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Objective:To evaluate the efficacy of perioperative analgesia with esketamine in the patients undergoing thoracoscopic surgery.Methods:A total of 90 patients of either sex, aged 18-64 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for elective thoracoscopic lobectomy under general anesthesia, were divided into 3 groups ( n=30 each) by a random number table method: control group (C group) and different doses of esketamine groups (S 1 group, S 2 group). Before induction of anesthesia, esketamine 0.1 and 0.2 mg/kg were intravenously injected in S 1 group and S 2 group, respectively, while esketamine was not given in group C. Anesthesia was routinely induced in all the three groups. During anesthesia maintenance, esketamine 0.1 and 0.2 mg·kg -1·h -1 were intravenously infused in group S 1 and group S 2, respectively, and the remaining drugs used for anesthesia maintenance were the same in the three groups. Patient-controlled intravenous analgesia (PCIA) was used after operation, and PCIA solution contained sufentanil 2 μg/kg in group C, and esketamine 1 mg/kg was mixed on the basis as previously described in S 1 and S 2 groups. Aminotriol ketorolac was given as rescue analgesia to maintain numeric rating scale score at rest ≤3. The total amount of propofol and remifentanil during operation, effective pressing times of PCIA in postoperative 0-24 h and >24-48 h periods, and requirement for rescue analgesia were recorded. The occurrence of adverse reactions such as respiratory depression, nausea and vomiting, dizziness and salivation, and emergence time were recorded after surgery. The serum interleukin-6 (IL-6) concentration was measured by enzyme-linked immunosorbent assay at 30 min before and after surgery, and the malondialdehyde (MDA) concentration in serum was measured by thiobarbituric acid colorimetric analysis. The postoperative recovery was assessed using the 50-item quality of recovery scale at 1 and 2 days after surgery. The development of chronic pain was followed up by telephone within 1-3 months after surgery. Results:Compared with group C, the intraoperative consumption of remifentanil, effective pressing times of PCIA in postoperative 0-24 h and >24-48 h periods, rate of rescue analgesia, and postoperative serum IL-6 concentration were significantly decreased, and the 50-item quality of recovery scale score was increased in S 1 and S 2 groups, and the postoperative serum MDA concentration was significantly decreased in group S 2 ( P<0.05). Compared with group S 1, the consumption of intraoperative remifentanil was significantly decreased ( P<0.05), and no significant change was found in postoperative serum IL-6 and MDA concentrations in group S 2 ( P>0.05). Compared with group S 2, the postoperative emergence time was significantly shortened in S 1 and C groups ( P<0.05). There was no statistically significant difference in the intraoperative consumption of propofol, incidence of adverse effects and incidence of chronic pain among the three groups ( P>0.05). Conclusions:Esketamine for perioperative analgesia (dose before anesthesia induction 0.1 mg/kg, dose for maintenance of anesthesia 0.1 mg·kg -1·h -1, dose for postoperative PCIA 1 mg/kg) can raise the quality of analgesia and improve the quality of early postoperative recovery in the patients undergoing thoracoscopic lobectomy.
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ObjectiveOur recent study has demonstrated that extracellular acidification promotes lipid accumulation in macrophages via the activation of acid sensing ion channel 1 (ASIC1), but the underlying mechanism remains unclear. This study aims to explore the effect of extracellular acidification on macrophage lipophagy and the underlying mechanism. MethodsRAW264.7 macrophages were incubated with 25 mg/Lox-LDL in a pH 6.5 culture medium for 24 h to build macrophage-derived foam cell models induced by extracellular acidification. Then, RAW264.7 macrophages were cultured in the acidic medium of pH 6.5 with or without PcTx-1 (ASIC1 specific blocker, 10 μg/L) or Nec-1 (RIP1 specific inhibitor, 20 μmol/L) for 24 h, intracellular lipid accumulation was observed by oil red O staining. The expressions of total ASIC1, plasma membrane ASIC1, RIP1, p-RIP1 Ser166, TFEB, p-TFEB Ser142, LC3 and p62 were measured by Western blot. The co-localization of lipids (indicated by Bodipy) with LC3II (autophagosomes) and LAMP1 (lysosomes) was analyzed by a confocal laser scanning microscopy, respectively. Morphological changes of lipophagy in the cells were observed by using transmission electron microscopy. ABCA1-mediated cholesterol efflux was determined by cholesterol fluorescence kits. ResultsCompared with pH 7.4+ox-LDL group, the intracellular lipid accumulation in the pH 6.5+ox-LDL group was significantly increased. Meanwhile, the expressions of plasma membrane ASIC1, p-RIP1 Ser166, p-TFEB Ser142, and p62 proteins were elevated significantly, while LC3II protein level and LC3II/LC3I ratio were decreased. Accordingly, compared with pH 7.4+ox-LDL group, the macrophage lipophagy of the pH 6.5+ox-LDL group was inhibited as indicated by the decreased localization of lipid droplets with LC3 and LAMP1, a decrease in the number of lipophagosomes as well as an increase in lipid droplets. Furthermore, ATP binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux from the macrophages of pH 6.5+ox-LDL group reduced dramatically. However, these above effects of extracellular acidification on RAW264.7 macrophages were abolished by PcTx-1 and Nec-1, respectively. ConclusionThese findings suggest extracellular acidification promotes the phosphorylation of TFEB at Ser142 via activating ASIC1/RIP1 pathway, thereby impeding lipophagy in RAW 264.7 macrophages, and that ASIC1 may be a new potential target for preventing aberrant lipid accumulation diseases including atherosclerosis.
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Objective:To evaluate the optimization efficacy of pressure-volume (P-V) curve-based individualized lung-protective ventilation strategy combined with pressure-controlled ventilation-volume guaranteed (PCV-VG) mode (LPVS+ PCV-VG) for one-lung ventilation (OLV) in elderly patients undergoing radical resection of lung cancer.Methods:Seventy American Society of Anesthesiologists Physical Status classificationⅡ-Ⅲ patients, aged 65-74 yr, with body mass index of 18-24 kg/m 2, undergoing elective thoracoscopic radical resection of lung cancer, were divided into 2 groups ( n=35 each) using a random number table method: PCV-VG group and LPVS+ PCV-VG group. Blood samples were collected from the radial artery for blood gas analysis before induction of general anesthesia (T 0), at 5 min of two lung ventilation after endotracheal intubation (T 1), at 30 min of OLV (T 2), at the end of OLV (T 3), and at 5 min of two lung ventilation in supine position (T 4). Ppeak, mean airway pressure (Pmean) and dynamic lung compliance (Cdyn) were recorded. The use of antibiotics, lung-related complications and rehabilitation were recorded within 7 days after operation. Results:Compared with PCV-VG group, PaO 2, PaCO 2 and Cdyn were significantly increased at T 2-4, Ppeak was decreased at T 2, 3, Pmean was increased at T 3, the requirement for antibiotics within 7 days after operation was decreased, the incidence of 1 grade lung-related complications was decreased, and the thoracic drainage tube indwelling time and length of hospital stay were shortened in LPVS+ PCV-VG group ( P<0.05). Conclusions:Individualized LPVS based on P-V curve combined with PCV-VG mode provides better efficacy for OLV in elderly patients undergoing radical resection of lung cancer.
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【Objective】 To retrospectively analyze the average carboplatin dosage and calculate the area under the curve (AUC) using the Calvert formula in first-line chemotherapy in patients with epithelial ovarian cancer in The First Affiliated Hospital of Xi’an Jiaotong University so as to evaluate the effect of the AUC difference in the Chinese population on therapeutic efficacy and safety. 【Methods】 We enrolled patients who underwent first-line chemotherapy with paclitaxel and carboplatin 3-week regimen in our hospital from January 1, 2012 to January 1, 2022. According to the median of AUC, the patients were divided into high-dose group and low-dose group. The overall response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of adverse events (AEs) were compared. 【Results】 A total of 153 patients were enrolled in this study and the median AUC of carboplatin was 3.981 (range 2.314-5.446). Only 10.46% patients (16/153) had an AUC above 5. There were 77 patients with the AUC0.05). The ORR in the low-dose group and the high-dose group was 59.74% and 57.89%, respectively, and the DCR was 87.01% and 85.53%, respectively. The median PFS of the two groups was 14 and 15.5 months, respectively, and the median OS was 50 and 55 months, respectively. None of the above outcomes were statistically different between the two groups (P>0.05). The two groups showed significant differences in the incidence of anemia, neutropenia, and thrombocytopenia (P<0.05). The incidence of nausea and vomiting, grade 1-2 diarrhea or constipation, and grade 1-2 fever showed significant differences (P<0.05). In addition, the incidence of dose limiting toxicity (DLT), including grade 4 thrombocytopenia and febrile neutropenia (FN), was significantly increased in the high-dose group (P<0.05). 【Conclusion】 Compared with the recommended AUC 5-6 of carboplatin abroad, the actual carboplatin dosage in the first-line chemotherapy for patients with epithelial ovarian cancer was generally insufficient in our hospital. There was no difference in therapeutic efficacy between the patients with AUC<4 and AUC≥4. However, considering the increased risk of some AEs and DLT in the high-dose group, it is not recommended to increase the carboplatin AUC blindly.
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Objective:To evaluate the effect of remimazolam combined with remifentanil used for painless gastroscopy.Methods:A total of 150 patients of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, aged 18-64 yr, with body mass index of 18-30 kg/m 2, scheduled for elective painless gastroscopy, were divided into 3 groups ( n=50 each) using a random number table method: propofol combined with remifentanil group (group P), remimazolam 0.3 mg/kg combined with remifentanil group (group R1) and remimazolam 12 mg combined with remifentanil group (group R2). Drugs were administrated according to body weight, and calculation was carried out according to ideal body weight.Remifentanil 0.25 μg/kg was injected intravenously, propofol 1.5 mg/kg was then injected intravenously in group P, remimazolam 0.3 mg/kg was injected intravenously in group R1, and remimazolam 12 mg was injected intravenously in group R2.When Modified Observer′s Assessment/Alertness and Sedation (MOAA/S) score was≤3, gastroscopy was performed.It was defined as sedation failure when MOAA/S score was still ≥4 at 3 min after administration of propofol or remimazolam.When intraoperative body movement occurred, 1/4 of the initial dose of propofol was injected intravenously in group P, 1/4 of the initial dose of remimazolam was injected intravenously in group R1, and remimazolam 2.5 mg was injected intravenously in group R2 to maintain MOAA/S score ≤3.It was defined as sedation failure when sufficient sedation was not maintained after the additional drugs were given more than 3 times within 15 min.The success of sedation, time for gastroscopy, emergence time and discharge time were recorded.The occurrence of intraoperative body movement, bradyeardia, hypotension, respiratory depression, hiccup, coughing and injection pain was recorded. Results:Compared with group P, no significant change was found in the success rate of sedation ( P>0.05), and the incidence of intraoperative body movement, bradyeardia, hypotension, respiratory depression, hiccup, coughing and injection pain was decreased in group R1, and the success rate of sedation was significantly decreased, the incidence of intraoperative body movement, bradyeardia, hypotension, respiratory depression, coughing and injection pain was decreased, and the incidence of hiccup was increased in group R2 ( P<0.05). Compared with group R2, the success rate of sedation was significantly increased, and the incidence of intraoperative body movement, coughing and hiccup was decreased in group R1 ( P<0.05). Conclusion:Remimazolam 0.3 mg/kg combined with remifentanil can be safely and effectively used for painless gastroscopy.
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Retinal ischemia-reperfusion injury (RIRI) is an important pathophysiological basis of diabetic retinopathy, glaucoma, central retinal arteriovenous obstruction and some other ischemic retinal diseases. At present, there are several theories about the pathogenesis of RIRI, which included oxidative stress, apoptosis, necrosis, necroptosis, vascular injury and inflammatory reaction. Aim at the above pathogenesis of RIRI, domestic and foreign scholars have put forward a lot of methods in treating RIRI, including anti-radical damage, anti-glutamic acid excitotoxicity, anti-apoptosis, anti-necrosis, anti-necroptosis, protection of tight junctions, protection of endothelial cells, anti-inflammatory response, etc. Although there are a lot of drug research on RIRI, the timing of drug interventions for RIRI is still unclear. It may achieve twice the result with half the effort to determine the most effective treatment time window, and will also play a vital guiding role in the clinical treatment of ophthalmic related diseases.
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Objective:To investigate the effects of high frequency repetitive transcranial magnetic stimulation (rTMS) on learning memory and neuroelectric activity in rats. Methods:Eight Wistar rats were randomly divided into control group (n = 4) and rTMS group (n = 4). rTMS group was stimulated 14 days by rTMS with the frequency of 5 Hz, and the stimulation intensity was 100% motor threshold. The control group did not accepted rTMS. Then, the 16 channel local field potentials (LFPs) and spikes were recorded from their prefrontal cortex (PFC) in each group during the working memory tasks. The time-frequency analysis based on the short-time Fourier transform was performed on the LFPs, and the spike was analyzed by the release rate method. Multitaper Spectral Coherence was used to analyze the Synchronization Degree of LFPs-spike. Results:In the working memory experiment, rTMS group needed less days than the control group to reach the task correction criterion (t = 2.51, P = 0.046). The energy intensity of the θ-band and γ-band of the LFPs was significantly higher in rTMS group than in the control group (t > 12.49, P < 0.001), θ-band and γ-band LFPs-spike were more synchronized (t > 8.82, P < 0.001), but there was no significant difference in the average rate of spike between groups (t = 1.73, P = 0.067). Conclusion:High frequency rTMS could increase the LFPs energy in working memory experiment, enhance cooperative coding process for LFPs and spike, and improve the working memory ability of the rats.
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Objective ToevaluateimagequalityoflowerextremityCTAoflowradiationdoseandlowcontrastmediumprotocol withsinogram-affirmediterativereconstruction(SAFIRE).Methods Thisstudyincluded116patientswhoreferredtolowerextremityCT angiographyusinga128-sliceCTscanner.Accordingtovoltageandcontrastmediumconcentration,patientsweredividedintofour groups:100kV+350mgI/mL,100kV+320mgI/mL,100kV+300mgI/mL,80kV+CarekV+300mgI/mL.Imagereconstructionunderwent conventionalfilteredback-projection (FBP)andSAFIREtechniqueineachprotocoltocompareSNR,CNRofarterialimages.Results Comparisonoftwosubgroupsinthesamegroup,SAFIREhadsignificantlyhigherimagequalitythanFBP.Comparisonamong groupsshowed:imagequalityinlowcontrastmediumandlowradiationdoseSAFIREgroupcouldreachsimilarorbetterthanthatin higherdoseFBPgroup.SAFIREcouldreduceimagenoiseandimproveimageSNRandCNR.Conclusion InlowerextremityCTA, 80kV+CarekV,300mgI/mLcontrastmediumwithSAFIREexamineprotocolcouldreducecontrastmediumconcentrationandradiationdose withnocompromiseddiagnosticdemand.
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OBJECTIVE@#To explore the effect of ambient particle matter 2.5 (PM2.5) collected in the urban center of Hangzhou on the lung injury of rats and on the activating of endoplasmic reticulum pathway.@*METHODS@#PM2.5 samples were collected on quartz fiber filters using a PM2.5 high-volume air sampler in the urban area of Hangzhou. The collected PM2.5 particles were extracted in ultrapure water and concentrated by vacuum freeze-drying. Twenty-four male Sprague-Dawly (SD) rats were randomly divided into 3 groups:saline control group, low dose PM2.5 exposure group (5 mg/kg BW) and high dose PM2.5 exposure groups (25 mg/kg BW). Each group received intratracheal instillation of PM2.5, once a week for 4 weeks. Twenty-four hours after the last exposure, the rats were narcotized and sacrificed, left lung was isolated and fixed with 4% paraformaldehyde for histopathological detection. The bronchoalveolar lavage fluid (BALF) was collected from the right lung. The total antioxidant capacity (T-AOC) level, the activities of superoxide dismutase (SOD) and lactic dehydrogenase (LDH) in BALF were detected by chemical colorimetry. The level of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) cytokines in BALF was measured by enzyme linked immunosorbent assay (ELISA). And the protein expressions of glucose-regulated protein 78 (GRP78), phosphorylated protein kinase receptor-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor (p-eIF2α), transcription factors C/EBP homologue protein (CHOP), inositol-requiring enzyme 1α (IRE1α) and X-box binding protein 1 (XBP1) in lung tissue were determined by Western blotting.@*RESULTS@#Compared with control group, rats in both low dose (5 mg/kg) and high dose (25 mg/kg) PM2.5-treated groups showed obviously dose-dependent pulmonary toxicity including thickening of alveolar walls, narrowing of alveolar space, interstitial hyperplasia and inflammatory cell infiltration. Compared with control group, T-AOC level and the SOD activity in BALF in both PM2.5-treated groups were decreased dose-dependently (<0.05), whereas the LDH activity in BALF were increased in a dose-dependent manner (<0.05). Exposure to PM2.5 resulted in a increasing of the release of proinflammatory cytokines including TNF-α, IL-1β and IL-6 in rat lung in a dose-dependent manner (<0.05). The levels of GRP78, p-PERK, p-eIF2α, CHOP, IRE1α and spliced XBP1 (XBP1-S) were significantly up-regulated, whereas the level of unspliced XBP1 (XBP1-U) was down-regulated in the rat lung tissue of high-dose PM2.5 treated group.@*CONCLUSIONS@#The PM2.5 in the urban area of Hangzhou can significantly cause lung inflammatory injury in rats. Both oxidative stress and activation of ER stress pathways may be related to such PM2.5 inhalation-induced lung inflammatory injury.
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Animals , Male , Rats , Bronchoalveolar Lavage Fluid , Interleukin-6 , Lung , Lung Injury , Particulate MatterABSTRACT
Objective To develop and validate a LC-MS/MS method for the determination of albiflorin in rat plasma. Meth?ods Plasma samples were extracted by liquid-liquid extraction with a mixture of ethyl acetate-isopropanol(95:5,V/V)to prepare samples for analysis. Chromatographic separation was performed on a Poroshell 120 EC-C18 column(50 mm × 2.1 mm I.D. 2.7μm). The mobile phase consisted of acetonitrile-water followed gradient elution. Detection of albiflorin and the internal standard(IS)lacos?amide was achieved by ESI MS/MS in the positive ion mode using m/z 498.5→m/z 197.1 and m/z 251.3→m/z 108.2 transitions,respec?tively. Results The method was linear in the range of 20 to 2000 ng/ml when 50μl plasma was analyzed. The lower limit of quantifi?cation was 20 ng/ml. The inter-and intra-day precision values were both below 15%,and the accuracy(relative error)was within ± 8.06%in all quality control samples. Conclusion The method provides a sensitive and rapid means for the determination of albiflorin in rat plasma,and completely meets the requirements for toxicokinetic study.
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Objective To investigate the correlations of Eotaxin-1,rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody with the activity of rheumatoid arthritis (RA).Methods A total of 58 patients with early RA,46 patients without RA and 53 healthy controls from our hospital during December 2014 and December 2015 were enrolled in our study.The activity of RA was evaluated by the swollen joint count (SJC),tender joint count (TJC) and DAS28 score.The levels of serum Eotaxin-1 and antiCCP antibody were detected by ELISA and serum RF levels were determined by the immunological turbidimetry.The comparisons of serum Eotaxin-1,anti-CCP antibody and RF levels between different groups were performed with ANOVA and their correlations with SJC,TJC and DAS28 score were analyzed by Spearman rank correlation.Results The levels of Eotaxin-1,anti-CCP antibody and RF in RA patients were (96.02 ± 2 1.07) pg/mL,(183.42 ± 87.45) U/mL and (119.09 ± 62.30) RU/mL,respectively,which were significantly higher than those in the patients without RA and healthy controls (P ＜ 0.01).The levels of serum Eotaxin-1 in RA patients were significantly related to TJC,SJC and DAS28 score (P ＜ 0.01),while the levels of anti-CCP antibody were related to TJC and DAS28 score.The levels of RF were only related to DAS28 score.Conclusion The levels of serum Eotaxin-1 and anti-CCP antibody in RA patients are significantly correlated with the activity of RA,which may be new serum markers to monitor the activity of RA.
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Objective To develop and validate a LC-MS/MS method for the determination of albiflorin in rat plasma. Methods Plasma samples were extracted by liquid-liquid extraction with a mixture of ethyl acetate-isopropanol (95:5, V/V) to prepare samples for analysis. Chromatographic separation was performed on a Poroshell 120 EC-C18 column (50 mm× 2.1 mm I.D. 2.7 µm). The mobile phase consisted of acetonitrile-water followed gradient elution. Detection of albiflorin and the internal standard (IS) lacosamide was achieved by ESI MS/MS in the positive ion mode using m/z 498.5→m/z 197.1 and m/z 251.3→m/z 108.2 transitions, respectively. Results The method was linear in the range of 20 to 2000 ng/ml when 50 µl plasma was analyzed. The lower limit of quantification was 20 ng/ml. The inter- and intra-day precision values were both below 15%, and the accuracy (relative error) was within ±8.06% in all quality control samples. Conclusion The method provides a sensitive and rapid means for the determination of albiflorin in rat plasma, and completely meets the requirements for toxicokinetic study.
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<p><b>OBJECTIVE</b>To explore the methylation status in promoter region of norepinephrine transporter gene (NET, SLC6A2) in heart failure ( HF) patients and its correlation with qi deficiency/blood stasis syndrome (QDS/BSS).</p><p><b>METHODS</b>Thirty-six patients with heart failure (NYHA classification III to IV) were recruited in the study (as the heart failure group) and their scores of QDS/BSS were evaluated. Besides, a healthy elderly group (30 cases) and a healthy youth group (30 cases) were also set up. They were recruited from Physical Examination Center of Fujian Provincial Hospital. Pyrosequencing was applied to detect the methylation in promoter region of SLC6A2 gene, and the total methylation index (MTI) of CpG island was calculated. The correlation between the methylation status in promoter region of SLC6A2 and scores of QDS/BSS was assessed using Pearson and Partial analyses. Risk factors were screened and adjusted using Logistic regression.</p><p><b>RESULTS</b>By one-factor analysis of variance, the total MTI in the HF group (219.72% ± 54.03%) was obviously higher than that in the healthy elderly group (194.47% ± 34.92%) and the healthy youth group (161.60% ± 41.11%) (all P < 0.05). Meanwhile, the total MTI was higher in the healthy elderly group than in the healthy youth group (P < 0.01). By covariance analysis , after controlling age and BMI, the total MTI was higher in the HF group than in the healthy elderly group (P = 0.041), while it was higher in the healthy elderly group than in the healthy youth group (P = 0.016). Age was found to play an essential role in affecting MTI of SLC6A2 gene promoter region among the 3 groups (F = 16.447, P = 0.01). The total MTI was quite lower in the healthy youth group. Results of Partial correlation analysis showed MTI was positively correlated with scores of qi deficiency and blood stasis respectively (r = 0.494 and 0.419 respectively, both P < 0.05). Logistic regression analysis showed after adjusting confounding factors, the relative risk (OR value) of total MTI of SLC6A2 gene in promoter region was 1.038 (95% CI, 1.006 to 1.071, P = 0.020).</p><p><b>CONCLUSIONS</b>Abnormally elevated methylation of the promoter region of SLC6A2 gene is one of risk factors for HF. In addition, the degree of methylation of the promoter region of SLC6A2 gene was positively correlated with the severity of QDS/BSS.</p>
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Adolescent , Aged , Humans , DNA Methylation , Heart Failure , Genetics , Logistic Models , Medicine, Chinese Traditional , Norepinephrine Plasma Membrane Transport Proteins , Genetics , Promoter Regions, Genetic , QiABSTRACT
<p><b>BACKGROUND</b>Epstein-Barr virus (EBV) commonly infects the general population and has been associated with nasopharyngeal carcinoma (NPC), which has a high incidence in certain regions. This study aimed to address how EBV variations contribute to the risk of NPC.</p><p><b>METHODS</b>Using logistic regression analysis and based on the sequence variations at EBV-encoded RPMS1, a multi-stage association study was conducted to identify EBV variations associated with NPC risk. A protein degradation assay was performed to characterize the functional relevance of the RPMS1 variations.</p><p><b>RESULTS</b>Based on EBV-encoded RPMS1 variations, a single nucleotide polymorphism (SNP) in the EBV genome (locus 155391: G>A, named G155391A) was associated with NPC in 157 cases and 319 healthy controls from an NPC endemic region in South China [P < 0.001, odds ratio (OR) = 4.47, 95% confidence interval (CI) 2.71-7.37]. The results were further validated in three independent cohorts from the NPC endemic region (P < 0.001, OR = 5.20, 95% CI 3.18-8.50 in 168 cases vs. 241 controls, and P < 0.001, OR = 5.27, 95% CI 4.06-6.85 in 726 cases vs. 880 controls) and a non-endemic region (P < 0.001, OR = 7.52, 95% CI 3.69-15.32 in 58 cases vs. 612 controls). The combined analysis in 1109 cases and 2052 controls revealed that the SNP G155391A was strongly associated with NPC (P(combined) < 0.001, OR = 5.27, 95% CI 4.31-6.44). Moreover, the frequency of the SNP G155391A was associated with NPC incidence but was not associated with the incidences of other EBV-related malignancies. Furthermore, the protein degradation assay showed that this SNP decreased the degradation of the oncogenic RPMS1 protein.</p><p><b>CONCLUSIONS</b>Our study identified an EBV variation specifically and significantly associated with a high risk of NPC. These findings provide insights into the pathogenesis of NPC and strategies for prevention.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Carcinoma , Case-Control Studies , China , Epidemiology , Epstein-Barr Virus Infections , Epidemiology , Virology , Genetic Association Studies , Genome, Viral , Herpesvirus 4, Human , Genetics , Incidence , Nasopharyngeal Neoplasms , Epidemiology , Virology , Neoplasm Proteins , Genetics , Pilot Projects , Polymorphism, Single Nucleotide , Risk Assessment , Methods , Tumor Cells, Cultured , Viral Proteins , GeneticsABSTRACT
BACKGROUND:The study confirmed that adding tricalcium phosphate or pearl powder in polylactic-co-glycolic acid can complement the performance of both, which provides a good environment for cels and makes a faster and better growth of cels. OBJECTIVE:We used polylactic-co-glycolic acid as matrix, composited with pearl powder or tricalcium phosphate to prepare scaffolds by low-temperature deposition manufacturing. METHODS:Low-temperature deposition manufacturing was utilized to prepare composite scaffold of polylactic-co-glycolic acid/pearl powder or polylactic-co-glycolic acid/tricalcium phosphate at the ratio of 10:0, 5:2, 7:3 and 6:4. Microstructure, contact angle and compression modulus of elasticity of scaffolds were detected. MC3T3-E1 cels basicaly fused at 1×104/cm3 were seeded in the pure nonporous polylactic-co-glycolic acid scaffold, pure polylactic-co-glycolic acid scaffold with holes, polylactic-co-glycolic acid/pearl powder at 5:2 and polylactic-co-glycolic acid/tricalcium phosphate at 5:2 separately for 1 and 3 hours. Cel adhesion rate was detected using flow cytometry. After incubation for 1, 4 and 7 days, cel proliferation was measured using Alamar Blue method. RESULTS AND CONCLUSION:Pure polylactic-co-glycolic acid scaffold had cross-linked microporous structure, with pore size of 3-15 μm. Scaffolds ofpolylactic-co-glycolic acid/pearl powder at 5:2 or polylactic-co-glycolic acid/tricalcium phosphate at 5:2 had good continuous porous structure, with pore size of 10-25 μm. With increased content of pearl powder or tricalcium phosphate, the hydrophilicity of the composite scaffold increased. The addition of pearl powder or tricalcium phosphate could elevate compressive mechanical properties of the composite scaffold. With increased content, the mechanical property of the scaffold enhanced and then reduced. The addition of pearl powder or tricalcium phosphate improved the celular affinity of polylactic-co-glycolic acid and the biocompatibility of the scaffold. The biocompatibility of polylactic-co-glycolic acid/pearl powder scaffold at 5:2 was the best.
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Micro- and integrated biosensor provides a powerful means for cell electrophysiology research. The technology of electroplating platinum black on the electrode can uprate signal-to-noise ratio and sensitivity of the sensor. For quantifying analysis of the processing method of electroplating process, this paper proposes a grid search algorithm based on the Monte-Carlo model. The paper also puts forward the operational optimization strategy, which can rapidly implement the process of large-scale nanoparticles with different particle size of dispersion (20-200 nm) attac- hing to the electrode and shortening a simulation time from average 20 hours to 0.5 hour when the test number is 10 and electrode radius is 100 microm. When the nanoparticle was in a single layer or multiple layers, the treatment uniformity and attachment rate was analyzed by using the grid search algorithm with different sizes and shapes of electrode. Simulation results showed that under ideal conditions, when the electrode radius is less than 100 /m, with the electrode size increasing, it has an obvious effect for the effective attachment and the homogeneity of nanoparticle, which is advantageous to the quantitative evaluation of electrode array's repeatability. Under the condition of the same electrode area, the best attachment is on the circular electrode compared to the attachments on the square and rectangular ones.
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Algorithms , Biosensing Techniques , Electrodes , Models, Theoretical , Monte Carlo Method , Nanoparticles , Particle Size , PlatinumABSTRACT
ObjectiveTo investigate the dosage of protamine to counteract heparin in patients with different pH values of after - surgery plasma of congenital heart defect.MethodsThe clinical data of 108 patients during March 2011 to April 2011 with congenital heart diseases who underwent cardiopulmonary bypass(CPB) surgery were reviewed.The volumes of chest tube drainage were analyzed to investigate the dosage of protamine in patients with different pH values in plasma.ResultsThe dosages of protamine and the volumes of chest tube drainage[ ( 136.8 ± 22.8 ) ml] in patients with an acidic environmental plasma were higher than the patients in another group [ ( 112.6 ± 22.7 ) ml ] ( P＜ 0.01 ).In patients with non-acidic environments,the mean ratio of dosage of protamine to heparin was 1.23:1 ; meanwhile in patients with pH＜7.30 or base excess (BE) ＜ -6,the mean ratio was 1.86:1.It suggested the dosage of protamine increased significantly in patients with an acidic environmental plasma.ConclusionsDifferent plasma pH values could change the dosage of protamine after cardiopulmonary bypass,and the acidic environment would increase the dosage of protamine and increase the volume of chest tube drainage after surgery.When pH ＜ 7.30 or BE ＜ - 6 at the end of CPB,to correct acid-base balance first and then calculate the dose of protamine was recommended.
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S-phase kinase-associated protein 2 (Skp2), which plays a role in cell cycle regulation, is commonly overexpressed in a variety of human cancers and associated with poor prognosis. However, its role in nasopharyngeal carcinoma (NPC) is not well understood. In this study, we examined the clinical significance of Skp2, with a particular emphasis on overall survival (OS) and disease-free survival (DFS), in NPC cases in South China, where NPC is an epidemic. Additionally, we explored the function of Skp2 in maintaining a cancer stem cell-like phenotype in NPC cell lines. Skp2 expression was assessed for 127 NPC patients using tissue microarrays and immunohistochemistry and analyzed together with clinicopathologic features, OS, and DFS. Skp2 expression was detectable, or positive, in 75.6% of patients. Although there was no correlation between Skp2 and any clinicopathologic factor, Skp2 expression significantly portended inferior OS (P = 0.013) and DFS (P = 0.012). In the multivariate model, Skp2 expression remained significantly predictive of poor OS [P = 0.009, risk ratio (RR) = 4.06] and DFS (P = 0.008, RR = 3.56), and this was also true for clinical stage (P = 0.012 and RR=3.201 for OS; P = 0.002 and RR=1.94 for DFS) and sex (P = 0.016 and RR=0.31 for OS; P = 0.006 and RR = 0.27 for DFS). After Skp2 knockdown, a colony formation assay was used to evaluate the self-renewal property of stem-like cells in the NPC cell lines CNE-1 and CNE-2. The colony formation efficiency in CNE-1 and CNE-2 cells was decreased. In Skp2-transfected CNE-1 and CNE-2 cells, side population (SP) proportion was increased as detected by flow cytometry. Skp2 is an independent prognostic marker for OS and DFS in NPC. Skp2 may play a role in maintaining the cancer stem cell-like phenotype of NPC cell lines.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Carcinoma , Cell Line, Tumor , China , Disease-Free Survival , Follow-Up Studies , Gene Knockdown Techniques , Nasopharyngeal Neoplasms , Genetics , Metabolism , Pathology , Neoplasm Staging , Neoplastic Stem Cells , Pathology , RNA, Small Interfering , Genetics , S-Phase Kinase-Associated Proteins , Genetics , Metabolism , Sex Factors , Survival Rate , Tissue Array Analysis , TransfectionABSTRACT
Objective To explore the feasibility of evaluating cardiac structure, coronary artery,pulmonary artery and cardiac function in one single scan by 320-row CT ECG-gated double phase cardiac function scan mode. MethodsForty patients underwent the 320-detector row CT double phase cardiovascular angiography. The pulmonary phase and aortic phase were reconstructed in order to evaluate the pulmonary and coronary artery. MPR reconstructions of both pulmonary and aortic phase were used to analyze the function of the two ventricles. And the results of the cardiac function were compared with those of transthoracic echocardiography. Thirty-five cases could be analyzed and diagnosed, while the other 5 cases had to be given up because of the poor imaging quality. The mean heart rate was (71.2 ± 11.2) beat per min (bpm). No arrhythmia case included. Results ( 1 ) Pulmonary embolism were diagnosed in 11 cases,coronary artery disease (CAD) were found in 5 cases, while post-stent implantation were observed in 7 cases. Six cases of congenital heart disease were diagnosed with 3 ASD and 3 primary pulmonary hypertension. Another one was diagnosed with left atrial myxoma, and 5 cases were pulmonary embolism associated with CAD. All of above cases were verified by final clinical diagnosis. (2) The heart function parameters including LVEDd , RVEDd, LVESd, RVESd and LVEF were (36.7 ±3.3), (43.3 ± 3.4) mm,(31.6±5.1), (41.3 ±5.1) mm and (47.1 ±15.1) for CT, while those were (40.3 ±3.1), (47.3 ±4.2) mm,(37.3 ±5.6), (45.3 ±3.3) mm,and (46.0 ± 14.8) for ultrasound, respectively. The CT results were correlated with the ultrasound ( n = 35, r = 0.886-0.988, P ＜ 0.01 ). (3) The average radiation exposure was ( 5.4 ± 0.5 ) mSv. Conclusions 320-row CT ECG-gated double phase cardiac function scan mode is feasible for the "one-stop-shop" examination of the cardiovascular disease. This noninvasive method is recommended for the diagnosis, differential diagnosis, treatment and prognosis of cardiovascular disease.
ABSTRACT
Objective To evaluate the combination of dual-energy CT angiography (DE-CTA) and dual-energy CT peffusion (DE-CTP) in the diagnosis of coronary artery disease. Methods Thirty-one patients with angina pectoris were examined using dual-source dual energy CT and conventional coronary angiography. For DE-CTA, we used a contrast-enhanced ECG-gated coronary scan protocol with energy levels of two tube detector arrays at 140 and 100 kVp. Two kinds of acquired images were fused for the CT angiogram and further calculated to construct a perfusion map (Siemens DE Heart PBV). The compared the following results: DE-CTA vs. CA, DE-CTP vs. CA to assess the sensitivity and specificity, and further compared DE-CTA plus DE-CTP with CA. Results DECT obtained diagnostic image quality in 28 patients.DE-CTA detected 41/112 arterial stenosis. Using CA as a reference, the sensitivity of DE-CTA was 81%(38/47), specificity was 95% (62/65), positive predictive value was 92% (38/41), negative predictive value was 87% (62/71), and accuracy was 89% (100/112). DE-CTP detected 46 perfusion defects in artery territories. Using CA as a reference, the sensitivity of DE-CTP was 76% ( 36/47), specificity was 85% (55/65), positive predictive value was 78% (36/46), negative predictive value was 83% (55/66),and accuracy was 81% (91/112). DE-CTA plus DE-CTP diagnosed 52 arteries stenosis. Using CA as a reference, combination of DE-CTA and DE-CTP gave sensitivity of 95% ( 45/47 ), specificity of 89%(58/65) , NPV of 97% (58/60), and accuracy of 92% (103/112). Conclusions DECT can provide perfusion blood volume information as well as vessel pathology in one scan. DECT can provide comprehensive diagnosis and improve diagnosis of CAD.