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Effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 protein vaccine in mice@#Objective To investigate the effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 crown protein vaccine in mice.Methods The amantadine dimer was synthesized by substitution reaction ligation,hydrolytic acidification reaction ligation and amide condensation reaction ligation,with which as adjuvant,female BALB/c mice were immunized with the receptor-binding domain(RBD).The mice were randomly divided into five groups,six for each as follows:R6A+RBD group[21 μg(0.033 μmol)amantadine dimer+10 μg RBD],Ada+RBD group[10 μg(0.066 μmol)amantadine+10 μg RBD],Alu+RBD group(35 μg aluminum adjuvant+10 μg RBD),RBD group(10 μg RBD)and Blank group(0.9% normal saline),which were immunized i.m.on day 0,14 and 28 respectively.Serum samples were collected from tail vein of mice 7 d after the second dose and 14 d after the last dose and determined for specific IgG antibody levels by ELISA.Results The amantadine dimer was purified by thin layer chromatography(TLC)and identified by electrospray ionization-MS(ESI-MS)positive/negative ion mode.After two times of immunization,the antibody levels in sera at various dilutions of mice in R6A+RBD group were all higher than those of Ada+RBD group,while lower than those of Alu+RBD group.However,after three times of immunization,the antibody levels in sera at various dilutions of mice in R6A+RBD group were all significantly higher than those of Ada+RBD and Alu+RBD groups(each F > 30,each P < 0.000 1 and each P < 0.01).Conclusion Amantadine dimer adjuvant enhanced humoral immune response induced by SARS-CoV-2 protein vaccine in mice with good adjuvant effect,which may be used as an alternative adjuvant.This strategy based on existing drug transformation provided a new idea for the development of novel adjuvants.
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OBJECTIVES@#To study the role of bronchoscopy in slide tracheoplasty.@*METHODS@#A retrospective analysis was conducted on the diagnosis and treatment of four children with tracheal stenosis admitted to Hunan Provincial People's Hospital from 2017 to 2020. The role of bronchoscopy was summarized in the preoperative evaluation, intraoperative positioning and measurement, and postoperative wound evaluation and treatment during slide tracheoplasty.@*RESULTS@#Bronchoscopy evaluation before slide tracheoplasty showed that 3 of the 4 children had complete trachea rings, 2 had pulmonary artery sling, and 2 had multiple stenosis. Slide tracheoplasty was performed in the hospital on 3 children, and the midpoint of the stenosis segment was judged under bronchoscopy, and the length of the stenosis segment was measured, which assisted in the resection of the stenosis segment of the trachea. The pathogens were identified by lavage after the surgery. One child who developed scar traction 9 months after slide tracheoplasty in another hospital was improved by interventional treatment under bronchoscopy. Mucosal changes were found under bronchoscopy in 2 children 4 days after surgery, and the treatment plan was adjusted. One month after surgery, 2 children had granulation hyperplasia, which was improved by cryotherapy under bronchoscopy. One child abandoned treatment due to anastomotic necrosis and died. Three survivors were followed up for over 6 months with good prognosis, but all had tracheobronchial malacia.@*CONCLUSIONS@#Bronchoscopy can be used for the management of slide tracheoplasty in children with tracheal stenosis, which is helpful to postoperative rehabilitation and follow-up.
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Child , Humans , Bronchoscopy , Constriction, Pathologic , Retrospective Studies , Trachea/surgery , Tracheal Stenosis/surgery , Treatment OutcomeABSTRACT
ObjectiveTo systematically review the effects of bilingual training on cognition for older adults. MethodsResearches about bilingual training for cognition for the older adults were retrieved from PubMed, Web of Science, ScienceDirect, SpringerLink, Wanfang Data, and CNKI from 2011 to May, 2021, supplemented by references backtracking and manual retrieval. The data was extracted for analysis. ResultsA total of 21 researches were included from twelve countries, which published mainly on journals of medicine, neurology, psychology, biology, etc., in 2017 and 2019. Most of the researches were prospective researches and retrospective researches, and the targeted groups including healthy people, people with dementia and people with Alzheimer's disease (AD). The objects mainly involved the effects of bilingualism on cognition, the pathways and the limitations. ConclusionBilingual training may improve the cognition for older adults, through the brain connection related with memory, attention and execution, to delay the onset of AD or dementia; which may associate with the improvement of brain structure and function, including connectivity among regions, activation of cortical circuits, and structural integrity and plasticity. The effects are mainly on execution and perception, and delaying the cognitive decline, which appear in a short term. Bilingual training may finally promote language function, maintain the integrity of the brain structures, and compensate cognitive decline using more potential neural circuits. However, these researches need more uniform criteria for subjects, more reasonable control conditions, and more uniform paradigms.
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Acute kidney injury (AKI) is a common clinical syndrome and an independent risk factor of chronic kidney disease and end-stage renal failure. At present, the treatments of AKI are still very limited and the morbidity and mortality of AKI are rising. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs (circRNAs), are RNAs that are transcribed from the genome, but not translated into proteins. It has been widely reported that ncRNA is involved in AKI caused by ischemia reperfusion injury (IRI), drugs and sepsis through different molecular biological mechanisms, such as apoptosis and oxidative stress response. Therefore, ncRNAs are expected to become a new target for clinical prevention and treatment of AKI and a new biomarker for early warning of the occurrence and prognosis of AKI. Here, the role and mechanism of ncRNA in AKI and the research progress of ncRNA as biomarkers are reviewed.
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Humans , Acute Kidney Injury/metabolism , MicroRNAs/metabolism , RNA, Circular , RNA, Long Noncoding/genetics , RNA, Untranslated/genetics , Reperfusion Injury/geneticsABSTRACT
Objective:To explore the role of nuclear transcription factor erythrocyte line-2p45 (NF-E2) related factor-2 (NRF2) on autophagy during malignant transformation of immortalized human keratinocytes (HaCaT) induced by sodium arsenite (NaAsO 2). Methods:Using cell culture methods, long-term cultured HaCaT cells in DMEM high-glucose medium containing 0.0 (control group) and 1.0 μmol/L NaAsO 2 (arsenic-exposed group) to the 35th generation were used to construct a cell malignant transformation model, and 0, 1, 7, 14, 21, 28 and 35th generation cells of control group and arsenic-exposed group were collected during establishment of cell malignant transformation model. The NRF2 siRNA, phosphatidylinositol-3-hydroxykinase (PI3K) inhibitor LY294002 and mammalian target of rapamycin (mTOR) inhibitor Rapamycin were used to treat the 35th generation of malignant transformed HaCaT cells in arsenic-exposed group (T-HaCaT). The protein expressions of NRF2, PI3K-protein kinase B (Akt)-mTOR signaling pathway related indicators PI3K, Akt, mTOR, phosphorylated (p)-PI3K, p-Akt, p-mTOR, autophagy-related proteins p62, Beclin1, microtubule-associated protein-1 light chain (LC)3Ⅰ, and LC3Ⅱof different generations HaCaT cells in control group and arsenic-exposed group, and T-HaCaT cells of each treatment group were determined by Western blotting. Results:There were significant differences in the NRF2 protein and the ratios of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR between different generations HaCaT cells in arsenic-exposed group ( F = 9.371, 16.035, 15.932, 27.739, P < 0.05), and they were higher than NRF2 protein and ratio of p-mTOR/ mTOR of the same generation in control group ( P < 0.05). Compared with HaCaT cells of the same generation, the expressions of NRF2, p-PI3K, p-Akt, p-mTOR and p62 proteins in T-HaCaT cells were significantly higher, Beclin1 protein expression and the ratio of LC3Ⅱ/LC3Ⅰ were significantly lower ( P < 0.05). The NRF2 silenced T-HaCaT cells had higher expression of Beclin1 and the ratio of LC3Ⅱ/LC3Ⅰ, and lower expressions of NRF2, p-mTOR and p62 than the corresponding control siRNA (Con siRNA) group ( P < 0.05). The T-HaCaT cells in LY294002 treatment group had higher expression of Beclin1 and the ratio of LC3Ⅱ/LC3Ⅰ, and lower expressions of NRF2, p-PI3K, p-Akt and p-mTOR proteins than the corresponding non-treatment group ( P < 0.05). The T-HaCaT cells in Rapamycin treatment group had higher expression of Beclin1 and the ratio of LC3Ⅱ/LC3Ⅰ, and lower expression of p-mTOR protein than the corresponding non-treatment group ( P < 0.05). Conclusions:During the arsenic-induced malignant transformation of HaCaT cells, NRF2 can act as a downstream factor of PI3K-Akt and an upstream factor of mTOR in PI3K-Akt-mTOR signaling pathway, an important regulatory mechanism of autophagy. This abnormal expression of autophagy may eventually lead to malignant transformation of cells.
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Objective:To explore the clinical feasibility and application method of speckle-tracking echocardiography (STE) in assessing left ventricular longitudinal strain in infants.Methods:One hundred and ten infants within one week of birth were randomly selected in the Third Affiliated Hospital of Guangzhou Medical University from June 2019 to February 2020, and the basic data were collected. STE was performed by two physicians with more than 5 years′ experience.Images of the same infant were analyzed by physicians with 5 years′ experience and 2 years′ experience, respectively, and the difference and correlation of the results between the two doctors were analyzed. The images of the same infant were analyzed twice by the doctor with 5 years′ experience, and the differences and correlations between the results were analyzed. The infants were divided into different groups according to weight to compare the correlations between inter-physicians and intra-physician. STE analysis indicators included global left ventricular longitudinal peak strain (Glps-avg), four-chamber left ventricular longitudinal strain (Glps-A4C), three-chamber left ventricular longitudinal strain (Glps-A3C), two-chamber left ventricular longitudinal strain(Glps-A2C), left ventricular anterior wall longitudinal strain (Glps-a), anterior interventricular septum longitudinal strain(Glps-ais), posterior interventricular septum longitudinal strain (Glps-pis), inferior wall of left ventricle longitudinal strain (Glps-i), posterior wall of left ventricle longitudinal strain (Glps-p), lateral wall of left ventricle longitudinal strain (Glps-l), left ventricular basal section longitudinal strain (Glps-bs), left ventricular middle section longitudinal strain (Glps-ms) and left ventricular apex section longitudinal strain (Glps-as), a total of 13 indicators. The differences were analyzed by paired t test, and the correlations were determined by intra-group correlation coefficient (ICC). Results:According to the inclusion and exclusion criteria, 95 patients were included. For the 13 STE indicators, inter-physicians comparison: the differences between the two physicians were statistically significant (all P<0.05) except for Glps-pis, and the ICC were 0.38-0.72 (all P<0.01). Intra-physician comparison: the differences of these indicators between two measurements were not statistically significant (all P>0.05) except for Glps-ais and Glps-I, ICC were 0.31-0.76 (all P<0.05). Among them, inter-physicians and Intra-physician ICC of Glps-avg, Glps-bs, Glps-ms were 0.68/0.75, 0.72/0.66 and 0.65/0.76 respectively. The group comparison by infants′ weight showed that: In very low weight infants group, the ICC of inter-physicians and intra-physician ranged 0.82-0.93(all P<0.05) and 0.80-0.95(all P<0.05). In low weight infants group, the ICC of inter-physicians and intra-physician ranged 0.65-0.94 (all P<0.05) and 0.69-0.93 (all P<0.01). In the normal weight infants group, ICC of inter-physicians ranged 0.06-0.68, with statistical significance except for Glps-A3C (all P<0.05); ICC of intra-physician ranged 0.36-0.59 (all P<0.05). In overweight infants group, there was no statistical significance in ICC of inter-physicians (all P>0.05), the ICC of intra-physician, Glps-bs and Glps-ms groups were 0.63 and 0.77 (all P<0.05), with no statistical significance in other indicators (all P>0.05). Conclusions:Left ventricular longitudinal strain by STE in infants has better repeatability, and the consistency of intra-physician is higher than inter-physicians, among which the Glps-avg consistency is the best, followed by Glps-bs and Glps-ms. STE is more reproducible in low and very low weight infants than in normal and overweight infants.
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Umbilical cord blood is an alternative hematopoietic stem cell source has been widely recognized.Initially,umbilical cord blood transplantation was limited,given the low engraftment.So the method of improving cord blood homing and engraftment has been widely studied in various fields.This paper briefly reviews the progress of main researches in recent years.
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In ischemic stroke, increased level of neuronal complex of nitric oxide synthase (nNOS)-postsynaptic density protein-95 (PSD-95) plays an important role in neuronal damage. We aimed to establish a screening model to identify compounds capable of uncoupling nNOS interaction with PSD-95. In this model, human embryonic kidney-293T (HEK-293T) cells were transfected with either pCDH-Flag-nNOS or pcDNA3.1-PSD-95 plasmid to obtain the protein of Flag-nNOS or PSD-95. Incubating Flag-nNOS with PSD-95 causes formation of the nNOS-PSD-95 complex. ZL006, a known uncoupler of nNOS-PSD-95 interaction, can disturb the interaction between Flag-nNOS and PSD-95, serving as a positive control. The method coupling antibodies to magnetic beads with glutaraldehyde was used to decrease the cost and increase the efficiency. To establish that our model is suitable for selecting nNOS-PSD-95 uncouplers, we evaluated the ability of IC87201, another reported uncoupler of nNOS-PSD-95 interaction, and structural analogs of ZL006. IC87201 and one structure analog of ZL006 showed uncoupling effect, supporting that our model can be used to select different types uncoupler blocking nNOS-PSD-95 interaction.
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Objective:Both antibiotic resistant bacteria (ARBs) and antibiotic resistant genes (ARGs) are considered as one of the most dangerous environmental pollutants in the 21st century by the WHO. This study aims to understand the ARGs of Klebsiella pneumoniae (K. pneumoniae) with multiple drug resistance bacterium from the marine water collected from a beach at Sanya Bay, and to explore the antibiotic resistance mechanism of the K. pneumoniae, providing a basis for exploring the transfer of drug resistance genes of beach, and preventing and controlling the health risk of entertainment population.Methods:The sample of marine water were collected and screened by Mcconkey plate. The drug sensitive test was detected by Merieux VITEK2, The DNA was extracted and one strain of 16srDNA was sequenced and identified as K. pneumoniae. Whole-genome resequencing was performed using Illumina HiseqXten platform, and the obtained sequences were compared with NCBI blasting. The reference bacterium were multi-resistant K. pneumoniae HS11286. Plasmids were extracted and the resistant genes were identified.Results:The ARGs encoding protein was 117/4801 (identity > 40%) and the carrying rate was 2.436 9%. The identity of following ARGs of OKPB, sul1, rpoB, ef-tu, phoP, sul2, AAC(6’)-ib-cr, QnrB, floR, aadA16 were more than 99%. The strain showed resistance to ampicillin, ticacillin/clavulanic acid and chloramphenicol, and was intermediate to ampicillin/sulbactam, compound sulfamethoxazole, ciprofloxacin, minocycline. Preliminary positioning showed that Qnrs, sul1, tetA, cat, QacE were carried on plasmid.Conclusion:The multiple drug resistant bacteria strain has a variety of different resistant phenotypes, some ARGs can be easily spread by plasmid. It probably will bring exposure risk to people for entertainment. Sensibility of some antibiotics were on the brink of resistance, It is necessary to tracking corresponding antibiotics pollution and strengthening monitoring of ARBs and mobile resistant elements of bacteria.
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Objective To investigate the relationship between the expression of linc-VLDLR in extracellular vesicles (EVs) and the development and drug resistance of esophageal carcinoma.Methods Fifty percent of inhibitory concentration (ICs0) ofadriamycin (ADM) for Eca109 cells was detected by MTT assay,after the treatment of esophageal squamous cell carcinoma Eca109 cell line with different concentrations of ADM for 24h.The culture medium was treated with 3 concentrations of ADM based on the IC50 for 24h for extracting EVs in Eca109 cells.linc-VLDLR mRNA expression in EVs was detected by qRT-PCR assay.ICs0 of ADM for Eca109 cells intervened by EVs for 48h was detected by MTT assay.Cell cycle was detected by FCM and linc-VLDLR and ABCG2mRNA expressions in Eca109 cells were detected by qRT-PCR after the treatment of the EVs for 48h.Results ICs0 of ADM acting on Eca109 cells for 24h was 0.44 ± 0.02μg/ml,so ADM concentrations of 0.2,0.4,0.8μg/ml were choosed in the following studies.EVs were extracted from the supernatant after the treatment of 0,0.2,0.4,0.8μg/ml ADM for 24h and were labeled as EVs1,2,3 and 4 respectively.LincVLDLR mRNA expression in EVs4 was significantly higher than that in EVs1-3 (P＜0.01).ADM ICs0 for Eca109 cells in EVs4 group was significantly higher than that in other groups after the treatment of EVs1-4 on Eca109 cells for 48h (P＜0.05).Flow cytometry results showed that the proliferation index of Eca109 cells in EVs4 group was significantly higher than that in EVs 1-3 and control groups (P＜0.01).Linc-VLDLR and ABCG2 mRNA expression levels in Eca109 cells of EVs4 group were significantly higher than these of EVs1-3 and control groups (P＜0.05).Conclusions High expression of linc-VLDLR and ABCG2 gene in esophageal cancer cells is involved in the formation of esophageal cancer resistance.EVs released by drug-resistant cells can upregulate the expression of ABCG2 in esophageal cancer cells and regulate the drug resistance of esophageal cancer cells,which is related to the linc-VLDLR gene carried by EVs.
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<p><b>OBJECTIVE</b>To investigate the distribution characteristics and clinical features of Burkholderia cepacia infection in children.</p><p><b>METHODS</b>A retrospective analysis was performed for the clinical data of 16 children with Burkholderia cepacia infection who were hospitalized between June 2012 and September 2017.</p><p><b>RESULTS</b>All 16 children with Burkholderia cepacia infection were sporadic cases. A total of 16 strains of Burkholderia cepacia were isolated, among which 8 were detected by sputum culture, 5 were detected by blood culture, 2 were detected by tracheal intubation tip culture, and 1 was detected by lung biopsy culture. Of the 16 children, there were 11 boys and 5 girls, with an age of 5 days to 6 years, and the children aged <1 year accounted for 69%. As for department distribution, 10 children were in the PICU/NICU and 6 were in the general wards. As for clinical manifestations, one child had disseminated intravascular coagulation, and the other 15 children had pulmonary infection, among who 11 had severe pneumonia (8 of them underwent mechanical ventilation during treatment). As for underlying diseases, 2 had severe congenital heart disease, 4 had primary immunodeficiency, 3 were highly suspected of immunodeficiency or inherited metabolic diseases, 1 had tracheal stenosis, 1 had Kawasaki disease, 1 was a preterm infant with bronchopulmonary dysplasia, 1 had severe cleft lip and palate, and 3 had no definite underlying diseases. Of all the children, 7 also had infections with adenovirus and Mycoplasma. The average length of hospital stay was 20.3 days for all children, and 12 were improved and 4 died after treatment. All 16 strains of Burkholderia cepacia had a drug resistance rate of 100% to amikacin and gentamicin and ≥80% to ampicillin/sulbactam and ticarcillin/clavulanic acid, as well as the lowest drug resistance rate to levofloxacin.</p><p><b>CONCLUSIONS</b>Burkholderia cepacia is an opportunistic pathogen often found in immunocompromised children and can produce drug resistance. The presence or absence of underlying diseases should be considered during anti-infective therapy. The children with Burkholderia cepacia infection often have a poor prognosis, and an understanding of the disease spectrum of Burkholderia cepacia infection helps with clinical diagnosis and treatment.</p>
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<p><b>OBJECTIVE</b>To analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion (I/R) injury.</p><p><b>METHODS</b>Myocardial I/R injury model was constructed in mice by 30 min of coronary occlusion followed by 24 h of reperfusion and pretreated with salvianolate 30 min before I/R (SAL group). The SAL group was compared with SHAM (no I/R and no salvianolate), I/R (no salvianolate), and ischemia preconditioning (IPC) groups. Furthermore, an ERK1/2 inhibitor PD98059 (1 mg/kg), and a phosphatidylinositol-3-kinase (PI3-K) inhibitor, LY294002 (7.5 mg/kg), were administered intraperitoneal injection (i.p) for 30 min prior to salvianolate, followed by I/R surgery in LY and PD groups. By using a double staining method, the ratio of the infarct size (IS) to left ventricle (LV) and of risk region (RR) to LV were compared among the groups. Correlations between IS and RR were analyzed. Western-blot was used to detect the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation changes.</p><p><b>RESULTS</b>There were no significant differences between RR to LV ratio among the SHAM, I/R, IPC and SAL groups (P>0.05). The SAL and IPC groups had IS of 26.1%±1.4% and 22.3%±2.9% of RR, respectively, both of which were significantly smaller than the I/R group (38.5%±2.9% of RR, P<0.05, P<0.01, respectively). Moreover, the phosphorylation of ERK1/2 was increased in SAL group (P<0.05), while AKT had no significant change. LY294002 further reduced IS, whereas the protective role of salvianolate could be attenuated by PD98059, which increased the IS. Additionally, the IS was not linearly related to the RR (r=0.23, 0.45, 0.62, 0.17, and 0.52 in the SHAM, I/R, SAL, LY and PD groups, respectively).</p><p><b>CONCLUSION</b>Salvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.</p>
Subject(s)
Animals , Male , Blotting, Western , Cardiotonic Agents , Pharmacology , Therapeutic Uses , Flavonoids , Pharmacology , Heart Ventricles , Pathology , MAP Kinase Signaling System , Mice, Inbred C57BL , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , Myocardial Reperfusion Injury , Drug Therapy , Pathology , Organ Size , Phosphorylation , Plant Extracts , Chemistry , Pharmacology , Therapeutic Uses , Protein Kinase Inhibitors , Pharmacology , Staining and LabelingABSTRACT
Objective: To investigate the effect of phospholipase C epsilon 1 (PLCε1) gene silencing on apoptosis and invasion of esophageal carcinoma Eca109 cells and its possible mechanism. Methods: The recombinant vectors targeting short hairpin RNA (shRNA) of PLCε1 (pGenesil-1-PLCε1-shRNA, pGenesil-1-PLCε1-shRNA2 and pGenesil-1-PLCε1-shRNA3) were transfected into Eca109cells by cationic liposome method and to screen out the expression vector with best interference effect. The apoptosis rate and invasive ability of Eca109 cells 48 h after transfection were determined by flow cytometry (FCM) and Transwell chamber method, respectively. After PLCε1 gene silencing, the expression levels of factorassociated suicide (Fas), Fas ligand (FasL), CD44, matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) mRNAs were detected by semi-quantitative reverse transcriptionpolymerase chain reaction (RT-PCR). Results: The pGenesil-1-PLCε1-shRNA2 had the best interference effect on PLCε1 gene. The apoptosis rate of Eca109 cells 48 h after transfection with PLCε1-shRNA2 was (30.27±5.13)%, which was significantly higher than that of the cells transfected with pGenesil-1-NC-shRNA (NC group) [(22.06±4.47)%, P < 0.05]. The number of Eca109 cells across the polycarbonate membrane of Transwell chamber in the NC group and PLCε1-shRNA2 group 48 h after transfection were 82.00±2.00 and 62.67±3.06, respectively. The number of Eca109 cells across the polycarbonate membrane in PLCε1-shRNA2 group was lower than that of the NC group (P < 0.05). The expression level of Fas mRNA in Eca109 cells of PLCε1-shRNA2 group was significantly up-regulated as compared with that of the NC group (P < 0.05), while the expression levels of FasL, MMP-9 and VEGF mRNAs in PLCε1 - shRNA2 group were significantly down-regulated (all P < 0.05). There was no significant difference in CD44 mRNA expression level between the NC group and PLCε1-shRNA2 group. Conclusion: Silencing PLCε1 gene might promote the apoptosis of Eca109 cells by up-regulating the expression of Fas and down-regulating the expression of FasL, and it can also suppress the invasive ability of Eca109 cells by down-regulating the expressions of MMP-9 and VEGF.
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BACKGROUND:Prefabricated customized bone flaps have the advantages of few trauma, good vascularization, ossification with predetermined shape, and can be used to restore bone defects with compromised blood bed. OBJECTIVE:To establish animal models of mandibular reconstruction with prefabricated, customized bone flaps. METHODS:After computed tomography scanning of nine rhesus’ head, customized meshes were made. After loading with recombinant human bone morphogenetic protein-2-incorporated demineralized freeze-dried bone al ograft (DFDBA) or coral ine hydroxyapatite (CHA), the constructs were implanted in latissimus dorsi muscle. Meanwhile, segmental mandibular defects were created, and the customized meshes loaded with DFDBA, CHA, or recombinant human bone morphogenetic protein-2-incooperated DFDBA and CHA were implanted in situ. At 13 weeks, prefabricated bone flaps with recombinant human bone morphogenetic protein-2-incorporated DFDBA or CHA were transferred to repair segmental mandibular defects. Clinical and histological analyses were used to evaluate the ossification and vascularization of the prefabricated implants in ectopic and orthotopic sites. RESULTS AND CONCLUSION:Segmental mandibular defects were successful y restored with prefabricated bone flaps and recombinant human bone morphogenetic protein-2-incorporated CHA in situ, but other segmental mandibular defects remained with recombinant human bone morphogenetic protein-2-incorporated DFDBA, DFDBA and CHA in situ. Moreover, mandibles reconstructed with prefabricated bone flaps revealed more regenerated and homogeneous bone formation than other reconstructions. These findings suggest that the animal model of mandibular reconstruction with prefabricated, customized bone in rhesus monkey is applicable.
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BACKGROUND:Alveolar distraction osteogenesis is an important method for treating alveolar bone atrophy, the osteogenesis process and biomechanics play a crucial role in the fol owing implantation and repair. At present, no related experimental studies are found. OBJECTIVE:To analyze the biomechanical and histological characteristics of alveolar distraction osteogenesis in a canine model. METHODS:Twelve adult mongrel canines received premolars extraction and alveoloplasty in mandible to establish an atrophy alveolar model. After 3 months, a segmental alveolar osteotomy was performed in the randomly selected unilateral atrophy alveolar and two intra-osseous distractors were placed. After a 7-days latency period, the alveolar ridge was augmented at a rate of 1.0 mm/d for 5 days. After a consolidation of 1, 2, and 3 months, the canines were sacrificed and the specimens of the distracted alveolar bone were harvested for clinical, radiographic, histological and biomechanical analysis. RESULTS AND CONCLUSION:The alveolar distractors obtained good healing with surrounding tissue. The atrophy alveolar bones were augmented for (4.80±0.50) mm and (5.12±0.47) mm by clinical and radiographic findings immediately after distraction, respectively. The bone trabeculae in the distracted chamber matured from 1 to 3 months of consolidation by histological analysis. The shearing force of alveolar distraction chamber increased from 1 to 3 months. After 3 months’ consolidation, the shearing force of distracted chamber was comparable to host bone. The histological and biomechanical property of distracted alveolar chamber is comparable to host bone after 3 months’ consolidation.
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<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of asthma at acute attack stage treated with "Shao's five needling therapy".</p><p><b>METHODS</b>The randomized controlled method was applied to divide 210 cases into an observation group and a control group, 105 cases in each one. In the observation group, "Shao's five needling therapy" [Feishu (BL 13), Dazhui (GV 14), Fengmen (BL 12)] and the combined therapy were adopted, including oxygen uptake, aerosol inhalation and oral administration of prednisone. In the control group, the oral administration of theophylline sustained release tablet and the combined therapy were applied. The treatment was continued for 7 days. The clinical symptoms and physical signs such as wheezing, cough, expectoration, chest stuffiness, wheezing rale and shortness of breath, as well as lung function indices such as forced expiratory volume one second (FEV1) and peak expiratory flow (PEF) were observed before and after treatment in the two groups.</p><p><b>METHODS</b>In the observation group, 69 cases were cured clinically, 20 cases effective remarkably, 7 cases effective and 0 case failed. In the control group, 49 cases were cured clinically, 31 cases effective remarkably, 15 cases effective and 0 case failed. The difference in the efficacy was significant in comparison of the two groups (P < 0.05). The therapeutic effect in the observation group was better than that in the control group. The total score of the symptoms and physical signs, FEV1 and PEF after treatment were all improved significantly in the two groups (all P < 0.01). And the results in the observation group were better than those in the control group (all P < 0.01).</p><p><b>CONCLUSION</b>"Shao's five needling therapy" achieves the significant efficacy on asthma at acute attack stage. It significantly relieves the symptoms and physical signs of the patients and improves lung functions. The effect is better than that of theophylline sustained release tablet.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Acupuncture Points , Acupuncture Therapy , Asthma , Therapeutics , Forced Expiratory Volume , Lung , Treatment OutcomeABSTRACT
<p><b>BACKGROUND</b>Volatile anesthetics (VAs) may affect varied and complex physiology processes by manipulating Ca(2+)-calmodulin (CaM). However, the detailed mechanism about the action of VAs on CaM has not been elucidated. This study was undertaken to examine the effects of VAs on the conformational change, hydrophobic site, and downstream signaling pathway of CaM, to explore the possible mechanism of anesthetic action of VAs.</p><p><b>METHODS</b>Real-time second-harmonic generation (SHG) was performed to monitor the conformational change of CaM in the presence of VAs, each plus 100 µmol/L Ca(2+). A hydrophobic fluorescence indicator, 8-anilinonaphthalene-1-sulfonate (ANS), was utilized to define whether the VAs would interact with CaM at the hydrophobic site or not. High-performance liquid chromatography (HPLC) was carried out to analyze the activity of CaM-dependent phosphodiesterase (PDE1) in the presence of VAs. The VAs studied were ether, enflurane, isoflurane, and sevoflurane, with their aqueous concentrations 7.6, 9.5, 11.4 mmol/L; 0.42, 0.52, 0.62 mmol/L; 0.25, 0.31, 0.37 mmol/L and 0.47, 0.59, 0.71 mmol/L respectively, each were equivalent to their 0.8, 1.0 and 1.2 concentration for 50% of maximal effect (EC50) for general anesthesia.</p><p><b>RESULTS</b>The second-harmonic radiation of CaM in the presence of Ca(2+) was largely inhibited by the VAs. The fluorescence intensity of ANS, generated by binding of Ca(2+) to CaM, was reversed by the VAs. HPLC results also showed that AMP, the product of the hydrolysis of cAMP by CaM-dependent PDE1, was reduced by the VAs.</p><p><b>CONCLUSIONS</b>Our findings demonstrate that the above VAs interact with the hydrophobic core of Ca(2+)-CaM and the interaction results in the inhibition of the conformational change and activity of CaM. This in vitro study may provide us insight into the possible mechanism of anesthetic action of VAs in vivo.</p>
Subject(s)
Humans , Adenosine Monophosphate , Anesthetics, Inhalation , Pharmacology , Anilino Naphthalenesulfonates , Calmodulin , Chemistry , Physiology , Cyclic Nucleotide Phosphodiesterases, Type 1 , Fluorescence , Hydrophobic and Hydrophilic InteractionsABSTRACT
This study was aimed to explore the immune escaping mechanisms based on expression and abscission of human natural killer (NK) cell activating receptors NKG2D and their ligands MICA/B, ULBP-1, 2, 3 in patients with acute leukemia (AL). 30 de novo AL patients and 10 healthy persons (control) were enrolled in study. Flow cytometry was used to detect the expression levels of MICA/B, ULBP-1, 2, 3 on leukemic cells. ELISA was used to detect the levels of soluble MICA (sMICA), solube MICB (sMICB) and soluble ULBP-1, -2, -3 in the serum. The results showed that sMICA, sMICB and ULBP-1, -2, -3 were not expressed or expressed at very low levels on leukemia cells of the patients; the levels of free sMICA and sMICB in serum of AL patients were higher than that in serum of healthy persons, there was significant difference (p<0.01). But the levels of ULBP 1-3 in serum of AL patients did not show obvious statistical difference as compared with healthy persons (p>0.05). It is concluded that the negative or low expression of NKG2D ligands (MICA, MICB and ULBPs) on surface of acute leukemia cells may lead to the immune escape of leukemia cells, the abscission of MICA and MICB, and the deficiency of ULBP expression on leukemia cells may be one of immune escape mechanisms of leukemia cells.
Subject(s)
Female , Humans , Male , Case-Control Studies , Flow Cytometry , GPI-Linked Proteins , Allergy and Immunology , Metabolism , Gene Expression Regulation, Leukemic , Histocompatibility Antigens Class I , Allergy and Immunology , Metabolism , Intercellular Signaling Peptides and Proteins , Allergy and Immunology , Metabolism , Intracellular Signaling Peptides and Proteins , Allergy and Immunology , Metabolism , Leukemia , Blood , Allergy and Immunology , NK Cell Lectin-Like Receptor Subfamily K , Allergy and Immunology , Metabolism , Tumor EscapeABSTRACT
<p><b>OBJECTIVE</b>To investigate the association of single nucleotide polymorphisms (SNPs) in VEGF gene with the risk of endometriosis and adenomyosis.</p><p><b>METHODS</b>Genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 344 endometriosis patients, 174 adenomyosis patients, 360 frequency-matched control women of endometriosis and 199 frequency-matched control women of adenomyosis.</p><p><b>RESULTS</b>No significant difference was found in allele frequencies and genotype distributions of the -460C/T polymorphism between patients (endometriosis and adenomyosis) and control women (all P value > 0.05). However, there were significant differences in genotype and allele distributions of the VEGF -1154G/A polymorphism between patients (endometriosis and adenomyosis) and control women (all P value < 0.05). The genotype frequencies of the VEGF -1154 AA, GA, and GG in endometriosis patients and control women were 1.7%, 28.8%, 69.5% and 5.8%, 32.8%, 61.4%, respectively; and the A and G allele frequencies in the two groups were 16.1%, 83.9% and 22.2%, 77.8%, respectively. The genotype frequencies of the VEGF -1154 AA, GA, and GG in adenomyosis patients and control women were 2.9%, 23.6%, 73.6% and 7.0%, 34.2%, 58.8%, respectively; and the A and G allele frequencies in the two groups were 14.7%, 85.3% and 24.1%, 75.9% respectively. Compared with GA+ AA genotype, GG genotypes could significantly increase the risk of endometriosis (OR:1.43,95%CI:1.05-1.96) and adenomyosis (OR:1.95,95%CI:1.26-3.03).</p><p><b>CONCLUSION</b>The VEGF -1154G/A polymorphism was associated with susceptibility to endometriosis and adenomyosis, and the GG genotype could significantly increase the risk of developing endometriosis and adenomyosis. However, the VEGF -460C/T polymorphism was not associated with susceptibility to endometriosis and adenomyosis in the population studied.</p>
Subject(s)
Adult , Female , Humans , 5' Untranslated Regions , Biophysical Phenomena , Endometriosis , Genetics , Gene Frequency , Genetic Predisposition to Disease , Genetics , Genotype , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Vascular Endothelial Growth Factor A , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the possible association of single nucleotide polymorphism (SNP) at the 41657C/T position and 4234G/C position of X-ray repair cross-complementing gene 2 (XRCC2) with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of high incidence region, Ci county and She county of Hebei.</p><p><b>METHODS</b>The genotypes of XRCC2 41657C/T and 4234G/C SNPs were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 330 ESCC patients, 254 GCA patients and 629 healthy controls.</p><p><b>RESULTS</b>The genotype frequency of XRCC2 41657C/T in ESCC patients (67.8%, 26.4% and 5.8%) was significantly different from that in controls (68.8%, 28.8% and 2.4%; chi square was 7.43, P was 0.02). Compared with CC genotype, TT genotype significantly increased the risk of developing ESCC (OR=2.12, 95%CI: 1.03-4.35). The genotype (59.9%, 35.8% and 4.3%) and allelotype distributions ofXRCC2 41657C/T in GCA patients were significantly different from that in controls (chi square was 7.46 and 7.23, P was 0.02 and 0.01). Compared with CC genotype, CT genotype significantly increased the risk of developing GCA (OR=1.38, 95%CI: 1.01-1.89). The genotype and allelotype distributions of the 4234G/C SNPs in ESCC and GCA patients were not significantly different from that in controls (all P values were above 0.05). Compared with GG genotype, the CG and CC genotype of XRCC2 4234G/C did not show significant effect on the risk of developing ESCC and GCA. When the two XRCC2 SNPs were combined analyzed, the haplotype distribution in GCA patients was significantly different from that in controls (chi square was 13.28, P was less than 0.01). Compared with 41657C/4234G haplotype, 41657C/4234C and 41657T/4234G haplotypes significantly increased the risk of developing GCA (OR were 1.44 and 1.55, 95%CI were 1.06-1.95 and 1.18-2.02, respectively).</p><p><b>CONCLUSION</b>In high incidence region of Hebei province, we conclude that XRCC2 41657C/T polymorphism has a potential to be a susceptibility factor for ESCC and GCA while XRCC2 4234G/C polymorphism may not provide a useful marker to predict susceptibility to ESCC and GCA. However, the 41657C/4234C and 41657T/4234G haplotypes might increase the risk of developing GCA.</p>