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.

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.

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air-blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.

Objective:To explore clustered epidemic of COVID-19 in Liaocheng city and analyze infection status and chain of transmission of the cases.Methods:A joint investigation team of emergency response for COVID-19 epidemic by CDC professional workers of Liaocheng city and district at two levels on January 30, 2020. According to a indicator case from ZH supermarkets, close contacts and related subjects were tracked and screened on February 1, including ZH supermarket employees, family members having contact history with related cases during January 13-26, supermarket clients during January 16-30 and family members of related cases. an epidemiological investigation was carried on and their swab of nose/throat were collected and were sent to Liaocheng CDC laboratory, real-time fluorescence quantitative RT-PCR was used to detect nucleic acids of SARS-CoV-2.Results:a total of 8 437 people were screened during January 30 to February 9, 2020 (120 employees of supermarket, 93 family members, and 8224 clients of supermarket). The epidemic was caused by ZH cases and brought clustered cases in four families. A total 25 cases of SARS-CoV-2 infection, the total infection rate of subjects was 0.30% (25/8 437) with 22 confirmed cases (0.26%, 22/8 437) and 3 asymptomatic patients (0.04%, 3/8 437), asymptomatic patients accounted for 12.00% (3/25) of all infection cases. The infection rates of supermarket employees, family members of confirmed cases and supermarket clients were 9.17% (11/120), 12.90% (12/93) and 0.02% (2/8 224).Conclusions:This was a cluster epidemic caused by one imported case of COVID-19 in a supermarket of Liaocheng city. Prevention and control of cluster epidemic should be focused on chain of community transmission and family cluster cases. It must also be an attention for transmission risk of asymptomatic patients.

The complement system is an important part of the innate immune system. More evidence showed that the function of complement was not only limited to the elimination of pathogens and other risk factors from the body but also affected the immune escape mechanism of the tumor through different activating pathways. Because of the complex and important role of complement in the tumor, this review expounds the mechanism of complement system participating in immune escape of the tumor from three aspects: complement inherent components, complement activation products and complement regulatory proteins. Additionally, these mechanisms are expected to provide a new application of complement in tumor immunotherapy with immune checkpoint inhibitors.

Objective:To study the correlation between serum homocysteine (Hcy) and the staging of gastric cancer,by comparing the concentrations of patients with gastric cancer at different pathological staging.Methods:90 patients with benign gastric diseases and 138 patients with gastric cancer were selected and admitted by Shandong University Qilu Hospital during the date from Mar 2014 to Jun 2015.The patients with gastric cancer were divided into 4 groups,according to the 7th AJCC Cancer Staging.To compare the difference of the concentration levels of Hcy and Tumor marks in different groups and analyze the relationship between benign disease and gastric cancer,and analyze it correlation with different pathological stagings of gastric cancer.Enzymatic cycling assay was used for detecting serum Hcy.Results:The serum Hcy concentration level in benign disease was (1 2.31 ± 3.22) μ mol/L,and significantly lower than cancer group(1 6.19 ± 4.84) μ mol/L,the difference was statistically significant (P＜0.05):The serum Hcy concentration levels increased gradually from staging I to staging Ⅳ,and the concentration level in staging Ⅰ was (13.94 ± 4.07) μ mol/L,in staging Ⅱ was (15.49 ± 4.09) μ mol/L,in staging Ⅲ was (17.10 ± 4.79) μ mol/L,in stagingⅣ was (19.81 ± 5.77) μ mol/L,the differences among the four groups were statistically significant(P＜0.05).Spearman Rank Correlation analysis confirmed that,the Hcy concentration level was positively related with pathological staging(r=0.503,P＜ 0.001).Logistic regression analysis showed that,the serum Hcy concentration level is significantly correlated with gastric cancer,after the adjustment of other risk factors (OR=1.208,P=0.003).Conclusions:The serum Hcy concentration level is closely correlated with gastric cancer staging,and increase significantly with the cancer staging (from staging Ⅰ to staging Ⅳ),so itcan be used to evaluate the severity of gastric cancer.