Cancer therapy resistance (CTR) is the development of cancer resistance to multiple therapeutic strategies, which severely affects clinical response and leads to cancer progression, recurrence, and metastasis. N6-methyladenosine (m6A) has been identified as the most common, abundant, and conserved internal transcriptional alterations of RNA modifications, regulating RNA splicing, translation, stabilization, degradation, and gene expression, and is involved in the development and progression of a variety of diseases, including cancer. Recent studies have shown that m6A modifications play a critical role in both cancer development and progression, especially in reversing CTR. Although m6A modifications have great potential in CTR, the specific molecular mechanisms are not fully elucidated. In this review, we summarize the potential molecular mechanisms of m6A modification in CTR. In addition, we update recent advances in natural products from Traditional Chinese Medicines (TCM) and small-molecule lead compounds targeting m6A modifications, and discuss the great potential and clinical implications of these inhibitors targeting m6A regulators and combinations with other therapies to improve clinical efficacy and overcome CTR.

The pathophysiology of psoriasis is a highly complicated one. Due to the disease's specificity, it not only affects the patient's skin negatively but also manifests systemic pathological changes. These clinical symptoms seriously harm the patient's physical and mental health. IFN, a common immunomodulatory factor, has been increasingly demonstrated to have a significant role in the development of psoriatic skin disease. Psoriasis is connected with a variety of immunological responses. New targets for the therapy of autoimmune skin diseases may emerge from further research on the mechanics of the associated IFN upstream and downstream pathways. Different forms of IFNs do not behave in the same manner in psoriasis, and understanding how different types of IFNs are involved in psoriasis may provide a better notion for future research. This review focuses on the involvement of three types of IFNs in psoriasis and related therapeutic investigations, briefly describing the three IFNs' production and signaling, as well as the dual effects of IFNs on the skin. It is intended that it would serve as a model for future research.

Background: Psoriasis is an immune-mediated inflammatory disease prone to recurrence. Some studies indicated that bloodletting cupping combined with conventional measures therapy had been proposed as a treatment strategy for psoriasis. Therefore, we performed a systematic review and meta-analysis to assess the effectiveness of this combination therapy in reducing the severity of disease in patients with psoriasis.Methods: The following electronic databases were searched for articles from January 1, 2000 to March 1, 2022: PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP database), Wan-Fang Database, and China National Knowledge Infrastructure (CNKI). The language was not restricted while performing the search. The quality of articles was evaluated using Rev. Man 5.4 software (provided by the Cochrane Collaboration), comparing bloodletting cupping combined with conventional measures therapy to conventional measures treatments. The studies obtained randomized controlled trials (RCTs) of bloodletting cupping combined with conventional standard treatment for treating psoriasis. Two trained researchers (Xiaoyu Ma and Jiaming He) independently reviewed the literature, extracted data based on exclusion and inclusion criteria, and assessed the quality of the included studies. We estimated the aggregate data using a random effects model.Findings: We identified 164 studies. Ten studies met the inclusion criteria for the meta-analysis. The primary outcome indicator was the total number of effective individuals. Secondary outcomes included the Psoriasis Area and Severity Index (PASI), adverse effects, and the Dermatology Life Quality Index (DLQI). Compared with conventional treatments, bloodletting cupping combined with conventional medicine yielded an improved total effective number of persons (RR = 1.15, 95%CI: 1.07 to 1.22, p < 0.00001), PASI (MD = −1.11, 95%CI: −1.40 to −0.82, p < 0.00001) and DLQI scores (MD = −0.99, 95%CI: −1.40 to −0.59, p < 0.0001). We found no significant difference in adverse reactions (RR = 0.93, 95%CI: 0.46 to 1.90, p = 0.85). The heterogeneity test showed the total effective numbers (p < 0.00001, I² = 43%) and PASI (p < 0.00001, I² = 44%) and DLQI scores (p < 0.00001, I² = 0%).Interpretation: Bloodletting cupping combined with conventional treatment can achieve the ideal treatment for psoriasis. However, the combined treatment in psoriasis needs to be further evaluated in high-quality RCTs with large sample sizes to enable future studies in clinical use.