Objective To explore the relationship between the gut microbiome (GM) and psoriasis using a two-sample two-way Mendelian randomization (MR) approach. Methods The forward analysis uses the gut microbiota as the exposure factor, and its genetic data are derived from the genome-wide association study dataset published by the MiBioGen consortium. Psoriasis was used as the outcome variable, and its genetic data were obtained from the UK Biobank. The reverse MR analysis, on the other hand, took psoriasis as the exposure and the specific gut microbiota taxonomic units identified in the forward analysis as the outcome variable. MR analysis was conducted using maximum likelihood, MR Egger regression, weighted median, inverse variance weighting (IVW), and weighted models to study the causal relationship between the gut microbiota and psoriasis. Then, sensitivity analyses including horizontal pleiotropy test, Cochran’s Q test, and leave-one-out analysis were used to evaluate the reliability of the results. Results A total of 51 single nucleotide polymorphisms from 5 fungi were included in the forward study. The forward IVW analysis results showed that, the class Mollicutes [odds ratio (OR)=1.003, 95% confidence interval (CI) (1.001, 1.006), P=0.004], genus Lachnospiraceae FCS020 group [OR=1.003, 95%CI (1.000, 1.006), P=0.041], and phylum Tenericutes [OR=1.003, 95%CI (1.001, 1.006), P=0.004] were causally associated with an increased risk of psoriasis. The family Victivallaceae [OR=0.998, 95%CI (0.997, 1.000), P=0.005] and order Pasteurellales [OR=0.998, 95%CI (0.996, 1.000), P=0.047] were also linked to a decreased risk of psoriasis. The results of the sensitivity analysis were robust. There was no evidence of a reverse causal relationship from psoriasis to the identified bacterial taxa found in the results of reverse MR analysis results. Conclusions The abundance of three species, class Mollicutes, genus Lachnospiraceae and phylum Tenericutes, may increase the risk of psoriasis. The abundance of two species, family Victivallaceae and order Pasteurellales may reduce the risk of psoriasis. These results provide new directions for the prevention and treatment of psoriasis in the future, but further research is needed to explore how the aforementioned microbiome affects the progression of psoriasis.
Objective To analyze whether there is a causal association between psoriasis and Alzheimer disease (AD) by a two-sample two-way Mendelian randomization (MR) method. Methods In the forward study, the single nucleotide polymorphisms (SNPs) associated with psoriasis were obtained from the comprehensive statistical data of the genome-wide association study database as the instrumental variables, and AD as the outcome; in the reverse study, the SNPs associated with AD were taken as instrumental variables, and psoriasis as the outcome. Using two-sample two-way MR analysis, the odds ratio (OR) value and 95% confidence interval (CI) of regression models, namely inverse variance weighted (IVW) method, MR-Egger regression method, weighted median method, simple pattern method, and weighted pattern method, were used to evaluate the causal relationship between psoriasis and AD. Cochran’s Q test was used to assess the heterogeneity of genetic instrumental variables, MR-Egger intercept method was used to test the horizontal pleiotropy of the assessment, “leave-one-out” method was used to assess the sensitivity of a SNP to the effect of causality, and the symmetry of funnel plot was observed to assess bias. Results A total of 19 SNPs associated with psoriasis were included as instrumental variables in the forward study. The IVW analysis of the forward study showed that there was a causal correlation between psoriasis and AD [OR=1.032, 95%CI (1.014, 1.051), P<0.001], and MR-Egger regression method [OR=1.042, 95%CI (1.012, 1.073), P=0.013], weighted median [OR=1.048, 95%CI (1.023, 1.074), P<0.001], and weighted model [OR=1.046, 95%CI (1.020, 1.073), P=0.002] all supported this result. Heterogeneity test (IVW result: Q=13.752, P=0.745; MR-Egger regression result: Q=13.134, P=0.727), MR-Egger intercept method (Egger intercept=–0.004, P=0.442), the results of “leave-one-out” method and funnel plot showed that the results of MR analysis were reliable. A total of 127 AD-related SNPs were included as instrumental variables in the reverse study. In reverse research, there was no evidence to support the AD could increase the risk of psoriasis (P>0.05). Heterogeneity test (IVW result: Q=232.496, P<0.001; MR-Egger regression result: Q=232.119, P<0.001) suggested heterogeneity, but MR-Egger intercept method (Egger intercept=0.003, P=0.652), the results of “leave-one-out” method and funnel plot showed that the results of MR analysis were reliable. Conclusion There is a causal association between psoriasis and AD, and psoriasis may increase the risk of AD.
Objective To assess the relationship between IFN-γ and psoriasis. Methods We searched The Cochrane Library (Issue 3, 2005), MEDLINE (1996 to 2005) and the China Biological Medicine Database (1978 to 2005). The search was conducted in November 2005. The quality of included clinical controlled trials, case studies and cohort studies was evaluated independently by three reviewers. RevMan 4.2.8 software was used. Results In total, 23 studies were included, involving 612 psoriasis patients and 441 healthy controls. All studies did not provide sufficient detail, on the random sampling and the specificity of the kits used for the analyses. Compared with the controls, the serum or plasma IFN-γ in psoriasis patients showed significantly higher levels (SMD=0.89, 95%CI 0.29 to 1.48; and RR=6.20, 95%CI 1.78 to 21.61). The concentration of IFN-γ in supernatant obtained from cultured cells showed slightly higher levels (SMD=0.99, 95%CI -0.01 to 1.99; and RR=5.54, 95%CI 2.03 to 15.13). Conclusion The evidence currently available shows that the increase of IFN-γ may be relevant to psoriasis. However, these results could be affected by the high risk of selection, confounding and detection bias of included studies. More persuasive evidence, from high quality studies, is needed.
Objective To assess the clinical effectiveness and safety of compound glycyrrhizin combined with acitretin for psoriasis. Methods The databases such as PubMed, The Cochrane Library, SpringerLink, CNKI, VIP, WanFang Data and CBM were searched to collect the randomized controlled trials (RCTs) about compound glycyrrhizin combined with acitretin vs. acitretin alone for psoriasis. Meanwhile, The Chinese Journal of Dermatovenereology, China Journal of Leprosy and Skin Diseases and the grey literature were also searched. The retrieval time was from January 2000 to March 2012. According to the Cochrane Reviewer’s Handbook, two reviewers independently screened the literature, extracted the data and assessed the methodological quality of the included studies. Then the meta-analysis was performed using RevMan5.0 software. Results A total of 17 RCTs involving 1 365 patients were included. The results of meta-analysis showed that, the regimen of compound glycyrrhizin combined with acitretin was superior to acitretin alone; there were significant differences in the total effective rate (OR=3.39, 95%CI 2.55 to 4.52, Plt;0.000 01) and in the incidence of skin and mucous membrane dryness (OR=0.54, 95%CI 0.32 to 0.98, P=0.04), skin erythema (OR=0.43, 95% CI 0.24 to 0.76, P=0.004), elevated AST and ALT (OR=0.13, 95%CI 0.04 to 0.41, P=0.000 5) and elevated blood lipid (OR=0.48, 95%CI 0.30 to 0.77, P=0.002). But no significant difference was found in the incidence of dry and cracked lips (OR=0.50, 95%CI 0.10 to 2.50, P=0.40). There was publication bias shown by funnel plot analysis. Conclusion The compound glycyrrhizin combined with acitretin for psoriasis can obviously increase the cure rate and effective rate, and reduce the incidence of adverse reaction, such as dryness of skin and mucous membrane, skin erythema, elevated AST and ALT, and elevated blood lipid. For the limitation of quality and quantity of included studies, this conclusion still needs to be proved by conducting more high quality researches.
Objective To assess the efficacy and safety of efalizumab in the treatment of psoriasis. Methods Randomized controlled trials (RCT) on efalizumab in the treatment of psoriasis were identified from The Cochrane Library ( issue 1, 2006) , specialized trials registered in Cochrane Skin Group (2006), MEDLINE (1966 - 2006) and EMBASE (1974 - 2006). The quality of the trials was assessed by two reviewers independently. RevMan 4.2.7 software provided by the Cochrane Collaboration was used for statistical analysis. Results Three RCTs involving 1 651 patients were included, all of which were of high methodological quality. All the patients were diagnosed as chronic moderate to severe plaque psoriasis with the age of 18-75 years. Meta-analysis indicated that at week 12, significantly more patients in both 1mg/kg/w and 2 mg/kg/w efalizumab subcutaneous groups achieved PASI50, PASI75, PASI90 improvement compared to the placebo group (Plt;0.0001), while there was no significant difference in PASI50, PASI75 and PASI90 responses between 1mg and 2mg efalizumab groups (P gt;0.05). No serious adverse effects were identified. Extended treatment for another 12w may contribute to further efficacy without increasing toxicty. Conclusions Efalizumab 12w therapy is safe and effective for treating adult patients with moderate to severe plaque psoriasis. More RCTs are required to assess the efficacy of the extended treatment.
【摘要】目的探讨生长抑素(somatostatin,SS)和表皮生长因子(epidermal growth factor,EGF)在银屑病治疗中的相互作用机制。方法选择2008年1月12月门诊和住院的寻常型银屑病患者68例,用放射免疫法检测正常组织和各期银屑病皮损中SS和EGF的表达。结果进行期银屑病皮损中EGF明显高于静止期、恢复期皮损和正常皮肤(P＜001);各期银屑病皮损与正常皮肤中SS差异无统计学意义(P＜005)。结论SS可能是通过抑制EGF而在银屑病的治疗中起关键作用。
Therapeutic drug monitoring (TDM) has been more widely used in small molecule agents, such as immuno-suppressants, antiepileptic drugs and antibiotics, with less attention in the field of therapeutic biological agents. Monoclonal drugs represented by tumor necrosis factor alpha (TNF-α) inhibitors have shown a good relationship between exposure and efficacy in clinical studies. There are corresponding guidelines and consensus for the recommendations of TDM based on current research evidence. Therefore, this paper introduced the current evidence, strategies and considerations for TDM in the optimal treatment of adalimumab from the perspective of adalimumab TDM to provide references for the clinical practice of adalimumab TDM.
目的 通过对白芍总苷治疗前后寻常型银屑病患者血清中白介素（IL）-22水平的研究，探讨其治疗寻常型银屑病的作用机制。 方法 2009年10月－2010年8月采用双抗体夹心酶联免疫吸附法，检测30例寻常型银屑病患者，经白芍总苷治疗前后及健康对照组20例外周血清中IL-22浓度的变化，分析其在治疗前、后与银屑病皮损面积和严重程度指数（PASI）评分的相关性。 结果 寻常型银屑病患者血清IL-22浓度[（90.50 ± 51.80）pg/mL]较对照组[（40.10 ± 17.20）pg/mL]升高，白芍总苷治疗后血清中IL-22水平[（48.70 ± 23.90）pg/mL]较治疗前降低（P＜0.05），并与对照组差异无统计学意义（P＞0.05）；治疗前、后患者血清IL-22水平与PASI评分呈正相关。结论 白芍总苷可能通过调节IL-22发挥治疗寻常型银屑病的作用。