The Benefit of the Optimized Formula of Yinxieling in Psoriasis Vulgaris via Regulation on Autophagy Based on microRNA Expression Profile and Network Pharmacology Analysis.

Background: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored. Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression. Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy. Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.

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.

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.

[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.

Role of an imbalanced miRNAs axis in pathogenesis of psoriasis: novel perspectives based on review of the literature.

BACKGROUND: Specific profile of microRNAs (miRNAs, miR) expressed in psoriasis has been identified in the past few years, while the studies on roles and molecular mechanisms of these miRNAs are still on the way. In our previous study, four specific miRNAs (miR-31, miR-203, hsa-miR-99a and miR-125b) were found to be specifically altered in psoriatic lesions.We therefore conducted a systematic literature review in this study to reveal the role of these miRNAs in the pathogenesis of psoriasis in order to inform future research. METHODS: The related articles indexed in PubMed (MEDLINE) database were searched and analyzed. We identified eligible studies related to the mechanism research of miR-31, miR-203, hsa-miR-99a and miR-125b in psoriasis or psoriatic lesional skin from inception up to July 2016. The experts in the field of miRNAs and Psoriasis were involved in analysis process. RESULTS: Both miR-31 and miR-203 are dramatically upregulated in psoriatic lesions. The former plays the pro-proliferative, pro-differentiative and pro-inflammatory roles and the latter holds the potentials for anti-proliferation, pro-inflammation and pro-differentiation in psoriatic keratinocytes. Conversely, both hsa-miR-99a and miR-125b are significantly downregulated in psoriatic skin. These two miRNAs are able to inhibit proliferation while promote differentiation of psoriatic keratinocytes, and miR-125b can also suppress inflammation in psoriatic lesions. By analyzing the contexts related to these miRNAs, we found that each of them does not act alone but rather work in concert with other miRNAs. The imbalance between miR-31/miR-203and hsa-miR-99a/miR-125b may contribute to the intense proliferation and abnormal differentiation of psoriatic keratinocytes, which is a characteristic of pathogenesis of psoriasis. CONCLUSION: An imbalanced miRNAs axis was for the first time outlined. Apparently, upregulation of miR-31/miR-203 and downregulation of hsa-miR-99a/miR-125b work together in concert to facilitate the development of psoriasis pathogenesis. Further work in this field holds the potentials to open a new way to study psoriasis.

Oral PSORI-CM01, a Chinese herbal formula, plus topical sequential therapy for moderate-to-severe psoriasis vulgaris: pilot study for a double-blind, randomized, placebo-controlled trial.

BACKGROUND: To provide evidence that the Chinese herbal medicine (CHM) PSORI-CM01 combined with Western medicine reduces the relapse rate of psoriasis vulgaris (PV), we plan to conduct a large-scale randomized control trial (RCT). In order to improve and perfect the RCT, this pilot study was designed to determine the feasibility and the potential of a modified protocol for the full-scale RCT. METHODS: Eligible patients with psoriasis vulgaris (PV) were enrolled into a randomized comparison in which all subjects received topical sequential therapy and PSORI-CM01 or placebo for 12 weeks. The primary outcome measure was the relapse rate. Treatment response was computed from Psoriasis Area and Severity Index (PASI), body surface area (BSA), and Dermatology Life Quality Index (DLQI). The secondary outcome measures included time to relapse, time to onset, rebound rate, PASI score, pruritus scores on the Visual Analog Scale (VAS), BSA, DLQI and SF-36 (short form health survey), and incidence of serious adverse events (SAEs). RESULTS: Six of 7 (86 %) subjects reached the PASI-50 in the CHM group compared with nine of 10 (90 %) in the placebo group during the treatment period. Among the subjects who reached PASI-50, one out of six subjects (17 %) relapsed in the CHM group during the treatment period compared with six out of nine patients in the placebo group (67 %). No subjects met the rebound criteria. Changes to baseline in the PASI scores were not significantly different between the two groups (t = 1.764, P = 0.098). CONCLUSION: Oral PSORI-CM01 combined with topical sequential treatment showed a smaller recurrence rate (P = 0.118) than placebo combined with the same topical therapy for moderate-to-severe PV in this pilot study. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/searchproj.aspx ) ChiCTR-TRC-13003233 ; date of registration: 15 April 2013.

Role of Micro RNAs in the Pathogenesis of Rheumatoid Arthritis: Novel Perspectives Based on Review of the Literature.

The contributions of micro RNAs (miRNAs) to rheumatoid arthritis (RA) are beginning to be uncovered during the last decade. Many studies in efforts to use miRNAs as biomarkers in disease diagnosis, prognosis, and treatment are ongoing.We conducted a systematic literature review to reveal the role of miRNAs in the pathogenesis of RA in order to inform future research.We analyzed all the literature which is searched by keywords "microRNA" and "arthritis" in PubMed from December 2007 to June 2015, and the references cited by the articles searched were also considered.Relevant literature focusing on the field of miRNAs and RA was identified. The searching process was conducted by 5 independent investigators. The experts in the field of miRNAs and Rheumatology were involved in the process of analyzing.Relevant literature was analyzed according to the objective of this review and the availability of full text.The crucial role of miRNAs in maintaining immune and inflammatory responses is revealed. In addition, it is now clear that miRNAs are implicated in the development of RA synovial phenotype including synovial hyperplasia and joint destruction. Intriguingly, the biomedical application of several miRNAs may result in the effects of "double-edged sword." Moreover, there appears to have a feedback loop for expression of some miRNAs related to disease activity in inflammatory milieu of rheumatoid joint.This review underscores the potential importance of miRNAs to diagnosis, prognosis, and treatment of RA. Further investigations are required to identify the unique miRNAs signatures in RA and characterize the mechanisms mediated by miRNAs in the pathology of RA.

Chinese medicine combined with calcipotriol betamethasone and calcipotriol ointment for Psoriasis vulgaris (CMCBCOP): study protocol for a randomized controlled trial.

BACKGROUND: Psoriasis causes worldwide concern because of its high-prevalence, as well as its harmful, and incurable characteristics. Topical therapy is a conventional treatment for psoriasis vulgaris. Chinese medicine (CM) has been commonly used in an integrative way for psoriasis patients for many years. Some CM therapies have shown therapeutic effects for psoriasis vulgaris (PV), including relieving symptoms and improving quality of life, and may reduce the relapse rate. However, explicit evidence has not yet been obtained. The purpose of the present trial is to examine the efficacy and safety of the YXBCM01 granule, a compound Chinese herbal medicine, with a combination of topical therapy for PV patients. METHODS/DESIGN: Using an add-on design, the trial is to evaluate whether the YXBCM01 granule combined topical therapy is more effective than topical therapy alone for the treatment of PV. The study design is a double-blind, parallel, randomized controlled trial comparing the YXBCM01 granule (5.5 g twice daily) to a placebo. The duration of treatment is 12 weeks. A total of 600 participants will be randomly allocated into two groups, YXBCM01 granule group and placebo group, from 11 general or dermatological hospitals in China. Topical use of calcipotriol betamethasone for the first 4 weeks and calcipotriol ointment for the remaining 8 weeks will be the same standard therapy for the two groups. Patients will be enrolled if they have a clinical diagnosis of PV, a psoriasis area severe index (PASI) of more than 10 or body surface area (BSA) of more than 10%, but PASI of less than 30 and BSA of less than 30%, are aged between 18 and 65-years-old, and provide signed informed consent. The primary outcome, relapse rate, is based on PASI assessed blindly during the treatment. Secondary outcomes include: (i) relapse time interval, (ii) time to onset, (iii) rebound rate, (iv) PASI score, (v) cumulative consumption of medicine, (vi) the dermatology quality life index (DLQI), and (vii) the medical outcomes study (MOS) item short form health survey (SF-36). Analysis will be on intention-to-treat and per-protocol subject analysis principles. DISCUSSION: To address the effectual remission of the YXBCM01 granule for PV, this trial may provide a novel regimen for PV patients if the granule can decrease relapse rate without more adverse effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry (http://cwww.chictr.org): ChiCTR-TRC-13003233, registered 26 May 2013.