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OBJECTIVE@#To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines.@*METHODS@#Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively.@*RESULTS@#MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC50) values of 7.04 ± 0.88, 10.92 ± 0.32, 9.35 ± 0.83, HT-29, with IC50 values of 14.90 ± 2.71, 20.50 ± 6.37, 13.90 ± 1.30, and CCD841, with IC50 values of 11.40 ± 0.68, 7.02 ± 0.44 and 7.83 ± 0.05 µg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G1 phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3β and APC, while down-regulate that of β-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/β-catenin pathway of HT-29 cells.@*CONCLUSION@#Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/β-catenin pathway-related mRNA and protein expressions.
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Humans , beta Catenin/metabolism , Caco-2 Cells , Quinones/pharmacology , Glycogen Synthase Kinase 3 beta/metabolism , Cell Proliferation , Colorectal Neoplasms/metabolism , Cell Line, Tumor , Apoptosis , Benzoquinones/pharmacology , RNA, Messenger , Wnt Signaling PathwayABSTRACT
Objective: To investigate the effects of combined blockade of interleukin-33 (IL-33) and inducible co-stimulatory molecule (ICOS) on carbon tetrachloride-induced chronic liver fibrosis and imbalance of T helper lymphocyte subsets in mice. Methods: There were 40 BALB/c mice in each model and control group. Flow cytometry was used to determine the proportion of Th1/Th2/Th17 cells in the splenic lymphocyte suspension of mice, the expression levels of interferon γ, IL-4, and IL-17 in the splenic lymphocyte suspension of liver fibrosis mice after combined blockade of IL-33 and ICOS, and the pathological changes of liver histopathology in mice with liver fibrosis. Two independent sample t-test was used to compare data between groups. Results: Compared with the non-blocking group, the proportion of Th2 and Th17 cells in the IL-33/ICOS blocking group was significantly down-regulated (Th2: 65.96% ± 6.04% vs. 49.09% ± 7.03%; Th17: 19.17% ± 4.03% vs. 9.56% ± 2.03%), while the proportion of Th1 cells and Th1/Th2 ratio were up-regulated (Th1: 17.14% ± 3.02% vs. 31.93% ± 5.02%; Th1/Th2: 0.28 ± 0.06 vs. 0.62 ± 0.23), and the difference was statistically significant (t = 5.15, 6.03, 7.14, 4.28, respectively, with P < 0.05). After entering the chronic inflammation stage of liver fibrosis in mice (10 weeks), compared with the non-blocking group, the expression levels of IL-4 and IL-17 in the blockade group were significantly down-regulated [IL-4: (84.75 ± 14.35) pg/ ml vs. (77.88 ± 19.61) pg/ml; IL-17: (72.38 ± 15.13) pg/ml vs. (36.38 ± 8.65) pg/ml], while the expression of interferon γ was up-regulated [(37.25 ± 11.51) pg/ml vs. (77.88 ± 19.61) pg/ml], and the difference was statistically significant (t: IL-4: 4.71; IL-17: 5.84; interferon γ: 5.05, respectively, with P < 0.05). Liver histopathological results showed that hepatic necrosis, hepatic lobular structural disorder, and fibrous tissue hyperplasia were significantly lower in the blockade group than those in the non-blocking group at 13 weeks of liver fibrosis. Conclusion: Combined blockade of the ICOS signaling pathway and IL-33 can regulate Th2 and Th17 polarization, down-regulate the inflammatory response, and inhibit or prevent the occurrence and progression of fibrosis.
Subject(s)
Mice , Animals , Interferon-gamma/metabolism , Interleukin-17/metabolism , Interleukin-33/metabolism , Cytokines/metabolism , Carbon Tetrachloride , Th2 Cells , Interleukin-4/metabolism , Liver Cirrhosis/pathology , Th1 Cells , Th17 Cells/pathology , ImmunityABSTRACT
Objective:To evaluate the therapeutic effect of hemopurification on acute chlorfenapyr poisoning according to the blood concentration of chlorfenapyr and to provide experience for clinical treatment.Methods:Two patients who presented to our Emergency Department following an ingestion of chlorfenapyr and then were treated with hemopurification in 2022 were included. The concentrations of chlorfenapyr and its highly toxic metabolite tralopyril were dynamically monitored, and the clinical data of the patients were collected.Results:Case 1 was given hemoperfusion for the first time 13 hours after ingestion. During l hour hemoperfusion, the tralopyril decreased by 28.82%. The concentration increased and exceeded the pre-perfusion level after 2 hours of hemoperfusion. After three times of hemoperfusion, the concentrations of chlorfenapyr and tralopyril were still higher than those before the first time, reaching 248 ng/mL and 1 307 ng/mL respectively. The concentration of chlorfenapyr showed a downward trend after 130 h, and the tralopyril in blood reached the peak 3 164 ng/mL at 130 h and decreased to 2 707 ng/mL at 178 h. In case 2, the blood chlorfenapyr and tralopyril concentration was 392 ng/mL and 7 598 ng/mL respectively 150 hours after ingestion. The blood chlorfenapyr concentration decreased by 37.75% respectively after first hemoperfusion, and the tralopyril concentration decreased by 38.02% respectively. During 85 hours of continuous veno-venous hemodiafiltration (CVVHDF), the concentration of tralopyril was maintained at 4 234~6 410 ng/mL. Case 1 was followed up to 12 days and lost follow-up. Case 2 died and the survival time was 247 hours.Conclusions:Hemoperfusion can scavenge tralopyril, but CVVHDF has poor scavenging ability for tralopyril. And the apparent volume of distribution (Vd) of chlorfenapyr and tralopyril are large. After ingestion, chlorfenapyr spreads to various tissues quickly, and it is easy to accumulate in the adipose tissue. The chlorfenapyr in the tissue slowly is released back to the blood and stays in the blood for a long time. The peak concentration of chlorfenapyr appeared earlier than that of tralopyril. Clinicians should pay attention to the early removal of toxins from the digestive tract.
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Objective:To investigate the safety of early whole body computed tomography (WBCT) combined with coronary angiography (CAG) in patients with extracorporeal cardiopulmonary resuscitation (ECPR) and its application value in the diagnosis of cardiac arrest and complications of cardiopulmonary resuscitation (CPR).Methods:This was a retrospective study. Patients who underwent ECPR in the Emergency Department of the First Affiliated Hospital of Nanjing Medical University from January 2017 to July 2021 were enrolled in this research. Patients younger than 18 years or with incomplete clinical data were excluded. The results of WBCT and CAG examinations after ECPR were collected.Results:A total of 89 patients with ECPR, aged (47±17) years, were enrolled in the study, all underwent WBCT examination, and no adverse events such as ECMO and tracheal tube shedding occurred. WBCT found 7 cases of pulmonary embolism, 3 cases of aortic dissection and 2 cases of cerebral hemorrhage. WBCT identified CPR-related complications in 42 cases, including rib fractures ( n=20), pneumothorax ( n=5), mediastinal emphysema ( n=5), subcutaneous emphysema ( n=6), and hematoma or swelling at puncture site ( n=6). Fifty-five patients underwent CAG examination, the most common culprit vessels were the left anterior descending branch disease (58.2%) followed by the left circumflex branch disease (27.3%), the right coronary artery disease (21.8%) and left main artery disease (12.7%). Conclusions:Early WBCT and CAG examinations are of great significance and safety for the guidance of treatment in ECPR patients.
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Objective:To explore the prognostic value of survival after veno-arterial ECMO (SAVE) score combined with 24-h lactate on the machine in patients with extracorporeal cardiopulmonary resuscitation (ECPR).Methods:Totally 59 patients treated with ECPR in the Emergency Department of the First Affiliated Hospital of Nanjing Medical University from April 2017 to June 2021 were retrospectively analyzed. According to the 28-day prognosis, the patients were divided into the death group ( n=36) and the survival group ( n=23). The differences in baseline data were analyzed, and multivariate logistic regression was performed to identify the influencing factors of 28-day mortality in patients with ECPR. The receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of SAVE score, 24-h lactate and their combined detection for predicting 28-day mortality risk in patients with ECPR. Results:The 28-day survival rate of patients with ECPR was 39% (23/59). SAVE score of the death group was significantly lower than that of the survival group (-11.67±4.60 vs. -2.43±4.77, P<0.001), and the 24-h lactate in the death group was significantly higher than that in the survival group [5.94 (3.37, 12.40) mmol/L vs. 1.65 (1.07, 3.15) mmol/L, P<0.001]. Multivariate logistic regression analysis showed that SAVE score ( OR=0.703, 95% CI: 0.566-0.873, P=0.001) and 24-h lactate ( OR=1.608, 95% CI: 1.025-2.523, P=0.039) were independent influencing factors of 28-day mortality in ECPR patients. ROC curve analysis showed that the best cut-off value of SAVE score was -6, the sensitivity was 78.30% and specificity was 91.70%. The best cutoff value of 24-h lactate was 4.7 mmol/L, the sensitivity was 63.90% and specificity was 100.00%. The sensitivity and specificity of the combined detection of SAVE score and 24-h lactate were 82.60% and 100.00%, respectively. The area under the curve (AUC) of SAVE score combined with 24-h lactate for predicting the 28-day mortality risk in patients with ECPR was larger than that of SAVE score and 24-h lactate alone (0.952 vs. 0.917; 0.952 vs. 0.847). Conclusions:Lower SAVE score and higher 24-h lactate are independently risk factors of 28-day mortality in patients with ECPR, and SAVE score combined with 24-h lactate on the machine has a good predictive value for the prognosis of patients with ECPR.
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Objective:To investigate the clinical significance of the acute physiology and chronic health evaluationⅡ (APACHEⅡ) combined with different systematic inflammation markers (SIMs) including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR)-in adult patients with venous-arterial extracorporeal membrane oxygenation (VA-ECMO).Methods:A total of 89 adult patients with VA-ECMO ( ≥ 3 d) in the Emergency Department of Jiangsu Provincial People's Hospital from January 2017 to June 2020 were retrospectively analyzed. Patients were divided into two groups: survivors ( n=39) and non-survivors ( n=50). The baseline APACHE Ⅱscore and PLR, NLR, LMR before ECMO implantation and at 1, 2, 3 day after ECMO were recorded. Binary logistic regression was used to analyze the risk factors of 28-day mortality in patients with VA-ECMO. The utility of APACHEⅡ score and SIMs alone or combination for predicting clinical prognosis was evaluated using receiver operating characteristic (ROC) curve analysis. The patients were divided into the high risk group and the low risk group according to the best cut-off value, and the difference of ECMO-related complications between the two groups was compared. Results:When combined APACHEⅡ score with SIMs, APACHEⅡ + PLR 48 h + LMR 24 h + LMR 72 h demonstrated the greatest predictive ability with an AUC of 0.833. Compared with the high-risk group, the low-risk group has a lower incidence of acute renal injury, infection, bleeding complications, the use of continuous renal replacement therapy, mechanical ventilation, and a higher hospital survival rate.Conclusions:The combination of APACHEⅡ score and SIMs-PLR, LMR- is better than a single one for death prediction, and it is expected to be a new predictive model for early identification of the risk of death or poor prognosis in patients with VA-ECMO.
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Objective:To explore the value of iterative decomposition of water and fat with asymmetry and least squares estimation-quantitative fat imaging (IDEAL-IQ) in quantitative evaluation of thigh muscle fat content and its correlation with muscle strength in middle-aged and elderly volunteers.Methods:From December 2020 to April 2021, 30 volunteers aged 45 to 70 were recruited prospectively, including 15 males and 15 females with 52.5 (49.0, 56.3) years old. All subjects were scanned at 3.0 T MR, including axial T 1WI, IDEAL-IQ and coronal T 2WI of the left thigh. The region of interest of the knee extensors (quadriceps femoris) and knee flexors (hamstrings) in the left mid-thigh were delineated, and muscle cross-sectional area (CSA), skeletal muscle index (SMI), intermuscular fat fraction (FF) and intramuscular FF were obtained. In addition, isokinetic muscle strength measurement was performed on the left knee joint of all subjects at angular speeds of 60°/s and 180°/s to obtain peak torque (PT) and total work (TW) of knee flexors and extensors. Independent sample t-test, paired t-test or Mann-Whitney U test were used to compare the differences of CSA, SMI, intermuscular FF, intramuscular FF, PT and TW between different genders and muscle groups. Pearson or Spearman correlation analysis, and multiple linear regression analysis were used to analyze the correlation between CSA, SMI, intermuscular FF, intramuscular FF and PT, TW of thigh muscles. Results:The CSA, PT and TW of thighs in males were higher than those in females ( P<0.05), while the intermuscular FF in males was lower than that in females ( P=0.005). The CSA, SMI and PT of the thigh extensors were higher than those of the flexors ( P<0.001), while the intramuscular FF and intermuscular FF were lower than those of the flexors ( P<0.001). Intramuscular FF of flexors and extensors were moderately negatively correlated with PT ( r=-0.635, P<0.001; r=-0.546, P<0.001), and highly, moderately negatively correlated with TW ( r=-0.718, P<0.001; r=-0.616, P<0.001). Intermuscular FF of flexors and extensors were moderately negatively correlated with PT ( r=-0.519, P=0.003; r=-0.443, P=0.014), and negatively correlated with TW ( r=-0.363, P=0.049; r=-0.552, P=0.002). There was no significant correlation between CSA, SMI and PT, TW in flexors and extensors of thigh ( P>0.05). Multiple linear regression analysis showed that intramuscular FF was still significantly correlated with PT and TW of flexors and extensors (flexors: R 2adj=0.505, P=0.001; R 2adj=0.540, P<0.001; extensors: R 2adj=0.351, P=0.006; R 2adj=0.470, P=0.002). Conclusion:FF based on IDEAL-IQ technology can accurately quantify the intramuscular and intermuscular fat content of thighs, and there are negative correlations between intramuscular FF, intermuscular FF and isokinetic muscle strength measurements including PT and TW. Among them, intramuscular FF is more significant.
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To investigate the clinical characteristics of metastatic hormone sensitive prostate cancer and explore the strategy of combination of new endocrine drugs.In April 2019, an 69-year-old man was admitted to the First People’s hospital of Changzhou with "gross hematuria" . Physical examination showed prostatic hyperplasia with an unsmooth hard surface. CT showed a mass in bladder and possible metastasis in right lung. Diagnostic TUR-Bt pathology showed prostatic acinar adenocarcinoma, and PET-CT showed malignant lesion of prostate with bladder invasion, multiple pelvic lymph node metastasis and lung metastasis. The diagnosis of mHSPC with lymphatic and lung metastasis was considered. The patient was treated with bicalutamide and then switched to goserelin plus acetate abiraterone with prednisone. Total prostate specific antigen (tPSA) decreased to 0.705 ng/ml after 1 month of ADT+ AAP treatment, and decreased to 0.007 ng/ml after 4 months, and then maintained at 0.003 ng/ml until January 2021. Serum testosterone decreased to 0ng/dl and maintained the whole follow-up period. After 3 months of treatment, the pulmonary metastasis was not obvious. Till the last follow-up at January 2021, the patient reported good quality of life with no serious adverse events. The efficacy of ADT combined with acetate abiraterone in the treatment of mHSPC with lung cancer was significant.
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Microdialysis is a novel technique for rapid and continuous sampling of body fluid in the extracellular space, especially for some hard-to-obtain samples, e.g. cerebrospinal fluid, interstitial fluid. Microfluidic technology plays a significant role in body fluid analysis because of its miniaturization, high-throughput, and automation, offering a feasible method for rapid and low-cost biochemical analysis. In clinical practice, body fluid analysis is often required to be fast and/or capable of long-termly monitoring certain biomarkers. However, current technologies are insufficient to meet this requirement. The combination of microdialysis and microfluidic technologies could provide a new perspective to solve this problem.
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【Objective】 To explore the effects of nerve growth factor (NGF) on bladder function and axon injury repair in rats with traumatic spinal cord injury (t-SCI) so as to explore its molecular mechanism. 【Methods】 Traumatic spinal cord injury model was constructed in 30 male SD rats by modified Allen’s beating method. The rats were randomly divided into sham-operation group, injury group and NGF group, with 10 rats in each group. We used the BBB score to observe the motor function of the rats’ hind limbs before and after the operation. The BL-420 biometer experimental system detected the urodynamics. Six anterior roots of the left lumbar taken from the distal end of the anastomosis were stained with toluidine blue, and the number of myelinated axons was counted. We used HE to stain rat bladder tissue, TUNEL to stain the rats’ severely injured spinal cord, and observed the spinal cord apoptosis rate. Western blotting was used to detect the protein expressions of Raf-1, p-MEK-2, MEK-2, ERK1/2, and p-ERK1/2 in spinal cord tissue. 【Results】 The BBB score results showed that there was no difference in the scores of the sham-operation group, the injury group and the NGF group before the operation. After the operation, the scores of the injury group and the NGF group were significantly lower than those in the sham-operation group (P0.05). 【Conclusion】 NGF may hinder the conduction of MAPK/ERK pathway, thereby affecting the repair of axon damage and improving the bladder function of t-SCI rats.
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Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses
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Objective:To analyze the potential role and prognostic value of platelet-to-lymphocyte ratio (PLR) at an early stage in arterial-venous extracorporeal membrane oxygenation (VA -ECMO).Methods:Totally 83 adult patients with VA-ECMO from June 2018 to June 2020 treated at Emergency Department of Jiangsu Provincial Hospital were retrospectively analyzed. Baseline characteristics between survivors ( n=46) and non-survivors ( n=37) were compared. Logistic regression analysis was used to predict the risk factors associated with 28-day mortality in VA-ECMO patients. The cut-off value was calculated by the receiver operating characteristic (ROC) curve. Results:PLR48-h ( OR=1.018,95% CI: 1.001-1.036, P=0.039) and continuous renal replacement therapy (CRRT) ( OR=7.095,95% CI: 1.099-45.799, P=0.039) were relevant risk factors of 28-day mortality in VA-ECMO patients. The cut-off value of PLR48-h was 156.3 [sensitivity: 57.8%, specificity: 86.1%, and area under the curve (AUC): 0.756]. Compared with the high PLR group (>156.3), the incidences of acute kidney injury (AKI) ( P<0.001) and bleeding events ( P=0.013) were significantly higher in the low PLR group (<156.3). Conclusions:The early PLR reduction and CRRT application during VA-ECMO support are related to poor prognosis.
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Objective:To analyze the knowledge, skills and self-efficacy of cardiopulmonary resuscitation among the public in mountainous areas of southern Ningxia, and provide scientific support for the popularization of cardiopulmonary resuscitation.Methods:According to inclusion and exclusion criteria, a total of 1 503 inhabitants in Ningxia district (Jan. 2018 to Jan. 2019) were chosen as research samples. The general data was analyzed; the self-made questionnaire was applied to evaluate the inhabitants ′ theory knowledge, skill mastery and self-efficacy by professional nurses. Multiple linear regression was used to analyze the influence factors of theory knowledge and skill mastery degree. Results:A total of 1 503 valid questionnaires were collected, the assessment scores of theory knowledge, skill mastery and overall self-efficacy were (53.11±12.34), (62.64±18.35) and (6.09±2.18) points; According to demographic characteristics, multiple linear regression indicated that the influence factors of theory knowledge and skill mastery assessment scores included age, occupational distribution, education backgrounds, training conditions, time of taking training to survey, "onlooker" experience and self-efficacy indicators ( t/ F values were 5.723, 4.393, 5.817, 6.435, 5.990, 6.438, 6.631, P<0.01). The positive correlations were assumed ( r values were 0.012, 0.016, P<0.05) . Conclusion:In Ningxia, the inhabitants generally have low theory knowledge, skill mastery and self-efficacy levels. Therefore, the relevant medical institutions shall enhance the inhabitants ′ cardio-pulmonary resuscitation training through multiple methods and approaches.
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Objective:To explore the application value of primary trauma treatment (PTC) teaching mode in special professional cardiopulmonary resuscitation (CPR) guide training.Methods:Cluster sampling method was adopted, and the residents' committee selected special occupation population from every town/sub-district office in the southern mountainous area of Ningxia Hui Autonomous Region for CPR training. A monthly session was held from January to December 2019, with personnel trained by traditional operation teaching and individual practice method from January to June 2019 as the control group and personnel trained by PTC teaching mode from July to December 2019 as the observation group. The two groups of trainers, training objectives and assessment standards were consistent. Questionnaire survey was conducted at the beginning and end of each training period, including the degree of mastery of first-aid knowledge and skills and the level of self-efficacy, etc., to evaluate the training effect.Results:There were 503 trainees in each group, and there was no significant difference in gender, age, education and occupation distribution between the two groups. There was no significant difference in the first aid principles, CPR skill level and self-efficacy between the two groups before the training. The first aid principle, CPR skills level and self-efficacy of the two groups after training were all improved, and the principle of first aid and CPR skills level in the observation group was obviously higher than that in the control group (first aid related concepts: 4.39±0.76 vs. 3.87±0.89, gold life-saving time: 5.71±0.49 vs. 4.53±0.62, the meaning of the first witnesses: 5.33±0.82 vs. 4.18±0.78, cardiac, respiratory cardiac arrest in the judgment: 5.12±0.73 vs. 4.07±0.73, CPR skills: 5.29±0.64 vs. 4.15±0.71, all P < 0.05). The self-efficacy score of the observation group was significantly higher than that of the control group (emergency attitude: 18.17±1.24 vs. 17.35±1.25, self-efficacy: 13.56±1.54 vs. 11.35±1.26, behavioral intention: 9.56±0.84 vs. 8.92±0.95, all P < 0.05). Conclusion:The application of PTC teaching mode in the training of CPR guidelines for special professions has significant effects, which can effectively help special professions to master CPR knowledge and skills, and has promotion value.
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OBJECTIVE@#To assess the value of preimplantation genetic test (PGT) based on next generation sequencing (NGS) for achieving pregnancy for 71 couples with one partner carrying a reciprocal or Robertsonian translocation.@*METHODS@#Following blastocyst biopsy, whole genome of single cell was amplified, and PGT was performed by NGS. The subjects included 60 couples with one partner carrying a reciprocal translocation and 11 with one partner carrying a Robertsonian translocation. The results of PGT, implantation and prenatal diagnosis for all of the couples were analyzed.@*RESULTS@#In total 301 embryos were obtained for the 71 couples through 92 ovulation cycles, 287 (95.3%) of which were successfully diagnosed by NGS. Eighty-five euploidy embryos were identified for the reciprocal translocation carrier group. In 18 cycles, no euploid embryo was obtained. Cancellation rate for the cycles was 19.5%. For reciprocal translocation carrier group and Robertsonian translocation carrier group, the rates for implantation, early abortion, and clinical pregnancy were 89.3% (42/47), 25.5% (12/47), 63.8% (30/47), and 88.8% (8/9), 22.2% (2/9), and 66.6% (6/9), respectively. The result of prenatal diagnosis was consistent with the that of PGT.@*CONCLUSION@#PGT based on NGS can effectively identify euploid embryos and reduce recurrent abortions and termination of pregnancies, achieving a satisfactory rate for clinical pregnancy.
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Female , Humans , Pregnancy , Fertilization in Vitro , Genetic Testing , High-Throughput Nucleotide Sequencing , Preimplantation Diagnosis , Methods , Translocation, GeneticABSTRACT
Objective The role and action mechanisms of NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4) in the development of human colorectal cancer (CRC) are not yet clarified. This article aims to study the effect of overexpressed NDUFA4 on the epithelial-mesenchymal transition (EMT) of human CRC cells. Methods The recombinant plasmid NDUFA4 (p-NDUFA4) and control plasmid (p-Cont) were transiently transfected into human CRC HCT116 cells. The expression of NDUFA4 in the cells was determined by real-time PCR and Western blot respectively, and the migration ability of the cells detected by Transwell migration and wound healing assays. The expression levels of MMP2, MMP9 and CXCR4 in the cells were measured by qRT-PCR, and those of Twist, Snail, E-cadherin and Vimentin by Western blot and by immunofluorescence assay, respectively. Results Compared with the p-Cont group, the human CRC HCT116 cells of the p-NDUFA4 group showed significantly up-regulated expressions of NDUFA4 mRNA ([0.96±0.15]% vs [1.94±0.08]%, P<0.05) and NDUFA4 protein ([0.06±0.05]% vs [1.07±0.12]%, P<0.05), increased in vitro migration ability ([29.51±3.17]% vs [54.36±4.08]%, P<0.01) and migrated cell rate ([0.99±0.12]% vs [1.85±0.10]%, P<0.01), elevated expression levels of MMP2, MMP9, CXCR4, N-cadherin,Vimentin, Snail and Twist, but down-regulated level of E-cadherin (P<0.05). Conclusion Overexpressed NDUFA4 promotes the epithelial-mesenchymal transition of human colorectal cancer cells.
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PURPOSE: This study aimed to investigate the effect of adipose-derived stem cell (ADSC) transplantation on atherosclerosis (AS) and its underlying mechanisms. MATERIALS AND METHODS: In our study, rat AS model was established, and ADSCs were isolated and cultured. Atherosclerotic plaque and pathological symptoms of thoracic aorta were measured by Oil Red O staining and Hematoxylin-Eosin staining, respectively. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by an automatic biochemical analyzer. Expressions of vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), aortic endothelin-1 (ET-1), interleukin-6 (IL-6), c-reactive protein (CRP), and tumor necrosis factor α (TNF-α) were measured by enzyme linked immunosorbent assay, VEGF, VCAM-1, ICAM-1, ET-1, respectively, and NF-κB p65 mRNA expressions were detected by quantitative real-time polymerase chain reaction. Protein expressions of VEGF, VCAM-1, ICAM-1, ET-1, NF-κB p65, p-NF-κB p65, and IκBα were measured by western blot. Moreover, NF-κB p65 expression was measured by immunofluorescence staining. RESULTS: ADSC transplantation alleviated the pathological symptoms of aortic AS. ADSC transplantation decreased the levels of TC, TG, and LDL-C and increased serum HDL-C level. Meanwhile, ADSC transplantation decreased the levels of IL-6, CRP, and TNF-α in AS rats. Moreover, the expressions of VEGF, ET-1, VCAM-1, and ICAM-1 were decreased by ADSC transplantation. ADSC transplantation inhibited phosphorylation of NF-κB p65 and promoted IκBα expression in AS rats. CONCLUSION: Our study demonstrated that ADSC transplantation could inhibit vascular inflammatory responses and endothelial dysfunction by suppressing NF-κB pathway in AS rats.
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Animals , Rats , Aorta, Thoracic , Atherosclerosis , Blotting, Western , C-Reactive Protein , Cholesterol , Endothelin-1 , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique , Intercellular Adhesion Molecule-1 , Interleukin-6 , Lipoproteins , Phosphorylation , Plaque, Atherosclerotic , Real-Time Polymerase Chain Reaction , RNA, Messenger , Stem Cell Transplantation , Stem Cells , Triglycerides , Tumor Necrosis Factor-alpha , Vascular Cell Adhesion Molecule-1 , Vascular Endothelial Growth Factor AABSTRACT
<p><b>BACKGROUND</b>Repetitive transcranial magnetic stimulation (rTMS) and event-related potentials (ERPs) are a noninvasive technique that widely used in neurophysiological field. Although rTMS has shown clinical utility for a number of neurological conditions, Recently,there was little understanding of the the efficacy of rTMS on Schizophrenia(SZ) and the change of ERP between before and after rTMS treatment. The objective of this study was to investigate the characteristics of N400, mismatch negativity (MMN), and P300 before and after treatment with rTMS in SZ.</p><p><b>METHODS</b>One hundred and twenty-seven SZ patients hospitalized in Shanghai Mental Health Center from March 2015 to July 2017, divided into two groups (85 patients were recruited as rTMS group and 42 were recruited as sham rTMS [ShrTMS] group) and 76 normal controls (NCs) who were the staff and refresher staff in our hospital were recruited at the same time. A Chinese-made rTMS and a Runjie WJ-1 ERPs instrument were used in the present experiment. N400 was elicited by congruent and noncongruent Chinese idioms. After rTMS treatment, N400, P300, and MMN characteristics were compared with those before treatment and NC group.</p><p><b>RESULTS</b>Compared with NC, the SZ patients exhibited delays in N400, P300, and MMN latency and decreased N400, P300, and MMN amplitudes in their frontal area (P < 0.05). After 25 rTMS treatments, N400 amplitudes in the frontal area (elicited by idioms with same phonic and different shape and meaning and with different phonic, shape, and meaning) were increased in the SZ patients (P < 0.05). However, there was no significant change in N400 before and after treatment with ShrTMS in SZ patients (P > 0.05). Amplitudes for MMN and target P300 also increased in SZ patients after rTMS treatment (P < 0.05).</p><p><b>CONCLUSIONS</b>Based on our preliminary findings, we believe that the combined usage of N400, MMN, and P300 could be a valuable index and an electrophysiological reference in evaluating the effects of rTMS treatment in SZ patients.</p>
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Objective: To summarize the selection criteria and clinical application of surgical methods for hip fractures (femoral neck fracture and intertrochanteric fracture) in the elderly. Methods: The related literature concerning the surgical methods for femoral neck fracture and intertrochanteric fracture in the elderly at home and abroad was extensively reviewed and summarized. Results: Among the elderly patients with femoral neck fracture, the closed reduction and internal fixation or dynamic hip screw (DHS), and total hip arthroplasty are recommended for patients under 65 years old and 65-80 years old respectively and without special surgical contraindication; whereas hemiarthroplasty is recommended for patients with poor physical conditions. Among the patients with intertrochanteric fracture, DHS or the 3rd generation of Gamma nails is recommended for patients with stable fracture while the intramedullary fixation systems (e.g., proximal femoral nail anti-rotation, intertrochanteric antegrade nail) and the extramedullary fixation systems (e.g., proximal femoral locking compression plate and less invasive stabilization system) can be applied to the patients with unstable fracture according to the fracture type and bone conditions. Notably, hip arthroplasty is recommended for elderly patients with comminuted fracture. Conclusion: The surgical method and internal fixator should be chosen according to the fracture type and bone condition in the elderly in order to improve the effectiveness and reduce the complication.
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<p><b>OBJECTIVE</b>To investigate expression features and correlation of genes expression on MyD88-dependent signaling pathway in synovial membrane (SM) of progression of knee osteoarthritis (OA).</p><p><b>METHODS</b>Sixty Wistar rats were randomly divided into 6 groups, including blank group (N), false surgical group, model groups[2 weeks (2W), 4 weeks (4W), 8 weeks (8W) and 12 weeks (12W)], with 10 rats in each group. The models were established by using Hulth method. Control group was experienced no surgery, while false surgical group was only opened joint cavity and sutured. The SM samples was collected according to the time designed above. The relative expression quantity of MyD88, TLR4 and NF-κB was detected by Real-time PCR after the extraction of the total RNA and reverse transcription. The correlation analysis was obtained by SPSS.</p><p><b>RESULTS</b>There was no significant difference in each gene mRNA expression between false surgical and blank group(> 0.05), while enhanced expression was found in the model groups(<0.05). The correlation index among MyD88, TLR4 and NF-κB was 0.91 and 0.86 respectively, and had significant difference among them.</p><p><b>CONCLUSIONS</b>Positively relative among MyD88, TLR4 and NF-κB played main role in TLR4/NF-κB signal passway, and could predicate the expression of other genes in the passway. It also could further provide the basis for clarify the pathologic mechanism of knee OA.</p>