Objective: To discover molecular markers associated with lung adenocarcinoma diagnosis/prognosis and drug resistance through screening of differentially expressed genes based on published chip data in gene expression databases using bioinformatics methods. Methods: Comprehensive analysis was performed in available mRNA microarray datasets including lung adenocarcinoma tissues dataset GSE32863 and lung adenocarcinoma taxane-platin resistance dataset GSE77209 from the gene expression omnibus(GEO) database. Gene ontology enrichment analysis, gene pathway enrichment analysis and protein interaction network analysis were performed based on significantly correlated genes. The expression level of genes was validated in the cancer genome atlas(TCGA) dataset. Survival differences were assessed by the log-rank test in TCGA lung adenocarcinoma dataset. Based on the publications genomics of drug sensitivity in cancer(GDSC) database in CellMiner cross database(CellMiner CDB), Pearson correlation analysis was used to analyze the correlation between differentially expressed genes and the half-maximal inhibitory concentration(IC50) of anticancer drugs. Results : There were a total of 77 genes which had a different expression in resistance lung adenocarcinoma cells and lung adenocarcinoma cancer tissues. The functional enrichment analysis showed that these co-different expression genes were mainly enriched in microtubule, extracellular exosome, cell cycle and signaling by nuclear receptors. Protein-protein interactions(PPI) network screened 6 most connected genes as molecular complex(MCODE). Among the MCODE, overexpressed ubiquitin conjugating enzyme E2 T(UBE2T), kinesin family member 20A(KIF20A), PCNA clamp associated factor(KIAA0101), pituitary tumor-transforming gene 1(PTTG1) and NIMA related kinase 2(NEK2) were associated with poor outcomes. Survival analysis results showed that these five genes were upregulated in lung adenocarcinoma tissues and drug-resistant cells and were significantly associated with poor prognosis in lung adenocarcinoma patients. Drug sensitivity analysis results suggested that high expression of PTTG1 and UBE2T was significantly associated with sensitivity to multiple anticancer drugs, including paclitaxel and docetaxel. RT-PCR validation showed that PTTG1 andUBE2T were highly expressed in docetaxel-resistant cells A549-TXR and H358-TXR. Conclusion PTTG1 andUBE2T holds the potential to be chemoresistance markers in lung adenocarcinoma.

Objective:To explore the effect and correlation of long non-coding RNA (lncRNA) IDI2-AS1/microRNA-33b-5p (miR-33b-5p)/nuclear receptor-associated protein NR4A2 competitive endogenous RNA (ceRNA) regulatory network on acute myocardial infarction (AMI), and to verify whether IDI2-AS1 regulates NR4A2 through miR-33b-5p to affect the occurrence and development of myocardial infarction.Methods:The miRNA and mRNA expression chips related to myocardial infarction were obtained from gene expression omnibus (GEO), and the differential expression was analyzed. The upstream regulatory mechanism of NR4A2 was predicted using TargetScan database. Thirty-two male C57/BL6 mice were divided into Sham group, AMI model group, miR-33b-5p mimic group [miR-33b-5p mimic lentivirus (5×10 7 TU) was injected locally into the heart tissue during ligation] and miR-33b-5p inhibitor group [miR-33b-5p inhibitor lentivirus (5×10 7 TU) was injected locally into the heart tissue during ligation] according to random number table method, with 8 mice per group. Left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were asseessed by echocardiography, left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) were calculated. After the last weighing, the anesthetized mice were sacrificed and the heart tissues were taken. Masson staining of the heart tissues was observed under light microscope, myocardial collagen volume fraction (CVF) and infarct size were calculated. Cardiomyocytes of SPF grade SD rats were collected. They were divided into normal control group (control group), ischemia-hypoxia model group, miR-33b-5p mimic transfection group (miR-33b-5p mimic transfection group before ischemia and hypoxia treatment) and miR-33b-5p inhibitor transfection group (miR-33b-5p inhibitor transfection group before ischemia and hypoxia treatment). The activity of caspase-3/7 in cardiomyocytes was measured. The levels of interleukins (IL-1β, IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The levels of malondialdehyde (MDA), superoxide dismutase (SOD), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) were detected by colorimetry. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of apoptosis-related proteins Bax and Bcl-2, cytochrome C (Cyt C) and IDI2-AS1/miR-33b-5p/NR4A2 regulatory axis genes. Results:The myocardial infarction microarray analysis showed that NR4A2 expression was significantly up-regulated in myocardial infarction, with predicted upstream regulatory mechanisms indicating its possible influence through the IDI2-AS1/miR-33b-5p/NR4A2 regulatory axis. Echocardiographic detection showed that compared with AMI model group and miR-33b-5p inhibitor group, LVEF and LVFS in the heart tissue of mice in miR-33b-5p mimic group were significantly increased, while the levels of LVEDD, LVESD, CK, CK-MB and LDH were significantly decreased, with statistical significance. Light microscope showed myocardial fibrosis and myocardial infarction in AMI model group and miR-33b-5p inhibitor group. In the miR-33b-5p mimic group, the degree of myocardial fibrosis was decreased and the myocardial infarction size was significantly reduced. Compared with AMI model group and miR-33b-5p inhibitor group, the levels of MDA, IL-1β, IL-6, TNF-α and the expressions of Bax and Cyt C in the heart tissue of mice in miR-33b-5p mimic group were significantly decreased, while the levels of SOD and Bcl-2 expression were significantly increased, and the differences were statistically significant. The expressions of IDI2-AS1 and NR4A2 in the heart tissue of mice in miR-33b-5p mimic group were significantly lower than those in AMI model group and miR-33b-5p inhibitor group [IDI2-AS1 (2 -ΔΔCt): 1.96±0.08 vs. 2.73±0.08, 3.10±0.05, NR4A2 (2 -ΔΔCt): 2.36±0.07 vs. 3.16±0.08, 3.80±0.08, all P < 0.01]. The expression of miR-33b-5p was significantly higher than that of AMI model group and miR-33b-5p inhibitor group (2 -ΔΔCt: 0.88±0.07 vs. 0.57±0.07, 0.23±0.01, both P < 0.01). The cell experiment results showed that the caspase-3/7 activity of rat neonatal cardiomyocytes in the miR-33b-5p mimic transfection group was significantly lower than that in the ischemia-hypoxia model group and the miR-33b-5p inhibitor transfection group, suggesting that miR-33b-5p can significantly reduce the apoptosis level of the ischemia-hypoxia model. The levels of peroxidation and inflammation indexes, important genes of apoptosis pathway and the expression of IDI2-AS1/miR-33b-5p/NR4A2 regulatory axis of rat neonatal cardiomyocytes in all groups were consistent with the above. Conclusion:IDI2-AS1 can regulate NR4A2 through miR-33b-5p, thus affecting the occurrence and development of AMI.

Objective:To explore the effect of variable priority cognitive-motor dual-task training in aged cognitive frailty patients with type 2 diabetes mellitus.Methods:From September 2022 to September 2023, a total of 108 aged cognitive frailty patients with type 2 diabetes mellitus were selected in the Department of Endocrinology of North China University of Science and Technology Affiliated Hospital as research subjects.The subjects were divided into three groups in the order of admission, with 36 people in each group.Three groups of patients were intervened for 8 weeks using variable priority cognitive-motor dual-task training (VP group), exercise combined cognitive intervention with sequential task (ST group), and endocrinology routine treatment and nursing (control group), respectively.The scores of mini-mental state examination(MMSE), frailty phenotype(FP) and Berg balance scale(BBS) were compared among the three groups before and after the intervention.Repeated measurement variance analysis was used to compare scale results by SPSS 22.0.Results:(1)The MMSE score of patients before and after intervention had significant interaction effect between time and groups ( F=69.929, P<0.05).The MMSE scores of the VP group and ST group after 8 weeks of intervention were higher than those before intervention and after 4 weeks of intervention, and the MMSE scores of the two groups after 4 weeks of intervention were also higher than those before intervention (all P<0.05).After 4 weeks and 8 weeks of intervention, the MMSE score of the VP group was higher than that of the ST group and the control group, and the MMSE score of the ST group was higher than that of the control group after 8 weeks of intervention(all P<0.05).(2)The FP score of patients before and after intervention had a significant interaction effect between time and groups ( F=46.425, P<0.05).The FP score of the VP group at 8 weeks of intervention (2.64±0.59) was lower than that after 4 weeks of intervention (3.28±0.51) and before intervention (3.56±0.61), and the FP score after 4 weeks of intervention was lower than before intervention (all P<0.05).The FP score of the ST group after 8 weeks of intervention (3.44±0.56) was lower than before the intervention (3.59±0.56) ( P<0.05); After 4 weeks of intervention, the FP score of the VP group was lower than that of the control group (3.36±0.54) ( P<0.05).After 8 weeks of intervention, the FP score of the VP group was lower than that of the ST group and the control group (3.39±0.55) (both P<0.05).(3)The FP score of patients before and after intervention had a significant interaction effect between time and groups ( F=135.791, P<0.05).The BBS scores of the VP group and ST group after 8 weeks of intervention were higher than those before and after 4 weeks of intervention, and the BBS scores after 4 weeks of intervention were also higher than those before intervention (all P<0.05).After 4 weeks of intervention, the BBS score of the VP group was higher than that of the control group ( P<0.05).After 8 weeks of intervention, the BBS score of the VP group was higher than that of the ST group and the control group, and the BBS score of the ST group was also higher than that of the control group (all P<0.05). Conclusion:The variable priority cognitive-motor dual-task training can improve the cognitive function, physical frailty and balance function in aged cognitive frailty patients with type 2 diabetes mellitus, and the intervention effect is better than that of exercise combined cognitive intervention with sequential task and endocrinology routine treatment and nursing.

Objective To explore the value of nomogram model based on clinical data and MRI findings for predicting simultaneous liver metastasis(SLM)of rectal cancer.Methods Clinical and MRI data of 356 patients with rectal cancer were randomly divided into training set(n=249,45 cases of SLM)and validation set(n=107,27 cases of SLM)at a ratio of 7∶3.Logistic regression analysis were used to screen the independent factors for predicting SLM of rectal cancer.The nomogram model was then constructed,and the efficacy of this model was evaluated.Results Tumor N-stage,serum carcinoembryonic antigen,carbohydrate antigen 19-9 and involvement of mesorectal fascia(MRF)or not were all independent factors for predicting SLM of rectal cancer.The area under the curve(AUC)of this nomogram model for predicting rectal cancer SLM in training set and validation set was 0.834(95％CI[0.776,0.893])and 0.769(95％CI[0.662,0.877]),respectively.The calibration curve showed good consistency between the predicted values and the measured values,and the decision curve analysis showed that the nomogram model had good clinical practicality.Conclusion The nomogram model based on clinical data and MRI findings could be used to predict SLM of rectal cancer.

Five universities with health policy and management ranked top level worldwide, including Harvard University, John Hopkins University, Stanford University, University of North Carolina at Chapel Hill and National University of Singapore were selected in our study. From above universities, we found that the curriculum of PHD students was focused on research concentration, methodology courses, and numerous elective courses. Hence, in China, the curriculum of PHD students should be improved with emphasis on course studying, management courses and highlighting curriculum content according to research area to enhance the quality of doctoral education.

Objective:To investigate the expression of miRNA-21 in serum of patients with multiple myeloma (MM) and its significance.Methods:The data of 55 MM patients and 20 healthy controls in the Second Hospital of Hebei Medical University from July 2019 to June 2020 were retrospectively analyzed. Among the MM patients, 20 cases were diagnosed without treatment, 15 cases were in complete remission (CR), and 20 cases were clinically relapsed. Blood samples were collected from all subjects, and the relative expression levels of miRNA-21 were detected by real-time quantitative polymerase chain reaction (qRT-PCR), and the correlation of miRNA-21 expression with β 2-macroglobulin (β 2-MG), creatinine, hemoglobin, albumin, t(4;14) mutation, 13q14 mutation and prognosis were analyzed. The MM cell line LP-1 was selected, and normal bone marrow CD138-positive plasma cells were sorted by immunomagnetic beads as control cells. The relative expression levels of miRNA-21 in the two groups of cells were detected by qRT-PCR. Results:The serum relative expression level of miRNA-21 in MM group was higher than that in healthy control group (1.50±0.10 vs. 1.03±0.06, t = 7.04, P = 0.002). The serum expressions of miRNA-21 in newly diagnosed untreated MM patients and relapsed/refractory MM patients were high (1.50±0.10 and 3.13±0.32), and compared with the healthy control group, the differences were statistically significant ( t values were 7.04 and 10.22, both P < 0.05). The relative expression level of miRNA-21 in MM patients with complete remission (CR) was 1.27±0.25, which had no significant difference compared with the healthy control group ( t = 1.76, P = 0.152). The serum expression level of miRNA-21 in MM patients with high β 2-MG, high creatinine, low hemoglobin, low albumin, t(4;14) mutation, 13q14 mutation, non-remission and recurrence was significantly increased (all P < 0.05). The relative expression level of miRNA-21 in LP-1 cell line was higher than that in control cells (1.56±0.05 vs. 1.00±0.06), and the difference was statistically significant ( t = 11.73, P < 0.01). Conclusions:The miRNA-21 may be a molecular marker to assist in the diagnosis and efficacy evaluation of MM.

Objective To assess the ability of quantitative ultrasound index to predict the severity of CCl4?induced liver fibrosis in a rat model us?ing logistic regression analysis. Methods In a rat model of 40%CCl4?induced liver fibrosis,ultrasound detected the portal vein diameter,blood flow velocity,and Young's modulus. The degree of hepatic fibrosis was determined using a light microscope after hematoxylin and eosin staining of tissue. Results Portal vein diameter and Young's modulus were useful predictors of the severity of liver fibrosis,with statistical significance(P<0.05). Young's modulus was most effective with an R2 value 0.788. Young's modulus combined with the distal diameter of portal vein effectively improved the predictive ability,showing an R2 value 0.821. Conclusion Young's modulus is the most predictive index to assess the severity of liver fibrosis. A combination of multiple indices can improve the ability to predict the severity of liver fibrosis.

Objective To translate the English version of Comprehensive Frailty Assessment Instrument (CFAI) into Chinese and evalu-ate its reliability and validity. Methods CFAI was translated into Chinese with the Brislin's translation mode. From May to July, 2015, 200 community aged people in Shijiazhuang, China were assessed with the Chinese version of CFAI and World Health Organization Quality of Life-BREF (WHOQOL-BREF), and 30 of them were assessed with CFAI again after a week. The content validity was rated by six experts of gereology. The total scores of CFAI and WHOQOL-BREF were analyzed with Pearson's correlation, as well as the scores of CFAI test and retest. The CFAI were analyzed with Factor Analysis. The Cronbach's α was tested. Results There were 23 items in 4 dimensions. The content validity index was 0.782. Six factors were extracted by Factor Analysis and the cumulated variance was 64.05%. The total score of CFAI correlated with the score of WHOQOL-BREF (r=-0.764, P<0.001). The Cronbach's α was 0.704~0.897 in dimensions (P<0.001), and the r= 0.604~0.941 (P<0.001) between test and retest. Conclusion The Chinese version of CFAI is reliable and valid, that can be applied to evaluate frailty in community aged people.

Objective To understand the loneliness of elderly people,and to analyze the correlation between frailty,family social support and loneliness.Methods The elderly people aged 75 and over from 10 community health service centers in Tangshan were selected and evaluated with the CFAI comprehensive e-valuation tool and the loneliness scale.Results The frailty rate was 100% in 3 448 elderly people.The score of the frailty of elderly was(47.27±0.77),and the degree of frailty was increased with the increase of age. The social support level of general and below accounted for 95.92%.The total average score of social support for the elderly was(32.72±6.21);and the medium or above loneliness accounted for 68.94%.The total aver-age score of loneliness in the elderly was(40.24± 10.23).The most needed caregiver was the children and their daughters. Multivariate analysis showed that the degree of education,the degree of frailty,family support (the relationship with children,with the children who do not support the elderly,communicating with chil-dren,taking the views of the elderly,importance of being at home and the visiting frequency of the children), community support(received the services provided by the neighborhood committee,often keep up with rela-tives and friends,the frequency of neighborhood interaction,have received community psychological counse-ling and have received volunteer service)and social support entered the regression equation.The regression coefficient were -0.084,1.167,1.016,1.212,0.914,1.029,1.025,1.264,1.400,0.889,1.053,1.307,1.466, 1.332,-0.405,respectively.Conclusion Frailty,family function and community social support are important factors of loneliness among the elderly.The support system construction should be strengthened to reduce the loneliness of the elderly,and improve the quality of life.

Objective To investigate the efficacy of BrainHQ visual training in rehabilitating memory function among stroke survivors.Methods Sixty stroke patients with memory disorders were recruited from the rehabilitation center of Tangshan Workers' Hospital.They were randomly assigned to a control group or an intervention group,each of 30.Both groups accepted conventional rehabilitation,while the intervention group was additionally given BrainHQ visual training five times a week for 30 minutes,lasting four weeks.Before and after the treatment,both groups completed the Rivermead behavioral memory test.Results After the 4 weeks of treatment,the average scores in recalling full names,recalling hidden items,recalling appointments,recognizing pictures,recognizing faces,recalling a story immediately,delayed story recall,recalling a route promptly,delayed route recall and the average total score in both groups were all significantly higher than before the treatment.The treatment group scored significantly better than the control group except in recalling hidden items,and recognizing faces and pictures.Conclusion BrainHQ visual training can improve the memory of stroke survivors.