OBJECTIVE To investigate the equivalence of different decoction processes based on rat model of hypertension with liver-yang hyperactivity. METHODS Inductively coupled plasma mass spectrometry （ICP-MS） was used to compare the dissolution differences of inorganic elements in the powder-directly-decocted decoction versus the pieces-decocted-first decoction of Ostreae Concha- Haliotidis Concha- Margaritifera Concha drug pair. Six SD rats were included in the normal group. The spontaneously hypertensive rats were given Aconite decoction for six weeks to induce the hypertension model with liver-yang hyperactivity. After successful modeling， 48 rats were randomly divided into the model group， the captopril group [positive control， 8 mL/（kg·d） ] ， as well as low-， medium-， and high-dose groups of pieces decocted first or directly powder decocted [2.02， 4.05， 8.10 mL/（kg·d） ] ， with 6 rats in each group. Each group received the corresponding drug or equal volume of pure water intragastrically， once a day， for two consecutive weeks. After the last administration， the degree of irritability， facial temperature， pressure pain threshold， blood pressure， and pathological changes of the thoracic aorta were observed in each group. Serum nitric oxide （NO） and plasma angiotensin Ⅱ （Ang Ⅱ）， renin， and aldosterone （ALD） levels were also measured. RESULTS ICP-MS analysis results showed statistically significant differences in the contents of macroelements Li， Na， Mg， Ca， Mn， Ga， Sr， Mo， Cd， Sn， and Sb， between the powder-directly-decocted decoction and the pieces-decocted-first decoction （ P ＜0.05） ，the elements P， Cr， Fe， Ni， Zn， Hg， Tl， and Pb were not detected in either decoction. Animal experiments showed that after two weeks of administration， compared with the model group， the facial temperature， and blood pressure decreased in all treatment groups， while the pressure pain threshold increased； plasma levels of Ang Ⅱ， renin and ALD， as well as the serum level of NO were all decreased， and thoracic aortic media thickness was significantly reduced， most of the differences in the above indicators were statistically significant （ P ＜0.05 or P ＜0.01 or P ＜0.001）. Pathological observation showed improvement in thoracic aortic pathological injury. CONCLUSIONS The powder-directly-decocted process for the Ostreae Concha- Haliotidis Concha- Margaritifera Concha drug pair significantly promotes the dissolution of key elements such as Ca， Mg， and Sr without increasing the dissolution of harmful elements. It is equivalent to the traditional pieces-decocted-first in alleviating liver-yang hyperactivity syndrome， lowering blood pressure， and protecting the vascular endothelium， and even shows better performance in some indicators.

Objective To explore the application value of CT-based radiomics in differentiating pneumonia-type mucinous adenocarcinoma(PTMA)from organizing pneumonia(OP).Methods A total of 52 PTMA patients and 102 OP patients were retrospectively included and randomly divided into training set(n=124)and test set(n=30)in an 8∶2 ratio.Eight PTMA patients and 22 OP patients from another hospital during the same period were included as external validation set(n=30).Clinical characteristics and CT signs of the patients were selected to construct the clinical model.Radiomics features were extracted and dimensionality reduction was performed through the least absolute shrinkage and selection operator(LASSO)algorithm.A radiomics model was constructed and the Radiomics score(Radscore)was calculated.The Radscore was combined with clinical factors to establish the combined model and a nomogram was illustrated.The models' fitting degree was analyzed by the calibration curve,while their efficacy was evaluated by the receiver operating characteristic(ROC)curve and decision curve analysis(DCA).Results The clinical model,established based on the border,cystic space and bronchial leafless tree sign,achieved area under the curve(AUC)of 0.850,0.782,and 0.759 in the training set,test set,and external validation set,respectively.Thirteen features were obtained to construct the radiomics model,with AUC of 0.925,0.865,and 0.830,respectively.The AUC of the combined model were 0.970,0.905,and 0.864,respectively,in which the calibration curve demonstrated good model fitting.DCA indicated that the combined model had the greatest clinical net benefit.Conclusion The combined model based on CT radiomics can effectively distinguish PTMA from OP.

Epidermal growth factor receptor inhibitor (EGFRI) -related paronychia is a condition clearly related to EGFRI therapy, characterized by periungual erythema, edema, purulent exudates, periungual or subungual granulomatous lesions, and sometimes accompanied by thinning, fragility or even splitting and seperation of nail plates. Inhibition of epidermal function, inflammation and secondary infections, as well as angiogenesis are the core processes in the occurrence and development of EGFRI-related paronychia. This review summarizes epidemiology, pathogenesis, clinical manifestations, prevention and treatment of EGFRI-related paronychia.

Objective To explore the application value of CT-based radiomics in differentiating pneumonia-type mucinous adenocarcinoma(PTMA)from organizing pneumonia(OP).Methods A total of 52 PTMA patients and 102 OP patients were retrospectively included and randomly divided into training set(n=124)and test set(n=30)in an 8∶2 ratio.Eight PTMA patients and 22 OP patients from another hospital during the same period were included as external validation set(n=30).Clinical characteristics and CT signs of the patients were selected to construct the clinical model.Radiomics features were extracted and dimensionality reduction was performed through the least absolute shrinkage and selection operator(LASSO)algorithm.A radiomics model was constructed and the Radiomics score(Radscore)was calculated.The Radscore was combined with clinical factors to establish the combined model and a nomogram was illustrated.The models' fitting degree was analyzed by the calibration curve,while their efficacy was evaluated by the receiver operating characteristic(ROC)curve and decision curve analysis(DCA).Results The clinical model,established based on the border,cystic space and bronchial leafless tree sign,achieved area under the curve(AUC)of 0.850,0.782,and 0.759 in the training set,test set,and external validation set,respectively.Thirteen features were obtained to construct the radiomics model,with AUC of 0.925,0.865,and 0.830,respectively.The AUC of the combined model were 0.970,0.905,and 0.864,respectively,in which the calibration curve demonstrated good model fitting.DCA indicated that the combined model had the greatest clinical net benefit.Conclusion The combined model based on CT radiomics can effectively distinguish PTMA from OP.

Epidermal growth factor receptor inhibitor (EGFRI) -related paronychia is a condition clearly related to EGFRI therapy, characterized by periungual erythema, edema, purulent exudates, periungual or subungual granulomatous lesions, and sometimes accompanied by thinning, fragility or even splitting and seperation of nail plates. Inhibition of epidermal function, inflammation and secondary infections, as well as angiogenesis are the core processes in the occurrence and development of EGFRI-related paronychia. This review summarizes epidemiology, pathogenesis, clinical manifestations, prevention and treatment of EGFRI-related paronychia.

Objective As a signaling molecule,NO regulates key physiological processes and is closely related to periodontitis.To investigate the effect of flavonoid NO donor composite nanoparticles(G10@HAP/MSN@ZnO@COS)on osteogenic differentiation of periodontal ligament stem cells(PDLSCs)by regulating macrophage polarization.Methods The novel NO donor drug G10 was loaded on hydroxyapatite/mesoporous silicanant particles(HAP/MSN),filled with zinc oxide(ZnO),and then coated with chitosan(COS)to prepare composite nanoparticles(G10@HAP/MSN@ZnO@COS).The best concentration of G10@HAP/MSN@ZnO@COS was screened to promote cell proliferation by CCK-8 cell experiment.After the mouse mononuclear macrophages were stimulated by lipopo-lysaccharide,the mice were divided into four groups:Control group,G10 group,HAP/MSN@ZnO@COS group and G10@HAP/MSN@ZnO@COS group.Each group was cultured with fresh medium,5 μg/mL G10,5 μg/mL HAP/MSN@ZnO@COS and 5 μg/mL G10@HAP/MSN@ZnO@COS for 72 h respectively.ELISA and RT-qPCR were used to detect the expression of cytokines(TNF-α,IL-6,IL-1β,iNOS,IL-10)and mRNA expression in each group,and the phenotypic changes of M1/M2 were evaluated.The supernatant of each culture medium was used as conditioned medium to culture PDLSCs,and the osteogenic ability and cell miner-alization were evaluated by alkaline phosphatase activity test and alizarin red staining.Results CCK-8 experiment showed that G10@HAP/MSN@ZnO@COS of 5 μg/mL could significantly promote the proliferation of PDLSCs.The results of ELISA showed that compared with Control group,the expression of M1 type marker IL-1β,IL-6,TNF-α and iNOS in G10@HAP/MSN@ZnO@COS group was significantly decreased(P＜0.000 1),while the expression of M2 type marker IL-10 was significantly increased(P＜0.000 1).The results of RT-qPCR were consistent with those of ELISA,which showed that the expression of M1-related genes in G10@HAP/MSN@ZnO@COS group decreased significantly(P＜0.01).The results of alizarin red staining and alkaline phosphatase activity test showed that the number of mineralized nodules and alkaline phosphatase activity in G10@HAP/MSN@ZnO@COS-CM group were significantly higher than those in other groups(P＜0.000 1).Conclusion Composite nanoparticles(G10@HAP/MSN@ZnO@COS)can effectively inhibit the polarization of macrophages to M1 phenotype and promote it to M2 phenotypic polarization.The anti-inflammatory microenvironment regulated by G10@HAP/MSN@ZnO@COS can en-hance the osteogenic differentiation of PDLSCs.

Objective:To construct the prediction model of knee degeneration in patients with knee osteoarthritis based on bioelectrical impedance index, and evaluate the prediction performance and application efficiency of the model.Methods:This was a cross-sectional study. From May to July 2021, 248 knee joints of 124 patients with knee osteoarthritis at home from Shijiazhuang Yuqiang Community Health Service Center who participated in physical examination were selected by convenience sampling to establish the model. According to Kellgren-Lawrence (K-L) grading system, the knee joints were divided into four groups, namely K-L1 ( n=19) , K-L2 ( n=103) , K-L3 ( n=96) , and K-L4 ( n=30) . The indicators included in the model were selected through analysis of variance or Kruskal-Wallis test, and a prediction model of knee degeneration was established using support vector machine, and the model was optimized using grid parameter optimization method. The prediction performance of the model was evaluated by the area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, accuracy, positive predictive value and negative predictive value. Results:The indicators in the model included age, complications, lumbar/back/hip pain, high-risk occupation, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) -pain, WOMAC-function, capacitive reactance and phase angle. The area under the ROC curve of the training set model was 0.999, the prediction accuracy was 0.920, and the 95% confidence interval was 0.868 to 0.957. The area under the ROC curve of the test set model was 0.833, the prediction accuracy was 0.682, and the 95% confidence interval was 0.572 to 0.780.Conclusions:The prediction model of knee degeneration has good prediction performance and is easy to use, which can be used as a screening tool for knee degeneration in patients with knee osteoarthritis.

People as third-party observers, without direct self-interest, may punish norm violators to maintain social norms. However, third-party judgment and the follow-up punishment might be susceptible to the way we frame (i.e., verbally describe) a norm violation. We conducted a behavioral and a neuroimaging experiment to investigate the above phenomenon, which we call the "third-party framing effect". In these experiments, participants observed an anonymous perpetrator deciding whether to keep her/his economic benefit while exposing a victim to a risk of physical pain (described as "harming others" in one condition and "not helping others" in the other condition), then they had a chance to punish that perpetrator at their own cost. Our results showed that the participants were more willing to execute third-party punishment under the harm frame compared to the help frame, manifesting a framing effect. Self-reported anger toward perpetrators mediated the relationship between empathy toward victims and the framing effect. Meanwhile, activation of the insula mediated the relationship between mid-cingulate cortex activation and the framing effect; the functional connectivity between these regions significantly predicted the size of the framing effect. These findings shed light on the psychological and neural mechanisms of the third-party framing effect.
Empathy ; Female ; Gyrus Cinguli ; Humans ; Neuroimaging ; Pain ; Punishment/psychology*

Epidermal growth factor receptor (EGFR) is one of the most common targeted oncogenes in non-small cell lung cancer (NSCLC). The third-generation EGFR tyrosine kinase inhibitors (TKIs) have become the standard treatment for metastatic or recurrent NSCLC patients harboring EGFR positive or concomitant T790M mutations. However, the inevitable emergence of acquired resistance markedly limits their prolonged clinical benefits, although the third-generation EGFR TKIs have shown potent clinical outcomes in initial several months. This paper firstly reviews the characEpidermal growth factor receptor (EGFR) is one of the most common targeted oncogenes in non-small cell lung cancer (NSCLC). The third-generation EGFR tyrosine kinase inhibitors (TKIs) have become the standard treatment for metastatic or recurrent NSCLC patients harboring EGFR positive or concomitant T790M mutations. However, the inevitable emergence of acquired resistance markedly limits their prolonged clinical benefits, although the third-generation EGFR TKIs have shown potent clinical outcomes in initial several months. This paper firstly reviews the characteristics and clinical efficacy of the third-generation EGFR TKIs in the market or in the clinical development. Then this article summarizes the detailed mechanisms behind the acquired drug resistance of third-generation EGFR TKIs，and further expounds the current treatment strategies to overcome the resistance. Collectively, this review could provide more information for the development and clinical application of drugs targeting EGFR.

Pyroptosis, a pro-inflammatory programmed cell death, is different from apoptosis and necroptosis, which is characterized by the activation of inflammasome and caspase family members and the cleavage of gasdermin family members, resulting in pores in the cell membrane accompanied by the release of inflammatory cytokines and a series of inflammatory reactions. Pyroptosis has a dual effect on tumors: on one hand, pyroptosis can inhibit tumor growth; on the other hand, a series of inflammatory responses triggered by excessively activated pyroptosis increase the risk of tumorigenesis. Pyroptosis can activate anti-tumor immune responses and induce pyroptosis in patients with low immune activity or no response to other immunotherapies, which has certain application prospects for tumor therapy.