Refractory Palmoplantar Pustulosis Successfully Treated with JAK Inhibitor Tofacitinib: A Case Series.

Background: Palmoplantar pustulosis (PPP) is a common chronic and recurrent skin disease of the palms and soles with significant pain, mental distress, and functional disability. PPP is challenging to treat and usually requires prolonged management. Therapy resistance and frequent relapse discourages patients from follow-up. No unified standard and no published therapeutic guidelines have yet been defined on PPP treatment. In general, all therapeutic options known for autoimmune diseases, psoriasis in particular, have been tested in PPP. Tofacitinib, an oral JAK inhibitor, has been approved for the treatment of rheumatoid arthritis and shows promise in the treatment of moderate-to-severe plaque psoriasis. However, no clinical trials or case reports have been conducted to confirm the efficacy of tofacitinib in palmoplantar pustulosis. Methods: Six in total with 6 PPP patient, aged 42-58 years were recruited according to the inclusion and exclusion criteria. Patient characteristics, including triggering factors, concomitant diseases, and previous therapeutic drugs, were investigated. All patients experienced a lack of response to topical drugs and at least one systemic agent. During treatment, visits were scheduled at the start of treatment and at 2, 4, and 12 weeks, and efficacy was assessed using the PPP ASI and PPP PGA. Results: Our six patients showed an excellent response to tofacitinib as all patients did achieve at least 50% reduction and half of our patients with more than 80% reduction in PPPASI after 4 weeks treatment; at week 12, 5 (83.3%) patients had 80% reduction in PPPASI with no serious adverse events were reported. Conclusion: The JAK inhibitor tofacitinib is a promising treatment for refractory palmoplantar pustulosis that requires further clinical observation and research.

Jingfang granules exert anti-psoriasis effect by targeting MAPK-mediated dendritic cell maturation and PPARγ-mediated keratinocytes cell cycle progression in vitro and in vivo.

BACKGROUND: Jingfang granules (JFG), derived from JingFangBaiDu San (JFBDS), are a traditional herbal formulas used for the treatment of respiratory tract infections. They were initially prescribed to treat skin disease, such as psoriasis in Chinese Taiwan, but are not widely used for psoriasis treatment in mainland China because of the lack of anti-psoriasis mechanism research. PURPOSES: The present study was designed to evaluate the anti-psoriasis effect of JFG and reveal the correlated mechanisms of JFG in vivo and in vitro using network pharmacology, UPLC-Q-TOF-MS technology and molecular biotechnology methods. RESULTS: An imiquimod-induced psoriasis-like murine model was used to verify the anti-psoriasis effect in vivo, with inhibition of lymphocytosis and CD3+CD19+B cell proliferation in the peripheral blood and prevention of the activation of CD4+IL17+T cells and CD11c+ MHC Ⅱ+ dendritic cells (DCs) in the spleen. Network pharmacology analysis demonstrated that the targets of the active components were significantly enriched in pathways involved in cancer, inflammatory bowel disease and rheumatoid arthritis, which were closely related to cell proliferation and immune regulation. The drug-component-target networks and molecular docking analysis demonstrated the active ingredients to be luteolin, naringin and 6'-feruloylnodakenin, which had a good binding affinity to PPARγ, p38a MAPK and TNF-a. Finally, UPLC-Q-TOF-MS analysis to validate the active ingredients in drug-containing serum and in vitro experiments showed that JFG inhibited the maturation and activation of BMDCs via the p38a MAPK signaling pathway and translocation of the agonist PPARγ into the nuclei to reduce the activity of NF-κB/STAT3 inflammatory signaling pathway in keratinocytes. CONCLUSIONS: Our study demonstrated that JFG improved psoriasis by inhibiting the maturation and activation of BMDCs and proliferation and inflammation of keratinocytes, which may facilitate the applications of JFG in anti-psoriasis therapy in clinical settings.

Effect of dexmedetomidine combined with propofol on stress response, hemodynamics, and postoperative complications in patients undergoing laparoscopic cholecystectomy.

OBJECTIVE: This research was designed to probe the effect of dexmedetomidine combined with propofol on stress response, hemodynamics, and postoperative complications in patients undergoing laparoscopic cholecystectomy. METHODS: Altogether 144 patients who underwent laparoscopic cholecystectomy in the Beibei Traditional Chinese Medical Hospital, the Sixth People's Hospital of Chongqing from January 2018 to July 2020 were research subjects. The control group (CG) (n=68) received propofol continuous pumping sedation, while the research group (RG) (n=76) was given dexmedetomidine combined with propofol continuous pumping sedation. The quality of postoperative recovery and incidence of postoperative complications of the two groups were observed and compared. The hemodynamic indexes (HR, SpO2 and MAP) before anesthesia induction (T0), tracheal intubation (T1), at the commencement of operation (T2), at the end of operation (T3), and extubation (T4) were observed. The stress response indexes (Cortisol, ACTH and norepinephrine, NE) were monitored, and the scores of pain, anxiety and cognitive dysfunction before and after operation were evaluated. RESULTS: Compared with the CG, the incidence of postoperative complications in the RG was lower, and the quality of postoperative recovery (time of breathing recovery, eye opening, consciousness and extubation) was better. Besides, the hemodynamic indexes of the RG were more stable, and the levels of stress indexes Cortisol, ACTH, and NE were lower. The RG had VAS and SAS scores that were lower, and MMSE scores were higher. CONCLUSION: Dexmedetomidine combined with propofol can effectively alleviate the stress response of patients undergoing laparoscopic cholecystectomy, stabilize perioperative hemodynamics, and reduce postoperative complications.