Adverse reactions to cosmetics reported to the Chongqing adverse drug reaction monitoring centre system in China.

BACKGROUND: Cosmetic adverse reactions (CARs) are becoming widespread in China. However, a comprehensive analysis of data is lacking. OBJECTIVE: To analyse the clinical characteristics of patients with reported adverse reactions to cosmetics in Chongqing, China. METHODS: Cases with CARs reported to the Chongqing Adverse Drug Reaction Monitoring Centre System from 2017 to 2021 were analysed. RESULTS: A total of 23 245 cases were identified, of which 94.5% were women. Contact dermatitis (84.3%) was the most common diagnosis of CARs, followed by acne (3.1%). The most frequently reported clinical signs were erythema (70.1%), followed by papules (35.5%). The majority of CARs were reported to be due to ordinary cosmetics (87.9%), of which 81.0% were skin care products and 7.1% were makeup products. Cosmetics with special functions constituted 12.2%, of these, skin whitening (54.0%) and sunscreen (28.0%) products were most frequently reported. CONCLUSION: Our results suggest that adverse reactions to cosmetics are of concern in China, and dermatologists should actively identify and diagnose CARs. In addition, we should establish a convenient and effective model for collecting, reporting, and evaluating CARs.

A multicenter, randomized, double-blinded, placebo-controlled, dose-ranging study evaluating the efficacy and safety of vunakizumab in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Vunakizumab (SHR-1314) is a novel interleukin 17A monoclonal antibody that has shown preliminary efficacy and tolerability in phase I trials. OBJECTIVE: To evaluate the efficacy and safety of vunakizumab in moderate-to-severe plaque psoriasis. METHODS: In this 36-week, multicenter, double-blinded, phase II study (NCT03463187), 187 eligible patients with moderate-to-severe plaque psoriasis were randomized 1:1:1:1:1 to receive vunakizumab (40, 80, 160, or 240 mg) or placebo subcutaneously, every 4 weeks, until week 12 (2 more drug administrations for the vunakizumab groups on weeks 16 and 20). The primary end point was at least 75% improvement in the Psoriasis Area and Severity Index at week 12. RESULTS: At week 12, there were significantly greater proportions of responders with at least 75% improvement in the Psoriasis Area and Severity Index in all vunakizumab groups compared to placebo (40, 80, 160, and 240 mg: 56.8%, 65.8%, 81.6%, and 86.5%, respectively, vs 5.4%; P < .001 for all); the proportions of patients achieving Physician's Global Assessment responses of 0 or 1 were also higher with vunakizumab (45.9%, 47.4%, 60.5%, and 73.0%, respectively, vs 8.1%). No unexpected adverse effects were observed. LIMITATIONS: The study was relatively short in duration and included no active control. CONCLUSION: Vunakizumab showed promising efficacy for moderate-to-severe plaque psoriasis, with good tolerability, warranting further investigation in larger and longer-term studies.

The efficacy and safety of topical Tretinoin combined with superficial X-ray therapy (SXRT) in treating periungual warts.

There are multiple treatment modalities for periungual warts (PWs), although most are destructive and painful, limiting their application. Radiotherapy is a non-invasive method suitable for treating PW patients with contraindications to invasive procedures. To investigate the efficacy and safety of topical Tretinoin combined with Superficial X-ray therapy (SXRT) in treating PWs. This study included patients with 65 PWs who underwent treatment and a 3-month follow-up. Twenty four PWs were subjected to SXRT alone (group A). The remaining 41 PWs were subjected to SXRT combined with the application of the Tretinoin cream from the first day (group B). The overall clinical response rate, recurrence rates, cosmetic outcomes, and adverse events were observed during the follow-up period. The complete clearance rate (75% vs. 92.7% in groups A and B, respectively) and healing times (19.9 vs. 16.0 days in groups A and B, respectively) between the two groups were significantly different (p < 0.046 and 0.04), indicating the combination treatment is more effective. Notably, there was no damaging or permanent deformation on the nail, and the other adverse effects were mild and bearable. Topical Tretinoin combined with SXRT therapy is an effective strategy for treating PWs, with minor side effects. It is painless and with excellent cosmetic outcomes.

Efficacy and safety of omalizumab in Chinese patients with anti-histamine refractory chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is characterized by the spontaneous development of wheals, itching, and/or angioedema, for ≥6 weeks. In China, non-sedating H1-antihistamines (H1AH) are the recommended first-line treatment, with escalation up to 4× the standard dose in symptomatic patients to achieve control. Treatment options for Chinese patients who remain symptomatic on H1AH treatment are limited. This 20-week randomized, double blind, placebo-controlled, parallel-group study investigated the efficacy and safety of omalizumab as an add-on therapy for the treatment of patients with CSU who remained symptomatic despite H1AH treatment in China. Adult patients (N = 418) diagnosed with refractory CSU for ≥6 months were randomized (2:2:1) to receive omalizumab 300 mg (OMA300), omalizumab 150 mg (OMA150) or placebo, subcutaneously, every 4 weeks. Primary outcome was change from baseline to week 12 in weekly itch severity score (ISS7). Safety was assessed by rates of adverse events (AEs). Demographic and disease characteristics at baseline were comparable across treatment groups. At week 12, statistically significant greater decreases from baseline were observed in ISS7 with OMA300 (least square mean difference [LSM]: -4.23; 95% confidence interval [CI]: -5.70, -2.77; p < 0.001) and OMA150 (LSM: -3.79; 95% CI: -5.24, -2.33; p < 0.001) versus placebo. Incidence of treatment-emergent AEs over 20 weeks was slightly higher with OMA300 (71.3%) compared to OMA150 and placebo groups (64.7% and 63.9%, respectively). The incidences of serious AEs were balanced between groups. This study demonstrated the efficacy and safety of omalizumab in Chinese adult patients with CSU who remained symptomatic despite H1AH therapy.

Tazarotene/Betamethasone Dipropionate Cream in Patients with Plaque Psoriasis: Results of a Prospective, Multicenter, Observational Study.

BACKGROUND: Topical agents are still the mainstay for the treatment of mild-to-moderate plaque psoriasis, in which fixed combinations play an important role. Tazarotene/betamethasone dipropionate (Taz/BD) cream is a novel fixed combination approved for treating plaque psoriasis in China, but its efficacy and safety have not been verified in a real-world environment. OBJECTIVES: The primary objective was to investigate the efficacy and safety of Taz/BD cream in treating plaque psoriasis. The secondary objectives were to assess its relapse after discontinuation and the efficacy and safety profiles during retreatment. METHODS: A prospective, multicenter, large-scale observational study was conducted. Adult patients with chronic plaque psoriasis involving <20% of the body surface area were enrolled. Taz/BD cream was applied once daily for 4 weeks. Patients who achieved ≥90% improvement in the Psoriasis Area and Severity Index (PASI) from baseline to week 4 were followed up to investigate relapse after drug withdrawal. Relapsed patients underwent another 4-week treatment. RESULTS: In total, 2,299 eligible patients were enrolled, and 2,095 patients (91.1%) completed the 4-week study. The mean PASI improvement at week 4 was 53.7%, and the PASI 50/75 response rates were 62.5 and 26.8%, respectively. The mean PASI reduction in plaque induration, desquamation and erythema were 58.3, 61.0 and 40.0%, respectively (p < 0.001). Adverse reactions occurred in 445 patients (20.8%) at week 4. The most frequently reported adverse reactions were local skin irritation, including pruritus (10%), pain (6.7%), erythema (6.1%) and desquamation (1.8%). During the post-treatment period, 47 patients (24.0%) relapsed within 8 weeks after drug discontinuation. Forty-five patients were retreated for another 4 weeks, and the PASI 50/75 response rates were 72.7 and 40.9%, respectively. There were no unexpected safety signals during retreatment. CONCLUSION: Taz/BD cream is effective and well tolerated in treating mild-to-moderate plaque psoriasis under near real-world conditions and demonstrates efficacy and safety during retreatment.

Heme oxygenase 1 facilitates cell proliferation via the B-Raf-ERK signaling pathway in melanoma.

BACKGROUND: Despite therapeutic advancements (e.g. B-RAF inhibitors) targeting cutaneous melanoma, many cellular processes, including inducible heme oxygenase 1 (HO-1), counteract treatments for malignancies. So there is an urgent need to find biological treatment targets, develop new therapeutic approaches and achieve longer responses. This study aimed to explore the relationship of HO-1 and B-Raf via mediating ERK1/2 signaling on cell cycle in melanoma. METHODS: Immunohistochemistry was applied to evaluate the levels of HO-1 and B-Raf expression in melanoma tissues and adjacent healthy tissues. Co-immunoprecipitation (Co-IP) assessed the interaction of HO-1 with B-Raf. Further study overexpression and knock-down of HO-1 in A375 cell lines, especially knockout HO-1 using CRISPR-Cas9, verified HO-1 regulate cell proliferation in vivo and in vitro. Finally, Western blot analysis and qRT-PCR were performed to investigate the mechanisms by which HO-1 mediates cell cycle by B-RAF-ERK1/2 signaling. RESULTS: First, histology and Co-IP show that HO-1 interacts with B-Raf directly in melanoma tissue. Further study illustrated that HO-1 overexpression promotes melanoma cell proliferation while HO-1 reduction represses melanoma cell proliferation because of HO-1 affects cell cycle. Mechanistic studies revealed that HO-1 was associated with a marked activation of B-RAF-ERK1/2 signaling and led to CDK2/cyclin E activation, thereby promoting melanoma proliferation. CONCLUSIONS: Our result reveals a previously unknown mechanism that the HO-1-B-RAF-ERK axis plays an important role in melanoma cell proliferation. Therapeutic target on HO-1 could be a novel method for treating melanoma.

Effects of 9-cis-retinoic acid on the proliferation and apoptosis of cutaneous T-cell lymphoma cells.

The vitamin A derivative 9-cis-retinoic acid (9-cis-RA) has been used for the treatment and prevention of cutaneous T-cell lymphoma (CTCL). However, the precise mechanism by which 9-cis-RA treatment ameliorates CTCL remains elusive. Our research shows that 9-cis-RA inhibits proliferation and induces apoptosis in CTCL cells in a dose-dependent and time-dependent manner. 9-Cis-RA also induced G0/G1 cell cycle arrest by downregulation of cyclin D1. We confirmed that 9-cis-RA significantly decreased phosphorylation of JAK1, STAT3, and STAT5 and downregulated Bcl-xL and cyclin D1, indicating that 9-cis-RA inhibited the activation of JAK/STAT signaling. Meanwhile, 9-cis-RA also activated classical RA-mediated transcription by retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) in a CTCL cell line. Thus, 9-cis-RA may be effective for chemotherapy and may prevent human CTCL by inhibiting proliferation and inducing apoptosis by inhibition of the JAK/STAT pathway and activation of the RAR/RXR pathway.

MicroRNA let-7b inhibits keratinocyte differentiation by targeting IL-6 mediated ERK signaling in psoriasis.

BACKGROUND: The extensive involvement of microRNA (miRNA) in the pathophysiology of psoriasis is well documented. However, in order for this information to be useful in therapeutic manipulation of miRNA levels, it is essential that detailed functional mechanisms are elucidated. This study aimed to explore the effects of IL-6 targeting by let-7b and ERK1/2 mediated signaling on keratinocyte differentiation in psoriasis. METHODS: Following imiquimod cream (IMQ) application to let-7bTG (keratinocyte-specific let-7b overexpression mouse) and control mice for 7 days, we analyzed erythema, scaling and thickening of skin. A dual luciferase reporter assay and bioinformatics was carried out to detect target gene of let-7b. Additionally, the differentiation markers were measured. Immunohistochemistry analyses demonstrate a relationship of let-7b with IL-6 and ERK signaling. RESULTS: we found let-7bTG inhibits acanthosis and reduces the disease severity by treatment with IMQ compared to wild-type mice. Further study illustrated that let-7b promotes differentiation of keratinocytes in vivo and in vitro. Using bioinformatics and reporter gene assays, we found that IL-6 is a target gene of let-7b. In psoriasis, high expression levels of IL-6 lead to increased acivation of p-ERK1/2. High levels of let-7bTG transgene expression suppresses IL-6 expression and leads to increased keratinocyte differentiation. Moreover, let-7b acts as an upstream negative regulator of the ERK signaling pathway in keratinocytes of psoriasis. CONCLUSIONS: Our result reveals a previously unknown mechanism for regulation of IL-6 levels during psoriasis by let-7b and highlights a critical role for the ERK1/2 signaling pathway in epidermal differentiation during psoriasis. TRIAL REGISTRATION: The ethical approval for this study was from the Affiliated Hospital of Medical University of Anhui _ Fast_ PJ2017-11-14.

Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.

Efficacy and safety of fire needle therapy in treating non-segmental stable vitiligo: A randomized self-controlled clinical trial.

BACKGROUND: Vitiligo remains a challenging condition to treat. Fire needle therapy, a traditional Chinese medicine technique, has potential as an alternative therapeutic strategy. However, rigorous evidence on its efficacy is lacking. OBJECTIVE: We aimed to evaluate the efficacy and safety of fire needle therapy, alone and combined with topical tacrolimus ointment, for non-segmental stable vitiligo. METHODS: In this 6-month randomized self-controlled trial, 35 vitiligo patients were enrolled, providing three similar lesions each. Lesions were randomly allocated to receive fire needle monotherapy, 0.1% tacrolimus ointment monotherapy, or combined fire needle and tacrolimus ointment therapy. The main outcome was change in vitiligo surface area. RESULTS: In total, 29 patients completed the 6-month follow-up. The combination therapy group showed significantly greater reductions in vitiligo surface area compared to monotherapy groups starting at months 4 and 5. By the end of the study, combination therapy resulted in remarkably higher repigmentation responses, with 89.7% of lesions showing at least mild (≥25%) repigmentation and 51.7% showing good (≥50%) repigmentation. This significantly exceeded the outcomes with topical tacrolimus ointment alone, which only achieved 6.9% mild response and 6.9% good response. Fire needle monotherapy also demonstrated steady repigmentation over time, with 69% of lesions attaining a mild response by month 6. Importantly, no major adverse events occurred. CONCLUSION: This study provides promising preliminary evidence supporting the use of fire needle therapy, alone or in combination with topical tacrolimus ointment, for inducing repigmentation in non-segmental stable vitiligo. As a non-pharmacological approach, fire needle therapy warrants further study as an alternative vitiligo treatment.

Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial.

BACKGROUND: Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD. METHODS: This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied. RESULTS: At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. CONCLUSION: CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.

Adverse Cosmetic Reactions in a Pediatric Population Reported to the Chongqing Drug Administration in China From 2017 to 2021.

Background: Despite their ubiquitous use and several safety incidents involving cosmetics for children in China, there is little research on adverse reactions to cosmetics in children. Objectives: We assessed the cosmetic adverse reactions (CARs) reports submitted to the Chongqing Drug Administration in China for children, to understand the characteristics of CARs in a pediatric population and determine whether useful insights can be derived. Methods: We extracted the data file of the Chongqing Drug Administration's cosmetic adverse events reporting system from 2017 to 2021, and screened the information of people under the age of 18 years for analysis. Results: A total of 589 children were reported; of them, 475 female children and 114 male children, aged 1-17 years, and 89.6% were diagnosed with cosmetic contact dermatitis. Itching and burning were the most prominent symptoms and accounted for 83.4% and 40.2%, respectively. The most frequently reported clinical sign was erythema (73.3%) followed by papule (37.9%). The face is the most vulnerable location to lesions, accounting for 80.8% of all areas, with girls having a significantly higher rate of facial and scalp damage than boys. The majority of the CARs were reported with cream, lotion, and toner for the skin (45.9%) and facial or body cleansing products (15.4%), and most of these products were purchased from authoritative shops. Conclusion: Although adults are the main group of people who use cosmetics, due to the special physiological structure of children, the safety of children's cosmetics should be given more attention. In addition, pediatricians and dermatologists should be active in submitting reports of adverse cosmetic events and encouraging consumers to do so likewise in situations in which a product adversely affects a child's health.

Contact dermatitis associated with a cosmetic cream.

BACKGROUND: Cosmetic contact dermatitis (CCD) is a very common cosmetic adverse reaction, but there are few reports of adverse reactions to breast enhancement cream. METHODS: We reported a case of adverse skin reactions after applying a cosmetic cream and performed patch tests of cosmetic series and cosmetic product. RESULTS: After drug treatment, the patient's symptoms improved significantly. The cosmetic series patch test showed that she was allergic to thimerosal, and the cosmetic product patch also showed positive. CONCLUSIONS: The adverse reactions of dermatologists to cosmetics cannot be ignored, and it is suggested that in addition to common skin care products, the safety of other functional products should also be concerned.

Study on screening and evaluation methods of cosmetics for people with facial sensitive skin.

OBJECTIVE: The purpose of this study is to screen and evaluate cosmetic products for sensitive skin on the face. METHODS: Thirty-five subjects with positive lactic acid sting test (LAST) were recruited from the staff of our hospital from November 2019 to February 2020. First, the human skin enclosed patch test of cosmetic gel (abbreviated as gel) was performed, and then the tested products were continuously applied for 4 weeks to complete the long-term efficacy test. Subjects' sensation of application, pruritus, tingling and burning were assessed on a 0 to 9 scale prior to, 14, and 28 days after topical application. Moreover, the transepidermal water loss rate (TEWL), stratum corneum (SC) hydration, melanin index (MI), erythema index (EI) and dendritic cells and inflammatory cell infiltration were noninvasively detected by the tester. LAST were performed before applying, 14 and 28 days after application, and then the test results were compared. RESULTS: In this study, a total of 34 people participated in the test. The results of human skin enclosed patch test indicated that only 1 case of grade 1 reaction occurred among the tested subjects. The subjects felt good after applying the products, and the gel showed high degree of skin comfortable, no irritation and good tolerability. Subjective safety evaluation illustrated that the scores of pruritus, tingling and burning of the subjects decreased in D14 and D28 patient revisit, showing statistically significant differences (P < .05). When the gel was applied for 4 weeks, TEWL (8.42 ± 1.12) and EI (201.35 ± 13.51) were lower than the results before application (P < .05), and the SC hydration (65.36 ± 2.56) was higher than that before application (P < .05). There was no correlation between the SC hydration and TEWL (R = 0.092, P = .416). The results of skin CT indicated that the number of facial dendritic cells decreased in 17 subjects (accounting for 50%) in D28 patient revisit, and the degree of inflammatory cell infiltration decreased in 27 subjects (accounting for 80%). Compared with the baseline value, the LAST score and total sensory score decreased after application the product for 4 weeks, and the difference was statistically significant (the mean value of P < .05). CONCLUSION: The subjective feeling of application and efficacy of cosmetics in people with sensitive skin could be successfully evaluated by the comprehensive application of human skin enclosed patch test, long-term trial test, subjective safety evaluation and objective efficacy evaluation. And it provides the basis to judge whether the cosmetic is consistent with the efficacy claim of sensitive skin.

Chalcone Derivatives From Abelmoschus manihot Seeds Restrain NLRP3 Inflammasome Assembly by Inhibiting ASC Oligomerization.

Three chalcone derivatives, abelmanihotols A-C (1-3), and nine known compounds were isolated from A. manihot seeds, and their structures were determined using HRESIMS and NMR spectroscopic analysis. Compound 1 exhibited the most potent inhibitory effect (IC50 = 4.79 ± 0.72 µM) against lipopolysaccharide (LPS)-induced NO release in THP-1 cells, and significantly inhibited interleukin 1ß (IL-1ß) secretion, which is stimulated by LPS plus nigericin (IC50 = 11.86 ± 1.20 µM), ATP or MSU, in THP-1 cells. A preliminary mechanism of action study indicated that compound 1 blocked the formation of nucleotide oligomerization domain-like receptor protein-3 (NLRP3) inflammasome formation by suppressing apoptosis-associated speck-like protein oligomerization, thereby attenuating caspase-1 activation and IL-1ß release. These results reveal that compound 1 is not only a potent and efficacious NLRP3 inflammasome inhibitor but also a promising drug for the treatment of NLRP3-related diseases.

[Design, manufacture and evaluation of a multi-parameter controllable automatic fire-acupuncture instrument].

A multi-parameter controllable automatic fire-acupuncture instrument was developed by integrating traditional fire needling with modern medical device technology. A gun-like appearance was designed for easy hand-held operation, the electromagnetic induction was for heating needle body, a scale knob was for controlling the needle insertion depth, the combination of electromagnetic ejection and spring return was for the precise control of the needle retention time; and the changeable single ste-rile needle or multiple needles were adopted to meet individual demand, obtain high efficiency and prevent infection. All of these designs are associated with the overall process control system to ensure the exact controllability of needle body temperature, needling density, insertion depth and needle retention time. Besides, this device is advantageous at handy and aseptic operation with high efficiency, conformability and visualization. In this research, this instrument was tested in animals for the impacts of automatic fire needling on skin damage and fur growth. It is found that the accurate control of each parameter is of the significant advantage in the safety and effectiveness of treatment, which lays a solid foundation for the subsequent systematic review on safety and effectiveness.