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BACKGROUND@#Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.@*METHODS@#A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.@*RESULTS@#The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production.@*CONCLUSION@#Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
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Humanos , Aspergilosis Broncopulmonar Alérgica/complicaciones , Aspergillus fumigatus/genética , Asma/genética , Aspergillus , Mutación/genética , Proteínas Adaptadoras de Señalización CARD/genéticaRESUMEN
Objective:To investigate the differences of integral alpha 3 (ITGA3) mRNA and protein expressions in gliomas of different grades and different cell lines, and gliomas tissues of different clinical and molecular characteristics, and evaluate their prognostic values in brain glioma patients.Methods:(1) ITGA3 mRNA expression data in the brain gliomas and clinical data of these glioma patients were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). The differences of ITGA3 mRNA expressions in glioma patients with different gender, ages, WHO grading, isocitrate dehydrogenase 1 ( IDH) mutation statuses, and 1p/19q co-deletion statuses were compared. Kaplan-Meier method was used to plot and compare the survival curves of patients with ITGA3 mRNA high expression and ITGA3 mRNA low expression. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficiency of ITGA3 mRNA expression in survival rate of gliomas. Univariate and multivariate Cox regression analyses were used to explore the independent influencing factors for prognoses in glioma patients. The independent influencing factors for prognosis were used to construct nomograms and the calibration diagram was used to verify the reliability of nomograms in predicting the prognoses of these patients. (2) Intracellular localization of ITGA3 and ITGA3 protein expression in low- and high-grade gliomas were determined by on-line database of Human Protein Atlas (HPA). (3) Brain glioma cells U87, U118, U251 and human astrocytes SVG were cultured in vitro, and the ITGA3 mRNA and protein expressions in cells were detected by Western blotting and reverse transcription (RT)-PCR, respectively. Results:(1) In TCGA database, the ITGA3 mRNA expressions in gliomas of WHO grading II, III and IV increased successively, with significant differences (P<0.05). In CGGA database, the ITGA3 mRNA expression in glioma of WHO grading IV was statistically higher than that in glioma of WHO grading II and III ( P<0.05). In TCGA and CGGA databases, the ITGA3 mRNA expressions in glioma patients aged ≤40 years and >40 years, patients with IDH wild-type and IDH mutation, and patients with chromosome 1p/19q deletion and chromosome 1p/19q non-deletion were statistically different ( P<0.05). The survival rate of patients with low ITGA3 mRNA expression was significantly higher than that of patients with high ITGA3 mRNA expression, no matter in low-grade glioma, glioblastoma, or entire glioma samples ( P<0.05). ROC curve showed that, in TCGA database, the area under the curve (AUC) of ITGA3 mRNA in predicting 1, 3, and 5 years survival was 0.791, 0.786, and 0.708 in glioma patients; in CGGA database, the AUC of ITGA3 mRNA in predicting 1, 3, and 5 years survival was 0.661, 0.667, and 0.659. Multivariate Cox regression analysis showed that, in TCGA database, age, WHO grading, IDH mutation, chromosome 1p/19q deletion and ITGA3 mRNA expression ( HR=1.018, 95%CI: 1.006-1.030, P=0.0.003) were independent influencing factors for prognoses of glioma patients ( P<0.05); and in CGGA database, WHO grading, IDH mutation, chromosome 1p/19q deletion, and ITGA3 mRNA expression ( HR=1.445, 95%CI: 1.132-1.844, P=0.003) were independent influencing factors for prognoses of glioma patients ( P<0.05). Nomograms showed that age had the greatest influence in survival, followed by ITGA3 mRNA expression. Calibration plots showed that nomogram was reliable in predicting 1-, 3-, and 5-year survival in glioma patients. (2) Immunofluorescence localization showed that ITGA3 protein mainly aggregated in cell membrane and vesicles. Immunohistochemical staining showed that the ITGA3 protein expression in high-grade glioma tissues was obviously higher than that in low-grade glioma tissues. (3) The results of RT-PCR and Western blotting revealed that the ITGA3 mRNA and protein expressions in glioma cell lines U87, U118 and U251 were significantly higher than those in SVG cells ( P<0.05). Conclusion:The ITGA3 mRNA and protein expression levels are correlated with the malignant degrees of glioma; patients with ITGA3 mRNA low expression tend to have a high overall survival; ITGA3 mRNA expression can be used as an index to evaluate the prognoses of glioma patients.
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Objective:To investigate the relations between gene polymorphisms of angiotensin II receptor 1 ( AGTR1) and interleukin-6 ( IL-6) and aneurysmal subarachnoid hemorrhage (SAH). Methods:One hundred and forty-two patients with aneurysmal subarachnoid hemorrhage admitted to our hospital from May 2018 to May 2020 were selected as an observation group, and 284 healthy subjects underwent physical examination at the same period were selected as a control group. Fasting peripheral venous blood was collected for genomic DNA extraction and PCR amplification. Restriction endonuclease was used to perform enzyme digestion reaction on the amplified products, and the differences of AGTR1 gene polymorphism at A1166C locus and IL-6 gene polymorphism at C-572G locus were compared between the two groups and among the SAH patients with different clinical features. Results:(1) The frequency of AA genotype in AGTR1 gene at A1166C locus in the observation group was significantly higher than that in the control group, while that of AC+CC genotype in the observation group was significantly lower than that in the control group ( P<0.05); the observation group had significantly higher frequency of A allele and statistically lower frequency of C allele than the control group ( P<0.05). The CC genotype frequency in IL-6 gene at C-572G locus in the observation group was significantly lower than that in the control group and the CG+GG genotype frequency were significantly higher than that in the control group ( P<0.05); the observation group had significantly lower C allele frequency and significantly higher G allele frequency than the control group ( P<0.05). (2) AA genotype frequency in AGTR1 gene at A1166C locus in SAH patients with diabetes mellitus was significantly higher than that in SAH patients without diabetes mellitus, while AC and CC genotype frequency was significantly lower than that in SAH patients without diabetes mellitus ( P<0.05). The frequency of CC genotype in IL-6 gene at C-572G locus in SAH patients with multiple aneurysms or diabetes mellitus was significantly lower than that in SAH patients with single aneurysm or without diabetes mellitus, respectively; and that of CG+GG genotype was significantly higher than that in SAH patients with single aneurysm or without diabetes mellitus, respectively ( P<0.05). Conclusion:Patients with AA genotype of AGTR1 gene at A1166C locus are prone to have aneurysmal subarachnoid hemorrhage, and these patients combined with diabetes mellitus have higher incidence; and patients with CG+GG genotype of IL-6 gene at C-572G locus are prone to have aneurysmal subarachnoid hemorrhage, and these patients with diabetes mellitus or multiple aneurysms have higher incidence.
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【Objective】 To explore the effect of Genistein on the proliferation and cell cycle regulation of ovarian cancer cells. 【Methods】 Ovarian cancer OVCAR-5 cells were treated with Genistein. Cell counting and MTS assays were performed to determine the alterations of cell proliferation. Real-time PCR and Western blotting were conducted to examine the expression changes of key cell cycle regulators. 【Results】 Genistein significantly promoted the proliferation and viability of OVCAR-5 cells. After Genistein treatment, cellular mRNA and protein expression levels of cell cycle activators such as PCNA, Cyclin D1 and CDK4 were increased, but those of cell cycle inhibitors such as p21 and p27 were decreased. 【Conclusion】 Genistein can upregulate the proliferation and G1-S transition of ovarian cancer OVCAR-5 cells. The discrepancy may be caused by diverged experimental conditions and/or different ER expression patterns of cell lines. The findings may provide basic information for in-depth analysis of the role(s) and mechanisms by which genistein confers its effect on ovarian cancer cells.
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Objective:To compare the clinical efficacy of long/short segment posterior instrumentation combined with transpedicular impaction bone grafting for stage III Kümmell's disease.Methods:A retrospective case control study was conducted to analyze the clinical data of 45 patients with stage III Kümmell's disease admitted to Zhengzhou Orthopaedics Hospital from June 2012 to June 2019, There were 8 males and 37 females, aged 58-84 years [(68.8±3.5)years]. Segment of injury was T 11 in 5 patients, T 12 in 18, L 1 in 15, and L 2 in 7. A total of 24 patients were treated with posterior long segment pedicle screw fixation combined with pedicle screw compression and bone grafting (long segment group), and 21 patients were treated with posterior short segment pedicle screw fixation combined with pedicle screw compression and bone grafting (short segment group). For patients with severe osteoporosis, pedicle screws were augmented with bone cement. The operation time and blood loss were compared between the two groups. The visual analogue scale (VAS) was used to evaluate the degree of low back pain, and the Japanese Orthopaedic Association (JOA) score was used to evaluate the lumbar function at postoperative 2 weeks and 1 year. According to X-ray film and CT examination, the bone healing of the grafted vertebral body and the changes of Cobb angle of injured vertebrae were further evaluated. The complications were observed. Results:All patients were followed up for 15-48 months[(31.2±2.3)months]. There were no significant differences between the two groups in operation time and intraoperative blood loss ( P>0.05). The bone grafts in the vertebrae healed well in both groups at 1 year after operation. The Cobb angle, VAS and JOA score in both groups improved at 2 weeks and 1 year after operation ( P<0.01). There was no significant difference in Cobb angle, VAS and JOA score between the two groups at 2 weeks after operation ( P>0.05). The Cobb angle in short segment group [(14.8±6.3)°] was significantly higher than that in long segment group [(8.5±3.3)°] at 1 year after operation ( P<0.01), but there was no significant difference in VAS and JOA scores between the two groups ( P>0.05). There was no loosening or breakage of internal fixation in both groups. Conclusions:For stage III Kümmell's disease, both long and short segment posterior instrumentation combined with transpedicular impaction bone grafting can effectively restore the vertebral height, improve kyphosis and reduce dysfunction. However, long segment can better maintain spine stability, prevent vertebral collapse and progression of local kyphosis Cobb angle when compared with short segment fixation.
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Objective:To investigate the efficacy of stage I anterior cervical reduction, decompression, interbody fusion and internal fixation of single-segment lower cervical injury of AO type C subtype F4.Methods:A retrospective case series study was made on 45 patients with single-segment lower cervical injury of AO C type F4 subtype admitted to Zhengzhou Orthopedic Hospital from January 2012 to December 2019. The study included 31 males and 14 females with the age of (48.5±3.7)years (range, 23-78 years). Segment of injury was located at C 4/5 in 11 patients, at C 5/6 in 19, and at C 6/7 in 15. Under general anesthesia, all patients (16 unilateral injury and 29 bilateral injury) underwent stage I anterior cervical reduction, decompression, interbody fusion and internal fixation within 24 hours after injury. The interbody fusion methods included autogenous iliac bone in 28 patients and cervical fusion cage in 17. The operation time, blood loss, reduction time and correction rate of zygapophysial joints, postoperative complications and incision healing were analyzed. The height of cervical intervertebral space and Cobb angle were measured through X-ray of lateral cervical vertebrae before operation and3 months after operation to assess the cervical physiological curvature. The type of injury was clarified according to Lenke classification through coronal and sagittal CT scanning to determine the intervertebral bone graft fusion rate. The intraspinal spinal cord decompression was observed through MRI. The nerve function was assessed before operation and 3 months after operation using American Spinal Injury Association (ASIA) scale and Japanese Orthopedic Association (JOA) score, and the improvement rate was measured. Results:All the patients were followed up for (6.1±3.6)months (range, 3-9 months). The operation time was (55.1±8.2)minutes (range, 40-75 minutes), and intraoperative blood loss was (45.2±5.3)ml (range, 40-80 ml). The Zygapophysial joint reduction took (2.1±0.5)minutes (range, 1.5-3.0 minutes), with a success rate of 100%. Surgical procedures were performed with no postoperative complications such as aggravated spinal cord injury, large vascular injury or esophageal lesion. All the patients obtained Class I incision healing at first stage. The height of cervical intervertebral space was improved from preoperative (3.3±0.6)mm to (4.9±0.8)mm at postoperative 3 months ( P<0.05). The Cobb angle was increased from preoperative (-4.6±3.6)° to (6.5±2.1)° at postoperative 3 months ( P<0.01). According to Lenke classification, the intervertebral body fusion was good at postoperative 3 months, including Grade A in 41 patients and Grade B in 4. The rest of the patients showed varying degrees of neurological recovery according to ASIA scale, except for 6 patients with ASIA Grade A. The JOA score was improved from preoperative (7.4±2.3)points to (15.0±3.2)points at postoperative 3 months ( P<0.05), with the improvement rate of (73.3±17.6)%. Conclusion:For stage I anterior cervical reduction, decompression, interbody fusion and internal fixation of single-segment lower cervical injury of AO type C subtype F4, early surgical decompression is needed so as to reduce the perched facet or dislocated zygapophyseal joints and effectively improve the cervical spinal cord function.
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Objective To explore the signs of consistent changes of intestinal flora in type 2 diabetes mellitus (T2DM) and diabetes kidney disease (DKD) patients, by studying the key change characteristics of intestinal flora in these patients. Methods Thirty patients with T2DM,twenty-five patients with DKD were involved. Thirty healthy patients with matching age and sex were also involved as the control group. Fecal and serum specimens were collected from both the study group and the control group. High-throughput sequencing technology was used to sequence the 16S rDNA-v4 region of fecal samples;interleukin-6 (IL-6) and C-reactive protein (CRP) were detected by electrochemical luminescence and immunoturbidimetry. Microbiome analysis software QIIME (v1.9.1) was used to analyze the composition and diversity of intestinal flora. Microbial diversity analysis software LEfSe was used to compare intestinal bacteria markers differences between the study group and the healthy control group. The diagnosis model was established by the random forest method. The change characteristics of intestinal flora function were predicted by the PICRUSt. Results The intestinal flora diversity of DM and DKD patients was significantly different from that of the healthy control group (P<0.05). T2DM and DKD patients harbored lots of similar changes. For example, there was a significant decrease in Lachnospira, Faecalibacterium, Roseburia and Coprococcus(P<0.05). However, there was also a disease-specific pattern of imbalance between the two disease. There was a significant increase in Bacteroides in T2DM patients, and in Lactobacillus, Slackia, Anaerotruncus,Haemophilus and Enterococcus in DKD patients. Functional prediction was also confirmed that T2DM and DKD patients had more consistent changes. The correlation analysis between serum inflammatory indicators of T2DM and DKD and bacteria suggested that the decrease of beneficial bacteria in the intestinal tract of T2DM and DKD patients may be the cause of the increase of serum inflammatory indicators. Conclusion T2DM and DKD patients harbored lots of similar changes in intestinal flora, a decrease of bacteria producing butyrate,but there was also a disease-specific change between the two disease,providing a data basis for further studies to evaluate the risk of nephropathy in patients with diabetes by intestinal flora .
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Objective To investigate the effects of ginkgo biloba extracts ( EGb761) on learning and memory and the protective effect on hippocampal neurons in rats with vascular dementia (VD). Meth-ods Ninety rats were randomly divided into sham-operated group,model group and EGb761-treated group, with 30 rats in each group. Rats in each group were examined at 15 days,1 month and 2 months,with 10 rats in each time point. VD model was established by bilateral carotid artery occlusion combinding with injection of sodium nitroprusside. Morris water maze test was used to detect the learning and memory function of rats. The expression of glial fibrillary acidic protein (GFAP) was observed by immunofluorescence. Western-blot was used to detect the protein expression of P-glycoprotein ( P-GP ), excitatory amino acid transporters 2 ( EAAT2),caspase-3 and cleaved caspase-3. RT-PCR was used to detect the mRNA expression of P-GP and EAAT2 in the hippocampus of rats in each group. Results Compared with sham-operated group,the escape latency (EL) was significantly prolonged at each time point in model group ( sham-operated group:15 days (15. 52±3. 23) s,1 month ( 14. 21 ± 2. 62) s,2 months ( 15. 37 ± 1. 66) s;model group:15 days ( 30. 35 ± 2. 30)s,1 month(40. 78± 3. 55) s, 2 months( 33. 88± 1. 47) s; all P<0. 01). The EL of EGb761-treated group was significantly shorter than that of the model group(EGb761-treated group:15 days(25. 69±2. 44)s, 1 month(20. 78±1. 72)s,2 months(18. 23±1. 67)s,all P<0. 01). Immunofluorescence showed that the ex-pression of GFAP in EGb761-treated group was lower than that of the model group (P<0. 01). Western blot showed that cleaved caspase-3 protein expression in EGb761-treated group at each time point was significant-ly lower than that in the model group (P<0. 01). Western-blot and RT-PCR results showed that the protein and mRNA expression of P-GP and EAAT2 in EGb761-treated group at 15 day and 1 month time points were significant increased than those in the model group (P<0. 01). At 2 month time point,which were lower than those in the model group (P<0. 01). Conclusion EGb761 can improve the learning and memory ability of VD rats,and regulate the protein and mRNA expression of P-GP and EAAT2 in hippocampus of VD rats at different time points (up-regulated in 1 month and down-regulated in 2 month),and down-regulate the ex-pression of cleaved caspase-3 and GFAP at different time points,thereby delaying the brain damage of VD rats and protecting neurons.
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Objective To evaluate the effect of doxepin on the expression of p38 mitogen-activated protein kinase (p38 MAPK) in the spinal cord of rats with neuropathic pain (NP).Methods Sixty clean-grade male Wistar rats in which intrathecal catheters were successfully implanted,weighing 200-250 g,were divided into 3 groups (n =20 each) by a random number table method:sham operation group (S group),NP group and doxepin group (D group).NP was induced by chronic constriction injury (CCI) to sciatic nerve.Doxepin 20 mmol/L (10 μl) was intrathecally injected at 3,7,14 and 21 days after CCI (T1-4) in group D.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before CCI (T0) and at T1-4.The rats were sacrificed after measurement of pain threshold at T4,and L4-6 segments of the spinal cord were removed for determination of the expression of p38MAPK protein by Western blot.Results Compared with S group,MWT was significantly decreased and TWL was shortened at T2-4,and the expression of p38MAPK protein was up-regulated in NP and D groups (P＜0.05).Compared with NP group,MWT was significantly increased and TWL was prolonged at T2-4,and the expression of p38MAPK protein was down-regulated in D group (P＜0.05).Conclusion The mechanism by which doxepin mitigates NP is related to down-regulating p38MAPK expression in the spinal cord of rats.
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Objective To identify microbiome biomarkers in patients with inflammatory bowel disease ( IBD) in different regions and establish predictive models , and to explore the various gut microbiota function in IBD patients .Methods The 16 srRNA gene sequences of 1510 IBD patients and 496 healthy controls were collected from China , the United States ( RISK and PRISM cohort ), Germany, India and Lithuania cohort.QIIME ( v1.9.1) was used to analyze microbiota data.LEfSe was used to identify biomarkers for IBD.Random forest method was used to establish the prediction model to distinguish IBD from HC.PICRUSt was used to predict the functional changes of gut microbiota in IBD patients .Resultsɑdiversity of gut microbial in IBD patients was significantly lower than in HC (Wilcoxon,P<0.05).The gut microbiota of IBD patients was different from HC significantly ( Adonis,P<0.05) in all of the cohort study but Indian.LEfSe analysis showed that the IBD patients from China and the U .S.cohort harbored similar dysbiosis patterns , while those from Lithuania , Germany and India have highly localized dysbiosis patterns.Generally, enterococcus was significantly increased in IBD patients in China , the U.S.and Germany cohort.Enterobacteriaceae was significantly increased in IBD patients in China and the U .S. cohort.Ruminococcus was significantly decreased in the intestines of IBD patients in China , the U.S.and India cohort.When predicting IBD status using machine learning models built on local population , the area under the curve ( AUC) was 86.48％ ±4.91％.Meanwhile, when predicting IBD status using machine learning models built on other populations , China and the U.S.had a relatively high AUC for cross-predicting, whilethe other pairs were failed when cross-applied to each other.The model established based on all samples was used to predict each population ,which showed that China , the United States ( RISK and PRISM cohort ), Germany, Lithuania and India cohorts having AUCs of 90.1％, 82.3％, 79.6％, 61.9％, 65.5％and 54.2％respectively.For functional analysis, in China, the United States (RISK and PRISM cohort ) and India cohort , glutathione metabolism and quinones biosynthesis was significantly increased in IBD patients.In China, Germany and Lithuania cohort , flagella assembly and bacterial motility proteins functions were significantly decreased in the IBD patients .Conclusions The intestinal microbiota of IBD patients from different countries could have consistent dysbiosis patterns , but geographical factors still exert a great effect on the microbiota , which needs to be further explored in subsequent studies .
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Objective To observe the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the prevention and treatment of oral mucositis induced by concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma. Methods A total of 64 patients with locally advanced nasopharyngeal carcinoma from April 2015 to April 2017 in the Second Affiliated Hospital of Xi'an Jiaotong University were enrolled. The patients were randomly divided into the observation group (32 cases) and the control group (32 cases) according to the random number table method. Both groups were treated with intensity modulated radiotherapy (IMRT) and synchronized with TP regimen (docetaxel + cisplatin) chemotherapy for 2 cycles. Both groups were treated with mouthwash at the beginning of radiotherapy to prevent oral mucositis. The observation group was given rhGM-CSF mouthwash, and the control group was given compound borax mouthwash. The oral mucositis and the oral pain during the treatment and the end of the treatment were evaluated by using American Radiation Oncology Group (RTOG) grading criteria and visual analogue scoring method(VAS) grading criteria. The time of onset of oral mucositis and the total time of radiotherapy in both groups was also recorded. Results All the patients were treated with concurrent chemoradiotherapy. The total radiotherapy time in the observation group was less than that in the control group [(46.4±1.6) vs. (48.2±3.2) d, t= -2.720, P= 0.009]. The clinical total effective rate was 93.8 %(30/32) in the observation group and 96.9 %(31/32) in the control group respectively (χ2= 0.35, P =0.554).The occurrence of grade 1,2 and 3 oral mucositis in the observation group was(20.9±2.5), (29.3±2.4), and (34.5±1.8) d respectively, which was latter than that in the control group [(16.3 ±2.0), (24.2 ±2.2) and (31.0 ±2.2) d] respectively (t= 8.125, P= 0.000; t= 8.840, P= 0.000; t= 6.944, P= 0.001). During concurrent chemoradiotherapy,the incidence of grade 3 oral mucositis in the observation group was lower than that in the control group[31.2 %(10/32)vs.56.2 %(18/32);Z=-2.197,P=0.028].At the end of concurrent chemoradiotherapy, the total incidence of grade 2 and grade 3 oral mucositis in the observation group was lower than that in the control group [53.1 % (17/32) vs. 81.2 % (26/32); Z= -2.708, P= 0.007]. The incidence of moderate and severe oral pain caused by oral mucositis in the observation group was lower than that in the control group[46.9 %(15/32)and 6.2 %(2/32)vs.59.4 %(19/32)and 15.6 %(5/32),respectively;Z= -2.009, P= 0.045]. Conclusion rhGM-CSF mouthwash can delay the occurrence of oral mucositis, reduce the incidence of oral mucositis and oral pain to effectively prevent and treat oral mucositis induced by concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma, which is worthy of clinical application.
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BACKGROUND:The cervical pedicle screws provide ideal three-column stability for cervical vertebra, but there is stil no a standard with the choice of pedicle screw place methods in cervical vertebra. Here, we try to seek a simpler, safer and accurate pedicle screw place method.OBJECTIVE:To evaluate the accuracy and security of transpedicular screw placement assisted by rapid prototyping individual navigation template. METHODS:Eight cadaver cervical specimens (C3-6) were selected to take CT-scan and data were saved in DICOM format. Three-dimensional (3D) software MIMICS was used to establish the C3~6 3D model, and designed the best pedicle screw channel. According to the morphological feature of the posterior cervical spine elements, the reverse template was designed. Then, the best pedicle screw channels were fused into bilateral navigation template. The navigation template was manufactured by rapid prototyping, and saved in STL format. Rapid prototyping technology was used to print out the navigation template. Cervical pedicle screws were inserted with the assistance of navigation templates fitted with the posterior structure of the vertebral body. Postoperative X-ray and CT scan were used to evaluate the accuracy of screw placement. RESULTS AND CONCLUSION:(1) Total y 64 screws were inserted with the assistance of individual navigation templates. Of them, 62 screws were completely in the pedicle;1 screw perforated the medial cortex of pedicle;1 screw perforated the lateral cortex of pedicle. Accuracy of screw placement was 97%. (2) The individual navigation template with a high accuracy rate is a feasible and safe method for cervical pedicle screw placement, which has great prospects for clinical application.
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Objective@#To establish to paraquat poisoning acute lung injury animal model to study the therapeutic effect of Salvia polyphenols acid salt of paraquat-induced acute lung injury.@*Methods@#Adult male Wister rats 120, were randomly divided into three groups: the paraquat exposure group, the start of the experiment to give a one-time 20% paraquat dope orally 50 mg/kg body weight of rats; salvianolate treatment group, the start of the experiment paraquat to give a one-time 20% the stock solution orally 50 mg/kg body weight of rats, and then given daily intraperitoneal injection of 200 mg/kg body weight of rats salvianolate; blank control group was given the same amount normal saline. The exposure group, the treatment group and control group rats were sacrificed after anesthesia in the 3rd, 7th, 14th, 21st day from the beginning of the experiment respectively, and taken out and preserved venous blood specimens and lung tissue to be tested. Venous detection heme oxygenase-1 (HO-1) , the lung tissue detection heme oxygenase-1 (HO-1) , hydroxyproline (HYP) . And do biopsy specimens from some of the lung tissue, HE and Masson staining observed by optical microscope.@*Results@#Compared with control group, model group 7, 14, 21 days had elevated levels of serum and lung tissue HO-1 (all P<0.05) ; Treatment group 3, 7, 14, 21 days increased (all P<0.05) , and 3, 7, 14 days is higher than the model group (compared with model group, P<0.05) . Compared with control group, treatment group 3 days and model group, 14, 21 days HYP content in lung tissue increased significantly (all P<0.05) ; 21 days, compared with model group, HYP content of treatment group reduce obviously, the difference was statistically significant (P<0.05) . Optical microscope observation, lung tissue damage and aggravated with the experimental increase in the number of days, inflammatory cell infiltration, alveolar septal fibrosis gradually formed. The treatment group experimental animal lung tissue to reduce inflammation, lung fibrosis relief.@*Conclusion@#Paraquat (50 mg/kg body weight) to fill the stomach can be induced model of acute lung injury in the rats. The serum HO-1 expression and HO-1, HYP content in lung tissue increased obviously in model rats. Salvia miltiorrhiza polyphenols acid salt to a certain degree and stage influenced the expression of HO-1 and HYP, relieve acute lung injury and pulmonary fibrosis, has certain curative effect in the treatment of paraquat poisoning.
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Objective To investigate the expression of GRP78 in breast cancer,the relationships among the expression and the clinicopathological characteristics,prognosis were also investigated.Methods The expression of GRP78 was detected in 172 paraffin-embedded breast cancer samples with immunohistochemistry Envision method,the relationships among the expression and the clinicopathological characteristics,prognosis were investigated.Results Positive expression of GRP78 is common in breast cancer.Strong expression of GRP78 was detected in 71 cases (41.28％),and weak expression was detected in 101 cases (58.72％).GRP78 expression wasn't associated with the clinicopathological characterristics except T stage and Her-2 status.Univariate analysis (log-rank test) showed that GRP78 expression correlated with disease free survival and overall survival significantly.Patients with strong GRP78 expression had poorer prognosis compared to those with weak GRP78 expression(P ＜ 0.05).Multivariate analysis utilizing Cox regression analysis showed that GRP78 is an independent biomarker of disease free survival (P ＜ 0.05),but not an independent biomarker of overall survival (P ＞ 0.05).Conclusions Positive expression of GRP78 is common in breast cancer and strong expression is associated with poorer survival.
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Objective To investigate the effect on ER expression in MCF-7 cell by siRNA against survivin mediated by adenovirus vector.Methods An adenovirus vector of siRNA against survivin was constructed and used to infect MCF-7 cell.The change of expression of survivin and ER was detected by Western Blot.Results The expression strength of survivin are 0.09 ± 0.04、0.86 ± 0.08、0.82 ± 0.17;expression strength of ER are 1.57 ± 0.09、1.16 ± 0.10、1.23 ± 0.01 respectively in the experimental group,negative control group and blank control group.Statistics analysis shows that the adenovirus vector of siRNA against survivin constructed in the study can suppress the expression of survivin significantly,and suppress the expression of survivin can up-regulate the estrogen receptor (ER) expression.Conclusions The results suggest that there may be a certain regulatory mechanism between survivin and ER signal pathway in MCF-7 cell and siRNA against survivin is of important potential value in the endocrine therapy of hormone receptor positive breast cancer.
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ABSTRACT:Objective To investigate the differential gene expression of nasopharyngeal carcinoma cell line CNE-2 and CNE-2R exposed to X-rays.Methods We used neutral comet assay to detect the intrinsic radiosensitiv-ity of tumor cells,immunofluorescence to detect the phosphorylated histone γH2AX and Rad5 1 foci formation and to assay the time-dose effects on cell radiation injury and radiation radiosensitivity change after irradiation.The dif-ferential gene expression was screened with cDNA microarray by DNA damage repair related gene chip.Differenti-ally expressed proteins screened were confirmed by Western blot.Results After 2 h of 4 Gy 9MeV-β-ray irradia-tion,CNE-2R cells had aggravated DNA damage compared to CNE-2 cells and the damage was more obvious with the prolongation of time.It suggested that cell DNA damage severity was more obvious.The immunofluorescence showed the positive rates ofγH2AX cells in CNE-2 cell line were higher than those in CNE-2R cell line.There were 37 different genes related to DNA damage repair in CNE-2 cell line compared with CNE-2R cell line,while 24 up-regulated and 13 down-regulated genes were found in SiHaR cells.In them,there were 6 genes whose ratios were 6 times higher and 3 genes whose ratios were lower than 0.1.Western blot verified the results of four differentially expressed proteins compared with CNE-2 cells,in which GADD45a and RRAD1 expression levels were significantly lowered in CNE-2R while the RAD9a and RCF2 protein significantly increased.Conclusion The radioresistance of CNE-2R cells is significantly related to DNA damage repair capacity in certain mutations at the gene level.It is possible to regulate cell radiosensitivity by regulating the related gene.
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Objective To investigate the effects of supreme laryngeal mask airway (SLMA) and endotracheal intubation on the elderly hypertensive patients treated with knee arthroplasty. Methods Forty cases of elderly hypertensive patients ASA Ⅰ-Ⅲ treated with knee arthroplasty in our hospital were selected and randomly divided into laryngeal mask airway group (group LMA)and endotracheal intubation (group TT),20 cases for each group.The same protocol for induction and maintenance of general anesthesia was used.After the patients entering,the changes of SpO2 and ECG were performed continuous noninvasive monitoring and SBP,DBP and HR were performed con-tinuous invasive monitoring.SBP,DBP and HR of two groups were recorded at different time points:before anesthesia induction (T0 ,based value),at intubation immediate (T1 ),5 mins after intubation (T2 )and 1 5 mins after intubation (T3 ).At the same time,the content of cortisol (Cor),atrial natri-uretic peptide (ANP)and the concentration of epinephrine (E)and norepinephrine (NE)were meas-ured at the corresponding time points above.Results Compared with T0 ,SBP and DBP at T1-T3 in group LMA were decreased(P <0.05 or P <0.01);SBP and DBP at T1 in group TT were increased while decreased at T2 ,T3 ,HR at T1 were increased(P < 0.05 or P < 0.01 ).Compared with group LMA,SBP and DBP at T1-T3 and HR at T1 ,T2 in group TT were increased (P <0.05 or P <0.01). Compared with T0 and group LMA,the content of E,NE and Cor at T1-T3 increased(P <0.05 or P <0.01).The level of ANP in both groups at T1-T3 were higher than those at T0 ,and group TT were higher than group LMA(P <0.01).Conclusion Compared to endotracheal intubation,SLAM can ef-fectively reduce the stress reaction of elderly hypertensive patients treated with general anesthesia in knee arthroplasty.
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ObjectiveTo investigate the clinical significance of serum bone turnover indicators in diagnosis of elderly women with osteoporosis.MethodsOne hundred and twenty-eight cases of elderly women with osteoporosis were divided into bone loss group (46 cases),osteoporosis group (54 cases) and severe osteoporosis group(28 cases) according to degree of osteoporosis.Selected physical examination in 45 cases of elderly women as control group.Serum bone-specific alkaline phosphatase (B-ALP),osteocalcin (BGP),tartrate resistant acid phosphatase (TRACP5b) and parathyroid hormone (PTH) levels were detected using immunological method,and determination of bone mineral density (BMD).ResultsCompared with those of control group,BGP and B-ALP of bone loss group,osteoporosis group and severe osteoporosis group was significantly increased [ (25.88 ± 10.21 ),(21.59 ± 8.67 ),( 19.15 ± 7.35 ) μ g/L vs.(9.55 ± 4.05 ) μ g/L and( 181.25 ± 11.84),( 186.25 ± 15.84),( 190.38 ± 21.24) U/L vs.( 150.55 ± 10.05) U/L] (P ＜ 0.01 or ＜0.05).PTH of bone loss group and osteoporosis group was significantly higher than that of control group [ ( 63.79 ± 21.94 ),(58.89 ± 12.03 ) ng/L vs.(43.66 ± 19.66 ) ng/L ] ( P ＜ 0.05 ).B MD of osteoporosis group and severe osteoporosis group was significantly less than that of control group [ (0.64 ± 0.25 ),(0.61 ± 0.43) g/cm2 vs. (0.98 ± 0.11 ) g/cm2 ] (P ＜ 0.01 ).TRACP5b in bone loss group and severe osteoporosis group was significantly higher than that of control group [ (5.48 ± 0.98),(5.25 ± 1.06) U/L vs.(2.75 ± 1.35) U/L) ](P ＜ 0.01 or ＜ 0.05).Conclusions Serum bone turnover indicators such as B-ALP,BGP,TRACP5b and PTH are effective in auxiliary diagnosis of elderly women with osteoporosis.
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Objective Kunming strain(KM) mice were used as animal models. Nontoxic dextran conjugated with tetramethylrhodamine(TMR)and fluorecein isothiocyante(FITC)was microinjected to two of the 2-cell blastomere as molecular probe to trace the development fate of the blastomere ,in order to figure out the mechanisms of the formation of Em-Ab axis. Methods FITC- dextran was injected to zygote in order to make sure if it is noxious. Two blastomeres of 2-cell embryo were injected FITC- dextran and TMR- dextran respectively. Results When labeled embryo develeped to blastocyst, distribution of progeny of 2-cell embryo blastomeres can be detected.Conclusion The cells of blastomere randomly distributed either embryonic parts or extraembryonic parts of blastocyst.
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Objective To investigate reasonable surgical approaches for lower spine injuries.Methods The study involved 174 patients with lower cervical spine injuries treated with anterior approaches, posterior approaches, or anterior-posterior approaches in our hospital from August 2005 to September 2009. American Spinal Injury Association (ASIA) grading system was used to evaluate the surgical outcome. Results All patients were followed up for average 30 months (6-55 months), which showed that bone union was achieved in 169 patients, with no breakage, loosening or displacement of the internal fixators. There were five deaths. The ASIA grades of 125 patients were improved by 1 or 2 levels ( 1.12levels on average), with an improvement rate of 71.3%. Conclusion Comprehensive and accurate preoperative diagnosis is the basis for choose of correct surgical approaches for lower spine injury. Early and correct surgery is essential for a good prognosis.