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Metastasis is a major contributing factor that affects the prognosis of melanoma patients. Nevertheless, the underlying molecular mechanisms involved in melanoma metastasis are not yet entirely understood. Here, we identified ubiquitin‐specific protease 22 (USP22) as a pro‐oncogenic protein in melanoma through screening the survival profiles of 52 ubiquitin‐specific proteases (USPs). USP22 demonstrates a strong association with poor clinical outcomes and is significantly overexpressed in melanoma. Ablation of USP22 expression remarkably attenuates melanoma migration, invasion, and epithelial–mesenchymal transition in vitro and suppresses melanoma metastasis in vivo. Mechanistically, USP22 controls melanoma metastasis through the SIRT1/PTEN/PI3K pathway. In addition, we conducted an United States Food and Drug Administration‐approved drug library screening and identified topotecan as a clinically applicable USP22‐targeting molecule by promoting proteasomal degradation of USP22. Finally, we found that both pharmacological and genetic silence of USP22 sensitize RSL3‐induced ferroptosis through suppressing the PI3K/Akt/mTOR pathway and its downstream SCD, and ferroptosis inhibitor could partly rescued the decreased lung metastasis by topotecan in vivo. Overall, our findings reveal a prometastatic role of USP22 and identify topotecan as a potent USP22‐targeting drug to limit melanoma metastasis. [ABSTRACT FROM AUTHOR]

The epidemiological landscape of infantile hemangioma (IH) has been extensively explored through diverse data sources; however, a scarcity of systematically pooled and quantified evidence from comprehensive global studies persists. In this meta‐analysis, we systematically review available literature to elucidate the prevalence, distribution of lesions, complications, and risk factors associated with IH. A meticulous search encompassing the Cochrane Library, PubMed, Embase, and Web of Science identified 3206 records, of which 55 studies met the inclusion criteria. We found that the overall prevalence of IH is 2.8% [95% confidence interval (CI): 1.5–4.4%] (31,274,396 infants), and IH was located more frequently in the head and neck with a prevalence of 47.4% (95% CI: 39.5–55.4%). The overall prevalence of complications of IH is 24.3% (95% CI: 18.6–30.5%), ulceration is 16.0% (95% CI: 10.4–21.2%), bleeding is 5.6% (95% CI: 3.3–8.5%), visual impairment is 5.6% (95% CI: 3.0–8.9%), infection is 2.8% (95% CI: 1.5–4.8%), subglottic obstruction is 1.5% (95% CI: 0.5–3.0%), respectively. Through 27 studies, we have evaluated 35 factors encompassing perinatal factors, socioeconomic factors, maternal complications, drug factors, and antepartum procedures, and identified 18 risk factors that increase the prevalence of IH. These findings can greatly assist clinicians and family members in effectively evaluating the risk of IH, and determining whether pregnant women should undergo intensified monitoring or preventive measures. [ABSTRACT FROM AUTHOR]

Chinese guidelines prioritize the use of Azvudine and nirmatrelvir–ritonavir in COVID‐19 patients. Nevertheless, the real‐world effectiveness of Azvudine versus nirmatrelvir–ritonavir is still lacking, despite clinical trials showing their effectiveness compared with matched controls. To compare the effectiveness of Azvudine versus nirmatrelvir–ritonavir treatments in real‐world clinical practice, we identified 2118 hospitalized COVID‐19 patients, with a follow‐up of up to 38 days. After exclusions and propensity score matching, we included 281 Azvudine recipients and 281 nirmatrelvir–ritonavir recipients who did not receive oxygen therapy at admission. The lower crude incidence rate of composite disease progression outcome (7.83 vs. 14.83 per 1000 person‐days, p = 0.026) and all‐cause death (2.05 vs. 5.78 per 1000 person‐days, p = 0.052) were observed among Azvudine recipients. Azvudine was associated with lower risks of composite disease progression outcome (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.32–0.94) and all‐cause death (HR: 0.40; 95% CI: 0.16–1.04). In subgroup analyses, the results of composite outcome retained significance among patients aged <65 years, those having a history of disease, those with severe COVID‐19 at admission, and those receiving antibiotics. These findings suggest that Azvudine treatment showed effectiveness in hospitalized COVID‐19 patients compared with nirmatrelvir–ritonavir in terms of composite disease progression outcome. [ABSTRACT FROM AUTHOR]

To investigate the clinical characteristics of skin disorders among hospitalized patients before and during the coronavirus disease 2019 (COVID‐19) pandemic, a retrospective study was conducted based on hospitalized patients with skin diseases from Xiangya Hospital of Central South University, the largest hospital in the south‐central region of China, between January 1, 2018, and December 31, 2021. A total of 3039 hospitalized patients were enrolled in the study, including 1681 patients in the prepandemic group and 1358 patients in the pandemic group. The total number of hospitalized patients in the pandemic group decreased by 19.2%, with an increased proportion of patients over 60 years of age (39.8% vs. 35.8%). Moreover, compared with the prepandemic group, there were decreases in the occurrence of most skin diseases in the pandemic group, but the proportions of keratinolytic carcinoma (6.6% vs. 5.2%), dermatitis (24.0% vs. 18.9%), and psoriasis (18.0% vs. 14.8%) were higher in the pandemic group. In addition, longer hospital stays (β = 0.07, SE = 0.02, P = 1.35 × 10−3) and higher hospital costs (β = 0.06, SE = 0.03, p = 0.031) were found in the pandemic group through general linear models, even after the corresponding adjustment. In summary, the COVID‐19 pandemic has had a lasting impact on patients with skin diseases, with fewer hospitalized patients, increased proportions of older patients, longer hospital stays, and increased hospital costs. These findings will facilitate better preparation for the most effective response to future pandemics. [ABSTRACT FROM AUTHOR]

To summarize the clinical characteristics and explore the role of treatment types in outcomes among psoriasis patients with coronavirus disease 2019 (COVID‐19). The principal summary measures were pooled prevalence and risk ratio (RR) with 95% confidential interval (CI). R statistic software was used for all the analysis. A total of 19 studies including 4073 psoriasis patients with COVID‐19 were eligible for the meta‐analysis. The overall hospitalization rate is about 20.2% (95% CI: 12.7%–28.7%), and changed to be 18.0% (95% CI: 9.9%–27.6%) or 14.1% (95% CI: 5.9%–24.6%) after systemic or biologic treatment. Moreover, the overall fatality rate is 1.5% (95% CI: 0.4%–3.0%), and turned to be 0.7% (95% CI: 0%–2.0%) or 0.5% (95% CI: 0%–2.2%) after systemic or biologic therapy. Notably, a lower hospitalization RR was found in patients receiving biologic therapy than those receiving other treatments (RR = 0.62, 95% CI: 0.42–0.94). The results were consistent after sensitivity analysis and trim‐and‐fill analysis. Systemic, especially biologic therapy could lessen the clinical severity in psoriasis patients with COVID‐19. Our finding will help to guide current recommendations and provide a reference for clinical decision‐making. [ABSTRACT FROM AUTHOR]

Background: Recent large cohorts have reported that melanoma survivors are at risk of developing second keratinocyte carcinoma (KC). However, the detailed proportion and risk are still unknown. We aimed to comprehensively analyze the risk of developing keratinocyte carcinoma after primary melanoma. Methods: We conducted systematic literature research in PubMed, Embase, Web of Science, and Cochrane Library published prior to September 13, 2021. Proportion and standardized incidence ratios (SIR) with its corresponding 95% confidence interval (CI) were pooled for assessing the risk. Results: A total of 15 studies encompassing 168,286 patients were included in our analysis. The pooled proportions of melanoma survivors that developed a subsequent basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and KC were 4.11% (95% CI, 1.32–6.90), 2.54% (95% CI, 1.78–3.31), and 5.45% (95% CI, 3.06–7.84), respectively. The risks of developing a second BCC, SCC, and KC in melanoma survivors were 5.3‐fold (SIR 5.30; 95% CI, 4.87–5.77), 2.6‐fold (SIR 2.58; 95% CI, 1.33–5.04), and 6.2‐fold (SIR 6.17; 95% CI, 3.66–10.39) increased in comparison with the general population. Both fixed effects and random effects models were applied in conducting meta‐analysis and reached a consistent conclusion. Conclusions: Our results indicated melanoma survivors are at elevated risk of experiencing second primary BCC and SCC, which suggested the significance of surveillance for second primary KC and efforts for prevention in patients with a history of melanoma. [ABSTRACT FROM AUTHOR]

Background: Despite the remarkable breakthroughs achieved in the management of metastatic melanoma using immunotherapy and targeted therapies, long‐term clinical efficacy is often compromised due to dose‐limiting toxicity and innate or acquired resistance. Therefore, it is of vital importance to further explore the molecular mechanisms underlying melanoma progression and identify new targeted therapeutic approaches. Methods: The function of eukaryotic elongation factor‐2 kinase (EEF2K) in melanoma were investigated in vitro and in vivo. RNA‐seq and chromatin immunoprecipitation (ChIP) assay were undertaken to explore the mechanisms. The antitumor effect of bromodomain and extra terminal domain (BET) inhibitors combined with cytarabine were assessed in melanoma both in vitro and in vivo. Results: EEF2K silencing markedly attenuated the malignant phenotypes of melanoma cells, including proliferation, migration, invasion and metastasis. In contrast, EEF2K overexpression promoted melanoma cell proliferation, migration and invasion. Mechanistically, we demonstrated that EEF2K upregulates the phosphorylation of STAT3 (p‐STAT3) at Tyr705, which binds to the promoter region of SPP1 and enhances its transcription, thus facilitating melanoma progression. Transfection‐induced re‐expression of SPP1 partly negated the inhibitory effect of EEF2K silencing on melanoma, whereas inhibition of SPP1 or STAT3 significantly abolished the efficacy of EEF2K on melanoma cells. Intriguingly, EEF2K silencing combined with BET inhibitor treatment further inhibited cell proliferation and promoted apoptosis in melanoma. We further screened the US FDA‐approved antitumour drug library and identified cytarabine as a potential clinically applicable EEF2K inhibitor that could synergise with BET inhibitors in melanoma treatment. Conclusion: EEF2K/p‐STAT3/SPP1 may be a novel oncogenic pathway in melanoma progression, which could be a target for novel combination therapy for melanoma. [ABSTRACT FROM AUTHOR]

Objective: To establish nomogram based on inflammatory indices for differentiating intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). Methods: A cohort of 422 patients with HCC or ICC hospitalized at Xiangya Hospital between January 2014 and December 2018 was included in the study. Univariate and multivariate analysis was performed to identify the independent differential factors. Through combining these independent differential factors, a nomogram was established for differential diagnosis between ICC and HCC. The accuracy of nomogram was evaluated by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). The results were validated using a prospective study on 98 consecutive patients operated on from January 2019 to November 2019 at the same institution. Results: Sex (OR = 9.001, 95% CI: 3.268‐24.792, P <.001), hepatitis (OR = 0.323, 95% CI: 0.121‐0.860, P =.024), alpha‐fetoprotein (AFP) (OR = 0.997, 95% CI: 0.995‐1.000, P =.046), carbohydrate antigen 19‐9 (CA199) (OR = 1.016, 95% CI: 1.007‐1.025, P <.001), and aspartate transaminase‐to‐neutrophil ratio index (ANRI) (OR = 0.904, 95% CI: 0.843‐0.969, P =.004) were the independent differential factors for ICC. Nomogram was established with well‐fitted calibration curves through incorporating these 5 factors. Comparing model 1 including gender, hepatitis, AFP, and CA199 (C index = 0.903, 95% CI: 0.849‐0.957) and model 2 enrolling AFP and CA199 (C index = 0.850, 95% CI: 0.791‐0.908), the nomogram showed a better discrimination between ICC and HCC, with a C index of 0.920 (95% CI, 0.872‐0.968). The results were consistent in the validation cohort. DCA also confirmed the conclusion. Conclusion: A nomogram was established for the differential diagnosis between ICC and HCC preoperatively, and better therapeutic choice would be made if it was applied in clinical practice. [ABSTRACT FROM AUTHOR]

We appreciate the interest in our article entitled "Real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19: A retrospective cohort study." They further praised the benefits of nirmatrelvir-ritonavir in COVID-19 patients and demonstrated their results supporting a faster time to nucleic acid-negative conversion compared to patients receiving Azvudine. Nevertheless, it was not necessary for our study, which aimed to evaluate the real-world clinical effectiveness (composite outcomes and mortality).[3] Azvudine and nirmatrelvir-ritonavir were recommended for the treatment of COVID-19 patients as early as possible, but these drugs were not strictly used according to the instructions during the special period. [Extracted from the article]

GLO:OCQ/01dec22:jmv28196-gra-0001.jpg PHOTO (COLOR): . gl Footnotes 1 Yu Meng and Furong Zeng have equal contribution. B Back Cover Caption b : The cover image is based on the Research Article I Clinical characteristics and outcomes of patients with COVID-19 and psoriasis i by Yu Meng et al., https://doi.org/10.1002/jmv.28085. [Extracted from the article]

The introduction of immunotherapy‐based strategies has significantly improved the prognosis for melanoma patients. Nevertheless, some patients still have dismal outcomes, emphasizing the significance of survival predictive indicators in immunotherapy‐based approaches. We systematically searched randomized controlled clinical trials investigating dual immunotherapy or chemoimmunotherapy versus placebo or mono‐immunotherapy or chemotherapy alone in advanced melanoma patients. R version 4.3.0. was employed to perform all analyses. A comprehensive analysis was conducted on a total of 13,809 patients with advanced melanoma from 19 randomized clinical trials. Immunotherapy‐based strategies (alone or in combination) could significantly lengthen the overall survival(OS) and recurrence‐free survival (RFS) compared with corresponding controls. Mono‐immunotherapy improved RFS and OS in PD‐L1 positive patients, in stage AJCC IIIC, and with 4 or more positive lymph nodes, compared with chemotherapy. Combined immunotherapy statistically improved RFS and OS in those aged < 65, with an Eastern Cooperative Oncology Group (ECOG) status of 0, and LDH ≤ ULN at baseline compared with single treatment alone. Our findings indicated that certain clinicopathological and molecular features could assist in choosing appropriate melanoma patients for immune‐based treatments. [ABSTRACT FROM AUTHOR]