Systemic sclerosis (SSc) refers to an autoimmune disease, which is manifested by inflammation, vasculopathy, and fibrosis of the skin and internal organs. There are a number of different animal models recapitulating specific aspects of SSc. The experimental mouse model of bleomycin‐induced skin fibrosis is commonly used to study the pathogenesis observed in SSc. In this model, repetitive intradermal injections of the cytotoxic agent bleomycin trigger progressive skin thickening, associated with excessive accumulation of collagen, infiltration of immune cells, and formation of α‐smooth muscle actin (α‐SMA)‐positive myofibroblasts. In this article, we provide a detailed protocol for the induction of skin fibrosis in experimental mice by bleomycin. Moreover, we describe procedures for processing and analyzing affected skin tissue, provide troubleshooting, highlight advantages and limitations of the presented model, and critically discuss representative results. © 2019 by John Wiley & Sons, Inc. Basic Protocol 1: Intradermal bleomycin injections to induce skin fibrosis in mice Support Protocol: Mouse tissue collection for fibrosis evaluation and for other molecular assays Basic Protocol 2: Evaluation of mouse skin thickness using Masson's trichrome staining Basic Protocol 3: Measurement of hydroxyproline content in skin tissue using a colorimetric assay Basic Protocol 4: Evaluation of myofibroblasts in mouse skin by immunohistochemistry

Some herbal medicines combined chemotherapy compared with chemotherapy alone showed more beneficial effects in improving 1-year, 3-year survival and quality of life.

Background: In China, heat-clearing and detoxifying Chinese medicines combined with conventional therapy are commonly applied to treat the mild hand, foot, and mouth disease (HFMD). However, there is lack of solid evidence on the efficacy and safety of such therapies. Methods: We conducted a pooled analysis with individual patient data from 5 strictly randomized controlled clinical trials to assess the efficacy and safety of this combination therapy for mild HFMD. An intention-to-treat analysis was performed. A 2-stage meta-analysis method was adopted to analyze the pooled effect size. Results: In total, 947 patients were included. Compared with conventional therapy, the combination therapy significantly reduced the progression rate of HFMD from mild to severe (odds ratio [OR] 0.43, 95% confidence interval [CI]: 0.22 to 0.83, P = .01). Meanwhile, the healing time of skin rash and oral ulcer in the combination therapy group was significantly shorter than that of conventional therapy. The overall hazard ratio (HR) of healing time of the skin rash or oral ulcer was 1.22 (95%CI: 1.04 to 1.43; P = .02). However, except Jinlianqingre effervescent tablets, the combination therapy cannot shorten the time to fever resolution (HR 1.12, 95%CI: 0.97 to 1.29, P = .14). Because of the heterogeneity, Jinlianqingre effervescent tablets were analyzed separately and the HRs of the time to fever resolution and the healing time of skin rash or oral ulcer were 3.88 (95%CI: 3.19 to 4.72; P < .0001) and 3.79 (95%CI: 2.81 to 5.11; P < .0001), respectively. There were 30 adverse events reported in total; 2 cases were related to Chinese medicines. Conclusion: In conclusion, the heat-clearing and detoxifying Chinese medicines on top of conventional therapy can effectively reduce the progressive rate of mild HFMD and improve healing of skin and oral mucosal lesions. More studies are needed for the time to fever resolution.

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