Methotrexate and electrostimulation cooperate to alleviate the relapse of psoriasiform skin inflammation by suppressing memory T cells.

Methotrexate (MTX) is an immunosuppressant used to treat autoimmune diseases, including psoriasis. However, like other immunosuppressants, MTX alone does not prevent their recurrence. Electrostimulation (ES) has been utilized to treat some inflammatory disorders without any major side-effect. But it remains unknown if ES alone, or together with MTX, ameliorates autoimmune disease relapse: a sticky medical problem. In particular, the mechanisms underlying ES action remain unclear. The objective of this study was to determine an impact of ES and/or MTX on psoriasis relapse and their potential cooperation. We found that regional ES, but not MTX, ameliorated psoriasiform skin inflammation recurrence. Interestingly, treatment with both MTX and ES further prevented psoriasis recurrence compared to ES alone. Moreover, ES downregulated potassium channel Kv1.3 on T-cells and reduced CD4+/CD8+ effector memory (TEM) and CD8+ skin-resident memory T (TRM) cells, while ES plus MTX further decreased CD8+ TEM/TRM cells compared to ES alone. However, ES failed to further attenuate psoriasis recurrence or suppress T cell memory in Kv1.3-deficient mice, whereas lack of Kv1.3 itself ameliorated psoriasis relapse by shrinking T cell memory pool. Importantly, ES moderately inhibited T-cell proliferation in vitro. ES also reduced human CD8+ TRM cells and attenuated human skin lesions in humanized mice grafted with lesional skin from patients with recurrent psoriasis, with an enhanced efficacy in mice treated with both ES and MTX. Thus, ES and MTX cooperated to prevent psoriasis relapse by reducing T-cell memory via targeting potassium channel Kv1.3. Our studies may be implicated for treating human psoriasis.

Potential biomarkers for psoriasis topical treatment by in-depth serum proteomics.

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 < 0.05). Then pathway analysis showed that the responders focused more on signaling molecules and interaction, complement and coagulation cascades, whereas the non-responders more on signal transduction and IL-17 signaling pathways. We further identified four candidate biomarkers (COLEC11, C1QA, BNC2, ITIH4) response to treatment. We also found 125 DEPs (p < 0.05) after treatment compared with before treatment in responder group. Pathway analysis showed an enrichment in pathways related to complement and coagulation cascades, phagosome, ECM-receptor interaction, cholesterol metabolism, vitamin digestion and absorption. CD14 was validated as potential biomarkers for the disease severity of psoriasis and treatment targets. CONCLUSION: In this work, we analyzed the response to topical sequential therapy and finally identified four biomarkers. Additionally, we found that topical sequential therapy may alleviate psoriasis by regulating lipid metabolism and modulating the immune response by affecting the complement activation process.

Microglial LRRK2-mediated NFATc1 attenuates α-synuclein immunotoxicity in association with CX3CR1-induced migration and the lysosome-initiated degradation.

Synucleinopathies refer to a range of neurodegenerative diseases caused by abnormal α-synuclein (α-Syn) deposition, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Their pathogenesis is strongly linked to microglial dysfunction and neuroinflammation, which involves the leucine-rich-repeat kinase 2 (LRRK2)-regulated nuclear factor of activated T-cells (NFAT). Of the NFAT family, NFATc1 has been found to be increasingly translocated into the nucleus in α-syn stimulation. However, the specific role of NFATc1-mediated intracellular signaling in PD remains elusive in regulating microglial functions. In the current study, we crossbred LRRK2 or NFATc1 conditional knockout mice with Lyz2Cre mice to generate mice with microglia-specific deletion of LRRK2 or NFATc1, and by stereotactic injection of fibrillary α-Syn, we generated PD models in these mice. We found that LRRK2 deficiency enhanced microglial phagocytosis in the mice after α-Syn exposure and that genetic inhibition of NFATc1 markedly diminished phagocytosis and α-Syn elimination. We further demonstrated that LRRK2 negatively regulated NFATc1 in α-Syn-treated microglia, in which microglial LRRK2-deficiency facilitated NFATc1 nuclear translocation, CX3CR1 upregulation, and microglia migration. Additionally, NFATc1 translocation upregulated the expression of Rab7 and promoted the formation of late lysosomes, resulting in α-Syn degradation. In contrast, the microglial NFATc1 deficiency impaired CX3CR1 upregulation and the formation of Rab7-mediated late lysosomes. These findings highlight the critical role of NFATc1 in modulating microglial migration and phagocytosis, in which the LRRK2-NFATc1 signaling pathway regulates the expression of microglial CX3CR1 and endocytic degradative Rab7 to attenuate α-synuclein immunotoxicity.

Association of the characteristics of the blood metabolome and gut microbiome with the outcome of methotrexate therapy in psoriasis.

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.

Imaging characteristics of a rare case of monostotic fibrous dysplasia of the sacrum: A case report.

BACKGROUND: Fibrous dysplasia (FD) is a common benign intramedullary fibro-osseous lesion. Involvement of the spine is rare, with the literature including only case reports, and cases of monostotic FD (MFD) in the sacrum are extremely rare. A correct preoperative diagnosis of spinal MFD is important for clinicians to select proper treatment. CASE SUMMARY: We retrospectively assessed a case report of MFD in the sacrum. This patient was examined by computed tomography (CT) and magnetic resonance imaging (MRI), and the diagnosis was confirmed by pathology. A review of the literature was performed to analyze the imaging characteristics and differential diagnoses of spinal MFD. For our patient, the CT scan showed the lesion to be expansile, with ground glass opacity and a sclerotic rim. On MRI, the lesion showed iso-low signal intensity on T1WI and iso-high signal intensity on T2WI. A low signal rim was found on T1WI and T2WI. Our patient was treated by posterior focal excision, decompression, bone grafting, fusion and pedicle screw fixation. A satisfactory result was achieved, with pain disappearance. No complications had occurred at the 1-year follow up. CONCLUSION: MFD is an expansile osteolytic change. Ground glass opacity and a sclerotic margin are obvious characteristics. The lesion often involves the vertebral body and posterior element. Knowledge of these imaging characteristics of spinal FD could be helpful for diagnosis and prevent unnecessary procedures.

Comparison of PSORI-CM01 granules and Yinxieling tablets for patients with chronic plaque psoriasis: a pilot study for a randomized, double-blinded, double-dummy, multicentre trial.

BACKGROUND: To compare the efficacy and safety of PSORI-CM01 granules with Yinxieling tablets in patients with chronic plaque psoriasis (CPP), we plan to conduct a multicentre, randomized, double-blinded, double-dummy, controlled trial. This pilot study was conducted to determine the feasibility and the potential of the protocol for the full-scale randomized controlled trial (RCT). METHODS: This pilot study was conducted in three centers, and compared PSORI-CM01 granules with Yinxieling tablets in patients with CPP during a 12-week treatment and 3-month follow-up period. The primary efficacy endpoint was the decrease of the psoriasis area severity index (PASI) at week 12. The secondary outcome measures included reduction rates of PASI, pruritus scores on the Visual Analogue Scale (VAS), body surface area (BSA), and the Dermatology Life Quality Index (DLQI). Safety was assessed via the incidence of adverse events (AEs) in each treatment group. RESULTS: A total of 211 patients were screened, and 63 subjects who met the inclusion criteria were randomised to PSORI-CM01 granule group (N=31) or Yinxieling tablets group (N=32) while 39 subjects finished the study. The primary outcome measure showed a mean decrease of PASI of 2.03 in the PSORICM01 group compared to 0.89 in the Yinxieling group at week 12. Except for the VAS score (t=-2.261, P=0.027), the secondary outcomes showed no significant improvement from baseline in both groups at week 12. No safety or tolerability concerns related to the drugs were observed in either group. CONCLUSIONS: This pilot study showed that the RCT is feasible for randomization, patient recruitment, and assessment. Major strategies are necessary to reduce the patient dropout rate before conducting the full RCT. In this pilot study, the PSORI-CM01 granule exhibited greater potential for development compared to its original formula (Yinxieling tablets) for the treatment of CPP.

Add-on effect of PSORI-CM01 to topical calcipotriol for moderate psoriasis vulgaris: A multi-center, randomized, double-blind pilot study.

BACKGROUND: Mild-moderate psoriasis vulgaris is a common dermatological autoimmune condition with limited conventional therapeutic options. Safe and effective adjunct therapies to topical non-steroidal antipsoriatic therapy are needed. The oral Chinese herbal medicine (CHM) formula PSORI-CM01 has been evidenced potential antipsoriatic pharmacological activity. This article reports a pilot study which was designed as a double-blinded, placebo-controlled randomized controlled trial (RCT) evaluating the effects of PSORI-CM01 when added to topical calcipotriol cream. METHODS: People with moderate psoriasis vulgaris were randomized to receive oral PSORI-CM01 or placebo administered for 12 weeks in combination with calcipotriol. The primary clinical outcome was the change of psoriasis area severity index (PASI) score at week 12 and week 24. Secondary clinical outcomes were PASI75, PASI50, relapse rate, change in body surface area, dermatology life quality index and Skindex29, and adverse events (AEs). Participants' satisfaction and willingness to repeat were also assessed. RESULTS: The pilot study was conducted in Australia and China, 29 participants were randomized with 26 completed the treatment and follow-up. Participants' baseline basic characteristics were comparable. No between-group statistical significance was found on pre-defined clinical outcome measures, although there seemed a trend of treatment effects favoring the combination of PSORI-CM01 with calcipotriol. Frequency and severity of AEs were similar between two groups, with no severe AEs reported. CONCLUSIONS: The design and duration of the study appears feasible. A proper powered RCT with slight adjustments in the methods is needed to reveal the add-on effects of oral CHM PSORI-CM01. The experience and results from this pilot study will contribute to the refine of objectives and design of a future study, and assist the sample size calculation for the full-scale RCT.

P. granatum Peel Polysaccharides Ameliorate Imiquimod-Induced Psoriasis-Like Dermatitis in Mice via Suppression of NF-κB and STAT3 Pathways.

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-1ß, 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.

The Gene Expression Analysis of Peripheral Blood Monocytes From Psoriasis Vulgaris Patients With Different Traditional Chinese Medicine Syndromes.

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).

Metagenomic Analysis Reveals the Distribution of Antibiotic Resistance Genes in a Large-Scale Population of Healthy Individuals and Patients With Varied Diseases.

The human gut microbiome is a reservoir for antibiotic resistance gene (ARG). Therefore, characterizing resistome distribution and potential disease markers can help manage antibiotics at the clinical level. While much population-level research has highlighted the strong effect of donor geographic origin on ARG prevalence in the human gut, little is known regarding the effects of other properties, such as age, sex, and disease. Here we employed 2,037 fecal metagenomes from 12 countries. By quantifying the known resistance genes for 24 types of antibiotics in each community, we showed that tetracycline, aminoglycoside, beta-lactam, macrolide-lincosamide-streptogramin (MLS), and vancomycin resistance genes were the dominant ARG types in the human gut. We then compared the ARG profiles of 1427 healthy individuals from the 2,037 samples and observed significant differences across countries. This was consistent with expectations that regional antibiotic usage and exposure in medical and food production contexts affect distribution. Although no specific uniform pattern of ARG was observed, a significant increase in resistance potential among multiple disease groups implied that the disease condition may be another source of ARG variance. In particular, the co-occurrence pattern of some enriched bacterial species and ARGs that were obtained in type 2 diabetes (T2D) and liver cirrhosis patients implied that some disease-associated species may be potential hosts of enriched ARGs, which could be potential biomarkers for the prediction and intervention of such diseases. Overall, our study identifies factors associated with the human gut resistome, including substantial effects of region and heterogeneous effects of disease status, and highlights the value of ARG analysis in disease research and clinical applications.

Metabonomics Study on Serum Characteristic Metabolites of Psoriasis Vulgaris Patients With Blood-Stasis Syndrome.

Psoriasis is a chronic, refractory, systemic inflammatory skin disease. Traditional Chinese medicine (TCM) shows unique advantage in the treatment of psoriasis based on syndrome differentiation. An untargeted high-throughput metabonomics method based on liquid chromatography coupled to mass spectrometry was applied to study the serum metabolic characteristics in different TCM syndrome types in patients with psoriasis vulgaris (PV), and to discover potential serum biomarkers for its pathogenesis on the endogenous metabolite differentiation basis. The serum metabolic profiles of 45 healthy controls and 124 patients with PV (50 in the blood-stasis group, 30 in the blood-heat group, and 44 in the blood-dryness group) were acquired. The raw spectrometric data were processed using multivariate statistical analysis, and 14 biomarkers related to TCM syndrome differentiation and psoriasis types were screened and identified. The blood-stasis syndrome group showed abnormal lipid metabolism, which was characterized by a low level of phosphatidylcholine (PC) and a high level of lysophosphatidylcholine (LPC). We propose that platelet-activating factor can be applied as a potential biomarker in clinical diagnosis and differentiation of PV with blood-stasis syndrome. The difference in the serum metabolites among PV types with different TCM syndromes and healthy control group illustrated the objective material basis in TCM syndrome differentiation and classification of psoriasis.

The Protective Effects of 18ß-Glycyrrhetinic Acid on Imiquimod-Induced Psoriasis in Mice via Suppression of mTOR/STAT3 Signaling.

Psoriasis is recognized as an autoimmune and inflammatory dermatosis, which is estimated to affect 2-3% of the population worldwide. 18ß-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-1ß 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.

Dihydroartemisinin ameliorates psoriatic skin inflammation and its relapse by diminishing CD8+ T-cell memory in wild-type and humanized mice.

Conventional immunosuppressants cause side effects and do not prevent the recurrence of autoimmune diseases. Moreover, they may not inhibit autoimmunity mediated by pathogenic memory T-cells. Dihydroartemisinin (DHA) has been shown to regulate autoimmunity. However, it remains unknown whether DHA impacts psoriasis and its recurrence. The objective of this study was to determine therapeutic effects of DHA on psoriasis and its relapse as well as its underlying mechanisms. Methods: We established animal models of imiquimod (IMQ)-induced psoriasis-like wild-type mice and humanized NSG mice receiving lesional human skin from patients with psoriasis. Many immunoassays, including immunohistochemistry, flow cytometry, quantitative RT-PCR and Western blotting, were performed. Results: We found that DHA not only ameliorated acute skin lesion of psoriatic mice, but also alleviated its recurrence by diminishing CD8+ central memory T (TCM) and CD8+ resident memory T (TRM) cells. It attenuated epidermal pathology and T-cell infiltration in the skin of IMQ-induced psoriatic mice while suppressing expression of IL-15, IL-17 and other proinflammatory cytokines in the skin. Surprisingly, DHA reduced the frequency and number of CD8+, but not CD4+, subset of CD44highCD62Lhigh TCM in psoriatic mice, whereas methotrexate (MTX) lowered CD4+, but not CD8+, TCM frequency and number. Indeed, DHA, but not MTX, downregulated eomesodermin (EOMES) and BCL-6 expression in CD8+ T-cells. Furthermore, DHA, but not MTX, reduced the presence of CD8+CLA+, CD8+CD69+ or CD8+CD103+ TRM cells in mouse skin. Interestingly, treatment with DHA, but not MTX, during the first onset of psoriasis largely prevented psoriasis relapse induced by low doses of IMQ two weeks later. Administration of recombinant IL-15 or CD8+, but not CD4+, TCM cells resulted in complete recurrence of psoriasis in mice previously treated with DHA. Finally, we demonstrated that DHA alleviated psoriatic human skin lesions in humanized NSG mice grafted with lesional skin from psoriatic patients while reducing human CD8+ TCM and CD103+ TRM cells in humanized mice. Conclusion: We have provided the first evidence that DHA is advantageous over MTX in preventing psoriasis relapse by reducing memory CD8+ T-cells.

Corrigendum: PSORI-CM02 Formula Increases CD4+ Foxp3+ Regulatory T Cell Frequency and Ameliorates Imiquimod-Induced Psoriasis in Mice.

[This corrects the article DOI: 10.3389/fimmu.2017.01767.].

Analysis of microRNA expression in peripheral blood monocytes of three Traditional Chinese Medicine (TCM) syndrome types in psoriasis patients.

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.

[Adsorption Properties of Ammonia Nitrogen in Aqueous Solution by Various Materials].

Focusing on the removal of ammonia nitrogen from polluted water, the absorption properties of five materials (zeolite, maifanite, diatomite, bentonite, and activated carbon) were tested. Results showed that the pseudo-second-order kinetic equation was suitable for data fitting for the five materials. The maximum theoretical adsorption capacities of the five materials were 2.0673 mg·g-1, 0.9982 mg·g-1, 0.7580 mg·g-1, 1.7486 mg·g-1, and 1.0160 mg·g-1, respectively, which were close to the experimental value. Chemical-based adsorption was the main mode of adsorption. Data for diatomite were fitted using the Langmuir isotherm equation, and belonged to the single-layer molecular adsorption group, while the other four materials were fitted using the Freundlich isotherm equation, belonging to the multi-layer molecular adsorption group. Moreover, the results showed that the removal rates of ammonia nitrogen by zeolite, diatomite, bentonite, and activated carbon increased with an increase in dosage, and the maximum removal rates were 100%, 10.46%, 49.25%, and 16.87%, respectively. A maifanite dosage of 0.4g achieved the maximum removal rate of 48.85%. At pH 4-10, the adsorption capacities of zeolite and maifanite first increased and then decreased, while that of diatomite, bentonite, and activated carbon slowly increased. The desorption capacity of the five tested materials increased with an increase in the initial concentration of ammonia nitrogen.

Auricular acupressure as a complementary therapy for psoriasis vulgaris: study protocol for a multicenter randomized controlled trial.

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.

In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine.

Serum and plasma contain abundant biological information that reflect the body's physiological and pathological conditions and are therefore a valuable sample type for disease biomarkers. However, comprehensive profiling of the serological proteome is challenging due to the wide range of protein concentrations in serum. Methods: To address this challenge, we developed a novel in-depth serum proteomics platform capable of analyzing the serum proteome across ~10 orders or magnitude by combining data obtained from Data Independent Acquisition Mass Spectrometry (DIA-MS) and customizable antibody microarrays. Results: Using psoriasis as a proof-of-concept disease model, we screened 50 serum proteomes from healthy controls and psoriasis patients before and after treatment with traditional Chinese medicine (YinXieLing) on our in-depth serum proteomics platform. We identified 106 differentially-expressed proteins in psoriasis patients involved in psoriasis-relevant biological processes, such as blood coagulation, inflammation, apoptosis and angiogenesis signaling pathways. In addition, unbiased clustering and principle component analysis revealed 58 proteins discriminating healthy volunteers from psoriasis patients and 12 proteins distinguishing responders from non-responders to YinXieLing. To further demonstrate the clinical utility of our platform, we performed correlation analyses between serum proteomes and psoriasis activity and found a positive association between the psoriasis area and severity index (PASI) score with three serum proteins (PI3, CCL22, IL-12B). Conclusion: Taken together, these results demonstrate the clinical utility of our in-depth serum proteomics platform to identify specific diagnostic and predictive biomarkers of psoriasis and other immune-mediated diseases.

Betulinic acid suppresses Th17 response and ameliorates psoriasis-like murine skin inflammation.

Psoriasis is a common inflammatory skin disease. Current treatment for psoriasis relies on conventional immunosuppressive agents. However, long-term treatment with global immunosuppression may cause various side effects. Thus, it is compelling to seek alternative drugs for treating psoriasis with potentially less side effects. Betulinic acid (BA) is a naturally occurring pentacyclic triterpene, an ingredient that originally exists in natural plants and lacks systemic toxicity. BA can regulate immunity with anti-fibrotic, anti-inflammatory and antioxidant properties. However, it's unknown whether BA has a therapeutic effect on psoriasis. The objectives of this study were to investigate whether BA attenuates psoriatic skin inflammation and to identify its mechanisms of action. A murine model of imiquimod-induced psoriasis was utilized to evaluate skin lesion while flow cytometry, immunohistochemistry, quantitative RT-PCR and Western blotting analyses were performed for immunoassays. We found that BA treatment alleviated psoriatic symptoms and inflammatory skin lesion. BA lowered the PASI scores, decreased epidermal thickness and reduced T cell infiltration in the skin lesion. Moreover, BA reduced the frequency of IL-17A-expressing CD4+ and γδ T cells in psoriatic mice, but did not alter CD4+FoxP3+ Treg frequency. BA also reduced IL-17A production but increased anti-inflammatory cytokine IL-10 level in serum of the psoriatic mice. Furthermore, BA inhibited gene expression of pro-inflammatory mediators in skin lesions, including RORγt, IL-17A, IL-6 and TNFα. Importantly, it suppressed NFκB signaling in the skin lesion. Finally, BA inhibited T cell proliferation and IL-17A production by CD4+ T-Cells in vitro. Thus, BA attenuates psoriasis and inhibits Th17 development.

Using animated vehicles with real emotional faces to improve emotion recognition in Chinese children with autism spectrum disorder.

The objective of the present study was to conduct an intervention study which aimed to improve emotion recognition for Chinese children with ASD by using animated vehicles with real emotional faces. A total of 21 children participated in the current study; participants consisted of 14 children (2 girls) with a formal diagnosis of ASD and 7 typically developing children. Participants were measured on emotional vocabulary and situation-facial expression matching before and after the intervention. Results indicated that the intervention significantly improved ASD children's emotion recognition compared to their pre-intervention scores. Our findings suggest that this emotional recognition intervention using animated vehicles (i.e. The Transporters) is an effective early intervention for Chinese children with ASD.