Objective To investigate the therapeutic effect of tumor necrosis factor (TNF)-αsiRNA on typeⅡcolla-gen induced arthritis (CIA) in rats. Methods The expression vectors of siRNA against TNF-αgene were constructed suc-cessfully and were injected by tail veil into CIA rats. Twenty-four CIA rats were randomly divided into 4 groups including model group, empty vector group, TNF-α-siRNA1 group and TNF-α-siRNA2 group. CIA rats were injected with the same dose of phosphate buffered sodium (PBS) and pGFP-V-RS vector respectively in model group and empty vector group, while TNF-α-siRNA1 group and TNF-α-siRNA2 group were injected with TNF-α-siRNA1 eukaryotic expression vector and TNF-α-siRNA2 eukaryotic expression vector respectively. Another 6 rats, which were not established CIA model, were in-jected with PBS (blank control group). The serum expression levels of IL-1 were detected by ELISA on day 1, 5, 9 and 13 af-ter injection. The expression level of TNF-αmRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR) on day 13. Results The expression level of IL-1 was significantly higher on day 1, 5, 9 and 13 in model group than that of blank group (P＜0.05). The expression levels of IL-1 were significantly lower on day 1, 5 and 9 in TNF-α-siRNA1 group and TNF-α-siRNA2 group than that of model group and blank group (P ＜ 0.05). The expression level of TNF-αmRNA was significantly higher on day 13 in model group than that of blank group (P＜0.05). The expression levels of TNF-αmRNA were significantly lower in TNF-α-siRNA1 group and TNF-α-siRNA2 group than those of model group and emp-ty vector group (P＜0.05). Conclusion TNF-αspecific siRNA can suppress the levels of TNF-αmRNA and IL-1, which provides experimental basis for gene therapy of rheumatoid arthritis.

Objective To explore the clinical significance of dyslipidemia in patients with systemic lupus erythematosus (SLE).Methods By independent-samples t test,serum lipid level was compared between 326 SLE patients and 300 healthy controls.The total cholesterol (TC),triglyceride (TG),lowdensity lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were partially compared in subgroups of SLE patients.The correlation of serum TC,TG,LDL-C and HDL-C with clinical manifestations and laboratory findings in SLE was analyzed by Pearson or Spearman correlation analysis.Results ①The serum levels of TC [(3.8±1.5) mmol/L],TG [(2.1±1.6) mmol/L] and LDL-C [(2.1±0.9) mmol/L] were significantly higher in SLE group than those of the control group [(3.4±0.6),(0.8±0.4),(1.9± 0.5) mmol/L],and the serum level of HDL-C [(1.2±0.9) mmol/L] was significantly lower in SLE group than that of the control group [(2.0±0.5) mmolFL] (t=4.953,P=0.000; t=14.569,P=0.000; t=3.204,P=0.001; t=-14.335,P=0.000].② The serum levels of TC [(4.0± 1.7) mmol/L],TG [(2.5± 1.7) mmol/L] and LDL-C [(2.2±1.0) mmol/L] were significantly higher in LN group than those of the non-LN group [(3.6±1.0),(1.6± 1.0),(1.9±0.7) mmol/L; t=2.646,P=0.009; t=6.292,P=0.000; t=3.261,P=0.001].③ The serum level of TG [(2.2±1.6) vs (1.8±1.4) mmol/L] was significantly higher in SLE patients with hypocomplementemia than that of the normal ones (t =2.098,P=0.038).The serum level of HDL-C [(1.1 ±0.4) vs (1.6± 1.7) mmol/L] was significantly lower in SLE patients with hypocomplementemia than that of the normal ones (t=-2.375,P=0.020).④ The serum level of TG [(2.3±1.7) vs (2.0±1.4) mmol/L] was significantly higher in anti-dsDNA antibody positive patients than that of negative ones (t=1.989,P=0.048).The serum level of HDL-C [(1.5± 0.4) vs (1.4±1.2) mmol/L] was significantly lower in anti-dsDNA antibody positive patients than that of negative ones (t=-2.979,P=0.003).⑤ The lipid level was correlated with the clinical manifestations and laboratory findings in SLE patients.Conclusion Dyslipidemia exists in patients with SLE and has close correlation with LN,hypocomplementemia and positive anti-dsDNA antibody.

OBJECTIVETo investigate the reliability of magnetic-activated cell sorting (MACS) combined with multiplex ligation-dependent probe amplification (MLPA) in the detection of the molecular cytogenetic abnormalities in multiple myeloma.

METHODSThe bone marrow cells were collected from 29 patients with multiple myeloma. The immuno magnetically sorted and unsorted cells were detected for TP53 and RB1 expressions using MLPA probes and the results were compared with fluorescent in situ hybridization (FISH).

RESULTSThe detection success rate was 100% for MLPA, which yielded results with an concordance rate of 99.1% with the FISH results. The positivity rates of MLPA and FISH were both increased after immunomagnetic sorting of the bone marrow cells.

CONCLUSIONMLPA can well suit the clinical needs for detecting molecular cytogenetic abnormalities in multiple myeloma, and the samples should be immuno magnetically sorted before the assay.

Adult ; Aged ; Aged, 80 and over ; Chromosome Aberrations ; Female ; Humans ; Immunomagnetic Separation ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma ; diagnosis ; genetics ; Multiplex Polymerase Chain Reaction

Objective:To develop and validate a predictive model for post-anesthesia care unit (PACU) hypotension in elderly patients undergoing painless gastrointestinal endoscopy.Methods:The medical records of elderly patients of both sexes, aged ≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, undergoing painless gastrointestinal endoscopy at the Endoscopy Center of Subei People′s Hospital from March to June 2021, were retrospectively collected. The patients were randomly divided into training and validation sets according to the ratio of 3∶1. In the training set, the characteristic variables associated with PACU hypotension were screened by Lasso regression, and the independent risk factors for PACU hypotension were identified by multivariate logistic regression analysis of the characteristic variables, according to which a nomogram model predicting the risk for PACU hypotension was established.The discrimination, calibration and accuracy of the model were evaluated by calibration curve and receiver operating characteristic(ROC)curve. And the clinical practicability of the model was determined by decision curve analysis and further assessed by external validation.Results:Of the 973 patients ultimately included, 378 patients experienced PACU hypotension, with an incidence of 38.8%. Multivariate logistic regression analysis showed that age, prolonged preoperative water deprivation time, increased percentage of changes in SBP before and after induction, and intraoperative MAP <65 mmHg were independent risk factors for hypotension in the PACU, and intraoperative use of norepinephrine was a protective factor. The nomogram model was then developed based on the results. The area under the ROC curve was 0.710 (95% confidence interval [ CI] 0.672-0.748) in training set and 0.778 (95% CI 0.720-0.837) in validation set. In training and validation sets, the calibration curves were tested by Hosmer-Lemeshow good of fit test, the P values were 0.590 and 0.950, respectively. The decision curve analysis curve showed that the risk threshold of the prediction model in the training and validation sets were between 20% and 82% and between 18% and 92%, respectively, in the external validation. Conclusions:The nomogram model for prediction of PACU hypotension is successfully established based on age, prolonged preoperative water deprivation, percentage of change in SBP before and after induction, intraoperative MAP <65 mmHg and use of norepinephrine in elderly patients undergoing painless gastrointestinal endoscopy, and the model can visually and individually predict the risk of PACU hypotension.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.