Additional file 1: Fig. S1. Overall workflow diagram of our research. Fig. S2. Landscape and clinical prognostic value of PI3K pathway mutation in the MD-Anderson cohort as well as heatmaps of immune cells infiltration and boxplots of immunomodulators expression. (A) Oncoplot depicts the landscape of PI3K pathway gene mutation in the MD-Anderson cohort. (B) Multivariate Cox regression analysis of PI3K pathway mutation phenotype in the MD-Anderson cohort. (C-D) Kaplan-Meier survival analysis of OS (C) and DFS (D) between the PI3K pathway mutation and wild groups in the MD-Anderson cohort. (E-F) Assess infiltration abundance of 22 immune cells calculated by CIBERSORT (E) as well as 39 immune cells and stromal cells calculated by xCell (F). (G) Boxplots represent different expression levels of 18 ligand molecules between the two groups. WT, wild type; MT, mutant type; *P < 0.05. Fig. S3. The relationship between PI3K pathway mutation and HPV status and patient prognosis in the TCGA-HNSC cohort. (A) Boxplots represent different expression levels of 19 receptor molecules between the PI3K pathway mutation and wild groups. (B) Composition percentage of HPV status between the PI3K pathway mutation and wild groups. (C) Composition percentage of PI3K pathway mutation status between the HPV-negative and HPV-positive groups. (D) Kaplan-Meier survival analysis of the HPV status in the TCGA-HNSC cohort. (E) Kaplan-Meier survival analysis of PI3K pathway mutation in the HPV-negative group patients of TCGA-HNSC cohort. (F-G) Kaplan-Meier survival analysis of HPV status in the PI3K pathway wild (F) and mutation (G) group patients of TCGA-HNSC cohort. WT, wild type; MT, mutant type; *P < 0.05; **P < 0.01. Table S1. The 29 PI3K pathway genes used to define samples as PI3K pathway mutation or wild groups.
Ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) consists of various toxic constituents. However, the health effect of PM2.5 may differ depending on its constituents, but the joint effect of PM2.5 constituents remains incompletely understood.Our goal was to evaluate the joint effect of long-term PM2.5 constituent exposures on dyslipidemia and identify the most hazardous chemical constituent.This study included 67,015 participants from the China Multi-Ethnic Cohort study. The average yearly levels of PM2.5 constituents for all individuals at their residences were assessed through satellite remote sensing and chemical transport modeling. Dyslipidemia was defined as one or more following abnormal blood lipid concentrations: total cholesterol (TC) ≥ 6.22 mmol/L, triglycerides (TG) ≥ 2.26 mmol/L, high-density lipoprotein cholesterol (HDL-C) < 1.04 mmol/L, and low-density lipoprotein cholesterol (LDL-C) ≥ 4.14 mmol/L. The logistic regression model was utilized to examine the single effect of PM2.5 constituents on dyslipidemia, while the weighted quantile sum regression model for the joint effect.The odds ratio with a 95 % confidence interval for dyslipidemia positively related to per-SD increase in the three-year average was 1.29 (1.20-1.38) for PM2.5 mass, 1.25 (1.17-1.34) for black carbon, 1.24 (1.16-1.33) for ammonium, 1.33 (1.24-1.43) for nitrate, 1.34 (1.25-1.44) for organic matter, 1.15 (1.08-1.23) for sulfate, 1.30 (1.22-1.38) for soil particles, and 1.12 (1.05-1.92) for sea salt. Stronger associations were observed in individuals < 65 years of age, males, and those with low physical activity. Joint exposure to PM2.5 constituents was positively related to dyslipidemia (OR: 1.09, 95 %CI: 1.05-1.14). Nitrate was identified as the constituent with the largest weight (weighted at 0.387).Long-term exposure to PM2.5 constituents poses a significant risk to dyslipidemia and nitrate might be the most responsible for the risk. These findings indicate that reducing PM2.5 constituent exposures, especially nitrate, could be beneficial to alleviate the burden of disease attributed to PM2.5-related dyslipidemia.
mTOR signaling pathway is closely related to cell proliferation,cell cycle and other pathological processes about tumor.Rapamycin plays an anti-tumor effect through inhibiting mTOR,but it prone to drug resistance,which leads to limited clinical application.Its resistant mechanism is related with the activation of PI3K-Akt,which is regulated with negative feedback.Dual inhibitors of related proteins of mTOR pathway are expected to reverse the drug resistance.
Key words:
Sirolimus ; Drug resistance ; mammalian target of rapamycin
Objective To investigate a modified technique in the surgical treatment of Dupuytren' s contracture and its clinical outcomes. Methods Eleven cases in 9 patients of Dupuytren's contracture were treated by partial resection of the palmar aponeurosis from September 2008 to August 2009. The conventional method was modified by treating the skin flap as a skin graft. Results Primary wound healing was achieved in all cases. There was no infection, hematoma or skin necrosis. The follow-up period ranged from 1 to 6 months,with an average of 3.3 months. There was no recurrence. The results were graded as good in 9 cases and fair in 2 cases according to the upper limb functional evaluation criteria issued by the Hand Surgery Society of the Chinese Medical Association. The overall satisfactory rate was 100%. Conclusion Early postoperative complication rate can be greatly reduced by treating palmar skin flap as free skin graft after partial resection of the palmar aponeurosis.
Key words:
Surgical flaps; Dupuytren's contracure; Skin graft
Abstract Objective Little is known about the magnitude of the relation of ambient fine particulate matter (PM 2.5 ) constituents with hyperuricemia and serum uric acid (SUA) levels. Therefore, we aimed to assess the associations and to identify the most hazardous constituent. Methods This study included 72,840 participants from the China Multi-Ethnic Cohort. Annual average concentrations of PM 2.5 mass and its major 7 constituents were matched to individuals by residential address. SUA levels exceeding 7.0 mg/dL (417 μmol/L) for men and 6.0 mg/dL (357 μmol/L) for women were considered to be hyperuricemia. Multiple logistic and linear regressions were performed on the association of single exposure to PM 2.5 constituents with hyperuricemia and SUA, separately. The weighted quantile sum method was applied to examine the joint effect of PM 2.5 constituents on hyperuricemia/SUA. Results Significant positive associations were discovered between PM 2.5 constituents and SUA/hyperuricemia. For example, the odds ratio (95% confidence interval) of hyperuricemia for per standard deviation increase of PM 2.5 mass, black carbon, organic matter, ammonium, and nitrate concentrations were 1.22 (1.12–1.32), 1.17 (1.08–1.27), 1.20 (1.10–1.31), 1.21 (1.11–1.31), and 1.28 (1.18–1.40), respectively. The joint exposure to PM 2.5 constituents was significantly positively correlated with hyperuricemia (1.09, 1.05–1.14) and SUA (1.05, 1.03–1.06). And the weight of nitrate was the largest (0.668 for hyperuricemia, 0.586 for SUA). Conclusions Our findings suggest that long-term exposure to PM 2.5 constituents is associated with increased SUA levels and a higher risk of hyperuricemia. In particular, nitrate seems to be the main contributor. This study may help prevent hyperuricemia by promoting the introduction of precise preventive measures. Graphical Abstract
"Generalized lichen sclerosus et atrophicus combined with ankylosing spondylitis responding to secukinumab." Scandinavian Journal of Rheumatology, 52(2), pp. 217–218
Abstract Although the involvement of insulin‐like signaling in cancer has been well documented in various types of cancers, the association between the genetic variants in the insulin‐like signaling and the development of hepatitis B virus ( HBV )‐related hepatocellular carcinoma ( HCC ) remains unclear. In this study, a total of 498 individuals including 173 HBV related cirrhosis patients, 171 HBV ‐related HCC patients, and 154 healthy controls were enrolled. Sixteen single nucleotide polymorphisms (SNPs) in IGF1 , IGF2 , IGF1R and IGF2R have been genotyped by employing SNaPshot assays. We found A/A genotype at rs3743251 of IGF1R was negatively associated with HBV related HCC [odds ratio ( OR ) = 0.38, 95% confidence interval ( CI ) = 0.20–0.72, P = 0.037]; A/G genotype decreased the risk of portal vein thrombosis ( OR = 0.38, 95% CI = 0.18–0.82, P = 0.01). These results indicate that rs3743251 polymorphism in IGF1R is associated with the susceptibility of HBV ‐related HCC .
Abstract Background PI3K pathway is the most frequently mutated pathway in head and neck squamous cell carcinoma (HNSC), which plays a crucial role in tumorigenesis and progression. In the present study, we aimed to investigate the role of PI3K pathway mutation in clinical prognosis prediction and the relationship with immune microenvironment and response rate to immunotherapy. Methods We collected 129 samples with immunotherapy information from MSKCC-2019 cohort as well as 501 and 40 samples from TCGA-HNSC and MD-Anderson non-immunotherapy cohorts, respectively. Somatic mutation data was utilized to characterize the mutational status of the PI3K pathway. Subsequently, we further analyzed the differences in prognosis, immunotherapy response, genomic alterations, functional characteristics, and immune microenvironment between the mutation and wild groups. Results The Kaplan-Meier survival curves displayed that PI3K pathway mutation predicted observably prolonged overall survival (OS) in the immunotherapy cohort MSKCC-2019 ( p = 0.012) but did not reach statistical significance in the non-immunotherapy cohorts TCGA-HNSC ( p = 0.68) and MD-Anderson ( p = 0.68). After incorporating several clinicopathologic features such as age, gender, and tumor mutation burden (TMB), the results of multivariate Cox regression analysis also demonstrated that the PI3K pathway mutation could indicate better immunotherapy outcomes in HNSC patients with a hazard ratio (HR) of 0.533 (95% CI: 0.313–0.910; p = 0.021) in the immunotherapy cohort MSKCC-2019, compared with 0.888 (95% CI: 0.636–1.241; p = 0.487) and 1.939 (95% CI: 0.483–7.781; p = 0.351) in the non-immunotherapy cohorts TCGA-HNSC and MD-Anderson. In addition, the results of the subclass mapping (SubMap) and the tumor immune dysfunction and exclusion (TIDE) also consistently suggested that patients in the mutation group are more likely to benefit from immunotherapy. And further studies showed that the mutation group owned significantly higher TMB, activated immune-related pathways, richer abundance of immune cells, and higher expression levels of immunomodulators. To improve the prognosis of the wild group, we identified five relatively sensitive potential drugs for the wild group, including “BMS-536924,” “linsitinib,” “NVP-TAE684,” “PLX-4720,” and “clonazepam.” Conclusions The PI3K pathway mutation status could be considered as a potential biomarker to predict better immunotherapeutic efficacy and clinical outcomes after immunotherapy in HNSC patients.
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