Objective:To discuss the anti-inflammatory and antioxidant effect of mesalazine(MSZ)in the RAW264.7 cell model,and to elucidate its therapeutic effect on periodontitis in the rats.Methods:The proliferation rates of RAW264.7 cells stimulated by different concentrations(0,62.5,125.0,250.0,500.0,1 000.0,and 2 000.0 mg·L-1)of MSZ were detected by CCK-8 method to determine the optimal concentration of MSZ for cell treatment.Porphyromonas gingivalis lipopolysaccharide(P.g-LPS)and MSZ were used to treat the RAW264.7 cells,and the cells were divided into control group,P.g-LPS group,and MSZ+P.g-LPS group.The levels of reactive oxygen species(ROS)in the cells in various groups were detected by the DCFH-DA fluorescent probe assay;the malondialdehyde(MDA)levels,glutathione(GSH)levels and superoxide dismutase(SOD)activities in the cells in various groups were detected by ELISA method;the expression levels of inflammatory factors interleukin-8(IL-8)and interleukin-1β(IL-1β)mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.The periodontitis rat model was established by the ligation method combined with the injection of P.g bacterial fluid.A total of 18 rats were randomly divided into control group(without treatment),model group(making period ontits model),and drug administration group(making periodontits model and given MSZ),and there were 6 rats in each group.Micro-CT was used to assess the alveolar bone destruction of the rats in various groups;HE staining was used to observe the morphology of periodontal tissue of the rats in various groups.Results:Compared with control group,the proliferation rate of the cells in 500.0 mg·L-1 MSZ group was significantly increased(P＜0.01),so 500.0 mg·L-1 MSZ was subsequently selected to treat the cells.Compared with control group,the levels of ROS and MDA in the cells in P.g-LPS group were significantly increased(P＜0.01),and the level of GSH and activity of SOD were significantly decreased(P＜0.01),and the expression levels of IL-1β and IL-8 mRNA were significantly increased(P＜0.01);compared with P.g-LPS group,the levels of ROS and MDA in the cells in MSZ+P.g-LPS group were significantly decreased(P＜0.01),the level of GSH and activity of SOD were significantly increased(P＜0.01),and the expression levels of IL-1β and IL-8 mRNA were significantly decreased(P＜0.01).The micro-CT assay results showed that compared with control group,the distance from the cemento-enamel junction to alveolar bone crest(CEJ-ABC)of the rats in model group was significantly increased(P＜0.01),and the bone volume fraction(BV/TV)was significantly decreaced(P＜0.05);compared with model group;the CEJ-ABC of the rats in drug administration group was decreased(P＜0.01),and the BV/TV was increased(P＜0.05).The HE staining results showed that the inflammatory cell infiltration in periodontal tissue of the rats in drug administration group was reduced,and epithelial attachment was restored.Conclusion:MSZ effectively inhibits the production of pro-inflammatory factors and peroxides in the P.g-LPS-induced RAW264.7 cells,improves the cellular anti-inflammatory and antioxidant capacity,inhibits the alveolar bone resorption,and alleviates the inflammation of periodontal tissues in the periodontitis rats.

Objective:To discuss the effects of superelastic nickel-titanium archwires(SENT)and heat-activated nickel-titanium archwires(HANT)on the initial alignment efficiency of mandibular anterior teeth and pain levels of the patients with extraction orthodontic treatment and non-extraction orthodontic treatment by using low-friction self-ligating brackets,and to provide the basis for the selection of the most suitable archwire in orthodontic clinical practice.Methods:Eighty patients underwent fixed orthodontic treatment with self-ligating brackets were randomly assigned to SENT or HANT subgroups,and there were 40 patients in extraction orthodontic treatment group and 40 patients in non-extraction orthodontic treatment group.A single operator fully engaged a 0.014-inch straight archwire into the brackets.The patients,operators,and data measurers were all blinded;the initial clinical alignment efficiency of the archwires of the patients in various groups was observed,and the Little's index was calculated;the visual analog scale(VAS)scores and pain perception of the patients in various groups were recorded 4 h after initial bonding of the appliances and every day before breakfast during the first week of orthodontic treatment;multivariate regression analysis was performed for the initial Little's index,gender,and age,and the influence factors of pain in the patients was analyzed.Results:There were no significant differences in age,gender,and initial Little's index among the patients in extraction group and non-extraction group(P＞0.05).Compared with before treatment,the Little's indexes of the patients in both HANT and SENT subgroups in non-extraction orthedontic treatment group were decreased 4 weeks after treatment,but the difference between groups was not significant(P＞0.05).Compared with SENT subgroup in non-extraction orthodontic treatment group,the Little's index of the patients in HANT subgroup was decreased(P＜0.05).In extraction orthodontic treatment group,there were no significant differences in Little's indexes of the patients between the HANT and SENT subgroups before and after treatment(P＞0.05).The pain perception peaked on the first day after initial bonding and gradually decreased to baseline levels.The patients in SENT and HANT subgroups in both extraction and non-extraction orthodontic treatment groups showed the similar patterns of pain change.There were no significant differences in the average VAS scores and maximum pain intensity scores between the patients in SENT and HANT subgroups at different time points(P＞0.05).The type of archwire had no significant effect on the degree of pain,while time significantly affected the degree of pain.The multivariate regression analysis results showed a significant correlation between initial Little's index and maximum VAS scores of the patients in extraction orthodontic treatment group(b=0.359,P=0.033).Gender and age did not affect the degree of pain of the patients in either group.Conclusion:When applying low-friction self-ligating brackets for orthodontic treatment,the initial alignment efficiency with 0.014-inch HANT archwires is superior to 0.014-inch SENT archwires in non-extraction treatment group,while both archwires show the same efficiency in extraction patients.SENT and HANT archwires do not affect the initial degrees of pain of the orthodontic patients.

Objective:To discuss the regulatory effect of physiological tensile stress on the differentiation of chondrocytes,and to clarify the associated signaling pathway mechanism.Methods:The ATDC5 chondrocytes were cultured in vitro and subjected to physiological tensile stress by four-point bending cell mechanical loading device.Initially,the cells were divided into control group and tensile stress group(2 000 μstrain/2 h group),and further divided into different stress magnitudes(1 000,2 000,and 3 000 μstrain)for 2 h,and 2 000 μstrain for different duration time(1,2,and 4 h)groups;the cells without tensile stress were used as control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of type Ⅱ collagen(Col-Ⅱ),type Ⅹ collagen(Col-Ⅹ),aggregated proteoglycom(Aggrecan),sex-determining region Y-box protein 9(SOX9),vascular endothelial growth factor(VEGF),proliferating cell nuclear antigen(PCNA),Nel-like molecule tyep 1(Nell-1),Runt-related transcription factor 2(Runx2),Indian hedgehog(Ihh),patched homolog 1(Ptch-1),GLI family zinc finger protein 1(Gli-1),and hedgehog interacting protein 1(Hhip-1)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1,Runx2,and Ihh proteins in the cells in various groups.The ATDC5 cells were divided into control group,cyclopamine group,tensile stress group,and cyclopamine + tensile stress group.RT-qPCR method was used to detect the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1 and Ihh proteins in the cells in various groups.Results:Compared with control group,the expression levels of Col-Ⅱ,Col-Ⅹ,Aggrecan,SOX9,VEGF,and PCNA mRNA in the cells in 2 000 μstrain/2 h group were significantly increased(P<0.01);after treated with 2 000 μstrain tensile stress for different duration time(1,2,and 4 h)or different tensile stresses(1 000,2 000,and 3 000 μstrain)for 2 h,compared with control group,the expression levels of Runx2 mRNA in the cells in other groups were increased with the prolongation of time or the increasing of tensile stress(P<0.01),and the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA were gradually increased(P<0.01),the expression levels reached the peaking at 2 000 μstrain/2 h,and then decreased but remained significantly higher than that in control group(P<0.01).The Western blotting results showed that the expression levels of Nell-1,Runx2,and Ihh proteins in the cells were consistent with the change trend of mRNA expression levels.After pre-treated with cyclopamine,compared with control group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine group were significantly decreased(P<0.01),and the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in tensile stress and cyclopamine+tensile stress groups were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine+tensile stress group were significantly increased(P<0.01);compared with tensile stress group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine + tensile stress group were significantly decreased(P<0.01).Compared with control group,the expression level of Ihh protein in the cells in cyclopamine group was significantly decreased(P<0.01),but there was no significant difference in expression level of Nell-1 protein in the cells between control group and cyclopamine group(P>0.05),while the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with tensile stress group,in the expression levels of Nell-1 and Ihh proteins in the cells in cyclopamine + tensile stress group had no significant differences(P>0.05).Conclusion:After stimulated with physiological tensile stress,Nell-1 can activate the Ihh signaling pathway upstream,and regulate the differentiation of the ATDC5 chondrocytes.

Objective:To investigate the risk factors of the occurrence of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis and the effect of proton pump inhibitor (PPI) on OHE.Methods:This study was led by the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) and Shanghai East Hospital of Tongji University School of Medicine, and a total of 13 hospitals participated. From July 31, 2020 to December 10, 2021, a total of 184 liver cirrhosis patients without prior OHE and with ≥2-year follow-up from the above 2 leading hospitals, and other hospitals such as Guangzhou Eighth People′s Hospital of Guangzhou Medical University and Affiliated Hospital of Zunyi Medical University were enrolled. According to whether OHE occurred during the 2-year follow-up period, the 184 patients were divided into OHE group (22 cases) and non-OHE group (162 cases). The clinical data of all the patients were collected, including the laboratory parameters such as international normalized ratio (INR), the usage of PPI, the occurrence of gastrointestinal bleeding, infection, liver cancer and other complications, and survival status. Multivariate logistic regression model was used to analyze the independent risk factors for OHE in patients with liver cirrhosis. Kaplan-Meier survival curve was performed to analyze the effect of PPI on the survival rate of patients with liver cirrhosis. Chi-square test and Cochran-Mantel-Haenszel test were used for statistical analysis.Results:The result of multivariate logistic regression analysis showed that INR ( OR=11.331, 95% confidence interval (95% CI) 2.415 to 53.156, P =0.002) and PPI ( OR=6.794, 95% CI 2.359 to 19.567, P<0.001) were independent risk factors for OHE in patients with liver cirrhosis. The rate of PPI usage of the OHE group was higher than that of the non-OHE group (72.7%, 16/22 vs. 30.9%, 50/162), and the difference was statistically significant ( χ2=14.76, P<0.001). After the patients with gastrointestinal bleeding, infection and liver diseases-related deaths were excluded respectively, the rates of PPI usage of the OHE group were still higher than that of the non-OHE group (8/12 vs. 21.3%, 27/127; 11/16 vs. 25.0%, 35/140; 12/15 vs. 29.0%, 45/155), and the differences were all statistically significant ( χ2=9.71, 11.20 and 15.94; all P<0.01). Kaplan-Meier survival curve analysis showed that the 2-year cumulative survival rate of liver cirrhosis patients with PPI usage was lower than that of the patients without PPI usage (86.4%, 57/66 vs. 95.8%, 113/118), and the difference was statistically significant ( χ2=5.37, P =0.020). Conclusion:PPI is an independent risk factor for OHE in patients with liver cirrhosis, and may increase the risk of liver disease-related death.

Objective:To investigate the risk factors of the occurrence of overt hepatic encephalopathy (OHE) in patients with liver cirrhosis and the effect of proton pump inhibitor (PPI) on OHE.Methods:This study was led by the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) and Shanghai East Hospital of Tongji University School of Medicine, and a total of 13 hospitals participated. From July 31, 2020 to December 10, 2021, a total of 184 liver cirrhosis patients without prior OHE and with ≥2-year follow-up from the above 2 leading hospitals, and other hospitals such as Guangzhou Eighth People′s Hospital of Guangzhou Medical University and Affiliated Hospital of Zunyi Medical University were enrolled. According to whether OHE occurred during the 2-year follow-up period, the 184 patients were divided into OHE group (22 cases) and non-OHE group (162 cases). The clinical data of all the patients were collected, including the laboratory parameters such as international normalized ratio (INR), the usage of PPI, the occurrence of gastrointestinal bleeding, infection, liver cancer and other complications, and survival status. Multivariate logistic regression model was used to analyze the independent risk factors for OHE in patients with liver cirrhosis. Kaplan-Meier survival curve was performed to analyze the effect of PPI on the survival rate of patients with liver cirrhosis. Chi-square test and Cochran-Mantel-Haenszel test were used for statistical analysis.Results:The result of multivariate logistic regression analysis showed that INR ( OR=11.331, 95% confidence interval (95% CI) 2.415 to 53.156, P =0.002) and PPI ( OR=6.794, 95% CI 2.359 to 19.567, P<0.001) were independent risk factors for OHE in patients with liver cirrhosis. The rate of PPI usage of the OHE group was higher than that of the non-OHE group (72.7%, 16/22 vs. 30.9%, 50/162), and the difference was statistically significant ( χ2=14.76, P<0.001). After the patients with gastrointestinal bleeding, infection and liver diseases-related deaths were excluded respectively, the rates of PPI usage of the OHE group were still higher than that of the non-OHE group (8/12 vs. 21.3%, 27/127; 11/16 vs. 25.0%, 35/140; 12/15 vs. 29.0%, 45/155), and the differences were all statistically significant ( χ2=9.71, 11.20 and 15.94; all P<0.01). Kaplan-Meier survival curve analysis showed that the 2-year cumulative survival rate of liver cirrhosis patients with PPI usage was lower than that of the patients without PPI usage (86.4%, 57/66 vs. 95.8%, 113/118), and the difference was statistically significant ( χ2=5.37, P =0.020). Conclusion:PPI is an independent risk factor for OHE in patients with liver cirrhosis, and may increase the risk of liver disease-related death.

Objective:To screen highly expressed inflammatory factors in diabetic nephropathy models using protein microarray, analyze differential genes and their regulatory networks, and predict potential therapeutic small molecular compounds.Methods:The inflammatory factor microarray was used to screen the inflammatory factors with the same tendency in the cell model and animal model of diabetic nephropathy. The differential genes screened by R language were enriched and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). STRING builds a protein interaction network online, Cytoscape software analyzes the core subnetwork, and Connectivity Map searches for and predicts small molecule compounds.Results:Diabetic nephropathy model was established using 16-week-old db/db mice and mesangial cells stimulated with high glucose, and the expression of C-X-C motif chemokine ligand 1(CXCL1) was elevated in both models. Multiple GEO datasets indicated a strong association between the high expression of CXCL1 and diabetic nephropathy. Specifically, GSE30122 showed an upregulation of 30 genes and a downregulation of 23 genes. GO enrichment analysis focused on biological processes such as humoral immunity and lipopolysaccharide response; While KEGG enrichment was mainly in pertussis and coagulation cascade pathways. CytoHubba identified 10 hub genes, such as ALB, LUM, and CXCL1. In addition, 10 small molecule compounds were predicted as potential therapeutic drugs using Connectivity Map.Conclusions:CXCL1 may serve as a key gene in the occurrence and development of diabetic nephropathy. ALB, LUM, CXCL1, MMP7, TGFBI, CCL2, S100A4, SOX9, VCAN, and CLU may participate in the regulatory network centered around CXCL1. There are 10 small molecular compounds demenestrating the potential to be therapeutic agents.

Objective:To analyze the risk factors of Intensive Care Unit-Acquired Weakness, and to develop and verify the model.Methods:A total of 247 patients admitted to ICU patients from November 2018 to October 2019 were selected, and risk factors between ICU acquired weakness group ( n=106) and non-ICU acquired weakness group( n=141)were compared using logistic regression for model construction.The Hosmer-Lemeshow test was used to verify the goodness of fit of the model. The area under the ROC curve was used to test the model to predict the effects. From November 2019 to May 2020, 106 patients were recruited for application of the model. Results:The incidence of ICU acquired weakness in this study was 42.91%(106/247), and 44.34%(47/106),the study finally included age ( OR=1.043) ,mechanical ventilation time ( OR=1.140) , APACHE II score ( OR=1.081) , blood sugar ( OR=1.117) , lactic acid( OR=1.459) ,and neuromuscular blockers ( OR=3.499) to construct the risk prediction. The model formula was P=1/1+exp (- Z) =1/1+exp (8.808-0.042×age -1.252×neuromuscular blockers-0.078×APACHE II score -0.110×blood sugar -0.378×lactic acid -0.131×mechanical ventilation time. The area under the ROC curve of this model was 0.896 (95% CI: 0.824-0.914) , the maximum value of the Youden index was 0.577, and the corresponding sensitivity was 0.754,the specificity was 0.823,the cutoff value was 0.503. The model verification results the sensibility of 70.2%, the specificity of 88.1%, and the accuracy of 80.2%. Conclusion:The predictic model of ICU acquired weakness couducted in this study has satisfactory prediction effect, which can provide a reference for clinical screening of high-risk patients.

Objective:To explore the risk factors for myelosuppression in elderly lung cancer patients undergoing chemotherapy and construct a risk prediction model for myelosuppression in elderly lung cancer patients undergoing chemotherapy.Methods:Using the convenient sampling method, data of 228 elderly patients with lung cancer undergoing chemotherapy in Respiratory Department of a Class Ⅲ Grade A hospital in Zhenjiang from May 2018 to May 2019 were selected, and risk factors of adverse reactions of myelosuppression in patients were analyzed statistically. The binomial Logistic regression was applied to construct the prediction model and the area under the ROC curve was used to test the prediction effect of the model. The patient data from January to May 2020 were collected to validate the model.Results:Among the 228 patients, 75 patients developed myelosuppression, with an incidence of 32.89%. Multivariate analysis results showed that platinum-containing chemotherapy regimens, combined with other adverse reactions, decreased albumin before chemotherapy and decreased hemoglobin before chemotherapy were independent risk factors for myelosuppression in elderly lung cancer patients during chemotherapy ( P<0.05) , which were included in the model. The area under the ROC curve of the final model was 0.823, the maximum Youden index was 0.5, sensitivity was 81.3%, and specificity was 70.5%. The results of the verification data showed that the area under the ROC curve was 0.846, sensitivity was 90.4% and specificity was 68.2%. Conclusions:The prediction effect of this model is good, which can provide reference basis for clinical treatment and formulating nursing measures to prevent myelosuppression.

Objective To study the mathematical predicting model of parotid DVH for the NPC IMRT planning, and its accuracy with the analysis of medical data. Methods 50 NPC radiotherapy treatment plans with same beam setup were chosen as sample data set, then their parotid DVHs and distance of voxels in the parotid to the target volumes were calculated with self-developed program to form the distance to target histogram ( DTHs);principal component analysis was applied to DVHs and DTHs to acquire their principal components ( PCs) ,and then nonlinear multiple variable regression was used to model correlation between the DTHs' PCs, parotids volume, PTVs and the DVHs. Another 10 plans were chosen as test data set to evaluate the efficacy and accuracy of the final model by comparing the DVHs calculated from our model with those calculated from the TPS. Results Up to 97% information of DTHs and DVHs can be represented with 2 to 3 components, the average fitting error of sample data set was (0±3. 5)%;in the 10 test cases, the shapes of DVH curves calculated from predicting model was highly the same with those from the TPS, the average modeling error was (-0.7± 4. 4)%,the accuracy of prediction was up 95%. Conclusions Our developed model can be used as a quality evaluating tool to predict and assure the dose distribution in parotid of NPC radiotherapy treatment planning effectively and accurately.

BACKGROUNDTo elucidate the pattern and mechanism of cisplatin-induced apoptosis and its role in tumor chemotherapy.

METHODSApoptosis induced by cisplatin in human lung adenocarcinoma cell line A549 was detected by cell morphology, agarose gel electrophoresis, DNA-end-labeling and flow cytometry analysis techniques.

RESULTSCisplatin-induced apoptosis of A549 cells persisted and augmented gradually from 12 to 72 hours after treated with 3 mg/L cisplatin. All of A549 cells treated respectively with 1, 3, 5 and 7 mg/L cisplatin showed apoptosis. Apoptotic effects increased in a time-dependent pattern and a concentration-dependent pattern. A549 cells were blocked in G1 phase after treated with cisplatin.

CONCLUSIONSInduction of cell apoptosis may be an important mechanism of anti-tumor efficacy of cisplatin.