IL-17A, FOXP3, and RORγt were authenticated via immunohistochemistry, RT-qPCR, Western blot, and ELISA. RESULTS: CA exhibited a favorable safety profile and reduced the mRNA expressions of Th2 inflammatory cytokines in HaCaT cells. Modular pharmacology analysis pinpointed Th17 differentiation as the pivotal mechanism behind CA's therapeutic effect on AD. In vitro, CA fostered the differentiation of naïve T cells into Tregs while inhibiting their differentiation into Th17 cells. Furthermore, CA augmented the proliferation of human iTregs. In vivo, CA alleviated skin manifestations and decreased the levels of inflammatory mediators (IL-4, IL-5, IL-13, TSLP, and NF-κB related cytokines) in AD-like mouse models. Simultaneously, it regulated Treg/Th17 balance through suppressing IL-17A and RORγt expressions and bolstering FOXP3 expression. CONCLUSIONS: The study provides insights into the mechanistic pathways through which CA exerts its anti-inflammatory effects, particularly through promoting Treg cell differentiation and inhibiting Th17 cell differentiation. Furthermore, CA emerges as an alternative or adjunctive treatment strategy for managing AD.

Therapeutic effects of the Qingre-Qushi recipe on atopic dermatitis through the regulation of gut microbiota and skin inflammation.

Accumulating evidence has highlighted a strong association between gut microbiota and the occurrence, development, prevention, and treatment of atopic dermatitis (AD). The regulation of gut microbial dysbiosis by oral traditional Chinese medicine (TCM) has garnered significant attention. In the treatment of AD, the TCM formula Qingre-Qushi Recipe (QRQS) has demonstrated clinical efficacy. However, both the therapeutic mechanisms of QRQS and its impact on gut microbiota remain unclear. Thus, our study aimed to assess the efficacy of QRQS and evaluate its influence on the composition and diversity of gut microbiota in AD animal models. First, we investigated the therapeutic effect of QRQS on AD using two animal models: filaggrin-deficient mice (Flaky tail, ft/ft) and MC903-induced AD-like mice. Subsequently, we explored its influence on the composition and diversity of gut microbiota. Our results demonstrated that QRQS treatment ameliorated the symptoms in both ft/ft mice and MC903-induced AD-like mice. It also reduced the levels of serum IgE and pro-inflammatory cytokines, including IL-1ß, IL-4, IL-5, IL-9, IL-13, IL-17A, and TNF-α. Furthermore, QRQS remarkably regulated gut microbiota diversity by increasing Lactobacillaceae and decreasing Bacteroidales. The inflammatory factors in peripheral serum of ft/ft mice showed a close correlation with gut microbiota, as determined using the Spearman correlation coefficient. Additionally, PICRUSt analysis revealed an enrichment in ascorbate and aldarate metabolism, fatty acid metabolism and biosynthesis, and propanoate metabolism in the QRQS group compared to the ft/ft group. Finally, we identified liquiritin as the primary active ingredient of QRQS using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Our findings revealed that QRQS improved AD-like symptoms and alleviated skin inflammation in ft/ft and MC903-induced mice. This suggests that modulating the gut microbiota may help elucidate its anti-inflammation activation mechanism, highlighting a new therapeutic strategy that targets the intestinal flora to prevent and treat AD.

CircRTTN upregulates EPHA2 to aggravate the malignant process of melanoma via sponging miR-890.

BACKGROUND: Malignant melanoma is a kind of tumor derived from melanocytes, which has the characteristics of drug resistance and distant metastasis. Accumulating evidence has demonstrated that circular RNAs (circRNAs) are involved in the pathogenesis of melanoma. Our current study aimed to investigate the role and mechanism of circRTTN in melanoma progression. METHODS: The levels of circRTTN, microRNA-890 (miR-890) and EPH receptor A2 (EPHA2) were examined via quantitative real-time PCR (qRT-PCR) and Western blot. Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, transwell and tube formation assays were conducted to estimate the effects of circRTTN on growth, apoptosis, migration, invasion and angiogenesis of melanoma cells. Western blot was used to measure related marker protein levels. The interaction between miR-890 and circRTTN or EPHA2 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Xenograft assay was used to assess the effect of circRTTN in vivo. RESULTS: CircRTTN and EPHA2 levels were up-regulated, while miR-890 was down-regulated in melanoma tissues and cells. CircRTTN knockdown restrained cell proliferation, migration, invasion and angiogenesis, but promoted cell apoptosis in vitro. CircRTTN was an effective molecular sponge for miR-890, and negatively regulated miR-890 expression. The suppressive role of circRTTN knockdown on cell growth, metastasis and angiogenesis in vitro was abated by blocking miR-890. MiR-890 directly targeted EPHA2. MiR-890 overexpression elicited a similar anti-tumor role in melanoma cells, which was abrogated by overexpression of EPHA2. In addition circRTTN knowdown markedly attenuated xenograft tumor growth in vivo. CONCLUSION: Our findings demonstrated that circRTTN mediated melanoma progression via regulating the miR-890/ EPHA2 axis.

METTL14 promotes IL-6-induced viability, glycolysis and inflammation in HaCaT cells via the m6A modification of TRIM27.

Interleukin-6 (IL-6) is a cytokine generated by healthy constituents of the skin, but is also up-regulated by a wide range of skin lesions and inflammatory conditions to trigger cytopathy of skin cells. TRIM27 was identified to contribute to the functional effects of IL-6 on skin cells. However, the underlying mechanism was not clear. Lentivirus infection was used for gene overexpression or silencing. RT-PCR and Western blot were used to respectively assess mRNA and protein levels. Cell viability was assessed by CCK-8 assay. Extracellular flux analysis was used to assess the levels of oxygen consumption rate and extracellular acidification rate. Mouse back skin was treated with imiquimod to produce psoriasis-like inflammation in vivo. Histological assessment and immunohistochemistry staining were respectively applied to analyse lesioned mouse and human skin samples. IL-6-induced increased viability, glycolysis and inflammation in keratinocytes was inhibited both by a chemical methylation inhibitor and by METTL14 knockdown. Further investigation found that METTL14 induces m6A methylation of TRIM27, which is recognized by a m6A reader, IGF2BP2. Elevation of TRIM27 level and activation of IL-6/STAT3 signalling pathway were found in an in vivo psoriasis-like inflammation model, whereas inhibition m6A methylation strongly alleviated the inflammation. Finally, METTL14, TRIM27, STAT3, p-STAT3 and IL-6 expressions were all found to be increased in clinical skin samples of psoriatic patients. Our results unravelled METTL14/TRIM27/IGF2BP2 signalling axis in keratinocyte cytopathy, which plays a critical role in facilitating the activation of IL-6/STAT3 signalling pathway. Our findings should provide inspirations for the design of new therapeutics for skin inflammatory diseases including psoriasis.

The therapeutic efficacy and mechanism action of Si Cao formula in the treatment of psoriasis: A pilot clinical investigation and animal validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammation and relapsing disease that affected approximately 100 million individuals worldwide. In previous clinical study, it was observed that the topical application of Si Cao Formula (SCF) ameliorated psoriasis skin lesions and reduced the recurrence rate of patients over a period of three months. However, the precise mechanism remains unclear. AIM OF THE STUDY: The objective of this study was to assess the effectiveness and safety of SCF in patients diagnosed with psoriasis and explore the molecular mechanisms that contribute to SCF's therapeutic efficacy in psoriasis treatment. MATERIALS AND METHODS: A randomized, controlled, and pilot clinical study was performed. This study assessed 30 individuals diagnosed with mild to moderate plaque psoriasis. 15 of them underwent local SCF treatment, the others received calcipotriol intervention. The outcome measure focused on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and recurrence rate. In addition, IMQ-induced psoriasis-like mice model were used to assess the impact of SCF on ameliorating epidermal hyperplasia, suppressing angiogenesis, and modulating immune response. Furthermore, we performed bioinformatics analysis on transcriptome data obtained from skin lesions of mice model. This analysis allowed us to identify the targets and signaling pathways associated with the action of SCF. Subsequently, we conducted experimental validation to confirm the core targets. RESULTS: Our clinical pilot study demonstrated that SCF could ameliorate skin lesions in psoriasis patients with comparable efficacy of calcipotriol in drop of PASI and DLQI scores. SCF exhibited a significantly reduced recurrence rate within 12 weeks (33.3%). Liquid Chromatography Mass Spectrometry (LC-MS) identified 41 active constituents of SCF (26 cations and 15 anions). Animal experiments showed SCF ameliorates the skin lesions of IMQ-induced psoriasis like mice model and suppresses epidermal hyperkeratosis and angiogenesis. There were 845 up-regulated and 764 down-regulated DEGs between IMQ and IMQ + SCF groups. GO analysis revealed that DEGs were linked to keratinization, keratinocyte differentiation, organic acid transport epidermal cell differentiation, and carboxylic acid transport interferon-gamma production. KEGG pathway analysis showed that SCF may play a vital part through IL-17 and JAK/STAT signaling pathway. In addition, SCF could reduce the number of positive cells expressing PCNA, CD31, pSTAT3, CD3, and F4/80 within the epidermis of psoriatic lesions, as well as the expression of Il-17a and Stat3 in IMQ-induced psoriasis mice. CONCLUSIONS: Our research suggests that SCF serves as a reliable and efficient local approach for preventing and treating psoriasis. The discovery of plausible molecular mechanisms and therapeutic targets associated with SCF may support its broad implementation in clinical settings.

Pustular Psoriasis in a Patient Treated with Dupilumab for Atopic Dermatitis: A Case Report.

Psoriasis and atopic dermatitis are relatively common in clinical practice, but it is rare for the two diseases to co-occur in the same patient. Dupilumab, an anti-IL-4/IL-13 monoclonal antibody, has been approved for treating moderate to severe AD. In addition to its therapeutic effects, dupilumab may induce new cutaneous adverse reactions. We report a rare case of pustular psoriasis induced during the treatment of atopic dermatitis with dupilumab. This case demonstrates the need for caution while treating patients with moderate to severe atopic dermatitis and staying vigilant for the emergence of new symptoms, especially with biological agents.

Association of Inflammatory Indicators and Clinical Signs and Itch in Atopic Dermatitis Patients Treated with Simiao Pill Combined with Halomethasone Cream.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by symptoms such as itchiness, scaling, and erythema. Previous studies have suggested that inflammatory indicators obtained from peripheral blood cell count can serve as markers for atopic dermatitis pruritus and severity. The objective of this study was to investigate whether these indicators are associated with treatment efficacy in AD patients who received a combination of halomethasone cream and Simiao pill (SMP). Methods: 131 adult patients diagnosed with AD between January 2020 to August 2022 and treated with topical halometasone ointment combined with oral Simiao pill for a month were recruited and clinical dates of patients were collected. Inflammatory indicators included Eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), serum leukotriene B4 (LTB4), and thymic stromal lymphopoietin (TSLP) and clinical indexes for assessing eczema area and severity index (EASI) and peak pruritus-numerical rating scale (PP-NRS). Relationship of baseline and changes of these Inflammatory indicators and that of clinical indexes were analyzed. Results: ELR, NLR, LTB4, and TSLP levels have positive association with EASI before treatment, and baseline ELR and LTB4 levels have positive relationship with PP-NRS. ELR, NLR, LTB4, and TSLP showed a significant decrease at week 2 and the low levels were maintained until week 8 after treatment, while no significant changes were observed in levels of MLR and PLR. There was a significant correlation between the decrease of ELR and the decreases of EASI and PP-NRS at weeks 2, 4 and 8 of the treatment. Conclusion: ELR may serve as an effective and convenient indicator in assessing the disease severity and efficacy of SMP therapy for AD.

Qinzhu Liangxue inhibits IL-6-induced hyperproliferation and inflammation in HaCaT cells by regulating METTL14/SOCS3/STAT3 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis, an immune-mediated chronic inflammatory skin condition, is treatable with Qinzhu Liangxue (QZLX), a therapeutic medicinal plant formula used in clinical practice. However, further investigation is needed to clarify its molecular mechanisms of action. AIM OF THE STUDY: The potential biological mechanisms of QZLX to alleviate psoriasis involving IL-6-induced hyperproliferation and inflammation by regulating METTL14/SOCS3/STAT3 axis. MATERIALS AND METHODS: HaCaT cell model was induced by IL-6, and dealt with serum containing QZLX. In addition, shRNAs and siRNAs were used for gene silencing, viruses were collected 48 h post-transfection and infected HaCaT cells. Cell viability was detected by CCK-8 assay, cell cycle was determined by flow cytometry. Finally, psoriasis mice model was induced by IMQ cream, then back skin tissue was used for hematoxylin and eosin (H&E). The content of IL-1ß, IL-6, and IL-8 in cell supernatants were analyzed using ELISA kits. Analysis of SOCS3 was used by quantitative RT-PCR, the expression level of SOCS3, METTL3, METTL14, WTAP, SOCS3, YTHDF2, p-STAT3 and STAT3 in HaCaT cells transduced with METTL14 overexpression was detected by Western blot. RESULTS: All results indicated that QZLX could significantly alleviate IL-6-induced HaCaT cell viability, cell cycle progression, and inhibit the level of IL-1ß, IL-6, and IL-8. The m6A levels and level of METTL14 in HaCaT cells treated with IL-6 were enhanced, while it was reversed by QZLX. METTL14 silencing could inhibit IL-6-induced HaCaT cell viability, cell cycle progression and inflammation response, while SOCS3 overexpression also suppressed METTL14-induced HaCaT cell viability, cell cycle progression and inflammation. QZLX could significantly enhance the expression level of SOCS3, while inhibit the level of METTL14, and p-STAT3/STAT3. In addition, QZLX inhibits METTL14-induced HaCaT cell viability, cell cycle progression, and inhibits the level of IL-1ß, IL-6, and IL-8. CONCLUSIONS: Our finding suggested that QZLX ameliorated the inflammation response of psoriasis and performed the potential anti-psoriasis effect by regulating METTL14/SOCS3/STAT3 axis in both mice and HaCaT cells psoriasis model. Therefore, our study demonstrated a significant strategy for inhibiting psoriasis inflammation via targeting METTL14/SOCS3/STAT3 axis.

Perifolliculitis capitis abscedens et suffodiens treatment with tumor necrosis factor inhibitors and baricitinib: A case report and literature review.

Rationale: Perifolliculitis capitis abscedens et suffodiens (PCAS), also known as dissecting cellulitis of the scalp (DCS), is a part of the "follicular occlusion tetrad" that also includes acne conglobate (AC), hidradenitis suppurativa (HS), and pilonidal sinus, which share the same pathogenic mechanism, such as follicular occlusions, follicular ruptures, and follicular infections. Patient concerns: A 15-year-old boy had multiple rashes on the scalp accompanied by pain. Diagnosis: The patient was diagnosed with PCAS or DCS based on the clinical manifestations and laboratory examinations. Interventions: The patient was initially administered adalimumab 40 mg biweekly and oral isotretinoin 30 mg daily for 5 months. Because the initial results were insufficient, the interval between adalimumab injections was extended to 4 weeks, and isotretinoin was changed to baricitinib 4 mg daily for 2 months. When the condition became more stable, adalimumab 40 mg and baricitinib 4 mg were administered every 20 and 3 days, respectively, for two more months until now. Outcomes: After 9 months of treatment and follow-up, the original skin lesions of the patient were almost cured, and most inflammatory alopecia patches disappeared. Conclusion: Our literature review did not find any previous reports on treating PCAS with TNF-α inhibitors and baricitinib. Accordingly, we presented the first successful treatment of PCAS with this regimen.

Hypoxia-Induced miR-210 Promotes Endothelial Cell Permeability and Angiogenesis via Exosomes in Pancreatic Ductal Adenocarcinoma.

Background: Exosomes have been proven to play important diagnostic, regulatory, or communication roles in tumorigenesis, tumor progression, or metastasis; in recent studies, lots of molecules, including miRNAs, were found to be aberrantly expressed in tumor exosomes and were correlated with tumor development. However, studies about the expression, relationship, or control mechanisms of miRNAs in exosomes in pancreatic ductal adenocarcinoma (PDAC) are scarce and urgently needed. The aim of this article was to identify and investigate abnormally expressed miRNAs in PDAC exosomes in vivo and in vitro. Methods: Microarray studies were used to detect aberrantly expressed miRNAs in PDAC exosomes, and miR-210 expression in cells or exosomes was further analyzed by qRT-PCR. Bioinformatics analyses, dual-luciferase assays, WB, and other assays were utilized to explore the miRNA molecular mechanisms. The living cell coculture model and immunofluorescence analysis were employed to image the communication between PDAC cells and endothelial cells. Other biological experiments in the study include a real-time intravital imaging system, EdU, transwell, xenograft models, and so on. Results: miR-210 is significantly expressed in PDAC exosomes and malignant cells. High miR-210 significantly facilitated tumor angiogenesis, cell invasion, and proliferation in PDAC cells. Further mechanistic detection revealed that miR-210 negatively regulated EFNA3 expression and participated in the PI3K/AKT/VEGFA or Wnt/Β-catenin/RHOA pathways, thus promoting tumor angiogenesis and cellular permeability. PDAC cells promote endothelial angiogenesis or permeability via miR-210 transmission by tumor exosomes. Exosomal miR-210 promotes PDAC progression in vivo. Further detection of PDAC plasma exosomal miR-210 suggests that exosomal miR-210 expression was high and significantly associated with vascular invasion and TNM stage and was an independent risk factor for PDAC overall survival. Conclusions: PDAC cell-secreted exosomes could promote angiogenesis and cellular permeability of neighboring endothelial angiogenesis or permeability via miR-210 transmission. Exosomal miR-210 may play important roles in tumor biology and may be a useful prognostic marker in PDAC.

DNA Methylation Expression Profile of Blood Heat Syndrome and Blood Stasis Syndrome in TCM Psoriasis.

Objective: Traditional Chinese medicine (TCM) emphasizes treatment based on syndrome differentiation. This study aimed to clarify the characteristics of DNA methylation expression profiles in peripheral blood mononuclear cells (PBMCs) in patients with psoriasis and analyze the differences in these profiles among different TCM syndromes of psoriasis in order to provide a material basis for the diversity of these syndromes. Methods: Blood samples were collected from 32 participants, including 14 patients with psoriatic blood heat syndrome (BHS), 12 patients with psoriatic blood stasis syndrome (BSS), and 6 healthy controls. PBMCs were extracted and subjected to DNA quality inspection. An Illumina Human Methylation 850k chip was used to sequence each group of samples. According to gene annotation classification together with CpG island annotation classification, the differentially methylated regions between sample groups were screened, while Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were applied to perform functional analyses of DMGs. Finally, the DMGs closely correlating with psoriatic severity were screened using Spearman's correlation analysis. Results: Compared with normal controls, patients with psoriasis showed an overall trend of hypermethylation. In psoriasis, the differential methylation probes were mainly distributed on gene body region on the genome, while those in CpG regions were mainly distributed in CpG islands. Compared with healthy controls, the overall trends in methylation were similar in psoriatic BHS and BSS patients compared to healthy controls. However, bioinformatic analysis revealed different functions of DMGs. We also found that the methylation levels of TRIM14 and PRDM16 were closely correlated with PASI scores and could serve as potential biomarkers to assess the severity of psoriasis. Conclusions: Our study, for the first time, indicated the possible involvement of DNA methylation in regulating the characteristics of TCM syndromes of psoriasis, providing a new direction for research into TCM psoriatic syndromes.

Fibrinogen-Like Protein 1 as a Novel Biomarker of Psoriasis Severity.

Background: Psoriasis is an immune-mediated chronic systemic inflammatory skin disease whose diagnosis and severity assessment pose challenges for clinicians worldwide. The use of serum biomarkers facilitates the early diagnosis and treatment of psoriasis. Methods: This case-control study compared tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-17, IL-10, and fibrinogen-like protein 1 (FGL1) levels of 139 untreated psoriasis patients and 140 healthy controls. Serum samples were collected, and enzyme-linked immunosorbent assays were performed to quantify their levels. Subgroups were analyzed according to abnormal lipid metabolism status. Results: Compared to controls, patients with psoriasis exhibited lower concentrations of serum TNF-α, IL-17, and FGL1 (P < 0.05). A correlation analysis showed that FGL1 was inversely correlated with high-density lipoprotein cholesterol and IL-17 in the psoriatic state. Stepwise multiple regression analysis revealed that FGL1 and total cholesterol were the independent determinants of Psoriasis Area and Severity Index (PASI) score in psoriasis patients. The area under the receiver operating characteristic curve of FGL1 assessing moderate-to-severe psoriasis and mild psoriasis was 0.70, while the area under the curve (AUC) assessing severe psoriasis and mild-to-moderate psoriasis was 0.67, better than that of IL-17. In addition, FGL1, but not IL-17, was able to identify psoriasis with abnormal lipid metabolism to a certain extent (AUC = 0.60). Conclusion: In conclusion, serum FGL1 may be a promising biomarker for diagnosing and staging psoriasis. It may also be involved in its progression and comorbid abnormal lipid metabolism.