Off-label use of Baricitinib improves moderate and severe atopic dermatitis in China through inhibiting MAPK and PI3K/Akt/mTOR pathway via targeting JAK-STAT signaling of CD4+ cells

As an inflammatory disease with a disrupted immune system, cytokine disorders in atopic dermatitis (AD) are closely related to the abnormal activation of JAK-STAT signal pathway. The critical relevance of the JAK-STAT signaling pathway to the pathogenesis of AD provides a strong rationale for JAK inhibitor research. Baricitinib, a small-molecule oral JAK inhibitor, has been proven to inhibit JAK-STAT signaling in a variety of diseases, including AD. It is currently available in China for off-label use. However, its efficacy in China and its mechanism are rarely reported. In our study, we found that the immune status of patients with moderate and severe AD was hyperactive. Among the 49 known immunotherapy targets, JAK1 and JAK2 genes on lymphocytes of AD patients were significantly upregulated, which was closely related to the symptom severity in moderate and severe AD patients. Baricitinib can improve immune hyperresponsiveness and clinical symptoms in moderate and severe AD by inhibiting the activation of Th2 cell subsets and the secretion of Th2-type cytokines through MAPK, mTOR and PI3K-Akt signaling pathways, providing an important theoretical basis for clinical off-label use of Baricitinib to treat moderate and severe AD

First-line treatment with chemotherapy plus cetuximab in Chinese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety results of the randomised, phase III CHANGE-2 trial.

Abstract Background The EXTREME regimen (chemotherapy [CT; cisplatin/carboplatin and 5-fluorouracil]) plus cetuximab is a standard-of-care first-line (1L) treatment for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), as supported by international guidelines. The phase III CHANGE-2 trial assessed the efficacy and safety of a modified CT regimen (with a reduced dose of both components) and cetuximab versus CT for the 1L treatment of Chinese patients with R/M SCCHN. Methods Patients were randomised to receive up to six cycles of CT plus cetuximab followed by cetuximab maintenance until progressive disease or CT alone. The primary end-point was the progression-free survival (PFS) time assessed by the independent review committee (IRC). Results Overall, 243 patients were randomised (164 to CT plus cetuximab; 79 to CT). The hazard ratios for PFS by IRC and overall survival (OS) were 0.57 (95% CI: 0.40–0.80; median: 5.5 versus 4.2 months) and 0.69 (95% CI: 0.50–0.93; median: 11.1 versus 8.9 months), respectively, in favour of CT plus cetuximab. The objective response rates (ORR) by IRC were 50.0% and 26.6% with CT plus cetuximab and CT treatment, respectively. Treatment-emergent adverse events of maximum grade 3 or 4 occurred in 61.3% (CT plus cetuximab) and 48.7% (CT) of patients. Conclusions CHANGE-2 showed an improved median PFS, median OS and ORR with the addition of cetuximab to a modified platinum/5-fluorouracil regimen, with no new or unexpected safety findings, thereby confirming CT plus cetuximab as an effective and safe 1L treatment for Chinese patients with R/M SCCHN. Clinical trial registration number NCT02383966

Long non-coding RNA KCNQ1 opposite transcript 1 (KCNQ1OT1) regulates cell proliferation and invasion via targeting miR-124-3p in gastric carcinoma

No Abstract

Stress on Steel-concrete Composite Truss Joints Research Status and Application Overview

Based on the comprehensive analysis of various stress research schemes for steel-concrete composite truss joints, the current research status of steel-concrete composite truss joints and epoxy resin concrete at home and abroad are systematically elaborated. The existing problems in the current composite truss joints are analyzed, and possible solutions are proposed. At present, the research on epoxy resin concrete has been very extensive. Epoxy resin concrete has high strength, good toughness, high impact strength, good chemical corrosion resistance, wear resistance, water resistance, frost resistance, tensile resistance and compressive resistance, which make it widely used in engineering. The problem of using epoxy resin concrete instead of ordinary concrete in steel-concrete composite truss is put forward, analyzed and discussed

Impact of sarcopenia on the survival of patients undergoing liver transplantation for decompensated liver cirrhosis

Abstract Background Patients with decompensated cirrhosis (DC) are prone to skeletal muscle loss, namely, sarcopenia, before liver transplantation (LT). While sarcopenia is reportedly associated with adverse outcomes after LT, these findings are limited owing to mixed diseases and retrospective data. We investigated the association between sarcopenia and 1‐year overall survival (OS) in patients with DC after LT and established and validated a prediction model for postoperative OS based on sarcopenia. Methods Overall, 222 consecutive patients who underwent LT at our centre were registered between September 2020 and June 2022. Third lumbar spine skeletal muscle mass index was measured using computed tomography. Patients were divided into sarcopenia and non‐sarcopenia groups according to the skeletal muscle mass index, and baseline data and postoperative outcomes were collected, compared and analysed. The primary outcome was the 1‐year OS after LT. We established a dynamic nomogram of the OS predictive model. Results We included 177 DC patients [mean (standard deviation) age, 50.2 ± 9.3 years; 52 women (29.4%)]; 73 (41.2%) had sarcopenia. The mean (standard deviation) body mass index was 22.6 ± 4.5 kg/m2, 28 (15.8%) patients had weight loss ≥5% within 6 months before admission, and the mean (standard deviation) model for end‐stage liver disease (MELD) score was 18.4 ± 7.9. Patients with sarcopenia had a longer duration of intensive care unit stay (4.1 ± 2.2 vs. 3.1 ± 1.1 days, P = 0.008), higher rate of major complications (45.2% vs. 22.1%, P = 0.001) and higher postoperative mortality (15.1% vs. 2.9%, P = 0.003) than those without sarcopenia. The median 1‐year OS after surgery was shorter in patients with sarcopenia than in those without (P 102.9 points calculated using the nomogram) had a significantly reduced survival rate. Conclusions Sarcopenia is associated with adverse outcomes after LT in patients with DC. High‐risk patients should be classified by dynamic nomogram upon admission

Development and Validation of the Disability Index Among Older Adults

BACKGROUND: With the rapid population aging, the challenge to provide care for disabled older adults is becoming bigger. This study aims to develop the Disability Index (DI) to assess disability to indicate care needs, and we evaluated the reliability and validity of the DI among older adults aged 65-105. METHODS: A total of 12 559 older adults (54.0% women; mean age = 84.3; SD = 11.2) from 22 provinces in China were investigated in 2017-2018. We developed the 21-item DI covering 4 subdomains, including Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), physical performance, and cognitive function. Cronbach's alpha was used to determine internal consistency. The convergent and divergent validity were assessed by Spearman rank order correlation coefficients and Pearson correlation coefficients. The known-group validity was assessed by Mann-Whitney U tests. The concurrent validity was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: In the total sample, the internal consistency of the full DI and its subdomains were satisfactory with Cronbach's alpha ≥0.70; the convergent and divergent validity of the 4 subdomains were supported by all the alternative measures; the known-group validity of the full DI and its subdomains were supported by clear discriminative ability; and the concurrent validity of the full DI was supported with all the AUCs ≥0.70. The reliability and validity of the full DI and its subdomains were additionally supported by age subgroups and sex subgroups. CONCLUSIONS: The DI is a reliable and valid instrument to assess disability status among older adults