Objective To establish a model of isoniazid induced necrosis and apoptosis in HepG2 cell and to observe the expressions of Fas/Fas ligand (FasL) in this model.Methods HepG2 cells were treated with different dosages of isoniazid (0,1,2,4,6 and 8 mg/mL) or blank control for 24 hours.Flow cytometer was used to observe the cellular morphology of the HepG2 cell.Annexin V/propidium iodide double staining and flow cytometry were employed to detect the necrosis and apoptosis of HepG2 cells.The expressions of Fas/FasL on the cells were also determined by flow cytometry.The data were analyzed by one-way ANOVA.The comparisons between the drug groups and the control group were performed by using Dunnett t test. Results The higher the dose of isoniazid (4,6,8 mg/mL) was,the more necrosis and apoptosis were observed.In the 4,6 and 8mg/mL isoniazid arms,the total mortality rates were all higher than the control group [(32.1 ±7.5)％,(34.9±8.1)％,(38.2±9.4)％ vs (7.2±1.5)％ respectively](t=4.62,5.14 and 5.75,respectively; all P＜0.01 ).The expression levels of Fas increased along with the dose of isoniazid increasing [(8.7±2.2)％,(11.5±2.8)％,(12.3±3.0)％ and (10.6±2.9)％ in isoniazid 2,4,6and 8 mg/mL arms,respectively],which were all higher than that in control arm [(3.1 ±0.8) ％](t=2.97,P＜0.05; t=4.46,P＜0.01; t=4.88,P＜0.01; t=3.98,P＜0.05).Furthermore,the expressions of FasL increased as well when the dose of isoniazid increased.The expression levels of FasL were (16.2±3.5)％,(21.7±4.8)％ and (18.7±4.9)％,respectively in isoniazid 4,6 and 8 mg/mL arms,which were all higher than that in the control group [(7.4±1.4)％](t=3.11,P＜0.01; t=5.06,P＜0.01; t=3.99,P＜0.05).HepG2 cell necrosis increased with isoniazid of 8 mg/mL.However,the increase of apoptosis was not observed.Conclusion Isoniazid can induce HepG2 cell necrosis and apoptosis,and the apoptosis may be related with the increased expressions of the Fas/FasL on the cells.

Objective To investigate the relationship between the frequency of peripheral blood natural killer cells (NK) and HLA-Cw alleles in liver cirrhotic patients with chronic HBV infection and a-cute hepatitis B patients. Methods Thirty liver cirrhotic patients and 30 patients with acute hepatitis B were included in our study, and 41 healthy individuals were enrolled as controls. The numbers of circulating NK cells and activated NK ceils were analyzed by flow cytometry. HLA-Cw genotyping was conducted with polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO). Results The numbers of circu-lating NK cells and activated NK cells in liver cirrhotic patients were 13.22% ± 4.61% and 45.68% ± 14.64%, which was lower than that in healthy subjects (P < 0.05). The numbers of circulating NK cells and activated NK cells in acute hepatitis B patients were 22.62% ± 3.70% and 65.28%± 14.45%, which was higher than that in healthy subjects(P < 0. 05). There were statistically significant differences between the two groups(P < 0.01). The allele frequency of HLA-Cw * 15 in the patients with cirrhosis was signifi-cantly higher than that in the healthy (P < 0.05), and there was a significant negative correlation between the frequency of HLA-Cw * 15 and the numbers of activated NK cells in liver cirrhosis(r =4). 862, P < 0.05). No statistically significance was found between the group of acute hepatitis B and healthy subjects a- bout HLA-Cw(P > 0. 05). Conclusion The function of NK cells in liver cirrhotic patients is low, HLA-Cw * 15 gene may be one of the causes of effecting the antiviral function of NK ceils to induce the persistence of hepatitis B virus(HBV) infection.

Objective:To investigate the clinical value of radiomics based on computed tomography (CT) examination in preoperative differential diagnosis of pancreatic serous cystadenoma (SCA) and mucinous cystadenoma (MCA).Methods:The retrospective case-control study was conducted. The clinicopathological and imaging data of 154 patients with pancreatic cystic neoplasms who were admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from January 2012 to December 2019 were collected. There were 24 males and 130 females, aged (50±13)years. Of the 154 patients, 99 cases were diagnosed as SCA and 55 cases were diagnosed as MCA. All the 154 patients underwent plain and enhanced CT scan of pancreas before operation. The clinical characteristics, radiology features and radiomics features of all patients were collected to construct the clinical characteristics model, radiology model, radiomics model and fused model. The receiver operating characteristic (ROC) curve of each model was drawn, and those constructed models were evaluated by area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Based on the optimal model, the nomogram was constructed. Observation indicators: (1) establishment and validation of clinical characteristics model; (2) establishment and validation of radiology model; (3) establishment and validation of radiomics model; (4) establishment and validation of fused model; (5) nomogram of fused model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Results:(1) Establishment and validation of clinical characteristics model: 3 clinical characteristics, including age, symptoms and preoperative serum CA19-9, were selected using multinomial logistic linear regression analysis to construct the clinical characteristics model. Result of the multinomial logistic linear regression analysis was expressed by formula ①: clinical characteristics model score=0.635-0.007×age+0.054×clinical symptoms+0.108×preoperative serum CA19-9. The ROC curve for the test dataset of clinical characteristics model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of clinical characteristics model were 0.611(95% confidence interval as 0.488?0.734, P<0.05), 56.6%, 66.7%, 56.3%, 41.5%, 78.4% for the training dataset and 0.771(95% confidence interval as 0.624?0.919, P<0.05), 77.8%, 63.1%, 88.5%, 80.1%, 76.7% for the test dataset, respectively. (2) Establishment and validation of radiology model: 5 radiology characteristics, including tumor location, the number of tumors, tumor diameter of cross section, lobulated tumor and polycystic tumor (more than 6), were selected using multinomial logistic linear regression analysis to construct the radiology model. Result of the multinomial logistic linear regression analysis was expressed by formula ②: radiology model score=?0.034+0.300×tumor location+0.202×the number of tumors+0.014×tumor diameter of cross section?0.251×lobulated tumor?0.170×polycystic tumor (more than 6). The ROC curve for the test dataset of radiology model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of radiology model were 0.862(95% confidence interval as 0.791?0.932, P<0.05), 78.8%, 81.8%, 77.5%, 62.8%, 90.2% for the training dataset and 0.853(95% confidence interval as 0.713?0.994), P<0.05), 88.9%, 89.4%, 88.5%, 85.0%, 92.0% for the test dataset, respectively. (3) Establishment and validation of radiomics model: 4 categories of a total 1 067 radiomics features were extracted from 154 patients with pancreatic cystic neoplasms, including 7 first-order histogram features, 53 texture features, 848 wavelet features and 159 local binary pattern features. A total of 896 stable radiomics features were retained to construct the model, based on the condition of intraclass correlation coefficient >0.9. After selected by variance threshold and correlation coefficient threshold, 350 radiomics features were retained. Fifty synthetic radiomics features were constructed based on the original features in order to obtain potential radiomics features, and the total number of radiomics features was 400. After analyzed by the five-fold recursive feature elimination, 22 radiomics features were screened out, including 13 wavelet features, 7 synthetic radiomics features and 2 local binary pattern features. The support vector machine algorithm was used to construct the radiomics model. The penalty coefficient 'C' and parameter 'γ' of the radiomics model were 35.938 and 0.077, respectively. The kernel function of the radiomics model was 'radial basis function kernel'. The ROC curve of radiomics model using 5-fold cross validation was drawn. The average AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the radiomics model were 0.870 ( P<0.05), 83.1%, 81.8%, 83.8%, 73.8% and 89.2%, respectively. (4) Establishment and validation of fused model: the fused model was constructed after selecting the tumor location and lobulated tumor of radiology characteristics and radiomics score. Result of the multinomial logistic linear regression analysis was expressed by formula ③: fused model socre=?0.154+0.218×tumor location?0.223×lobulated tumor+0.621×radiomics score. The ROC curve for the test dataset of fused model was drawn. The AUC, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of fused model were 0.893(95% confidence interval as 0.828?0.958, P<0.05), 83.7%, 81.8%, 84.5%, 71.1%, 90.9% for the training dataset and 0.966(95% confidence interval as 0.921?0.999, P<0.05), 91.1%, 84.2%, 96.2%, 94.1%, 89.3% for the test dataset, respectively. (5) Nomogram of fused model: the nomogram of fused model was illustrated with the Youden index of 0.416. Conclusion:The prediction model based on the radiomics signature and radiological features extracted from preoperative CT examination can make the differential diagnosis of pancreatic SCA from MCA.

Objective: To analyze the trends on constituent ratio of non-ST-segment-elevation (NSTEMI) and ST-segment-elevation myocardial infarction (STEMI) and related in-hospital mortality in acute myocardial infarction (AMI) patients hospitalized in Beijing Anzhen Hospital from 2004 to 2014. Methods: This is a single-center, retrospective study. We reviewed all patients hospitalized for AMI in Beijing Anzhen Hospital from January 1 2004 to December 31 2014, and collected all related information including hospitalization stay, the type of AMI, revascularization and in-hospital mortality. We analyzed the trends of constituent ratio of NSTEMI and STEMI, and their in-hospital mortalities during the 11 years. Results: Data from a total of 23 864 patients with AMI, including 5 539 STEMI and 18 325 NSTEMI, were analyzed. Compared with STEMI patients, NSTEMI patients were older, less likely to be male (P<0.001), had higher prevalence of hypertension, hyperlipidemia, diabetes (P<0.001), and lower prevalence of smoking (P<0.001). Additionally, patients with NSTEMI were more likely to have prior history of MI (12.6% (695/5 539) vs. 7.4% (1 354/18 325), P<0.001) and coronary artery bypass graft surgery (2.7% (152/5 539) vs. 0.7% (124/18 325), P<0.001). The constituent ratio of NSTEMI was significantly increased during the observation period, rising from 15.8% (107/802) in 2004 to 35.7% (1 273/3 583) in 2014 (P value for trend <0.001). The in-hospital mortality of NSTEMI patients was significantly lower compared with those with STEMI (1.84% (102 cases) vs. 2.74% (502 cases), P<0.001). The mortality of both STEMI and NSTEMI were significantly decreased during the 11 years (both P value for χ² trend test <0.001). After adjusting for other risk factors, NSTEMI was independently associated with lower in-hospital mortality (OR=0.50, 95%CI 0.40-0.63, P<0.001). Conclusions In patients with AMI, the constituent ratio of NSTEMI versus STEMI is increased during the 11 years. The in-hospital mortality is decreased for both STEMI and NSTEMI patients in the past 11 years, and the in-hospital mortality rate of NSTEMI patients is lower than STEMI patients in this patient cohort during the observation period.

Objective:Through differential miRNA expression profiles and bioinformatics in the peripheral blood of patients with Keshan disease (KD) and healthy control, to explore the possible pathogenesis of KD.Methods:Ten patients with chronic KD (KD group) were selected in the severe disease area of KD in Wulian County, and 10 healthy subjects (control group) were selected in non-KD area of Dongchangfu District, Shandong Province. Blood sample of elbow vein was collected and plasma was separated. RNA-seq technology was used to construct the differential expression profiles of miRNA in KD and control groups. Target mRNAs were screened using Starbase, miRTarBase, miRDB and TargetScan. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to investigate the possible pathogenesis of KD.Results:Compared the control group and KD group, 132 differentially expressed miRNAs were screened out, including 90 upregulated and 42 downregulated miRNAs. Through Starbase, miRTarBase, miRDB and TargetScan, 53 miRNAs were obtained, 737 targeted mRNAs were obtained. GO analysis showed that the differential genes were mainly involved in the biological processes of Ras protein signal transduction, transmembrane transport, cell cycle regulation, cell adhesion, etc. KEGG pathway analysis showed that the differential genes were mainly involved in viral infection, endocytosis, adhesion spot and actin regulation.Conclusion:In this study, RNA-seq technology is used to obtain differential miRNA expression profiles of KD patients and healthy control, and target pathogenic genes and signaling pathways that may be related to KD are screened out.

Objective To explore the CT and MRI imaging and clinicopathological features of extranodal NK/T cell lymphoma (NK/TCL). Methods Sixty-six patients with NK/TCL diagnosed from 2002 June to 2016 April in Beijing Tongren Hospital with intact CT and/or MRI imaging results were enrolled in this study. All the patients had tailed clinical information and follow-up. The imaging and clinicopathological features were analyzed retrospectively and their prognostic value on overall survival was analyzed. Results There were 49 males and 17 females with median age of 42 years. The median follow-up time was 18 months. The cases showed surrounding invasions including 10 cases (15.2 %) in soft palate, 5 cases (7.6 %) in hard palate, 2 cases(3.0 %) in tonsil, 8 cases(12.1 %) in upper lip, 13 cases(19.7 %) in maxillofacial soft tissue, 9 cases (13.6 %) in eyelid, 10 cases (15.2 %) in orbital, 3 cases (4.5 %) in maxilla, 6 cases (9.1 %) in pterygopalatine fossa,6 cases(9.1 %)in infratemporal fossa,3 cases(4.5 %)in skull base, 3 cases(4.5 %) in eyeball and 2 cases (3.0 %) in brain tissue. Kaplan-Meier survival analysis found that the 2-year overall survival rates of the patients with the involvement of hard palate, upper lip, maxillofacial soft tissue, eyelid, orbital, maxillary, eyeball and brain organizer were lower than those of the patients without the involvement of these sites(χ2values were 4.470,4.041,4.456,13.933,8.986,4.000,44.121,6.527,16.822,respectively, all P< 0.05). Further multivariate Cox regression analysis showed that maxilla and brain involvement were independent adverse factors (RR=34.717, 95 % CI 3.404-354.035, P=0.003; RR=37.545, 95 % CI 3.188-442.187, P= 0.004). Conclusions MRI and CT examinations are of great value in diagnosis and prognostic assessment of NK/TCL. Clinicians can make correct and timely diagnosis by comprehensive clinical, radiological and pathological features and can make a detailed clinical assessment to give patients appropriate treatment,thus improving the outcome of the NK/TCL patients.

Objective To investigate the radiosensitizating effect of quercetin(QU)loaded manganese dioxide nanoparticles[Mn(QU)]on breast cancer cell line 4T1 and tumour-bearing mice.Methods Mang anese dioxide(MnO2)nanoparticles were synthesized by oleic acid template method.The morphology and chemical composition of MnO2 nanoparticles were characterized by transmission electron microscopy(TEM),scanning electron microscopy(SEM)and X-ray photoelectron spectroscopy.Then QU nanomaterials were encapsulated by using physical adsorption.The composition was characterized by ultraviolet spectrophotometer,and the ability of Mn(QU)nanoparticles reacting with different doses of hydrogen peroxide to produce oxygen at different pH values was detected by dissolved oxygen analyzer.CCK-8 assay was employed to detect the effects of different concentrations of Mn(QU)nanoparticles on the viability of 4T1 cells.Colony formation,γ-H2AX fluorescence staining,ROS fluorescence staining,LIVE/DEAD cell viability assay and flow cytometry were used to evaluate the radiosensitizing and pro-apoptotic effects of Mn(QU)nanoparticles on 4T1 cells.Finally,the effect of Mn(QU)nanoparticles combined with radiotherapy on tumor growth inhibition was evaluated in mouse model of 4T1 cell transplanted tumor.Results MnO2 nanoparticles with particle size of about 120 nm were successfully synthesized and encapsulated with QU.The oxygen generation capacity of the prepared Mn(QU)nanoparticles reacting with hydrogen peroxide was negatively correlated with pH value and positively with hydrogen peroxide concentration.The results of cell experiments showed that Mn(QU)nanoparticles at a concentration of 50 μg/mL had no obvious toxicity to 4T1 cells,but could significantly enhance the X-ray-induced killing effect on 4T1 cells,at a radiotherapy sensitization ratio of 1.61,improve DNA double-strand breaks and ROS production,and induce apoptosis of 4T1 cells.The results of tumor xenograft model experiment indicated that the inhibition of tumor volume was Mn(QU)nanoparticles combined with radiotherapy＞MnO2 nanoparticles combined radiotherapy＞QU combined radiotherapy＞Radiotherapy＞Control.Conclusion Mn(QU)nanoparticles combined with radiotherapy can significantly inhibit the proliferation and show radiosensitization of breast cancer 4T1 cells,and also exert a significant inhibitory effect on the growth of the transplanted tumor.

To explore the technical process and the therapeutic effect of using sequential surgical guide with independent intellectual property rights assisting immediate implantation and restoration of the full arch, with the support from the periodontal splint for mobile supporting teeth, patients with severe periodontitis who planned to undergo immediate full arch implantation were recruited from August 2019 to December 2020 at the Department of Prosthodontics, Department of Periodontology, Department of Implantology and First Clinical Division, Peking University School and Hospital of Stomatology. Through the procedure of collecting preoperative maxillofacial data, making systematic diagnostic design, making periodontal splints fixation, producing surgical guide, and carrying out guided surgery for full arch immediate implantation, eight cases were included. By registering the postoperative cone-beam CT (CBCT) with the preoperative data, the difference between the actual three-dimensional position of the implants and the virtual design was observed, and the accuracy of the implant placement position guided by the sequential guide was statistically analyzed using SPSS 25.0 software. Analysis indicators include coronal and apical global displacement, coronal horizontal and vertical displacement, apical horizontal and vertical displacement, and angular deviation. Results revealed that the 8 patients [2 males and 6 females, aged (49.0±9.3) years (38-65 years)] of recruited cases included 7 cases of maxilla and 1 cases of mandible. A total of 48 implants, of which 44 implants were placed upright and 4 were placed tilted, 16 implants in the anterior region and 32 implants in the posterior region. No guide plate fracture or damage to important anatomical structures were reported. The overall displacement at the coronal point [(0.83±0.48) mm] and the global displacement at the apical point [(1.36±0.57) mm] were within the clinically acceptable safety range, and the horizontal displacement and vertical displacement at the coronal point, horizontal displacement and vertical displacement at the apical point, and the angle deviation of implants axial have no statistic significant difference in the anterior and posterior region ( P>0.05). Periodontal splints combined with sequential surgical guides to assist patients with severe periodontitis for immediate full arch implantation and immediate restoration can expand the indications of guide assisted implant surgery. It meets the safety requirements in clinical applications.

ObjectiveTo explore the relationships between internet gaming disorder (IGD), interpersonal needs, loneliness, and depression in adolescents through the construction of a chain mediation model, to clarify the underlying mechanisms of these associations, and to provid a theoretical basis for depression prevention and intervention. MethodsBased on the data of the 7th Population Census, using convenient sampling method 1 106 adolescents aged between 10‒19 years in South China (176), North China (147), Central China (332), and East China (451) were selected to conduct a cross-sectional survey, with a ratio of 1∶1∶1.5∶2.5. The survey was conducted with a questionnaire consisting of general information (sex, age, grade, parents’ education level), the Chinese version of the IGDS9-SF, the INQ-15, the short-form of the ULS-8 and the PHQ-9 were used to evaluate the depression status of adolescents. Spearman correlation analysis was used to explore the correlation between the variables. A multiple-mediator model was constructed using IBM SPSS Statistics 22.0 PROCESS to examine the mediating effects of interpersonal needs and loneliness on the relationship between IGD and depression. The significance of the chain mediating effect was tested using the Bootstrap method. ResultsOverall, 39.06% (432/1 106) adolescents experienced depression. The incidence of depression among adolescents with smoking and without smoking was 62.50% and 38.36%, respectively. Similarly, the incidence of depression among adolescents with alcohol consuming and without alcohol consuming was 61.94% and 35.94%, respectively. There were statistically significant differences between IGD, interpersonal needs, loneliness, and depression (P<0.01). The chain mediation model demonstrated a good fit, and the bootstrap test showed that the 95%CI of each mediation path did not include 0, indicating significant mediation effects. The overall effect was 0.337. The direct effect of IGD on depression was significant (effect value=0.138, 95%CI:0.102-0.173, P<0.001). The mediation effects included three paths: ① IGD →interpersonal needs → depression (effect value=0.073, P<0.05), accounting for 21.47% of the total effect;② IGD→ loneliness → depression (effect value=0.093, P<0.05), accounting for 27.35%; and ③ IGD → interpersonal needs → loneliness → depression (effect value=0.036, P<0.05), accounting for 10.59%. ConclusionInterpersonal needs and loneliness independently and jointly mediate the relationship between IGD and depression among adolescents. To reduce depression and improve mental health in this population, measures should be taken to prevent and intervene in IGD, address adolescents’ social and emotional needs, enhance satisfaction of interpersonal needs, and reduce loneliness.