Abstract Background: Prurigo nodularis (PN) is a chronic inflammatory skin condition that has a significant unmet needs for effective treatment options. Objective: To assess the efficacy and safety of dupilumab in adult patients with PN refractory to traditional therapies. Methods: This ongoing, real-life study examined dupilumab treatment in 8 adult patients diagnosed with PN for at least 6 months. The included patients were prescribed 300 mg dupilumab biweekly for at least 16 weeks. Efficacy was the primary outcome by means of multiple standardized scale measurements while safety was also reported. Results: PN patients treated with dupilumab showed notable clinical improvement. After 16 weeks of dupilumab treatment, the mean Investigator Global Assessment (IGA) score reduced from 3.75 to 1.50. Patients mean Numerical Rating Scale Itch Intensity (NRSI), Dermatology Life Quality Index (DLQI), and Hospital Anxiety and Depression Scale (HADS) ratings reduced from 8.625, 15.13, and 14.50 to 1.563, 4.625, and 1.000 respectively. The majority of the patients (87.5%) reported dupilumab as effective while no adverse events have been reported. Study limitations: This study was limited to a small cohort of adult PN patients and a short-time observation period. Conclusions: Dupilumab is effective and tolerable in adult PN patients with significant improvement in skin lesions, itching, and quality of life.

Abstract Background: Recent evidences indicated that some local anaesthetic agents played a role in inhibiting the proliferation of cancer cells; Whether ropivacaine is able to promote apoptosis of hepatocellular carcinoma (HCC) cells is still unclear. The aim of this study was to investigate the effect of ropivacaine on the apoptosis of HCC cells. Methods: In the present study, we treated the HCC cell lines, Bel7402 and HLE with ropivacaine. MTT, DAPI stain, trypan blue exclusion dye assay, flow cytometry, electron microscopy, computational simulation, laser confocal microscope, Western blotting, and enzyme activity analysis of caspase-3 were applied to detect the growth and apoptosis of HCC cells and to explore the role mechanism of ropivacaine. Results: Ropivacaine was able to inhibit proliferation and promote apoptosis of HCC cells in a dose- and time-dependent manner. Ropivacaine also has a trait to inhibit the migration of HCC cells; ropivacaine damaged the mitochondria of HCC cells. The results also indicated that ropivacaine was able to interact with caspase-3, promote cytoplasmic caspase-3 migration into the nucleus, stimulate cleavage of caspase-3 and PARP-1, caspase-9 proteins, inhibit the expression of Bcl-2, promote expression of Apaf-1 and mitochondria release cytochrome C, and activate the activity of caspase-3. Conclusions: Ropivacaine has a novel role in promoting apoptosis of HCC cells; The role mechanism of ropivacaine maybe involve in damaging the function of mitochondria and activating the caspase-3 signalling pathway in HCC cells. Our findings provide novel insights into the local anaesthetic agents in the therapy of HCC patients.

AlCoCuFeMnNi high-entropy alloy coating was prepared by plasma cladding method. The phase structure and microstructure of AlCoCuFeMnNi coating was investigated by XRD, SEM and EDS respectively. The results show that AlCoCuFeMnNi caotings have two BCC phase structure and typical dendrite structure and form good metallurgical bonding with substrate. The dendrite is the typical spinodal decomposition structure. After CeO2 doping, the change of peak intensity and FWHM is obvious due to the effect of Ce on the improvement of grain growth, microstructure and crystallinity. The addition of CeO2 is beneficial to reduce the cladding defect, make dendrite arm spacing enlarged and spinodal decomposition structure refined, and improve element segregation owing to the melioration effect in the temperature gradient, solidification rate, fluidity, wettability, and surface tension.