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1.
J Clin Periodontol ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38566468

RESUMEN

AIM: This study aimed to reveal the unique microenvironment of peri-implantitis through single-cell analysis. MATERIALS AND METHODS: Herein, we performed single-cell RNA sequencing (scRNA-seq) of biopsies from patients with peri-implantitis (PI) and compared the results with healthy individuals (H) and patients with periodontitis (PD). RESULTS: Decreased numbers of stromal cells and increased immune cells were found in the PI group, which implies a severe inflammatory infiltration. The fibroblasts were found to be heterogeneous and the specific pro-inflammatory CXCL13+ sub-cluster was more represented in the PI group, in contrast to the PD and H groups. Furthermore, more neutrophil infiltration was detected in the PI group than in the PD group, and cell-cell communication and ligand-receptor pairs revealed most neutrophils were recruited by CXCL13+ fibroblasts through CXCL8/CXCL6-CXCR2/CXCR1. Notably, our study demonstrated that the unique microenvironment of the PI group promoted the differentiation of monocyte/macrophage lineage cells into osteoclasts, which might explain the faster and more severe bone resorption in the progression of PI than PD. CONCLUSIONS: Collectively, this study suggests a unique immune microenvironment of PI, which may explain the differences between PI and PD in the clinic. These outcomes will aid in finding new specific and effective treatments for PI.

2.
Int Endod J ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256997

RESUMEN

AIM: The influence of hypercholesterolemia on the development of apical periodontitis (AP) is inconclusive. Recent studies revealed that cholesterol metabolite 27-hydoxycholesterol (27HC) can affect cellular responses to bacterial infections and oestrogen status and raloxifene may influence its action. Herein, we aimed to examine the impact of 27HC on production of inflammatory mediators by macrophages and the regulatory function of raloxifene. The contribution of 27HC to AP development and the therapeutic effect of raloxifene were evaluated in a rat model. METHODS: Murine macrophages J774 cells were used. The expression of inducible nitric oxide synthase (iNOS) was examined by Western blot. The concentrations of C-C motif chemokine ligand (CCL) 2 and 27HC were assessed by enzyme-linked immunosorbent assay. Colorimetric assay was used to evaluate cholesterol levels. Experimental AP was induced in ovariectomized (OVX) or un-operated rats receiving high-fat/high-cholesterol diet (HFHCD) or normal diet (ND). Micro-computed tomography and immunohistochemistry were employed to evaluate disease severity and the therapeutic effect of raloxifene. RESULTS: Cholesterol enhanced 27HC production in macrophages. 27HC induced iNOS and CCL2 synthesis by macrophages and estradiol suppressed the responses. In our animal model of AP, HFHCD plus OVX significantly augmented serum and lesion tissue levels of 27HC (p < .05 versus the ND group). Lesion size, infiltration of CD68+ cells, and iNOS+ monocytes were increased in parallel with 27HC accumulation. Raloxifene inhibited pro-inflammatory effects of 27HC on macrophages and suppressed AP progression in HFHCD/OVX rats (p < .05 versus the vehicle control group). CONCLUSIONS: Our results suggested that 27HC contributes to AP aggravation associated with hypercholesterolemia. Oestrogen deficiency may both enhance 27HC production and exacerbate its downstream action.

3.
Zhonghua Bing Li Xue Za Zhi ; 53(9): 898-904, 2024 Sep 08.
Artículo en Zh | MEDLINE | ID: mdl-39231741

RESUMEN

Objective: To investigate the biological characteristics of triple negative breast cancer (TNBC) with low expression of HER2 (HER2-low). Methods: A total of 93 TNBC cases in Shanxi Cancer Hospital from 2017 to 2019 were collected and divided into HER2-negative and HER2-low groups according to HER2 expression status. The clinicopathological features and prognostic differences between the two groups were retrospectively analyzed and compared, and genetic detection of tumor tissues was performed to clarify somatic mutation status and differences between the two groups. Results: Ninety-three patients aged 26 to 86 years were enrolled, including 60 patients in the HER2-negative group and 33 patients in the HER2-low group. The distribution of HER2-low in luminal androgen receptor (LAR) subtype (14/23, 60.87%) and non-LAR subtype (19/70, 27.14%) was significantly different (P=0.005). There were no significant differences in age, pT stage, histological grade, infiltration mode, lymph node metastasis and survival analysis. The expression of HER2-low in the tumor was heterogeneous, including different proportions of weak, weak to moderate intensity, and incomplete to intact membrane staining. With the change of the proportion of HER2-positive cells, the different distribution of those cells in the total tumor cells was noted, including cluster, mosaic and scattered patterns. The concentration and quality of DNA extracted from 71 of the 93 samples met the requirements for making libraries, including 43 in the HER2-negative group and 28 in the HER2-low group. Genetic mutations were mainly missense mutations, single nucleotide mutations, and point mutations in which base C was replaced by base T. There was no significant difference in genes with mutation frequency>3 times between the two groups. CTNNB1 and FGFR3 genes were only mutated in HER2-low group; while ALK, CYP2D6 and FAT1 genes were only mutated in HER2-negative group. HER2-low group included 18 HER2 1+ cases and 10 HER2 2+ cases. Genes with mutation frequency>3 times between the two groups included PIK3CA, TP53, SLX4, ATM and BRCA1. The mutation frequency of PIK3CA in HER2 2+ was significantly higher than that in HER2 1+ group (P<0.05), and SLX4 gene was only mutated in HER2 1+ group. Conclusions: There are some differences of histological morphology and genetic variation between HER2-negative group and HER2-low group, and also differences in genetic variation between HER2 1+ and HER2 2+ in HER2-low group, which are helpful for more accurate stratification of TNBC and useful for finding the therapeutic target and precise treatment of HER2-low TNBC.


Asunto(s)
Receptor ErbB-2 , Neoplasias de la Mama Triple Negativas , Humanos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Femenino , Persona de Mediana Edad , Adulto , Anciano , Estudios Retrospectivos , Mutación , Anciano de 80 o más Años , Metástasis Linfática , Pronóstico , beta Catenina/metabolismo , beta Catenina/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/metabolismo , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo
4.
Zhonghua Wai Ke Za Zhi ; 62(7): 710-713, 2024 Jul 01.
Artículo en Zh | MEDLINE | ID: mdl-38808439

RESUMEN

Pancreatic cancer is one of the most malignant tumors with a 5-year survival rate of 13%. Difficulty in early diagnosis,high tumor heterogeneity,high rate of drug resistance,and lack of effective new drugs are the main reasons for the poor therapeutic effect. Traditional cell line models cannot simulate the tumor environment in vitro and cannot reflect the heterogeneity of pancreatic cancer,while animal models have a long culture process and cannot be used for high-throughput screening. Pancreatic cancer organoids can be continuously expanded and cultured in vitro,which can realistically reflect the heterogeneity of pancreatic cancer and allow high-throughput drug screening,making it an ideal tool for individualized precision diagnosis and treatment of pancreatic cancer. According to recent studies on the evaluation of clinical drug efficacy using pancreatic cancer organoids,the drug sensitivity of pancreatic cancer organoids is highly consistent with the clinical efficacy,demonstrating the feasibility of drug sensitivity of pancreatic cancer organoids in guiding clinical therapy,comfirming the ability to discover potential therapeutic drugs through high-throughput drug screening of pancreatic cancer organoids. At the same time,this review reveals the importance of pancreatic cancer organoids as a model of the pancreatic cancer microenvironment for the development of new drugs and tumor microenvironment research. and the role of pancreatic cancer organoids as a model that can reflect the specific microenvironment of pancreatic cancer for new drug discovery and microenvironmental evaluation. Pancreatic cancer organoids and organ-on-chips are powerful tools for precision companion therapy and new drug discovery.


Asunto(s)
Organoides , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patología , Terapia Combinada , Animales , Medicina de Precisión
5.
Artículo en Zh | MEDLINE | ID: mdl-35785892

RESUMEN

Objective: To explore the effects of mothers' exposure to polycyclic aromatic hydrocarbons during pregnancy on their children's neurobehavioral development. Methods: In November 2009 to April 2010, a total of 221 pairs of mother-newborn pairs were recruited from two cooperative hospitals in Taiyuan, and their children were followed up at age two. High performance liquid chromatography was used to determine the level of BPDE-DNA in cord blood leukocytes. The Neonatal behavioral neurological assessment (NBNA) was used to assess the neurodevelopment of newborns, and the Gesell Development Scale was used to measure neurodevelopmental indexes of 2-year-old children. NBNA includes behavior, active and passive tone, primitive reflexes and general assessment, with a total score of 40 points. The Gesell Developmental Schedules consisted of four sub-scales: motor development, adaptive behavior development, language development and personal-social behavior development. We used mean and standard deviation to describe continuous variables with normal distribution, median (interquartile range) to describe continuous variables with skewed distribution, and frequency and proportion to describe categorical variables. Restricted cubic spline models were applied to assess the dose-response relationships between maternal prenatal polycyclic aromatic hydrocarbons exposure and children's neurobehavioral development at two years old. Generalized linear models were applied to evaluate the effect of exposure to maternal prenatal polycyclic aromatic hydrocarbons exposure on children's neurobehavioral development at 0 and two years old. Results: The NBNA score was 38.0±0.8, and the scores of 2-year-old children's motor, adaptive, language and personal-social were 111.6±15.0, 110.5±14.6, 108.8±17.2 and 111.7±14.5, respectively. After adjusting for confounding factors, there is no dose-response association between the cord blood BPDE of pregnant women and neonatal NBNA scores, but there were dose-response associations between BPDE and scores of 2-year-old children's motor, adaptive, language and personal-social. A unit increase in cord blood ln (BPDE-DNA), the score of motor, adaptive, language and personal-social of 2-year-old children decreased on average by 4.54、6.29、8.41 and 7.02 points. Conclusion: Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy is associated with decreased children's neurobehavioral development at two years old.


Asunto(s)
7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido , Hidrocarburos Policíclicos Aromáticos , Cohorte de Nacimiento , Preescolar , Estudios de Cohortes , Aductos de ADN , Femenino , Sangre Fetal , Humanos , Lactante , Recién Nacido , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Embarazo
6.
Int Endod J ; 54(6): 902-915, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33369764

RESUMEN

AIM: To examine the role of palmitic acid in lipopolysaccharide (LPS)-stimulated chemotaxis of macrophages and the potential contribution of saturated fatty acid in signalling during the pathogenesis of apical periodontitis. METHODOLOGY: J774, a mouse macrophage cell line, was used in the experiments. After treatment with LPS, proteolytic maturation of sterol regulatory element-binding protein-1c (SREBP-1c) and expression of fatty acid synthase (FASN) were examined by Western analysis. Levels of palmitic acid were measured by reverse phase-high performance liquid chromatography-mass spectrometry. Knockdown of SREBP-1c and FASN was accomplished by small interfering RNA technology. Secretion of CC-chemokine ligand 2 (CCL2) and cellular chemotaxis were assessed by enzyme-linked immunosorbent assay and transwell migration assay, respectively. Sulfo-N-succinimidyl oleate (SSO) treatment was used to inhibit fatty acid signalling in vitro and also in a rat model of apical periodontitis. All data were first subjected to Levene's test. In vitro data were then analysed using ANOVA followed by Tukey's multiple comparison test. Data from animal experiments were analysed by independent t-tests. The significant level was set at 0.05. RESULTS: LPS stimulated proteolytic maturation of SREBP-1c and FASN expression in macrophages and significantly enhanced palmitic acid synthesis (P < 0.05). Knockdown of SREBP-1c attenuated LPS-enhanced FASN expression. Knockdown of FASN significantly suppressed LPS-enhanced palmitic acid synthesis (P < 0.05). LPS and exogenous palmitic acid significantly enhanced CCL2 secretion and macrophage chemotaxis (all P < 0.05). Inhibition of FASN expression significantly alleviated LPS-augmented CCL2 secretion (P < 0.05). SSO significantly suppressed CCL2 secretion and macrophage chemotaxis augmented by LPS and palmitic acid (all P < 0.05). In a rat model of induced apical periodontitis, SSO treatment significantly attenuated progression of apical periodontitis and macrophage recruitment (all P < 0.05). CONCLUSIONS: LPS/SREBP-1c/FASN/palmitic acid signalling contributed to tissue destruction caused by bacterial infection. Modulation of lipid metabolism and signalling may be helpful for the management of apical periodontitis.


Asunto(s)
Lipopolisacáridos , Periodontitis Periapical , Animales , Ácidos Grasos , Macrófagos , Ratones , Ratas , Proteína 1 de Unión a los Elementos Reguladores de Esteroles
7.
Zhonghua Gan Zang Bing Za Zhi ; 29(8): 771-775, 2021 Aug 20.
Artículo en Zh | MEDLINE | ID: mdl-34517459

RESUMEN

Objective: To analyze the risk factors that may affect the mutations in the reverse transcriptase region in chronic hepatitis B virus-infected patients. Methods: 678 hospitalized cases with chronic HBV infection who underwent HBV RT testing at Tianjin Second People's Hospital from January 1, 2016 to December 31, 2016 were collected retrospectively. Among them, 417 cases were diagnosed with chronic hepatitis B, 219 cases with liver cirrhosis and 42 cases with primary liver cancer. There were 268 cases of non-use of any antiviral therapy, 138 cases of discontinuation of antiviral drugs for 6 months or more, and 272 cases of continuous antiviral therapy. HBV genotyping and RT region mutation sites were detected by direct sequencing. The risk factors that may affect the drug resistant mutation in the HBV RT mutation, including age, genotype, antiviral drug selection and medication time, hepatitis B virus infection, and biochemical markers were analyzed by univariate analysis to screen out independent risk factors. Results: Among 678 HBV-infected cases, 290 cases (42.8%) were detected with RT-region mutation. Among them, the pre-existing drug resistant rate was 6.72%, and the drug resistant mutation rate was 23.19% in treated patients. The drug resistant mutation rate of patients with continuous antiviral therapy was 66.18%. Gene mutations highest rate for 1 ~ 5 years was 27.14% in chronic HBV patients treated with antiviral therapy. Logistic regression analysis of the factors that had led to HBV mutation showed that old age, the selection of nucleoside drugs at the beginning of treatment and medication time were the main factors affecting HBV RT mutations. Conclusion: Abnormal ALT level, HBV genotype, HBV DNA quantitative level are the main factors influencing non-drug resistant mutations. Age over 60 years old, and long-term use of low-barrier nucleoside drugs are high-risk groups for HBV resistant. Therefore, HBV resistant monitoring should be strengthened.


Asunto(s)
Hepatitis B Crónica , Preparaciones Farmacéuticas , Antivirales/farmacología , Antivirales/uso terapéutico , ADN Viral/genética , Farmacorresistencia Viral/genética , Genotipo , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Lamivudine/uso terapéutico , Persona de Mediana Edad , Mutación , ADN Polimerasa Dirigida por ARN/genética , ADN Polimerasa Dirigida por ARN/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo
8.
Zhonghua Gan Zang Bing Za Zhi ; 29(5): 421-426, 2021 May 20.
Artículo en Zh | MEDLINE | ID: mdl-34107578

RESUMEN

Objective: To observe the effect of tenofovir disoproxil fumarate (TDF) antiviral therapy on HBV-specific CD8(+)T cell function in peripheral blood of patients with HBeAg-positive chronic hepatitis B, and to assess its correlation with HBeAg sero-negativeness. Methods: Sixty-three cases with HLA-A02 restricted HBeAg-positive chronic hepatitis B who received TDF (300 mg/d) antiviral therapy were enrolled from October 2016 to July 2018. The peripheral blood CD8(+)T cells were separated at baseline and 48 weeks after treatment. The peripheral blood T cells count were detected by flow cytometry. The frequency of HBV-specific CD8(+)T cells secreting perforin, granzyme B, and interferon-γ (IFN-γ) were detected by enzyme-linked immunoblotting test. Direct and indirect contact co-culture system was established between HBV-specific CD8(+)T cells and HepG2.2.15 cells. HBV DNA was detected in the culture supernatant. Target cell mortality was calculated by lactate dehydrogenase level. Cytokines expression was detected by enzyme-linked immunosorbent assay. Virus-specific CD8(+)T cells cytokilling and non-cytokilling functions were evaluated. Measurement data of the two groups were compared by t-test or paired t-test. Results: Viral response, biochemical response, and HBeAg seroconversion rate at 48 weeks of TDF treatment were 100%, 90.48% (57/63), and 25.40% (16/63), respectively. There was no statistically significant difference in peripheral blood T cell count when compared with baseline and control group at 48 weeks of TDF treatment (P > 0.05). At 48 weeks of TDF treatment, the frequency of HBV-specific CD8(+)T cells secreting perforin, granzyme B, and IFN-γ in CHB patients was significantly higher than baseline (P < 0.001). Furthermore, the frequency of HBV-specific CD8(+)T cells secreting perforin, granzyme B, and IFN-γ was also significantly higher in CHB patients with HBeAg negative than that of non-negative (P < 0.05). HBV-specific CD8(+)T cells had induced significant down-regulation of HBV DNA in the supernatant of HepG2.2.15 cell culture (P < 0.001) and remarkable IFN-γ and interleukin-2 secretion (P < 0.05) at 48 weeks of TDF therapy in direct and indirect contact co-culture system. However, HepG2.2.15 cells death rate induced by virus-specific CD8(+)T cells was increased only in the direct contact co-culture system (21.7% ± 6.18% vs. 16.1% ± 4.15%, P < 0.001). Compared with HBeAg non-negative patients, HBeAg negative CHB patients with HBV-specific CD8(+)T cells had induced a strong decrease in HBV DNA (P < 0.001) and an increase in IFN-γ secretion level (P < 0.05). However, the target cell death proportion difference between HBeAg negative and non-negative patients was not statistically significant (P > 0.05). Conclusion: During TDF treatment, with the viral load reduction, virus-specific CD8(+)T cells cytokilling and non-cytokilling functions are significantly enhanced, and are closely related to HBeAg negative.


Asunto(s)
Hepatitis B Crónica , Antivirales/uso terapéutico , Linfocitos T CD8-positivos , ADN Viral , Antígenos e de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Tenofovir/uso terapéutico , Resultado del Tratamiento , Carga Viral
9.
Phys Rev Lett ; 125(19): 192503, 2020 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-33216609

RESUMEN

ß-delayed one-proton emissions of ^{22}Si, the lightest nucleus with an isospin projection T_{z}=-3, are studied with a silicon array surrounded by high-purity germanium detectors. Properties of ß-decay branches and the reduced transition probabilities for the transitions to the low-lying states of ^{22}Al are determined. Compared to the mirror ß decay of ^{22}O, the largest value of mirror asymmetry in low-lying states by far, with δ=209(96), is found in the transition to the first 1^{+} excited state. Shell-model calculation with isospin-nonconserving forces, including the T=1, J=2, 3 interaction related to the s_{1/2} orbit that introduces explicitly the isospin-symmetry breaking force and describes the loosely bound nature of the wave functions of the s_{1/2} orbit, can reproduce the observed data well and consistently explain the observation that a large δ value occurs for the first but not for the second 1^{+} excited state of ^{22}Al. Our results, while supporting the proton-halo structure in ^{22}Al, might provide another means to identify halo nuclei.

10.
J Microsc ; 276(1): 39-45, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31553060

RESUMEN

Although high-resolution single-particle cryo-electron microscopy (cryo-EM) is now producing a rapid stream of breakthroughs in structural biology, it nevertheless remains the case that the preparation of suitable frozen-hydrated samples on electron microscopy grids is often quite challenging. Purified samples that are intact and structurally homogeneous - while still in the test tube - may not necessarily survive the standard methods of making extremely thin, aqueous films on grids. As a result, it is often necessary to try a variety of experimental conditions before finally finding an approach that is optimal for the specimen at hand. Here, we summarize some of our collective experiences to date in optimizing sample preparation, in the hope that doing so will be useful to others, especially those new to the field. We also hope that an open discussion of these common challenges will encourage the development of more generally applicable methodology. Our collective experiences span a diverse range of biochemical samples and most of the commonly used variations in how grids are currently prepared. Unfortunately, none of the currently used optimization methods can be said, in advance, to be the one that ultimately will work when a project first begins. Nevertheless, there are some preferred first steps to explore when facing specific problems that can be more generally recommended, based on our experience and that of many others in the cryo-EM field.


Asunto(s)
Microscopía por Crioelectrón/métodos , Sustancias Macromoleculares/ultraestructura , Imagen Individual de Molécula/métodos , Manejo de Especímenes/métodos
11.
Int Endod J ; 52(5): 676-688, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30537112

RESUMEN

AIM: To assess the connection between mitophagy and hypoxia-induced apoptosis in osteoblasts and whether simvastatin alleviates bone resorption in apical periodontitis through modulation of mitophagy-related apoptosis. METHODOLOGY: Hypoxia-induced generation of reactive oxygen species in mitochondria and changes in mitochondrial membrane potential were evaluated, respectively, by MitoSOX and JC-1 fluorescence dye signalling. Accumulation of mitophagy markers PTEN-induced putative kinase 1 (PINK1) and Parkin in mitochondria was examined by Western blotting and immunofluorescence microscopy. Osteoblast apoptosis was assessed by Western analysis of cleaved-poly (adenosine diphosphate ribose) polymerase (PARP). In a rat model of induced apical periodontitis, the therapeutic effect of simvastatin and its action on osteoblast mitophagy and apoptosis were examined. anova, Fisher's and Student's t-test were used for data analysis. RESULTS: Hypoxia-induced mitochondrial dysfunction and stimulated mitophagy in osteoblasts. Hypoxia also provoked apoptosis in osteoblasts and inhibition of mitophagy decreased hypoxia-augmented apoptotic activity. Simvastatin alleviated hypoxia-induced mitochondrial dysfunction, mitophagy and apoptosis. The protective action of simvastatin against apoptosis was related to its antimitophagy activity. Experiments in the rat model of induced apical periodontitis supported the laboratory findings. Simvastatin treatment mitigated periapical bone loss and reduced the activities of apoptosis and mitophagy in regional osteoblasts. CONCLUSIONS: The results suggest that modulation of osteoblast mitophagy may help diminish bone loss associated with inflammation and has potential as an auxiliary therapy for apical periodontitis.


Asunto(s)
Resorción Ósea , Periodontitis Periapical , Animales , Apoptosis , Humanos , Mitofagia , Osteoblastos , Ratas , Simvastatina
12.
Rhinology ; 57(4): 268-272, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-30887967

RESUMEN

BACKGROUND: Azelastine hydrochloride (azelastine) nasal spray is a histamine receptor-1 (H1) antagonist often used in treating allergic rhinitis to relieve its symptoms. However, the effects of azelastine to influence decongestion on human nasal mucosa in patients with allergic rhinitis are not yet fully explored and merit further exploration. The effects of azelastine on the vasocontractile responses generated by smooth muscles in the vascular structures of human nasal mucosa were investigated directly in vitro. METHODS: We examined the effectiveness of azelastine on isolated human nasal mucosa by testing: 1) the effect on mucosa resting tension; 2) the effect on mucosal contraction caused by 10-6 M methoxamine as a sympathetic mimetic; 3) the effect of the drugs on electrically induced mucosal contractions. RESULTS: The results indicated that addition of methoxamine to the incubation medium caused the nasal mucosa to contract in a dose-dependent manner. Addition of azelastine at doses of 10â€"6 M or above elicited a significant dilation response to 10â€"6 M methoxamine-induced mucosal contraction. Azelastine could inhibit electrical field stimulation-induced spike mucosal contraction. Moreover, increase in concentration of azelastine had minimal effect on basal tension of nasal mucosa. CONCLUSIONS: The technique in our study is simple and reproducible. Azelastine could inhibit both EFS and methoxamine-induced nasal mucosal contractions in vitro. This study highlights that although azelastine nasal spray is often used in treating allergic rhinitis to improve symptoms, nasal obstruction may be not relieved immediately due to the anti-sympathetic effect of azelastine.


Asunto(s)
Antiinflamatorios no Esteroideos , Mucosa Nasal , Ftalazinas , Rinitis Alérgica , Rinitis , Administración Intranasal , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Método Doble Ciego , Humanos , Mucosa Nasal/efectos de los fármacos , Rociadores Nasales , Ftalazinas/farmacología , Ftalazinas/uso terapéutico , Rinitis/tratamiento farmacológico
13.
Zhonghua Yi Xue Za Zhi ; 99(10): 764-766, 2019 Mar 12.
Artículo en Zh | MEDLINE | ID: mdl-30884631

RESUMEN

Objective: To compare the etiology and incidence of pulmonary infection in patients with esophageal carcinoma accompanied by esophagotracheal fistula before and after the airway stent implantation. Methods: The clinical records of patients with esophageal carcinoma accompanied by esophagotracheal fistula in Respiratory Department and Oncology Department of Meitan General Hospital were retrospectively analyzed from March 2008 to January 2018. The demographic data, comorbidities, pathological results and etiology were collected before and after tracheal stents were implanted in all patients. The incidence of pulmonary infection was analyzed, and the classification of etiology was compared before and after tracheal stents implantation. Results: A total of 100 patients were included in the study. The incidence rate of pulmonary infection before stents implantation was 83.0%. A total of 105 bacterial strains were cultured, including 73 strains of gram-negative bacteria (69.5%) and mainly pseudomonas aeruginosa, 5 strains of gram-positive bacteria [all methicillin-resistant staphylococcus aureus (MRSA)] (4.8%), and 27 strains of fungi (25.7%) and mainly candida albicans. The incidence rate of pulmonary infection was lowered to 53.0% after tracheal stents implantation (χ(2)=29.102, P<0.001). A total of 79 bacterial strains were cultured, and the main bacteria were still gram-negative bacteria and fungi, in which pseudomonas aeruginosa and candida albicans accounted for the majority. However, 13 strains of MRSA were cultured (16.5%), significantly higher than those before stents implantation (χ(2)=7.451, P=0.005). Conclusions: The incidence rate of pulmonary infection in patients with esophageal carcinoma accompanied by esophagotracheal fistula is very high. Gram-negative bacteria and fungi are the main etiologies. Tracheal stents implantation can effectively reduce the incidence of pulmonary infection. However, the incidence rate of MRSA is significantly increased after stents implantation.


Asunto(s)
Fístula Traqueoesofágica , Humanos , Incidencia , Staphylococcus aureus Resistente a Meticilina , Estudios Retrospectivos , Stents
14.
Zhonghua Bing Li Xue Za Zhi ; 48(5): 352-357, 2019 May 08.
Artículo en Zh | MEDLINE | ID: mdl-31104673

RESUMEN

Objective: To investigate the expression of B7H3 and B7H4 in T lymphoblastic lymphoma/leukemia (T-LBL/ALL) in correlation with clinicopathological parameters and patient prognosis. Methods: Immunohistochemistry (IHC) was used to detect the expression of B7H3 and B7H4 protein in 100 cases of T-LBL/ALL(test group) and 30 cases of lymph node reactive hyperplasia (LH) (control group), diagnosed at Shanxi Cancer Hospital from January 2001 to June 2017. Real-time RT-PCR was used to detect the mRNA expression of B7H3 and B7H4 in 50 cases of T-LBL/ALL and 30 cases of LH (control group). Results: There were 79 males,21 females. Immunohistochemical results showed that the expression rates of B7H3 and B7H4 were 23%(23/100) and 54%(54/100), respectively. By real-time RT-PCR, the relative expression of B7H3 mRNA in the T-LBL/ALL group was 2.5 times of that of the LH group. The expression levels of B7H4 mRNA in T-LBL/ALL group and LH group were extremely low.Single factor analysis showed that B7H3 protein expression in T-LBL/ALL group was associated with B symptoms and primary nodal disease (P<0.05). B7H4 protein expression was associated with mediastinal broadening and bone marrow involvement (P<0.05). B7H3 protein, B7H3 mRNA, B7H4 protein expression and IPI score were associated with prognosis (P<0.05), and the combined expression of B7H3 and B7H4 was associated with T-LBL/ALL prognosis (P<0.05). Multivariate Cox regression analysis showed that overexpression of B7H3 mRNA was an independent risk factor for the prognosis of patients with T-LBL/ALL (P<0.05). Conclusion: Expression of B7H3 and B7H4 is closely corelated with clinicopathological parameters and prognosis of patients with T-LBL/ALL, suggesting that B7H3 and B7H4 expression play an important role in the development of T-LBL/ALL.


Asunto(s)
Antígenos B7 , Linfoma de Células T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Inhibidor 1 de la Activación de Células T con Dominio V-Set , Antígenos B7/metabolismo , Femenino , Humanos , Inmunohistoquímica , Linfoma de Células T/metabolismo , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Pronóstico , ARN Mensajero , Inhibidor 1 de la Activación de Células T con Dominio V-Set/metabolismo
16.
Int Endod J ; 51 Suppl 2: e74-e86, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28039864

RESUMEN

AIM: To investigate the attenuating effect of sirtuin 6 (SIRT6) on hypoxia-induced production of chemokine (C-C motif) ligand 2 (CCL2) by osteoblasts and the relevance of this action on the pathogenesis of periapical lesions. METHODOLOGY: Sirtuin 6 was overexpressed in MC3T3-E1 murine osteoblasts by lentivirus-mediated gene transfer. The relationship between the antiglycolytic/antioxidative activities of SIRT6 and its effect on hypoxia-induced CCL2 production were examined. Pathogenetic relevance of the actions of SIRT6 was assessed in a rat model of induced apical periodontitis. The data were analysed statistically using Student's t-test or one-way analysis of variance (anova) and then a Tukey's multiple comparison test. RESULTS: In cultured murine osteoblasts, 24-h hypoxic treatment significantly enhanced the generation of reactive oxygen species (P = 0.003), expression of lactate dehydrogenase A (LDHA) and production of lactate (P = 0.007). A reciprocal effect between hypoxia-induced redox imbalance and hypoxia-enhanced glycolysis was noted which in turn augmented the secretion of CCL2. Through its antiglycolytic and antioxidative effects, SIRT6 blocked the vicious cycle to suppress CCL2 production. In normal periapical tissues of rats, strong expression of SIRT6 and low levels of LDHA and 8-OHdG (a marker of oxidative DNA damage) were found in osteoblasts. In induced apical periodontitis, osteoblastic expression of SIRT6 was significantly suppressed (P = 0.001) which was associated with significantly elevated levels of LDHA (P = 0.003) and 8-OHdG (P = 0.004) and significantly enhanced recruitment of macrophages (P = 0.004). CONCLUSIONS: Sirtuin 6 has a therapeutic effect on periapical lesions through suppression of CCL2 synthesis. The anti-inflammatory action of SIRT6 is closely related to its regulatory activities in cellular metabolism and redox homoeostasis.


Asunto(s)
Quimiocina CCL2/metabolismo , Hipoxia/metabolismo , Osteoblastos/metabolismo , Periodontitis Periapical/metabolismo , Sirtuinas/metabolismo , Animales , Western Blotting , Células Cultivadas , Ácido Láctico/metabolismo , Ratones , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo
17.
Clin Otolaryngol ; 43(4): 1031-1035, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29495103

RESUMEN

OBJECTIVES: Sumatriptan (Imigran) is a potent and highly selective 5-HT1 receptor agonist often used in treating acute migraine. Intranasal sumatriptan is well absorbed and is generally effective in relieving headache. However, the effects of Imigran on human nasal mucosa have rarely been well explored, to verify the effect of Imigran, which act on human nasal mucosa directly in vitro. DESIGN AND PARTICIPANTS: We examined the effectiveness of Imigran on human nasal mucosa by testing: (i) effect on human nasal mucosa resting tension; (ii) effect on contraction caused by 10-6  mol/L methoxamine as a sympathetic mimetic; and (iii) effect of the drugs on electrically induced on human nasal mucosa contractions. RESULTS: The results indicated that addition of methoxamine to the incubation medium caused the nasal mucosa to contract in a dose-dependent manner. Addition of Imigran at doses of 10-4  mol/L elicited a significant relaxation response to 10-6  mol/L methoxamine-induced contraction. Imigran could not inhibit electrical field stimulation-induced spike contraction. It also had a minimal effect on the basal tension of nasal mucosa as the concentration increased. CONCLUSIONS: The study indicated that high concentrations of Imigran had a significant spasmolytic effect by antagonising α-adreoceptors and nasal obstruction could not be released in the patient combined with acute migraine and stuffy nose by concomitant α-adrenergic agonist nasal spray plus Imigran nasal spray.

18.
Zhonghua Zhong Liu Za Zhi ; 40(8): 626-630, 2018 Aug 23.
Artículo en Zh | MEDLINE | ID: mdl-30139035

RESUMEN

Objective: To evaluate the safety and efficiency of patient-controlled intravenous analgesia (PCIA) using hydromorphone supplement with dexmedetomidine on patients undergoing transcatheter arterial chemoembolization. Methods: One hundred and eighty patients, age ranged from 40 to 65 years, body mass index from 18 to 25 kg/m(2,) ASA physical status Ⅱ-Ⅲ, who were scheduled for transcatheter arterial chemoembolization (TACE) under monitor anesthesia care (MAC) were randomly divided into 3 groups: hydromorphone group (H group), hydromorphone supplement with dexmedetomidine 1 µg/kg group (D1 group), hydromorphone supplement with dexmedetomidine 2 µg/kg group (D2 group), 60 patients in every group. All the groups of patients received PCIA pump, in the H group, the PCIA reagent was composed of 120 µg/kg hydromorphone and 5 mg tropisetron in 100 ml of normal saline. In comparison, PCIA regiment was composed of 120 µg/kg hydromorphone, 1 µg/kg dexmedetomidine and 5 mg tropisetron in 100 ml of normal saline in the D1 group, while 120 µg/kg hydromorphone, 2 µg/kg dexmedetomidine and 5 mg tropisetron in 100 ml of normal saline in the D2 group. The visual analogue scale (VAS) score, the observer's assessment of alertness/sedation scale (OAA/S) score, patients' satisfaction index, consumption of hydromorphone, the additional dose of morphine, the effective pressing times of PCIA and adverse reactions were recorded in detail at 0, 0.5, 1, 4, 12 and 24 hours after the patients underwent TACE. Results: The total consumptions of hydromorphone were (4.3±0.1), (4.1±0.1), and (3.8±0.1) mg in group H, D1, and D2, respectively, and the effective pressing times were 13±3, 6±2 and 2±1, the additional doses of morphine were (30±5), (15±3), and (3±1) mg, and adverse reaction rates were 45.0%, 28.3%, and 10.0%, respectively. The manifestations mentioned above in D2 group were significantly lower than those in group H and group D1 (P<0.05). Immediately and 5 min after embolization, at the end of surgery and 0.5, 1, 4, 12 and 24 h after surgery, the VAS scores in the D2 group were 1.9±0.2, 2.1±0.3, 1.8±0.4, 1.8±0.3, 1.7±0.3, 1.6±0.3, 1.3±0.2, 1.3±0.3, respectively, lower than those in group H and group D1 (P<0.05); The satisfaction index in D2 group at these times were 8.7±1.1, 8.9±0.8, 9.2±0.9, 9.0±0.7, 9.1±0.8, 9.0±0.6, 9.1±0.7, 9.2±0.9, respectively, higher than those in group H and group D1 (P<0.05). No breath depression happened in these three groups. Conclusion: The formula of hydromorphone combined with dexmedetomidine to patients undergoing TACE is greatly safe and efficient, with advantages in alleviating pain, reducing hydromorphone consumption and the incidence of adverse reaction of hydromorphone, and without breath depression.


Asunto(s)
Analgesia Controlada por el Paciente/métodos , Analgésicos no Narcóticos/administración & dosificación , Analgésicos Opioides/administración & dosificación , Quimioembolización Terapéutica/métodos , Dexmedetomidina/administración & dosificación , Hidromorfona/administración & dosificación , Administración Intravenosa , Adulto , Anciano , Analgesia Controlada por el Paciente/efectos adversos , Analgésicos no Narcóticos/efectos adversos , Analgésicos Opioides/efectos adversos , Arterias , Quimioembolización Terapéutica/efectos adversos , Dexmedetomidina/efectos adversos , Quimioterapia Combinada , Humanos , Hidromorfona/efectos adversos , Indoles/administración & dosificación , Persona de Mediana Edad , Tropisetrón
19.
Phys Chem Chem Phys ; 19(5): 3706-3712, 2017 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-28094362

RESUMEN

DyMnO3 hosts the less addressed duality of multiferroicity, owing to the Dy-Mn exchange striction and inverse Dzyaloshinskii-Moriya interaction between Mn spin pairs. Although the duality in DyMnO3 has been discussed earlier, there remains a question whether the Mn magnetic sublattice is necessarily multiferroic for generating the Dy-Mn exchange striction. In this work, we investigate the multiferroicity of Dy(Mn1-xFex)O3 (0 ≤ x ≤ 0.1) through detailed magnetic and ferroelectric characterization. It is found that Fe-doping continuously suppresses the independent Dy spin order but instead promotes the Dy-Mn(Fe) coupling. This coupling benefits the Dy-Mn(Fe) exchange striction which remarkably enhances the ferroelectric polarization at a low doping level (x ≤ 0.015), beyond which the Mn spiral spin order breaks down leading to collapse of the macroscopic polarization at x ≥ 0.05. This work discloses the crucial role of Mn spiral spin order in stabilizing the Dy-Mn exchange striction and thus highlights the duality of multiferroicity in DyMnO3.

20.
Genet Mol Res ; 16(1)2017 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-28340262

RESUMEN

The poor egg-laying rate of geese hinders the development of the goose industry; therefore, the reproductive performance of geese is an important area of investigation. To evaluate the relationship between photoperiod, reproductive hormones, and reproductive activity during the egg-laying cycle in geese under natural conditions, we collected blood samples from Sichuan white geese and Xupu geese to quantify changes in prolactin (PRL), estradiol (E2), vasoactive intestinal polypeptide (VIP), follicle stimulating hormone (FSH), gonadotropin-inhibitory hormone (GnIH), and luteinizing hormone (LH). We also calculated the rate of egg laying for the two populations during the egg-laying cycle. We show that the egg-laying rate and the serum concentration of some hormones (PRL, E2, VIP, FSH, GnIH, and LH) differed significantly between the two populations during the pre-laying, laying, and ceased-laying periods. Serum LH concentrations may be associated with maturation of the ovary and oviducts, whereas FSH, PRL, and GnIH play important roles in egg laying. These results provide a useful resource for future studies examining the laying rate in geese.


Asunto(s)
Gansos/sangre , Hormonas/sangre , Fotoperiodo , Reproducción/fisiología , Animales , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Hormona Liberadora de Gonadotropina/sangre , Gonadotropinas/sangre , Hormona Luteinizante/sangre , Ovario/fisiología , Prolactina/sangre , Péptido Intestinal Vasoactivo/sangre
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