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.

A Case of Cutaneous Rosai-Dorfman Disease Treated by Intralesional Injections of Glucocorticoid.

A 45-year-old male presented with painless reddish-brown plaques and nodules that had infiltrated his shoulder and back for 3 months. From the clinical manifestations and histopathological findings, the patient was diagnosed with cutaneous Rosai-Dorfman disease. Intralesional injections of betamethasone (trade name: diprospan) were recommended and the lesions improved significantly after three treatments.

Experimental study and clinical observations of autologous hair follicle cell transplants to treat stable vitiligo.

BACKGROUND: Vitiligo is characterized by the loss and/or dysfunction of melanocytes in the skin and has a profound impact on the social interactions of patients. Although there are many treatment options for vitiligo, the outcome is frequently unsatisfactory, especially for patients with stable vitiligo. OBJECTIVES: To study the biological properties of melanocytes derived from human hair follicles and to observe the efficacy of using transplants of autologous hair follicle cells to treat patients with stable vitiligo. METHODS: From February 2014 to March 2017, 26 patients with stable vitiligo, who were refractory to all current routine therapy, underwent treatment with transplanted autologous hair follicle cells. The skin graft from each patient's occipital region was trimmed to remove excess adipose tissue and some of the upper part of the dermis. The remaining tissue, including hair follicles and dermal papillae, was cut into pieces and incubated in collagenase type IV and then in trypsin-ethylenediaminetetraacetic acid solutions. The cells were recovered, resuspended in the patient's own serum and then applied to the recipient area. Clinical observations continued for 6 months to 1 year. Laboratory experiments were also performed during this time on scalp specimens obtained from normal human volunteers. Cells migrating from the outer root sheath and the dermal papillae at various times of culture were observed using a microscope. RESULTS: Most of the repigmentation in the vitiligo areas appeared within 8 weeks of transplantation of autologous hair follicle cells. Early skin repigmentation was not uniform and appeared more repigmented than the surrounding normal skin. As time went by, the repigmentation became more obvious and matched the color of the skin around the lesion. Most of the pigmentation presented as a diffuse pattern and was not localized around the hair follicles. Among the 26 patients, 9 (34.6%) achieved excellent repigmentation, while 13 (50.0%) had good, 3 (11.5%) fair and 1 (3.9%) poor repigmentation. During the follow-up visit at 1 year, no excess hair growth was observed in the recipient areas and there was no scarring or ulcer formation in the donor or recipient areas. In the experimental part of the study, many keratinocytes, melanocytes and fibroblasts migrated from the adherent outer root sheath. In later subcultures using a specialized medium, pure melanocytes were obtained that had a strong proliferative capacity and had bipolar or poly-dendritic shapes. On the other hand, cells from the dermal papillae grew radially in primary culture and were almost fibroblast-like. However, a few bipolar melanocytes appeared in the later stage of culture. CONCLUSIONS: The results of our study show that transplantation of autologous hair follicle cells is a simple and effective method to treat patients with stable vitiligo. Hair follicles (especially the outer root sheath) harbor many melanocytes with potential proliferative ability. LIMITATIONS: There are a few limitations of the present study: a small sample size, a short follow-up period, no cell counting or viability testing.

Protective effect of curcumin against ultraviolet A irradiation­induced photoaging in human dermal fibroblasts.

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in skin, resulting in photoaging. Natural botanicals have gained considerable attention due to their beneficial protection against the harmful effects of UV irradiation. The present study aimed to evaluate the ability of curcumin (Cur) to protect human dermal fibroblasts (HDFs) against ultraviolet A (UVA)­induced photoaging. HDFs were treated with 0­10 µM Cur for 2 h and subsequently exposed to various intensities of UVA irradiation. The cell viability and apoptotic rate of HDFs were investigated by MTT and flow cytometry assays, respectively. The effect of UVA and Cur on the formation of reactive oxygen species (ROS), malondialdehyde levels, which are an indicator of ROS, and the levels/activity of antioxidative defense proteins, including glutathione, superoxide dismutase and catalase, were evaluated using 2',7'-dichlorofluorescin diacetate and commercial assay kits. Furthermore, western blotting was performed to determine the levels of proteins associated with endoplasmic reticulum (ER) stress, the apoptotic pathway, inflammation and the collagen synthesis pathway. The results demonstrated that Cur reduced the accumulation of ROS and restored the activity of antioxidant defense enzymes, indicating that Cur minimized the damage induced by UVA irradiation in HDFs. Furthermore, western blot analysis demonstrated that Cur may attenuate UVA­induced ER stress, inflammation and apoptotic signaling by downregulating the protein expression of glucose­regulated protein 78, C/EBP­homologous protein, nuclear factor­κB and cleaved caspase­3, while upregulating the expression of Bcl­2. Additionally, it was demonstrated that Cur may regulate collagen metabolism by decreasing the protein expression of matrix metalloproteinase (MMP)­1 and MMP­3, and may promote the repair of cells damaged as a result of UVA irradiation through increasing the protein expression of transforming growth factor­ß (TGF­ß) and Smad2/3, and decreasing the expression of the TGF­ß inhibitor, Smad7. In conclusion, the results of the present study indicate the potential benefits of Cur for the protection of HDFs against UVA­induced photoaging and highlight the potential for the application of Cur in skin photoprotection.

Effect of the topical application of calcipotriol on the expression levels of zinc finger protein A20 and nuclear factor-κB in the skin lesions of patients with psoriasis vulgaris.

The aim of the present study was to explore the effect of the topical application of calcipotriol on the expression levels of zinc finger protein A20 and nuclear factor-κB (NF-κB) in the skin lesions of patients with psoriasis vulgaris. The calcipotriol ointment was topically applied twice a day for 6 weeks by 26 patients with psoriasis vulgaris. At the end of weeks 2, 4 and 6 after the first application of calcipotriol ointment, the clinical efficacy and Psoriasis Area and Severity Index (PASI) score were compared with those prior to treatment. The expression of zinc finger protein A20 and NF-κB in the skin lesions prior to and following treatment with calcipotriol was measured by immunohistochemical staining and western blotting. At the end of week 6, the clinical effectiveness rate of calcipotriol was higher compared with that at the end of weeks 2 and 4 (χ2=8.12 and 9.06, respectively; P<0.05). The PASI score declined significantly at the end of weeks 2, 4 and 6 (t=9.37, 10.54 and 12.43; P<0.05, 0.05 and 0.001, respectively). At the end of week 6, the expression levels of zinc finger protein A20 and NF-κB were significantly lower compared with those prior to treatment (χ2=3.65 and 4.17, respectively; P<0.01). The expression levels of the two proteins were higher in the skin lesions of patients with psoriasis vulgaris prior to the initiation of treatment than in the skin of a normal control group. Following the 6-week treatment with calcipotriol, the expression levels of the two proteins in the psoriasis skin lesions were significantly lower than they were prior to treatment (P<0.01). Thus, the present study found that in addition to the typical pathway of NF-κB being targeted in the treatment of psoriasis with calcipotriol, the zinc finger protein A20 may also modulate the inflammatory response of psoriasis.

Increased functional connectivity strength of right inferior temporal gyrus in first-episode, drug-naive somatization disorder.

BACKGROUND: Evidence of brain structural and functional alterations have been implicated in patients with somatization disorder (SD). However, little is known about brain functional connectivity in SD. In the present study, resting-state functional magnetic resonance imaging (fMRI) and graph theory were used to obtain a comprehensive view of whole-brain functional connectivity and to investigate the changes of voxel-wise functional networks in patients with SD. METHODS: Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex- and education-matched healthy controls (HCs) underwent resting-state fMRI. The graph theory approach was employed to analyze the data. RESULTS: Compared to the HCs, patients with SD showed significantly increased functional connectivity strength in the right inferior temporal gyrus (ITG). There is a significant positive correlation between the z-values of the cluster in the right ITG and Hamilton Anxiety Scale scores. CONCLUSIONS: Our findings indicate that there is a disruption of the functional connectivity pattern in the right ITG in first-episode, treatment-naive patients with SD, which bears clinical significance.

Self-control study of combination treatment of 308 nm excimer laser and calcipotriene ointment on stable psoriasis vulgaris.

OBJECTIVE: This study aims to compare the differences of clinical efficacy and safety of treatment of stable psoriasis vulgaris with calcipotriene ointment in combination with 308 nm excimer laser to 308 nm excimer laser alone. METHODS: Randomized, open and self-control trial was conducted in 36 selected patients. The skin lesions from these patients with stable psoriasis vulgaris were divided into two sides along the midline of torso, one side was treated with 308 nm excimer laser, 2 times/week, at meantime Calcipotriene was applied externally, 2 times/day (treatment group); the other side was given 308 nm excimer laser alone, 2 times/week, the treatment period was 6 weeks (control group). Skin lesion area, PASI scores and cumulative doses of 308 nm excimer laser in patients with psoriasis were assessed before treatment and on weeks 2, 4 and 6 after treatment. RESULTS: 32 of 36 patients with stable psoriasis vulgaris completed study, effective rates in two groups were better on week 6 (84.37%, 56.25%) than on week 4 (53.12%, 37.5%) and on week 2 (31.25%, 18.75%) (P < 0.05). Effective rate on week 6 in control group (56.25%) was lower than treatment group (84.37%) (P < 0.05). The two groups showed that PASI scores on weeks 2 and 4 after treatment were significantly lower than before treatments (P < 0.05), and PASI scores on week 6 in treatment group was significantly lower than control group (P < 0.05). The average cumulative laser doses in treatment group at the end of trial was 4.69 (2.03) J/cm(2), which was significantly lower than in control group 8.41 (2.42) J/cm (P < 0.05). Treatment efficacies in the head, folds, back, abdomen and limbs were similar and no serious adverse effects, however the number of treatment and irradiation doses in the head and folds were significantly less than in back, abdomen and limbs (P < 0.05). CONCLUSIONS: Treatment of psoriasis vulgaris with 308 nm excimer laser in combination with external application of Calcipotriene ointment can improve long-term treatment efficacy, decrease cumulative laser doses, and reduce adverse effects induced by laser irradiations.

Zinc finger A20 and NF-κB correlate with high-risk human papillomavirus of squamous cell carcinoma patients.

Genital human papillomavirus (HPV) is associated with the development of cutaneous malignant tumors, and differences in HPV subtypes are found in several cancers by histology. NF-κB is persistently activated in most cancers and confers a survival advantage to cancer cells, while A20 is a critical negative regulator of NF-κB and is an important tumor suppressor inactivated in B cell lymphomas. This study was undertaken to identify HPV types in cutaneous squamous cell carcinoma (SCC) as well as to determine whether the crosstalk of A20/NF-κB was involved in HPV-induced SCC. Overall, HPV positivity was observed to be 66.2 %, with HPV16 being most common followed by infection with HPV18. Out of 43 HPV-positive samples, 35 samples were positive for one or more high-risk HPV (HR-HPV) types, suggesting a high association of SCC with HR-HPV infection, while only five HPV infections were detected in 21 normal skin samples and low-risk HPV (LR-HPV) infection was the most common. Both A20 and NF-κB were overexpressed in HPV-positive SCC samples (56 vs 87.4 %) and were closely correlated with TNM stage and lymph node transfer, respectively. More interestingly, the expression of A20 and NF-κB was much higher in HR-HPV samples than in LR-HPV samples. These results suggest that the crosstalk of A20 and NF-κB may contribute to HR-HPV-associated tumor growth and metastasis of SCC and may be a novel therapeutic target for SCC in the future.

Dissociation of regional activity in default mode network in medication-naive, first-episode somatization disorder.

BACKGROUND: Patients with somatization disorder (SD) have altered neural activity in the brain regions of the default mode network (DMN). However, the regional alteration of the DMN in SD remains unknown. The present study was designed to investigate the regional alterations of the DMN in patients with SD at rest. METHODS: Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex-, education- matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI) scan. The fractional amplitude of low-frequency fluctuations (fALFF) was applied to analyze the data. RESULTS: Patients with SD showed a dissociation pattern of resting-state fALFF in the DMN, with increased fALFF in the bilateral superior medial prefrontal cortex (MPFC, BA8, 9) and decreased fALFF in the left precuneus (PCu, BA7). Furthermore, significantly positive correlation was observed between the z values of the voxels within the bilateral superior MPFC and somatization subscale scores of the Symptom Check List (SCL-90) in patients with SD. CONCLUSIONS: Our findings indicate that there is a dissociation pattern of the anterior and posterior DMN in first-episode, treatment-naive patients with SD. The results provide new insight for the importance of the DMN in the pathophysiology of SD.

Expression of cyclin D1 and cyclin E significantly associates with human papillomavirus subtypes in Bowenoid papulosis.

Human papillomavirus (HPV) incorporates high-risk HPV (hrHPV) and low-risk HPV (lrHPV) subtypes according to its contribution to oncogenesis. Different HPV subtypes could regulate the cell cycle of infected cells at different levels. To date, the expression of cyclin D1 and cyclin E in Bowenoid papulosis (BP) tissues and its association with HPV infection still remains elusive. In the present study, genotyping was performed to identify the HPV subtypes in 44 BP specimens. In addition, immunohistochemistry was performed to detect the expression of cell cycle related proteins cyclin D1 and cyclin E in BP tissues as well as normal tissues. We found that there were 20 patients with hrHPV subtypes, 6 patients with lrHPV subtypes, and 18 patients with combined high and low (hr/lr) HPV subtypes. Cyclin D1 expression in patients with hrHPV subtypes (P=0.0408), in patients with lrHPV subtypes (P=0.0002) and in patients with hr/lr HPV subtypes (P=0.0047) was significantly higher than that in normal controls, respectively. Cyclin D1 expression in patients with hr/lr HPV subtypes (P<0.0001) and in patients with lrHPV subtypes (P=0.0244) was significantly higher than that in patients with hrHPV subtypes, respectively. Cyclin E expression in patients with hrHPV subtypes (P<0.0001), in patients with lrHPV subtypes (P=0.0005), and in patients with hr/lr HPV subtypes (P<0.0001) was significantly higher than that in normal controls, respectively. Cyclin E expression in patients with hrHPV subtypes was significantly higher than that in patients with lrHPV subtypes (P=0.0032). Our data suggest that HPV infection is strongly associated with the pathogenesis of BP, and further support the notion that HPV may be involved in the regulation of the expression of cell cycle related proteins, cyclin D1 and cyclin E, in the pathogenesis of BP.