A multicenter, randomized, double-blinded, placebo-controlled, phase â ¢ study evaluating the efficacy and safety of Xeligekimab (GR1501) in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Xeligekimab is a fully human monoclonal antibody that selectively neutralizes IL-17A and had shown potential efficacy in preliminary trials. OBJECTIVE: To evaluate the efficacy and safety of Xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg Xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by extending the treatment schedule to GR1501 every 4 weeks for further 40 weeks. Efficacy was assessed by evaluating the Physician's Global Assessment (PGA) 0/1 and Psoriasis Area and Severity Index (PASI) 75/90/100 improvement. The safety profile was also evaluated. RESULTS: At week 12, The PASI 75/90/100 were achieved in 90.7%/74.4%/30.2%% patients in GR1501 group compared with 8.6%/1.4%/0% patients in placebo group, respectively. The PGA 0/1 were achieved in 74.4% patients of GR1501 group and 3.6% patients in placebo group, respectively. The PASI 75 and PGA 0/1 maintained until week 52. No unexpected adverse events were observed. CONCLUSION: Xeligekimab showed high efficacy and is well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.

Evaluation of Susceptibility Genes/Loci Associated with Male Androgenetic Alopecia (MAGA) for Female-Pattern Hair Loss in a Chinese Han Population and a Brief Literature Review.

BACKGROUND Female-pattern hair loss (FPHL) is a common disorder affecting women, and FPHL can cause psychological dysfunction and affect the social activities of patients. The disease-causing mechanisms are believed to be similar to those of male androgenetic alopecia (MAGA). Although genome-wide association studies (GWAS) have confirmed susceptibility genes/loci for MAGA, the associations between these genetic loci and FPHL are largely unknown. We investigated the associations between susceptibility loci for MAGA and FPHL in a Chinese Han population; a literature review of susceptibility loci associated with MAGA for FPHL was also performed. MATERIAL AND METHODS Twenty-two previously reported sites were analyzed with the Sequenom iPlex platform, and the genotype statistical analysis consisted of a trend test and conservative accounting. The samples comprised 82 patients diagnosed with FPHL by dermatoscopy and 381 healthy controls from the Chinese Han population. RESULTS No significantly associated variants were found in this FPHL study. The examined 22 tag SNPs in MAGA may not be associated with FPHL. The results of the current study in a Chinese Han population support the previous negative association obtained for a European population. CONCLUSIONS This was the first study exploring whether identified MAGA-associated loci confer susceptibility to FPHL in a Chinese Han population, and dermatoscopy was used to improve the diagnostic accuracy. However, there was no evidence of a relationship between susceptibility genes for MAGA and FPHL, and the results indicated that FPHL and MAGA are etiologically separate entities. Therefore, a systematic GWAS approach to FPHL may be required to clarify associated pathophysiological uncertainties.

MiRNA-27a decreases ultraviolet B irradiation-induced cell damage.

MiRNAs were involved in the various biological process through mediating the posttranscriptional gene silencing. The abnormal expression of miRNAs is also involved in various disorders. Our previous study showed that miRNA-27a (miR-27a) was upregulated after ultraviolet B (UVB) irradiation. However, the function of miR-27a in UVB-induced cell damage is still unclear. In this study, we used the miR-27a overexpression and knockdown lentivirus to transfect UVB irradiated HaCaT cell line and observed the influence of miR-27a on UVB irradiated damages in cells. We found that miR-27a removed cyclobutane pyrimidine dimers (CPDs) and decreased the cell apoptosis after UVB radiation. Further studies showed that miR-27a directly decreased the expression and luciferase activity of target genes transactive response DNA-binding protein (TARDBP) and apoptotic protease activating factor-1 (APAF-1). In conclusion, miR-27a can inhibit CPDs, reduce the cell apoptosis and down-regulate its target genes TARDBP and APAF-1 induced by UVB irradiation in HaCaT cells. It is indicated that miR-27a may serve as a target for UVB irradiation protection.

The inhibition effect of cold atmospheric plasma-activated media in cutaneous squamous carcinoma cells.

AIM: This study investigated the effect and mechanism of cold atmospheric plasma (CAP)-activated media on A431 and HaCaT cells. MATERIALS & METHODS: Phosphate-buffered saline (PBS) and Dulbecco's Modified Eagle's Medium (DMEM) were treated by CAP to get CAP-activated media. A431 and HaCaT were incubated by CAP-activated media for 2 h. MTT, Annexin-V and propidium iodide (PI), Western blot and reactive oxygen species (ROS) detection assay were utilized to demonstrate the effect. RESULTS: The CAP-activated media decreased the proliferation of A431 cells in a dose/time-dependent manner. And the CAP-activated media could induce apoptosis in A431 cells. CAP-activated phosphate-buffered saline could increase intracellular ROS level but not CAP-activated DMEM. CONCLUSION: CAP-activated media could induce apoptosis in A431 cells by production of ROS.

Cold atmospheric plasma promotes different types of superficial skin erosion wounds healing.

Superficial skin erosion wounds are very common in the clinic, and conventional treatments are not always effective; thus, effective and novel therapy is needed. Cold atmospheric plasma (CAP) has been recognised as a promising approach to wound healing. The purpose of this study is to show the potential clinical application of CAP for the healing of different kinds of superficial skin wounds. Seven patients with different kinds of superficial skin wounds (two patients with pyoderma gangrenosum, two patients with trauma would, one patient with giant genital wart, one patient with diabetic foot, and one patient with chronic eczema) were recruited to this study. All patients accepted and received CAP treatment every other day till the wound healed. The expected results were complete wound healing after CAP treatment. All patients achieved complete wound healing after several rounds (range from two to eight) of CAP treatment, and there was no side effect observed. CAP may provide a new and effective choice to solve the problem of the healing of superficial wounds that are not only caused by trauma but also because of eczema. CAP has certain value in the treatment of superficial skin diseases in the future.

Superficial hemangioma is better treated by topical 5-aminolevulinic followed by 595-nm pulsed dye laser therapy rather than 595-nm laser therapy alone.

The aim of this study was to compare the efficacy and adverse effects of a 595-nm pulsed dye laser therapy alone (PDL alone) with a 5-aminolevulinic (5-ALA) local application followed by a 595-nm PDL (5-ALA PDL) in the treatment of superficial hemangioma (SH). A prospectively randomized study in 181 patients with SH was carried out over a period of 24 months. One hundred and ninety-three patients were seen. One hundred and eighty-one patients with SH were enrolled, of which 165 completed final follow-up. One hundred and nineteen patients received PDL alone and 46 received 5-ALA PDL. The patients were assessed clinically and the patient's parents were given a satisfaction questionnaire. Baseline patient data (gender, lesion size, lesion site, treatment times, cure rate, and adverse reactions) were recorded and the results of the treatment of the two groups were analyzed and compared. Complete clearing of the lesion (recovery grade 4) was achieved in 44/119 (37.0%) of the PDL alone group and 31/46 (67.4%) of the 5-ALA PDL group (X 2 = 10.30, p < 0.001). Atrophic scars, hyper- and hypopigmentation occurred in both groups (X 2 = 3.32, p = 0.564). The patients' parents' satisfaction was greater in the 5-ALA PDL group. The clinical outcome of 5-ALA PDL was superior to that of PDL alone in the treatment of SH and only minor adverse events occurred in each group.

Cold atmospheric plasma in combination with laser therapy provides a window for the treatment of hyperproliferative skin disease.

Modern medical understanding suggests that hyperproliferative skin diseases (HSDs) are complex syndromes characterized by localized hypertrophy or hyperplasia and infiltration of inflammatory cells. Various treatments, including systemic and topical pharmacotherapy, laser interventions, photodynamic therapy, and surgery, have been proposed for managing HSDs. However, challenges such as wound healing and recurrence after laser treatment have hindered the effectiveness of laser therapy. To overcome these challenges, we conducted a study combining laser therapy with cold atmospheric plasma (CAP) for the treatment of HSDs. Seven patients with different forms of HSDs, who had not responded well to conventional treatments, were enrolled in the study. These HSDs included cases of erythroplasia of Queyrat, pyoderma gangrenosum, keloids and hypertrophic scars, cellulitis, cutaneous lichen planus, and verruca vulgaris. Laser therapy was performed to remove the hyperplastic skin lesions, followed immediately by daily CAP treatment. The results were promising, with all patients successfully treated and no recurrence observed during the follow-up periods. The combined application of CAP and laser therapy proved to be an effective and complementary strategy for managing HSDs. This innovative approach provide evidence for addressing the limitation of laser therapy by utilizing CAP to promote wound healing and mitigate inflammatory responses. Chinese Clinical Trial Registry (ChiCTR2300069993).

In vitro study of cold atmospheric plasma-activated liquids inhibits malignant melanoma by affecting macrophage polarization through the ROS/JAK2/STAT1 pathway.

Melanoma is a prevalent malignant skin tumor known for its high invasive ability and a high rate of metastasis, making clinical treatment exceptionally challenging. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment and play a crucial role in tumor survival and development. Cold atmospheric plasma (CAP) is an emerging tool for tumor treatment that has garnered attention from scholars due to its interaction with non-tumor cells in the tumor microenvironment. Here, we used the macrophage lines THP-1 and RAW264.7, as well as the melanoma cell lines A375 and MV3, as research subjects to investigate the effect of plasma-activated liquid (PAL) on macrophage differentiation and its inhibitory effect on melanoma cell proliferation. We confirmed that the killing effect of PAL on melanoma cells was selective. Using flow cytometry and PCR, we discovered that PAL can influence macrophage differentiation. Through in vitro cell coculture, we demonstrated that PAL-treated macrophages can significantly impede tumor cell development and progression, and the effect is more potent than that of PAL directly targeting tumor cells. Furthermore, we have proposed the hypothesis that PAL promotes the differentiation of macrophages into the M1 type through the ROS/JAK2/STAT1 pathway. To test the hypothesis, we employed catalase and fludarabine to block different sites of the pathway. The results were then validated through Western Blot, qPCR and ELISA. This study illustrates that PAL therapy is an effective tumor immunotherapy and expands the scope of tumor immunotherapy. Furthermore, these findings establish a theoretical foundation for potential clinical applications of PAL.

Treatment of giant pyogenic granuloma with the Nd/YAG holmium laser: a case report.

Pyogenic granuloma (PG) is a common vascular tumor that can be treated using various means. However, some large lesions and those located on some difficult-to-treat body sites may represent a formidable selection to the clinician because of the residual pain after treatment, difficulties in surgical excision at one trial and covering with one dressing, and the risk of sequelae. We report a successful treatment of such a giant lesion that arises in the scar which was left because of port wine stain, using a Nd/YAG holmium pulsed dye laser.

Treatment of facial recalcitrant verruca vulgaris with holmium: YAG laser: an update.

OBJECTIVES: To evaluate the effect and safety of the holmium: YAG laser in the treatment of facial recalcitrant verruca vulgaris. METHODS: 42 patients with recalcitrant facial verruca vulgaris (64 warts in all) were enrolled in the study. Warts were treated with holmium: YAG pulsed dye laser with a top energy of 1.2-1.5 J, pulse frequency 10-12 Hertz, average power 10 Watt. Adverse reaction, complication, recurrence and clinical assessment of the lesion were documented with follow-up 6 months. RESULTS: Ages of patients ranged from 16 to 73 years. 62 warts in 42 patients were eliminated by only one treatment session. The average time for wound-healing is 10.3 days. No severe discomfort, bleeding, edema, ulceration and secondary infection developed. No obvious complications were found. Only 4 warts in 3 patients remained mild atrophy scar and 7 warts in 6 patients remained pigment change. These defects became slighter after 6-month follow-up and left no bad effect on aesthetic. Two of the patients encountered recurrence in the treated site follow-up 6 months. CONCLUSIONS: Holmium laser is an effective and safe therapy for recalcitrant verruca vulgaris. It is the choice of treatment for those lesions in cosmetically sensitive areas.

Application of improved high-risk sign board for older people inpatients: a retrospective study.

AIM: To observe the effect of the implementation of improved high-risk sign boards for older people inpatients. METHOD: The older people inpatients of the Department of Geriatrics at our hospital were selected as the research subjects and divided into two groups. The control group used the single-strip high-risk sign, and the intervention group used the improved double-layer card slot, push-pull integrated high-risk sign board (national patent). The sign-related nurse operation time, patient/attendant satisfaction, and high-risk-related adverse events were observed and compared between the two groups. RESULTS: After the adoption of the improved high-risk sign board, the nurse operation time was reduced from 94.3 ± 16.2 s to 53.9 ± 12.5 s, and patient/attendant satisfaction increased from 6.65 ± 0.38 points to 9.30 ± 0.52 points (P < 0.001). The incidence of high-risk-related adverse events decreased from 6.08 to 1.86%, but the difference was not statistically significant (χ2 = 3.675, P = 0.055). The implementation of the improved high-risk sign board can increase nursing efficiency and enhance the awareness of risk prevention in high-risk patients among nurses, older people inpatients, and attendants. CONCLUSION: The application of double-layer card slot and push-pull comprehensive high-risk identification card to older people inpatients can alert nurses, patients, and nursing staff more prominently, which can improve patient satisfaction, reduce installation time and reduce the incidence of adverse events to a certain extent.

Plasma activated Ezhangfeng Cuji as innovative antifungal agent and its inactivation mechanism.

Candida albicans is a highly drug-resistant fungus for which new treatments are urgently needed due to the lack of clinically effective options. In this study, we evaluated the antifungal activity and mechanism of plasma-activated Ezhangfeng Cuji (PAEC) against Candida albicans and compared it with physiological saline (PS), plasma-activated physiological saline (PAPS) and Ezhangfeng Cuji (EC). After dielectric barrier discharge (DBD) plasma treatment with EC for 20 min followed by a 10 min immersion of Candida albicans, the fungus was reduced by approximately 3 orders of magnitude. High performance liquid chromatography (HPLC) results showed an increase of 41.18% and 129.88% in the concentration of oxymatrine and rhein, respectively, after plasma-treated EC. The concentrations of reactive species (RS), such as H2O2, [Formula: see text], and O3, were found to be higher and the pH value was getting lower in PS after plasma treatment. Detailed analysis of intracellular material leakage, reactive oxygen species (ROS), apoptosis for Candida albicans and observation by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) demonstrated that PAPS, EC and PAEC disrupt the morphological structure of Candida albicans to varying degrees.Additionally, specific analyses on Candida albicans virulence factors, such as adhesion to tissue surfaces, cell surface hydrophobicity (CSH), the transition of yeast-phase cells to mycelium-phase cells, and the secretion of hydrolytic enzymes for Candida albicans were conducted and found to be inhibited after PAPS/EC/PAEC treatment. In our investigation, the inhibitory effects on Candida albicans were ranked from strong to weak as follows: PAEC, EC, PAPS, and PS.

Basic research and clinical exploration of cold atmospheric plasma for skin wounds.

Skin wounds, such as burns, diabetic foot ulcers, pressure sores, and wounds formed after laser or surgical treatment, comprise a very high proportion of dermatological disorders. Wounds are treated in a variety of ways; however, some wounds are greatly resistant, resulting in delayed healing and an urgent need to introduce new alternatives. Our previous studies have shown that cold atmospheric plasma (CAP) has antibacterial activity and promotes cell proliferation, differentiation, and migration in vitro. To further advance the role of CAP in wound healing, we evaluated the safety and efficacy of CAP in vitro by irradiation of common refractory bacteria on the skin, irradiation of normal skin of rats and observing reactions, treatment of scald wounds in rats, and treating clinically common acute wounds. Our findings revealed that CAP can eliminate refractory skin bacteria in vitro; CAP positively affected wound healing in a rat scalding wound model; and direct CAP irradiation of low intensity and short duration did not lead to skin erythema or edema. CAP promises to be a new, economical, and safe means of wound treatment.

Toxicity study of rats treated by plasma-activated solution.

Background: Cold atmospheric plasma (CAP) is an effective treatment for various skin diseases. Plasma-activated solution (PAS) is an indirect method of CAP treatment that produces biological effects similar to those of direct treatment with plasma devices. The anticancer and bacteriostatic effects of PAS have been demonstrated in vitro experiments; however, on the basis of the lack of toxicological studies on PAS, its effects on living mammals when administered by subcutaneous injection is poorly known. Purpose: The purpose of this study was to evaluate the effects of PAS on local skin tissue cells, blood system, heart, liver, lungs, kidneys and other vital organs of the rat when injected subcutaneously. Methods: PAS was prepared by CAP irradiation of phosphate-buffered saline (PBS). PBS and different PBS groups (CAP irradiation for 1, 3, or 5 min) were injected subcutaneously once every 48 h. The rats were euthanized immediately after 10 cycles of therapy. Results: No adverse effects were observed during the entire period of the experiment. Histopathological examination of organs and tissues revealed no structural changes. Moreover, no obvious structural changes were observed in skin tissue. DNA damage and cancerous proliferative changes were not detected in skin tissue treated with PAS. Subsequently, RNA sequencing and western blotting were performed. The results showed that PAS increased the expression of growth factors like transforming growth factor beta (TGF-ß) and vascular endothelial growth factor A (VEGFA). These results might be directly linked to the role of PAS in stimulating TGF-ß receptor signaling pathway and angiogenesis. Conclusion: The results showed that multiple subcutaneous injections of PAS did not show significant toxic side effects on local skin tissues and some vital organs in rats, providing a scientific basis to support the future treatment of skin diseases with PAS.

Topical application of 5-aminolevulinic acid followed by 595-nm pulsed dye laser irradiation for the treatment of recalcitrant port-wine stains: a primary study.

OBJECTIVE: To evaluate the effectiveness and safety of topical application of 5-aminolevulinic acid (ALA) followed by pulsed dye laser (PDL) irradiation for the treatment of recalcitrant port-wine stain (PWS). METHODS: Thirty-five patients (19 females and 16 males) with recalcitrant PWS were treated with topical application of 20% ALA and then irradiated with a 595-nm PDL (energy density of 6.5-9.0 J/cm(2) and pulse duration of 6 or 10 ms) at 6-8 weeks intervals. Clinical improvement of lesions was evaluated by comparing photographs of lesions at baseline and 2 months after the last treatment. RESULTS: Topical ALA spreading followed by irradiation with a 595-nm PDL improved PWS in 21 out of 35 patients who were previously recalcitrant to PDL treatment alone. Side effects were limited to transient erythema, vesicle formation, edema and mild purpura with no obvious subsequent scarring or undesirable pigment changes. CONCLUSION: The topical application of ALA followed by irradiation with a 595-nm PDL is an effective and safe treatment for PWS recalcitrant to PDL therapy alone.

Research on risk factors of ischemic cerebrovascular disease in postmenopausal women based on the social-ecological model.

OBJECTIVE: Based on the social-ecological model, this study aimed to comprehensively explore factors affecting the risk of ischemic cerebrovascular disease (ICVD) in postmenopausal women to provide theoretical bases for further prevention and intervention for postmenopausal women. METHODS: Postmenopausal women who underwent medical examinations in one health-checkup agency in Tianjin from May 2015 to October 2015 were enrolled in this study. The ICVD 10-year Risk Assesment Form developed by the research team of the National "Tenth Five-Year Plan" research project was used to assess the factors affecting the risk of ICVD. Based on the social-ecological model, multiple types of scales, including physical activities, depression, Type D personality, social supports, and environment score, were used to comprehensively explore the factors associated with ICVD in postmenopausal women. RESULTS: 300 valid questionnaires were obtained, with an effective rate of 92.0%. The subjects aged 44-74 years, with the average age of 62.06 ± 7.09 years. Among them, 58.67% of the subjects only obtained high-school diploma, 32.67% obtained college or university diploma, 90.33% were retirees, 95.33% were married, 92.33% experienced the natural menopause, 93.33% lived in urban or suburban areas, and 1.00% had a history of breast cancer. Multivariate logistic regression analysis suggested that monthly income (¥), parity, exposure to second-hand or third-hand smoke, easy access to healthy food, physical activities, depression, Type D personality, social support and environmental factors were associated with the risk of ICVD in postmenopausal women (P < 0.05). Among them, easy access to healthy food (OR = 0.242), social support (OR = 0.861) and environmental factors (OR = 0.866) were protective factors from ICVD. OR < 1 indicates that the exposure factor is negatively correlated with the disease, and the exposure factor has a protective effect on preventing the occurrence of the disease. Parity (OR = 3.795), exposure to second-hand or third-hand smoke (OR = 2.886), depression (OR = 1.193), and Type D personality (OR = 1.148) were risk factors of ICVD. OR > 1 means that the exposure factor is positively correlated with the disease, and the exposure factor increases the risk of disease occurrence. CONCLUSIONS: For postmenopausal women, in the future, in addition to prevention and management of the conventional risks, the conditions of their mentality and social support should be paid attention to, at the same time, and if they can, try to choose a good community environment to live in, which could better reduce the incidence and mortality of ICVD in postmenopausal women.

Membrane Attack Complex C5b-9 Promotes Renal Tubular Epithelial Cell Pyroptosis in Trichloroethylene-Sensitized Mice.

Trichloroethylene (TCE), a commonly used organic solvent, is known to cause trichloroethylene hypersensitivity syndrome (THS), also called occupational medicamentosa-like dermatitis due to TCE (OMDT) in China. OMDT patients presented with severe inflammatory kidney damage, and we have previously shown that the renal damage is related to the terminal complement complex C5b-9. Here, we sought to determine whether C5b-9 participated in TCE-induced immune kidney injury by promoting pyroptosis, a new form of programed cell death linked to inflammatory response, with underlying molecular mechanisms involving the NLRP3 inflammasome. A BALB/c mouse-based model of OMDT was established by dermal TCE sensitization in the presence or absence of C5b-9 inhibitor (sCD59-Cys, 25µg/mouse) and NLRP3 antagonist (MCC950, 10 mg/kg). Kidney histopathology, renal function, expression of inflammatory mediators and the pyroptosis executive protein gasdermin D (GSDMD), and the activation of pyroptosis canonical NLRP3/caspase-1 pathway were examined in the mouse model. Renal tubular damage was observed in TCE-sensitized mice. GSDMD was mainly expressed on renal tubular epithelial cells (RTECs). The caspase-1-dependent canonical pathway of pyroptosis was activated in TCE-induced renal damage. Pharmacological inhibition of C5b-9 could restrain the caspase-1-dependent canonical pathway and rescued the renal tubular damage. Taken together, our results demonstrated that complement C5b-9 plays a central role in TCE-induced immune kidney damage, and the underlying mechanisms involve NLRP3-mediated pyroptosis.