Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.

Objective:To evaluate the effect of the radiation dose of thoracic cage bone structure on clinical prognosis in patients with locally advanced non‐small cell lung cancer (LA‐NSCLC) receiving chemoradiotherapy, and to develop and verify a combined model combining the radiation dose of bone structure, the estimated radiation dose of immune cells (EDRIC) and other related factors to predict the prognosis of LA‐NSCLC.Methods:Clinical data of 197 patients with LA‐NSCLC who underwent chemoradiotherapy were retrospectively analyzed. All patients were randomly divided into the training set and testing set at a ratio of 7:3 using computer random partitioning. The EDRIC value was calculated using the model developed by Jin et al. and modified by Ladbury et al. The scope of the thoracic cage structure includes the ribs, sternal manubrium, sternal body, thoracic vertebral body, thoracic vertebral appendages, and thoracic vertebrae. The tumor volume, ERDIC, and average bone structure dose (D mean) were categorized into two groups using the P25, P50, P75 value from the quartile method. Univariate and multivariate Cox proportional hazards regression were used to analyze the influencing factors of overall survival (OS), local progression‐free survival (LPFS), and distant metastasis‐free survival (DMFS) for predicting the outcome, and significant correlated variables were retained to construct a combined prediction model with EDRIC. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curves were plotted for subjects at the 2‐year time point of the combined model to evaluate the predictive performance. The model was visualized through a nomograph. Results:In the thoracic cage bone structure, D mean > 47.3 Gy of the sternal manubrium was an independent risk factor of OS, LPFS, and DMFS of LA-NSCLC patients. D mean > 23.1 Gy of thoracic vertebral body was an independent risk factor of OS, and D mean > 14.4 Gy of thoracic vertebral body was an independent risk factor of DMFS. Among other variables, gross tumor volume (GTV) >50.2 cm 3 was a risk factor for OS, and GTV >87.0 cm 3 was a risk factor for LPFS. Planning target volume >571.9 cm 3 was a risk factor for DMFS. A combined prediction model for OS, LPFS, and DMFS was established with EDRIC using features significantly associated with these three predicted outcomes. The area under the ROC curve (AUC) of OS combined model in the training set and test set were 0.708 and 0.696, respectively, and the AUC of DMFS combined model were 0.675 and 0.639, respectively. The calibration curve and DCA curve of the two prediction endpoints showed that the combined model had good prediction accuracy and clinical benefit. However, the LPFS model was not good in accuracy and clinical applicability. Conclusions:The radiation dose of sternal manubrium and thoracic vertebral body in the thoracic cage bone structure is an independent influencing factor for the prognosis of LA‐NSCLC patients after chemoradiotherapy. The combined model has good predictive performance for OS and DMFS.

Objective:To evaluate the effect of the radiation dose of thoracic cage bone structure on clinical prognosis in patients with locally advanced non‐small cell lung cancer (LA‐NSCLC) receiving chemoradiotherapy, and to develop and verify a combined model combining the radiation dose of bone structure, the estimated radiation dose of immune cells (EDRIC) and other related factors to predict the prognosis of LA‐NSCLC.Methods:Clinical data of 197 patients with LA‐NSCLC who underwent chemoradiotherapy were retrospectively analyzed. All patients were randomly divided into the training set and testing set at a ratio of 7:3 using computer random partitioning. The EDRIC value was calculated using the model developed by Jin et al. and modified by Ladbury et al. The scope of the thoracic cage structure includes the ribs, sternal manubrium, sternal body, thoracic vertebral body, thoracic vertebral appendages, and thoracic vertebrae. The tumor volume, ERDIC, and average bone structure dose (D mean) were categorized into two groups using the P25, P50, P75 value from the quartile method. Univariate and multivariate Cox proportional hazards regression were used to analyze the influencing factors of overall survival (OS), local progression‐free survival (LPFS), and distant metastasis‐free survival (DMFS) for predicting the outcome, and significant correlated variables were retained to construct a combined prediction model with EDRIC. The receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curves were plotted for subjects at the 2‐year time point of the combined model to evaluate the predictive performance. The model was visualized through a nomograph. Results:In the thoracic cage bone structure, D mean > 47.3 Gy of the sternal manubrium was an independent risk factor of OS, LPFS, and DMFS of LA-NSCLC patients. D mean > 23.1 Gy of thoracic vertebral body was an independent risk factor of OS, and D mean > 14.4 Gy of thoracic vertebral body was an independent risk factor of DMFS. Among other variables, gross tumor volume (GTV) >50.2 cm 3 was a risk factor for OS, and GTV >87.0 cm 3 was a risk factor for LPFS. Planning target volume >571.9 cm 3 was a risk factor for DMFS. A combined prediction model for OS, LPFS, and DMFS was established with EDRIC using features significantly associated with these three predicted outcomes. The area under the ROC curve (AUC) of OS combined model in the training set and test set were 0.708 and 0.696, respectively, and the AUC of DMFS combined model were 0.675 and 0.639, respectively. The calibration curve and DCA curve of the two prediction endpoints showed that the combined model had good prediction accuracy and clinical benefit. However, the LPFS model was not good in accuracy and clinical applicability. Conclusions:The radiation dose of sternal manubrium and thoracic vertebral body in the thoracic cage bone structure is an independent influencing factor for the prognosis of LA‐NSCLC patients after chemoradiotherapy. The combined model has good predictive performance for OS and DMFS.

Objective:To determine the prevalence situation of adult female acne (AFA) patients and to explore the risk factors related to AFA.Methods:From September 2019 to June 2020, 290 female acne patients aged from 25 to 48 (29.57±4.50) years were surveyed with a questionnaire of risk factors and the prevalence situation of acne in the acne clinic of the Department of Dermatology, Wuxi No.2 Hospital Affiliated with Nanjing Medical University.Results:AFA occured more frequently in the jaw (95.17%), cheek (93.79%) and forehead (89.66%). Recurrent acne (38.62%) and comedonal acne (50.34%) more commonly occured. Cosmetics, endocrine, diet, genetics and other factors aggravated AFA. Age ( H=7.286, P>0.05; F=0.122, P>0.05), gonadal hormone concentrations ( Z=-0.365, P>0.05; χ 2=0.276, P>0.05), menstrual cycle ( Z=-0.274, P>0.05; χ 2=0.217, P>0.05), genetics ( Z=-1.244, P>0.05; χ 2=1.771, P>0.05) made no difference to acne grading and types. Excessive use of cosmetics could lead to increased comedo (χ 2=7.097, P<0.05). Cosmetics had no difference to acne grading ( Z=-0.065, P>0.05). Gonadal hormone concentrations were uncorrelated with menstrual cycle (χ 2=1.397, P>0.05). Conclusions:The pathogenesis of AFA is related to a variety of factors, which affect the skin barrier function and require comprehensive treatment.

Myeloid differentiation factor 88 (MyD88) plays an important role in tumorigenesis,development and malignant transformation,also participates in the microenvironment,proliferation,apoptosis,invasion,metastasis and tumor resistance.MyD88 may serve as a new and meaningful therapeutic target,which can promote the growth and development of tumors by regulating multiple signaling pathways and enhance the drug resistance of tumor cells.

AIM:To observe the expression of TLR2 and TLR4 on mast cells (MCs) in the periapical tissues from different types of human chronic periapical diseases , and to analyze the role of TLR 2 and TLR4 on tryptase-positive MCs in the immunopathogenesis of human chronic periapical diseases .METHODS: A total of 60 donors, including healthy control group , periapical granuloma group and periapical cyst group , were enrolled in the study .The periapical tis-sue specimens were fixed in 10%buffered formalin and stained with hematoxylin and eosin for histopathology , or stained with double-immunofluorescence for identification of TLR 2-tryptase and TLR4-tryptase double-positive MCs in the periapical tissues.RESULTS:Compared with the healthy control , the densities of TLR2-tryptase and TLR4-tryptase double-positive MCs in periapical tissues were significantly increased in human chronic periapical diseases (P<0.01).The densities of TLR2-tryptase and TLR4-tryptase double-positive MCs in periapical cyst group were significantly higher than those in peria-pical granuloma group (P<0.01).CONCLUSION:TLR2 and TLR4 were expressed on the MCs in the periapical tissues of human chronic periapical diseases .TLR2-tryptase and TLR4-tryptase double-positive MCs may participate in the patho-genesis of chronic periapical diseases .

Background Extracellular matrix (ECM) fibrosis leads to corneal scaring during the process of cornea wound healing.Transforming growth factor-β1 (TGF-β1) is known to mediate overproduce of ECM components.Our previous study developed a three-dimensional model for corneal stromal cells culture in vitro.Objective The hypothesis of this study was to apply TGF-β1 in the three-dimensional culture system to establish a corneal stroma ECM fibrosis model.Methods Fresh bovine corneas were extracted for the culture of bovine keratocytes in constructed three-dimension culture system.The Pellets were cultured in the DMEM/F12+ 10％ fetal bovine serum (FBS) medium with 0.5 ng/ml or 1.0 ng/ml TGF-β1 or without TGF-β1,respectively.Calcein AM/(propidium iodide) PI staining was employed to assay the cell viability 2 weeks after culture.The expressions of α-smooth muscle actin (α-SMA),type Ⅰ collagen (Col Ⅰ) and Col Ⅲ mRNA and protein in the cells were detected by real-time PCR and Western blot respectively 48 hours,1 week and 2 weeks after cultured.The results were statistically analyzed.Results Cultured for 48 hours in the Pellet system,corneal stromal cells clustered and was identified alive by Calcein-AM/PI staining in 2 weeks.The relative expression levels of α-SMA,Col Ⅰ and Col m mRNA were elevated in both the 0.5 ng/ml and 1.0 ng/ml TGF-β1 supplement groups in comparison with the only DMEM/F12+10％ FBS group,with marked difference among the three groups (Fgroup =696.745,P＜0.001;Fgroup =35.166,P＜0.001;Fgroup =33.677,P＜0.001),and the expression levels increased with the lapse of culture time (Ftime =5.863,P＜0.05;Ftime =298.614,P＜0.001;Ftime =607.472,P＜0.001).The synthetic rate of Col Ⅲ mRNA was obviously faster than that of Col Ⅰ mRNA.Western blot showed that only a trace of α-SMA,Col Ⅰ and Col Ⅲ were detected 48 hours and 1 week after culture.The expression levels of α-SMA,Col Ⅰ and Col Ⅲ in Pellet system in 0.5 ng/ml TGF-β1 medium were 0.395±0.208,1.060±0.175 and 0.629±0.382,and in 1.0 ng/ml TGF-β1 medium were 0.758±0.228,1.201 ±0.187 and 0.753±0.468,respectively 2 weeks after culture,significant differences were shown among the three groups (α-SMA:F=10.691,P＜0.05;Col Ⅰ:F=14.094,P＜0.05;Col Ⅲ:F=10.995,P＜0.05).Conclusions Addition of TGF-β1 and serum enhance the assembly and fibrosis of ECM,showing the higher expressions of specific fibrotic markers in bovine keratocytes Pellet.This culture systerm can be used as a candidate three-dimensional model for corneal stroma ECM fibrosis.