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1.
Artigo em Inglês | MEDLINE | ID: mdl-32439566

RESUMO

BACKGROUND: Linezolid is one of the last lines of defense for Gram-positive bacteria, and the increasing emergence of linezolid-resistant enterococci (LRE) has become an important problem in nosocomial infections. OBJECTIVE: To explore the mechanism of linezolid resistance and analyze the risk factor for the infection with LRE. METHOD: The known resistance mechanisms of linezolid were detected by PCR. Clinical data of patients with LRE infection were collected from the electronic medical record system. Risk factors associated with LRE were determined by comparing 2 case groups (LRE group and linezolid-susceptible enterococci (LSE) group) with control group (without enterococci infection) at a ratio of 1:1:2. Multivariate logistic regression models were used to evaluate independent risk factors for acquiring LRE and LSE. RESULTS: A total of 85 (4.5%) LRE isolates were detected during 5-year period. The main resistance mechanism was the acquisition of transferable gene optrA (98.8%), followed by the L4 protein mutation (37.7%), L3 protein mutation (4.7%). Then 85 LRE cases, 85 LSE cases, and 170 controls were enrolled in our study and multivariable analysis indicated that transfer from another hospital (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.5-7.3; P=0.004), malignant tumor (OR, 3.7; 95% CI, 1.6-8.8; P=0.003), polymicrobial infection (OR, 12.2; 95% CI, 1.4-106.2; P=0.023), and urinary tract infection (OR, 42.7; 95% CI, 11.4-159.3; P=0.000) were independent predictors for acquiring LRE. In addition, polymicrobial infection (OR, 43.3; 95% CI, 14.1-132.8; P=0.000), total length of hospital stay(≥30d) (OR, 5.7; 95% CI, 1.9-17.3; P=0.002) and exposure to glycopeptide (OR, 6.6; 95% CI, 1.1-38.8; P=0.035) were independently associated with LSE infection. CONCLUSION: Proper antibiotic management programs and monitoring of patient risk factors are necessary to control LRE infections.

2.
Nanoscale ; 12(16): 8775-8784, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32270841

RESUMO

The face-to-face contact of a vertical heterojunction is beneficial to charge interaction in photocatalysis. However, constructing a vertical heterojunction with uncompromised redox ability still remains a challenge. Herein, we report the successful synthesis of a WO3-TiO2 vertical heterojunction via establishing an internal electric field across the interface. Experimental investigation and computational simulations reveal that strong electric coupling occurs at the WO3-TiO2 interface forming an internal electric field. The internal electric field induces a Z-scheme charge-carrier transfer through the heterojunction under light irradiation, which leads to effective charge separation and maintains high reaction potentials of charge-carriers. The improved photocatalytic activity of the WO3-TiO2 heterojunction is proved by enhanced generation of reactive oxygen species and accelerated Escherichia coli (E. coli) disinfection. This study provides new insights into understanding and designing Z-scheme heterogeneous photocatalysts.

3.
BMC Infect Dis ; 20(1): 277, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293302

RESUMO

BACKGROUND: Clostridium difficile infection (CDI), especially hospital-acquired Clostridium difficile infection (HA-CDI), continues to be a public health problem and has aroused great concern worldwide for years. This study aimed to elucidate the clinical and epidemiological features of HA-CDI and the characteristics of C.difficile isolates in Chongqing, Southwest China. METHODS: A case-control study was performed to identify the clinical incidence and risk factors of HA-CDI. C. difficile isolates were characterised by polymerase chain reaction (PCR) ribotyping, multilocus sequence typing (MLST), toxin gene detection and antimicrobial susceptibility testing. RESULTS: Of the 175 suspicious patients, a total of 122 patients with antibiotic-associated diarrhea (AAD) were included in the study; among them, 38 had HA-CDI. The incidence of AAD and HA-CDI was 0.58 and 0.18 per 1000 patient admissions, respectively. Chronic renal disease and cephalosporin use were independent risk factors for HA-CDI. Fifty-five strains were assigned into 16 sequence types (STs) and 15 ribotypes (RTs). ST2/RT449 (8, 14.5%) was the predominant genotype. Of the 38 toxigenic isolates, A + B + CDT- isolates accounted for most (34, 89.5%) and 1 A + B + CDT+ isolate emerged. No isolate was resistant to vancomycin, metronidazole or tigecycline, with A-B-CDT- being more resistant than A + B + CDT-. CONCLUSIONS: Different genotypes of C. difficile strains were witnessed in Chongqing, which hinted at the necessary surveillance of HA-CDI. Adequate awareness of patients at high risk of HA-CDI acquisition is advocated and cautious adoption of cephalosporins should be highlighted.


Assuntos
Infecções por Clostridium/epidemiologia , Clostridium difficile/genética , Infecção Hospitalar/epidemiologia , Hospitais de Ensino , Centros de Atenção Terciária , Adulto , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , China/epidemiologia , Infecções por Clostridium/dietoterapia , Clostridium difficile/efeitos dos fármacos , Clostridium difficile/isolamento & purificação , Infecção Hospitalar/microbiologia , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Diarreia/microbiologia , Feminino , Humanos , Incidência , Masculino , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , Ribotipagem , Fatores de Risco , Vancomicina/uso terapêutico
4.
BMC Anesthesiol ; 20(1): 88, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32312233

RESUMO

BACKGROUND: Ultrasound-guided erector spine plane (ESP) block is widely used in perioperative analgesia for back, chest and abdominal surgery. The extent and distribution of this block remain controversial. This study was performed to assess the analgesia range of an ultrasound-guided ESP block. METHODS: This prospective observational volunteer study consisted of 12 healthy volunteers. All volunteers received an erector spinae plane block at the left T5 transverse process using real-time ultrasound guidance. Measured the cutaneous sensory loss area (CSLA) and cutaneous sensory declination area (CSDA) using cold stimulation at different time points after blockade until its disappearance. The CSLA and CSDA were mapped and then calculated. The block range was described by spinous process level and lateral extension. The effective block duration for each volunteer was determined and recorded. RESULTS: The cold sensory loss concentrates at T6-T9. The decline concentrates primarily at T4-T11. The lateral diffusion of block to the left side did not cross the posterior axillary line, and reached the posterior median line on the right. The area of cutaneous sensory loss was (172 ± 57) cm2, and the area of cutaneous sensory decline was (414 ± 143) cm2. The duration of cutaneous sensory decline was (586 ± 28) minutes. CONCLUSION: Ultrasound-guided erector spine plane block with 20 mL of 0. 5% ropivacaine provided a widespread cutaneous sensory block in the posterior thorax, but did not reach the anterior chest, lateral chest, or abdominal walls. The range of the blockade suggested that the dorsal branch of spinal nerve was blocked. TRIAL REGISTRATION: Chinese Clinical Trial Registry, CHiCTR1800014438. Registered 13 January 2018.

5.
Anesth Analg ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32332290

RESUMO

BACKGROUND: The proportion of live births by cesarean delivery (CD) in China is significant, with some, particularly rural, provinces reporting up to 62.5%. The No Pain Labor & Delivery-Global Health Initiative (NPLD-GHI) was established to improve obstetric and neonatal outcomes in China, including through a reduction of CD through educational efforts. The purpose of this study was to determine whether a reduction in CD at a rural Chinese hospital occurred after NPLD-GHI. We hypothesized that a reduction in CD trend would be observed. METHODS: The NPLD-GHI program visited the Weixian Renmin Hospital, Hebei Province, China, from June 15 to 21, 2014. The educational intervention included problem-based learning, bedside teaching, simulation drill training, and multidisciplinary debriefings. An interrupted time-series analysis using segmented logistic regression models was performed on data collected between June 1, 2013 and May 31, 2015 to assess whether the level and/or trend over time in the proportion of CD births would decline after the program intervention. The primary outcome was monthly proportion of CD births. Secondary outcomes included neonatal intensive care unit (NICU) admissions and extended NICU length of stay, neonatal antibiotic and intubation use, and labor epidural analgesia use. RESULTS: Following NPLD-GHI, there was a level decrease in CD with an estimated odds ratio (95% confidence interval [CI]) of 0.87 (0.78-0.98), P = .017, with odds (95% CI) of monthly CD reduction an estimated 3% (1-5; P < .001), more in the post- versus preintervention periods. For labor epidural analgesia, there was a level increase (estimated odds ratio [95% CI] of 1.76 [1.48-2.09]; P < .001) and a slope decrease (estimated odds ratio [95% CI] of 0.94 [0.92-0.97]; P < .001). NICU admissions did not have a level change (estimated odds ratio [95% CI] of 0.99 [0.87-1.12]; P = .835), but the odds (95% CI) of monthly reduction in NICU admission was estimated 9% (7-11; P < .001), greater in post- versus preintervention. Neonatal intubation level and slope changes were not statistically significant. For neonatal antibiotic administration, while the level change was not statistically significant, there was a decrease in the slope with an odds (95% CI) of monthly reduction estimated 6% (3-9; P < .001), greater post- versus preintervention. CONCLUSIONS: In a large, rural Chinese hospital, live births by CD were lower following NPLD-GHI and associated with increased use of labor epidural analgesia. We also found decreasing NICU admissions. International-based educational programs can significantly alter practices associated with maternal and neonatal outcomes.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32192201

RESUMO

The design of elements which exert pivotal effects on leisurely physical activity (LPA) in open space is an important part of urban development. However, little research has been done about the influence and discrepancies of those elements in different types of open space. To research these issues and to guide the design of urban open space, a survey from 8 open spaces (2 curtilage, 2 neighborhood squares (NS), 2 parks, and 2 campus) is conducted and a questionnaire is administered. Simultaneous analysis of several groups (SASG) of Structure equation model (SEM) is used, and the effects and discrepancies are acquired. In addition to this situation, interval type 2 (IT2) fuzzy hybrid decision making model is proposed in the second analysis. In this framework, IT2 fuzzy decision-making trial, evaluation laboratory (DEMATEL), and IT2 fuzzy technique for order preference by similarity to ideal solution (TOPSIS) methods are used. The results show that the influence relationships between elements and LPA did exist in four groups. Another important conclusion is that there were discrepancies of influence among different space groups. Physical environment (PE) has the greatest influence on LPA in the curtilage, whereas facilities exert the most effect in NS group. Additionally, amenities only have significant impact in parks and facilities only exercise remarkable influence on duration on campus. In addition to them, it is also identified that key design elements are presented for different types of space and that design strategy is provided through 4 specific examples.

7.
J Am Heart Assoc ; 9(6): e014122, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32174212

RESUMO

Background Elevated long-term systolic blood pressure and resting heart rate (RHR) variability are suggested to amplify the risk of all-cause mortality (ACM). However, the link between increased RHR and pulse pressure for ACM remained unclear. Methods and Results This study analyzed 46 751 individuals from Kailuan Cohort Study for the end outcome of ACM. A Cox regression model was used to estimate hazard ratios for death events. Kaplan-Meier analysis was performed to study the differences in survival as stratified by the SD, coefficient of variation, and average real variability of RHR and pulse pressure quartiles. A total of 1667 deaths (<65 years of age=866/40351, ≥65 years of age=801/6400) were recorded over 4.97±0.69 years follow-up. Participants under the age of 65 years in the third and fourth quartiles of pulse pressure SD had an independent increase in risk for ACM (hazard ratio [95% CI], 1.16 [1.06-1.28]; and 1.19 [1.05-1.35], respectively). Additionally, participants >65 years of age had a higher risk for ACM across quartiles of RHR-SD. The hazard ratio (95% CI) for the subjects in quartiles 2, 3, and 4 were 1.81 (1.10-2.97), 2.31 (1.37-1.3.90), and 2.64 (1.63-4.29), respectively. Conclusions An elevated long-term RHR variability combined with an increased pulse pressure variability or vice versa amplifies the risk of ACM.

9.
Oral Oncol ; 103: 104589, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32058295

RESUMO

OBJECTIVES: Distant metastasis is the leading cause of death in patients with N2-3 nasopharyngeal carcinoma (NPC). And aspirin is found to reduce metastasis and improve prognosis in some other malignancies, such as colorectal cancer. This study aimed to evaluate the clinical value of regular aspirin intake (RAI) in N2-3 NPC treated with standard chemoradiotherapy. MATERIALS AND METHODS: Totally 2064 patients diagnosed with TxN2-3M0 NPC from Jan. 2008 to Dec. 2015 and treated with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy were involved. According to RAI, these patients were divided into 2 groups between which a propensity score matching was made, with a ratio of 1:3 and a series of clinical characteristics (age, gender, T stage, N stage and EBV DNA) as covariates. Then survivals and acute toxicities were compared in the 464 matched patients. RESULTS: RAI appeared to bring better overall (87.7% vs. 79.6%, P = 0.031), metastasis-free (87.8% vs. 76.5%, P = 0.017) and disease-free (85.9% vs. 75.5%, P = 0.033) survivals. It simultaneously increased total incidences of myelosuppression (55.2% vs. 32.2%, P < 0.001), oral mucositis (60.3% vs. 38.2%, P < 0.001), cervical dermatitis (60.3% vs. 38.5%, P < 0.001) and xerostomia (49.1% vs. 33.3%, P = 0.002). But RAI failed to affect incidence of any grade 3/4 toxicity. CONCLUSIONS: Post-diagnosis RAI might be a tolerable approach to control distant metastasis and provide survival benefit for N2-3 NPC in combination with standard chemoradiotherapy.

10.
Oxid Med Cell Longev ; 2020: 4909103, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998438

RESUMO

Direct peritoneal resuscitation with pyruvate (Pyr-PDS) has emerged as an interesting candidate to alleviate injury in diverse organs, while the potential mechanism has yet to be fully elucidated. To explore the effect of autophagy in the spinal cord ischemia-reperfusion (SCIR) injury and the underlying mechanism, we established a model of SCIR in vivo and in vitro. In vivo, male SD rats underwent aortic occlusion for 60 min and then followed by intraperitoneally infused with 20 mL of pyruvate or normal saline for 30 min, and the spinal cords were removed for analysis after 48 h of reperfusion. The functional and morphological results showed that Pyr-PDS alleviated SCIR injury; meanwhile, the expression of autophagy-related genes and transmission electron microscopy displayed autophagy was activated by SCIR injury, and Pyr-PDS treatment could further upregulate the degree of autophagy which plays a protective part in the SCIR injury, while there is no significant difference after treatment with saline. In addition, SCIR injury inhibited expression of PHD2, which results to activate its downstream HIF-1α/BNIP3 pathway to promote autophagy. In the Pyr-PDS, the results revealed PHD2 was further inhibited compared to the SCIR group, which could further activate the HIF-1α/BNIP3 signaling pathway. Additionally, oxygen-glucose deprivation and reoxygenation were applied to SH-SY5Y cells to mimic anoxic conditions in vitro, and the expression of autophagy-related genes, PHD2, and its downstream HIF-1α/BNIP3 pathway showed the same trend as the results in vivo. Besides, IOX2, a specific inhibitor of PHD2 was also treated to SH-SY5Y cells during reoxygenation, in which the result is as same as the pyruvate group. Then, we observed the expression of autophagy-related genes and the HIF-1α signal pathway in the process of reoxygenation; the results showed that as the reoxygenation goes, the expression of the HIF-1α signal pathway and degree of autophagy came to decrease gradually, while treated with pyruvate could maintain autophagy high and stable through keeping PHD2 at a lower level during reoxygenation, and the latter was observed downregulated during reoxygenation process from 0 to 24 hours in a time-effect way. The above results indicated that direct peritoneal resuscitation with pyruvate showed effective protection to ischemia-reperfusion of the spinal cord through activating autophagy via acting on PHD2 and its downstream HIF-1α/BNIP3 pathway.

11.
Wound Repair Regen ; 28(1): 126-144, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31509318

RESUMO

Human skin wound repair may result in various outcomes with most of them leading to scar formation. Commonly seen in many cutaneous wound healing cases, hypertrophic scars are considered as phenotypes of abnormal wound repair. To prevent the formation of hypertrophic scars, efforts have been made to understand the mechanism of scarring following wound closure. Numerous in vivo and in vitro models have been created to facilitate investigations into cutaneous scarring and the development of antiscarring treatments. To select the best model for a specific study, background knowledge of the current models of hypertrophic scars is necessary. In this review, we describe in vivo and in vitro models for studying hypertrophic scars, as well as the distinct characteristics of these models. The choice of models for a specific study should be based on the characteristics of the model and the goal of the study. In general, in vivo animal models are often used in phenotypical scar formation analysis, development of antiscarring treatment, and functional analyses of individual genes. In contrast, in vitro models are chosen to pathway identification during scar formation as well as in high-throughput analysis in drug development. Besides helping investigators choose the best scarring model for their research, the goal of this review is to provide knowledge for improving the existing models and development of new models. These will contribute to the progress of scarring studies.

12.
J Diabetes Investig ; 11(1): 184-191, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31145541

RESUMO

AIMS/INTRODUCTION: To investigate the association between serum 25-hydroxyvitamin D (25-[OH]D) concentrations and metabolic syndrome (MetS) in the middle-aged and elderly Chinese population. METHODS: The present study included 2,764 participants (aged >50 years). The joint interim statement was used for the standard definition of MetS. Serum 25-(OH)D concentrations were measured by electrochemiluminescence immunoassay. The study participants were categorized into quartiles based on serum 25-(OH)D concentrations, and the quartiles were calculated for the differences using anova and the χ2 -test for continuous and categorical data, respectively. A logistic regression analysis model was applied to estimate the odds ratios and 95% confidence intervals (95% CI) for each quartile of serum 25-(OH)D concentrations compared with the highest quartile. RESULTS: Serum 25-(OH)D levels were markedly lower in men in the MetS group than in those without MetS. We observed a negative correlation between the higher quartiles of serum 25-(OH)D levels and the presence of MetS among men. The correlation between serum 25-(OH)D levels and the prevalence of MetS persisted even after adjusting for potential confounders, including age, cigarette smoking status, alcohol consumption, physical activity, low-density lipoprotein, creatinine and total serum cholesterol. Adjusted odds ratios of MetS in the second through fourth compared with the lowest quartile for serum 25-(OH)D levels were 0.93 (95% CI 0.54-1.59), 0.89 (95% CI 0.50-1.56) and 0.48 (95% CI 0.28-0.84), respectively. CONCLUSIONS: Decreased serum 25-(OH)D level is significantly correlated with MetS in middle-aged men.

13.
Lab Invest ; 100(3): 378-386, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31527830

RESUMO

Monocyte and adhesion infiltration into the arterial subendothelium are initial steps in hypertension development. The endothelial intercellular adhesion molecule-1 (ICAM-1) has been implicated in the recruitment and adhesion of leukocytes in several cardiac diseases. However, the role of ICAM-1 in angiotensin II (Ang II)-induced hypertension development remains unknown. Hypertension was induced by administering an infusion of Ang II (1000 ng/kg/min) to wild-type (WT) mice treated with an IgG control or ICAM-1 neutralizing antibody (1 and 2 mg/mouse/day, respectively). Blood pressure was determined using the tail-cuff system. Vascular remodeling was assessed by performing a histological examination. Inflammation and reactive oxygen species (ROS) levels were determined by using immunostaining. Vascular dysfunction was assessed by aortic ring assay. The expression of fibrotic markers, cytokines and NOX was evaluated by quantitative real-time PCR analysis. Our results demonstrate that Ang II infusion markedly increased the ICAM-1 level in the aorta. Blocking ICAM-1 with a neutralizing antibody significantly attenuated Ang II-induced arterial hypertension, vascular hypertrophy, fibrosis, macrophage infiltration, and ROS production and improved vascular relaxation. In conclusion, ICAM-1-mediated monocyte adhesion and migration play a critical role in Ang II-induced arterial hypertension and vascular dysfunction. ICAM-1 inhibitors may represent a new therapeutic strategy for the treatment of this disease.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1774-1778, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839037

RESUMO

OBJECTIVE: To investigate the clinical characteristics, etiology and drug susceptibility of bacterial bloodstream infections in acute leukemia(AL) patients. METHODS: Clinical data, etiology and drug susceptibility of acute leukemia patients with bacterial bloodstream infections from April 2009 to April 2018 were retrospectively analyzed. RESULTS: A total of 376 strains were isolated, 76.9% was Gram-negative bacterial and 23.1% was Gram-positive bacteria. Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae were listed as the top three of Gram-negative bacteria. The susceptibility of Escherichia coli to the tigacycline, imipenem and meropenem was 100.0%, 98.2% and 98.1%, respectively. The susceptibility of Klebsiella pneumoniae to the tigacycline, imipenem and meropenem were 100.0%, 98.3% and 94.4%, respectively. The adjustment rate for initial use of carbopenems was 3.8%, while the adjustment rate for initial use of noncarbopenems was 74.3% in patients with main Gram-negative bacterial blood stream infection. The susceptibility of Gram-positive bacteria to glycopeptide antibiotics, linezolid and tigacycline was 100.0%. CONCLUSION: Gram-negative bacteria is the majority type of bacteria in AL patients with bacteria blood stream infections. The susceptibility of Gram-negative bacteria to the carbapenems is high, and the treatment adjustment rate is obviously low. The glycopeptide, linezolid and tigacycline are effective for Gram-positive bacteria infections..


Assuntos
Bacteriemia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1986-1992, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839071

RESUMO

OBJECTIVE: To investigate the effect of human placental hematopoietic stem cells (PHSCs) on hematopoietic reconstruction in non-lethally irradiated mice. METHODS: Human placental HSCs were extracted by mechanical method combined with zymolysis and were identified by flow cytometry and colony formationtest. Twenty-five NOG mice were divided randomly into 4 groups: the blank control group (n=5), the irradiated group (n=4), the low dose PHSC group (n=8) and the high dose PHSC group (n=8). The mice in the irradiated, the low dose and the high dose PHSC groups were irradiated with X-rays at dose 1 Gy (100 cGy/min) under sterile condition. The mice in the low dose PHSC group and the high dose PHSC group were injected intravenously with 0.1 ml human placental HSC in dose of 2×106 and 1×107, respectively. The mice in the blank control and the irradiated group were injected with the same volume of saline. The mice were weighed weekly, and the changes of body weight were calculated. The peripheral blood was collected from each group at 4, 8 and 12 week for flow cytometrytic detection of human CD45+ and myeloid and lymphoid cells. RESULTS: The flow cytometry and cell-colong formation test showed that the human placental HSC accounted for more than 0.75% of total placental mononuclear cells, moreover possess the differentiation ability. Compared with the blank control group, the relative weight gain in the irradiated, the low dose PHSC, and the high dose PHSC groups decreased significantly, and the relative weight gain in the low dose PHSC and the high dose PHSC group increased significantly as compared with the irradiated group. Flow cytometry showed that at the tine-point of 12 weeks after transplantation, the human blood immune system in the high-dose PHSC mice began long-term reconstruction, while the ratio of human CD45+ cells in the low-dose PHSC mice was very low. CONCLUSION: After transplantation of human PHSC the non-lethally irradiated mice can obtain short-term and long-term reconstruetion of human blood cells, which demonstrated that human placental HSC can differentiate and reconstruct hematopoietic function in vivo of irradiated mice.


Assuntos
Células da Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Animais , Feminino , Citometria de Fluxo , Células-Tronco Hematopoéticas , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Gravidez
16.
Aging (Albany NY) ; 112019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31831714

RESUMO

Our previous studies discovered that tumor-specific hepatic stellate cells (tHSCs) induced dendritic cell-derived immunoglobulin receptor 2 (DIgR2) expression in bone marrow-derived dendritic cells (mDCs), inhibiting splenic T cell activation. The current study aims to explore the underlying mechanism of DIgR2 expression by focusing on Nrf2 (nuclear-factor-E2-related factor 2) signaling. We show that tHSCs co-culture induced significant Nrf2 signaling activation in mDCs. The latter was evidenced by Nrf2-Keap1 disassociation, Nrf2 protein stabilization, accumulation and nuclear translocation. Expression of Nrf2-dependent genes, including heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1), were detected in tHSCs-co-cultured mDCs. Importantly tHSCs-induced DIgR2 expression was blocked by Nrf2 shRNA or knockout (KO, by CRISPR/Cas9 method). Conversely, forced activation of Nrf2, by Keap1 shRNA or the Nrf2 activators (3H-1,2-dithiole-3-thione and MIND4-17), induced significant DIgR2 expression. tHSCs stimulation induced reactive oxygen species (ROS) production in mDCs. Conversely, ROS scavengers inhibited tHSCs-induced ROS production, Nrf2 activation and DIgR2 expression in mDCs. Significantly, tHSCs inhibited production of multiple cytokines (CD80, CD86 and IL-12) in mDCs, reversed by Nrf2 depletion. Moreover, Nrf2 shRNA or KO attenuated splenic T cell inhibition by tHSCs-stimulated mDCs. Together, we conclude that Nrf2 activation mediates tHSCs-induced DIgR2 expression in mDCs.

17.
Medicine (Baltimore) ; 98(47): e17875, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764782

RESUMO

BACKGROUND: This study aimed to explore the effect of YHJD (Yiqi Huayu Jiedu decoction) in patients with stages II and III gastric cancer. METHODS: A multicenter, prospective, cohort study was conducted in Jiangsu Province Hospital of Traditional Chinese Medicine, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital, People's Liberation Army Bayi Hospital, Changzhou Traditional Chinese Medicine Hospital, Changzhou Tumor Hospital, Traditional Chinese Medicine Hospital of Kunshan, Yangzhou Hospital of Traditional Chinese Medicine, and Yixing Tumor Hospital. A total of 489 patients with stage II or III gastric cancer were enrolled after radical gastrectomy. Among them, 238 were included in the chemotherapy group (received chemotherapy alone) and 251 in the YHJD group (received chemotherapy combined with YHJD). The DFS (disease-free survival) rate, 5-year survival rate, quality of life, and traditional Chinese medicine (TCM) symptoms of the 2 groups were compared. RESULTS: The DFS curve of the YHJD group was higher than that of the chemotherapy group (P = .0042). The HR (hazard ratio) was 0.672, and its corresponding 95% CI (confidence interval) was 0.511 to 0.884. For stage II patients, the P value was .8323, which indicated that the difference was not significant. The risk HR was 0.938, and the corresponding 95% CI was 0.521 to 1.689. For stage III patients, the P value was .0072, indicating a statistically significant difference. The HR was 0.653, and the corresponding 95% CI was 0.477 to 0.893. The 5-year survival rate of the YHJD group was 85.29%, which was higher than that of the chemotherapy group (71.05%). Compared with the chemotherapy group, the YHJD group had better quality of life and lower TCM symptom scores. CONCLUSION: YHJD decoction is effective in improving DFS rate in patients with gastric cancer stage III after radical gastrectomy. Moreover, it can reduce the risk of recurrence and metastasis and improve the quality of life in patients with gastric cancer stage II or III after radical gastrectomy.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Estudos de Coortes , Terapia Combinada , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento , Adulto Jovem
18.
J Med Chem ; 62(23): 10867-10896, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31725297

RESUMO

Human farnesyl pyrophosphate synthase (Homo sapiens FPPS, HsFPPS) is a target for treating bone resorption diseases and some cancers. HsFPPS is potently inhibited by bisphosphonates, but due to poor cell penetration and distribution in soft tissue, there is currently interest in the development of non-bisphosphonate inhibitors as cancer therapeutics. Here, we report the discovery and development of HsFPPS inhibitors based on the phenolic diterpene carnosic acid (CA), an antimicrobial found in rosemary and sage, which showed better cellular anticancer activities than the bisphosphonate drug zoledronate in pancreatic cancer cell lines, as well as an HsFPPS-dependent mechanism of action. Hit-to-lead optimization of CA improved HsFPPS inhibition by >100-fold. A slow dissociation inhibition pattern and a noncompetitive allosteric binding mode were found, and cellular mechanism-of-action studies showed that these inhibitors inhibit tumor cell growth primarily by inhibiting HsFPPS, leading to downregulation of Ras prenylation and cell apoptosis. The discovery of this series of compounds together with proof-of-mechanism in pancreatic cancer cells may pave the way for targeting HsFPPS in soft tissue cancers using natural-product-derived inhibitors.

19.
Am J Physiol Heart Circ Physiol ; 317(6): H1301-H1311, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31729904

RESUMO

Intercellular adhesion molecule-1 (ICAM-1) is a member of an immunoglobulin-like superfamily of adhesion molecules that mediate leukocyte adhesion to vascular endothelium and are involved in several cardiovascular diseases, including ischemia-reperfusion injury, myocardial infarction, and atherosclerosis. However, the role of ICAM-1 in angiotensin II (ANG II)-induced cardiac remodeling in mice remains unclear. Wild-type mice were administered an IgG control or ICAM-1 neutralizing antibody (1 and 2 mg/mouse, respectively) and ANG II (1,000 ng·kg-1·min-1) for up to 14 days. Cardiac contractile function and structure were detected by echocardiography. Hypertrophy, fibrosis, and inflammation were assessed by histological examination. The infiltration of lymphocyte function-associated antigen-1 (LFA-1+) monocytes/macrophages was assessed by immunostaining. The mRNA expression of genes was evaluated by quantitative RT-PCR analysis. Protein levels were tested by immunoblotting. We found that ICAM-1 expression in ANG II-infused hearts and ICAM-1 levels in serum from human patients with heart failure were significantly increased. Moreover, ANG II infusion markedly enhanced ANG II-induced hypertension, caused cardiac contractile dysfunction, and promoted cardiac hypertrophy, fibrosis, and LFA-1+ macrophage infiltration. Conversely, blockage of ICAM-1 with a neutralizing antibody dose-dependently attenuated these effects. Moreover, our in vitro data further demonstrated that blocking ICAM-1 inhibited ANG II-induced LFA-1+ macrophage adhesion to endothelial cells and migration. In conclusion, these results provide novel evidence that blocking ICAM-1 exerts a protective effect in ANG II-induced cardiac remodeling at least in part through the modulation of adhesion and infiltration of LFA-1+ macrophages in the heart. Inhibition of ICAM-1 may represent a new therapeutic approach for hypertrophic heart diseases.NEW & NOTEWORTHY Leukocyte adhesion to vascular endothelium is a critical step in cardiovascular diseases. ICAM-1 is a member of immunoglobulin-like superfamily of adhesion molecules that binds LFA-1 to mediate leukocytes adhesion and migration. However, the significance of ICAM-1 in ANG II-induced cardiac remodeling remains unclear. This study reveals that blocking of ICAM-1 prevents ANG II-induced cardiac remodeling via modulating adhesion and migration of LFA-1+ monocytes, may serve as a novel therapeutic target for hypertensive cardiac diseases.

20.
Zhongguo Gu Shang ; 32(9): 806-809, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31615175

RESUMO

OBJECTIVE: To analyze the clinical effect of Zhuang medicine tendon therapy combined with chiropractic manipulation in treating sacroiliac joint dislocation. METHODS: From January 2017 to May 2018, 60 patients with sacroiliac joint dislocation were divided into treatment group and control group according to the order of admission. There were 19 males and 11 females in the treatment group, aged from 23 to 52 (38.97±3.23) years old, with a course of 2 h to 5.1 months, with an average of (2.19±1.12) months. There were 14 males and 16 females in the control group, aged from 26 to 50 (39.07±3.30) years old, with a course of 3 h to 6 months, with an average of(2.41±1.05) months. The treatment group was treated with Zhuang medicine tendon therapy combined with chiropractic manipulation, while the control group was treated with conventional acupuncture and massage. Before treatment, the main clinical symptoms of the patients were lumbosacral pain, posterior superior iliac spine not at the same level and accompanied with dyskinesia. The pelvic separation test and the "4" test were positive. After treatment, the curative effect was evaluated according to the improved Macnab standard and the "score of treatment of lumbar diseases". RESULTS: Sixty patients were followed up for an average of 8 months. At the latest follow-up, the clinical effect of modified Macnab was better in the treatment group than in the control group(P<0.01). After treatment, the treatment group was better than the control group on lumbar function score (P<0.01). CONCLUSIONS: The treatment of sacroiliac joint dislocation by Zhuang medicine tendon therapy combined with chiropractic manipulation has good clinical effect and is worth further application and development.


Assuntos
Luxações Articulares , Manipulação Quiroprática , Adulto , Feminino , Fixação Interna de Fraturas , Humanos , Luxações Articulares/terapia , Masculino , Pessoa de Meia-Idade , Articulação Sacroilíaca , Tendões , Adulto Jovem
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