Synthetic Antibacterial Quaternary Phosphorus Salts Promote Methicillin-Resistant Staphylococcus aureus-Infected Wound Healing.

Background: Drug-resistant microbes pose a global health concern, requiring the urgent development of effective antibacterial agents and strategies in clinical practice. Therefore, there is an urgent need to explore novel antibacterial materials to effectively eliminate bacteria. The synthesis of quaternary phosphonium salt in haloargentate systems, wherein the phosphorus atom is represented in a cationic form, is a possible strategy for the development of antibacterial materials. Methods: Using (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 4, 6) as a template, we designed three kinds of quaternary phosphorus salts as effective antibacterial agents against drug-resistant bacteria. Results: The synthesized quaternary phosphorus salt of (1,4-DBTPP)Br2 effectively prevented the formation of the bacterial biofilms, and degraded bacterial membranes and cell walls by promoting the production of reactive oxygen species, which exhibited effective therapeutic effects in a rat model of a superficial wound infected with methicillin-resistant Staphylococcus aureus. Conclusion: The quaternary phosphorus salt (1,4-DBTPP)Br2 demonstrated hemocompatibility and low toxicity, revealing its potential in the treatment of clinical infections.

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.

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).

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.

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.

An overview of COVID-19.

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China in December 2019. By Feb. 11, 2020, the World Health Organization (WHO) officially named the disease resulting from infection with SARS-CoV-2 as coronavirus disease 2019 (COVID-19). COVID-19 represents a spectrum of clinical manifestations that typically include fever, dry cough, and fatigue, often with pulmonary involvement. SARS-CoV-2 is highly contagious and most individuals within the population at large are susceptible to infection. Wild animal hosts and infected patients are currently the main sources of disease which is transmitted via respiratory droplets and direct contact. Since the outbreak, the Chinese government and scientific community have acted rapidly to identify the causative agent and promptly shared the viral gene sequence, and have carried out measures to contain the epidemic. Meanwhile, recent research has revealed critical aspects of SARS-CoV-2 biology and disease pathogenesis; other studies have focused on epidemiology, clinical features, diagnosis, management, as well as drug and vaccine development. This review aims to summarize the latest research findings and to provide expert consensus. We will also share ongoing efforts and experience in China, which may provide insight on how to contain the epidemic and improve our understanding of this emerging infectious disease, together with updated guidance for prevention, control, and critical management of this pandemic.

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.

Efficacy and Safety of Tripterygium Wilfordii Hook F on Psoriasis Vulgaris: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Psoriasis is a chronic autoimmune-mediated skin disease that is characterized by persistent localized erythematous scaly plaque. Tripterygium wilfordii Hook F (TwHF), a well-known Chinese medicine that has been used for centuries in China to treat immune diseases, inflammation, and tumor, is accompanied by a degree of toxic effects. Its clinical efficacy and safety on psoriasis are incompletely understood. AIM: To summarize evidence concerning the efficacy and safety of TwHF in treating psoriasis. Methods. EMBASE, Ovid MEDLINE, PubMed, Web of Science, Springer, Cochrane Library, CNKI, CBM, Wanfang, and VIP database were searched up to October 2017. The included literature was assessed and extracted by two independent reviewers. To enhance the available evidence, a systematic review was performed to examine all relevant published literature relating to randomized controlled trials (RCTs) of TwHF. Relative ratios (RRs) and 95% confidence intervals (CIs) were calculated, and a meta-analysis was conducted with RevMan 5.3 software. RESULTS: Twenty eligible RCTs with 1872 participants were included for systematic review and meta-analysis. Studies were assessed using the Cochrane risk of bias tool. The meta-analysis of add-on effect of TwHF conferred benefit for psoriasis: combination treatment with compound glycyrrhizin (four studies, OR = 0.34, 95% CI 0.22-0.52, P < 0.00001, I2 = 0%), combination treatment with acitretin (three studies, OR = 0.25, 95% CI 0.10-0.63, P = 0.003, I2 = 50%), and combination treatment with compound amino-polypeptide tablet (three studies, OR = 0.37, 95% CI 0.22-0.63, P = 0.0002, I2 = 0%). CONCLUSIONS: Despite several mild side effects of TwHF, there is evidence that TwHF is an effective therapy for psoriasis. However, the conclusions are limited by the small number of included trials. More well-designed RCTs with extensive follow-up periods are warranted to clarify the effects and safety of TwHF in treating psoriasis. TRIAL REGISTRATION: This review was registered in the International Prospective Register of Systematic Reviews (CRD42016041363).

The Instrument for Measuring the Implementation Situation of Traditional Chinese Medicine Guideline: Evaluation and Application.

Clinical practice guidelines play an important role in reducing the variations in clinical practices and improving the quality of care. To assess the real effect, measuring its implementation situation is needed. The implementation situation can be reflected by testing the consistency between the actual clinical practice and the guideline. We constructed an instrument to measure the implementation situation of Traditional Chinese Medicine (TCM) guideline through consistency testing. The main objectives of our study were to validate the instrument and evaluate the implementation situation of menopause syndrome guideline of TCM, using the data from the consistency test of comparing the medical records with the guideline. A total of 621 cases were included for data analysis. Cronbach's Alpha coefficient is 0.73. The model fit of 7 items in four dimensions was good (SRMR = 0.04; GFI = 0.97; NFI = 0.97; TLI = 0.96; CFI = 0.98; AGFI = 0.90). This instrument is of good reliability and validity. It can help the guideline developers to measure the implementation situation, find the reasons affecting the implementation, and revise the guideline. The method of using consistency test to measure the implementation situation may provide a sample for evaluating the guideline implementation in other fields.

Oral Chinese herbal medicine for psoriasis vulgaris: protocol for a randomised, double-blind, double-dummy, multicentre clinical trial.

INTRODUCTION: Psoriasis vulgaris is a common skin disease that is characterised by persistent localised erythematous scaly plaques. Yinxieling is a Chinese herbal formula for psoriasis that has been used for more than 20 years in China. To facilitate application, PSORI-CM01 was developed based on the optimisation and simplification of Yinxieling tablets performed in a previous study and in clinical practice. However, the scientific evidence regarding whether PSORI-CM01 is more effective for psoriasis than the original Yinxieling remains insufficient. Therefore, we designed a randomised clinical trial to investigate the effect, safety and cost-effectiveness of PSORI-CM01 granules compared with those of Yinxieling tablets for the treatment of patients with psoriasis. METHODS AND ANALYSIS: This ongoing study is a two-arm parallel, randomised, double-blind, double-dummy clinical trial. Five hundred and fifty-six participants with psoriasis will be recruited and then randomly allocated into two groups in a 1:1 ratio. Participants in PSORI-CM01 group will receive a 5.5 g granule of PSORI-CM01 two times daily and five placebo tablets three times daily for 12 weeks. The participants in the Yinxieling group will receive five Yinxieling tablets three times daily and a placebo granule two times daily for 12 weeks. The primary outcome is the reduction of the Psoriasis Area and Severity Index. The secondary outcomes include relapse rate, Visual Analogue Scale scores, body surface area and the Dermatology Life Quality Index. Cost-effectiveness analysis will be performed from a health and community care provider perspective. ETHICS AND DISSEMINATION: This research protocol had been reviewed and approved by the institutional review boards of three trial centres (Guangdong Provincial Hospital of Chinese Medicine (B2014-026-01), Affiliated Hospital of Tianjin Chinese Medicine Academy (2014-KY-001) and Third Hospital of Hangzhou (B2014-026-01)). The findings will be disseminated to the public through conference presentations and open-access journals. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR-TRC-14005185); Pre-results.

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.

Acupuncture therapies for psoriasis vulgaris: a systematic review of randomized controlled trials.

The purpose of this review was to evaluate the efficacy and safety of acupuncture therapies in the treatment of psoriasis vulgaris. Embase, CENTRAL, PubMed, AMED, CINAHL, CNKI, CQVIP, CBM, and Wanfang databases were searched from inceptions to May 2013 for prospective randomized controlled trials evaluating acupuncture therapies for psoriasis vulgaris. No language limitations were applied. Studies were assessed using the Cochrane risk of bias tool. The primary outcome was Psoriasis Area Severity Index (PASI) score. Six studies (involving 522 participants) met the eligibility criteria for this review, and 5 were included in quantitative analysis. Due to the diversity of interventions, comparators and reported outcomes, meta-analysis was not possible. Results from single studies produced conflicting results for the outcomes PASI reduction, lesion reduction (non-PASI), PASI score, and relapse rate. There is some evidence of benefit of acupuncture therapies for the treatment of psoriasis vulgaris. However, the conclusions are limited by the small number of included trials and conflicting results from single studies. More research is needed to clarify the effect of acupuncture therapies for psoriasis vulgaris.

Application of metabolomics on diagnosis and treatment of patients with psoriasis in traditional Chinese medicine.

Traditional Chinese medicine (TCM) is one of the oldest forms of medical system. With syndrome as the core of diagnosis and therapy in TCM, it has the advantage of collecting macroscopic information of patients for diagnosis. To understand the in vivo mechanism of TCM, a metabolomics approach was used to investigate the global biological characterization of the urine of psoriasis patients with Blood Stasis Syndrome and the therapeutic metabolomics mechanism of the Optimized Yinxieling formula. A total of 41 cases of psoriasis patients with Blood Stasis Syndrome and 19 healthy volunteers were enrolled in this study. Fasting urine samples from patients with consecutive Optimized Yinxieling intake after 0, 4, 8 and 12 weeks and from healthy volunteers were analyzed by Orthogonal Projection on Latent Structures Discriminant Analysis (OPLS-DA), which was utilized for High Performance Liquid Chromatography (HPLC) analysis and temporal metabolic changes identification. For psoriasis group, the scores of PASI of patients decreased after 12 weeks of Optimized Yinxieling treating. The metabolic variations visualized not only in the healthy group and psoriasis group, but also in the psoriasis group before and after Optimized Yinxieling treatment, demonstrated that the metabolic characteristics of the two groups were significantly different. The optimized complex structure of the target proteins from Protein Data Bank was analyzed by software package Discovery Studio. With docking score of original inhibitor and the receptor as the threshold values, two compounds from Chinese medicinal chemical database were predicted to have good interactions with the target proteins. The Metabolomics technique combining molecular docking analysis enhanced our current understanding of the metabolic response to Blood Stasis Syndrome of Psoriasis and the action mechanism of Optimized Yinxieling. This article is part of a Special Issue entitled: Computational Proteomics, Systems Biology & Clinical Implications. Guest Editor: Yudong Cai.

Disease-syndrome combination clinical study of psoriasis: present status, advantages, and prospects.

Psoriasis is an immune-abnormal, chronic, proliferative skin disease determined by polygenic inheritance and induced by a number of environmental factors. It causes worldwide concern because of its high-prevalence, harmful and incurable characteristics. Over the years, Chinese medicine (CM) treatment of psoriasis has accumulated a wealth of clinical experience. Disease-syndrome combination, which achieves more satisfactory clinical effect, is the basis to highlight the special CM advantages in treating psoriasis. In this paper, we review the advantages of treating psoriasis with the combination of disease and syndrome, analyze the prospects of research on treating psoriasis combining disease with syndrome. We also make a point that there are several key points for the clinical research of combination of disease and syndrome. It can be expected that carrying out clinical research on the combination of disease and syndrome will help improve the clinical efficacy of medical treatment of psoriasis, which will be the main direction of research in the future.