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Ribosome-inactivating proteins (RIPs) are a class of cytotoxic rRNA N-glycosylase, which widely exist in higher plants in different taxonomy, including many traditional Chinese medicinal materials and vegetables and fruits. In this paper, the traditional Chinese medicinal plants containing RIPs protein were sorted out, and their pharmacological effects and clinical applications were analyzed. Since many RIPs in traditional Chinese medicine plants exhibit antiviral and antitumor activities and show great clinical application potential, people's interest in these proteins is on the rise. This paper summarizes the possible mechanism of RIPs's anti-virus and anti-tumor effects, and discusses its potential problems and risks, laying a foundation for subsequent research on how to exert its anti-virus and anti-tumor effects.
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This study aims to discern the possible molecular mechanism of the effect of ubiquitin-specific peptidase 18 (USP18) on the resistance to BRAF inhibitor vemurafenib in BRAF V600E mutant melanoma by regulating cyclic GMP-AMP synthase (cGAS). The cancer tissues of BRAF V600E mutant melanoma patients before and after vemurafenib treatment were collected, in which the protein expression of USP18 and cGAS was determined. A BRAF V600E mutant human melanoma cell line (A2058R) resistant to vemurafenib was constructed with its viability, apoptosis, and autophagy detected following overexpression and depletion assays of USP18 and cGAS. Xenografted tumors were transplanted into nude mice for in vivo validation. Bioinformatics analysis showed that the expression of cGAS was positively correlated with USP18 in melanoma, and USP18 was highly expressed in melanoma. The expression of cGAS and USP18 was up-regulated in cancer tissues of vemurafenib-resistant patients with BRAF V600E mutant melanoma. Knockdown of cGAS inhibited the resistance to vemurafenib in A2058R cells and the protective autophagy induced by vemurafenib in vitro. USP18 could deubiquitinate cGAS to promote its protein stability. In vivo experimentations confirmed that USP18 promoted vemurafenib-induced protective autophagy by stabilizing cGAS protein, which promoted resistance to vemurafenib in BRAF V600E mutant melanoma cells. Collectively, USP18 stabilizes cGAS protein expression through deubiquitination and induces autophagy of melanoma cells, thereby promoting the resistance to vemurafenib in BRAF V600E mutant melanoma.
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Melanoma , Proteínas Proto-Oncogénicas B-raf , Animales , Ratones , Humanos , Vemurafenib/farmacología , Vemurafenib/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , Ratones Desnudos , Indoles/farmacología , Indoles/uso terapéutico , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Resistencia a Antineoplásicos/genética , Mutación , Línea Celular Tumoral , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , Inhibidores de Proteínas Quinasas/farmacología , Autofagia/genética , Nucleotidiltransferasas/genética , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/farmacologíaRESUMEN
Objective: This study aims to evaluate the efficacy of various conventional synthetic DMARDs, including Tripterygium wilfordii Hook F (TwHF) for treating rheumatoid arthritis (RA) by network meta-analysis. Methods: We retrieved the related literature from online databases and supplemented it by using a manual retrieval method. Data was extracted from the literature and analyzed with STATA software. Results: A total of 21 trials (5,039 participants) were identified. Assessment of ACR20 response found that TwHF combined with methotrexate (MTX) had the greatest probability for being the best treatment option among the treatments involved, while TwHF used singly was second only to TwHF combined with MTX. Assessment of ACR50 response found that TwHF combined with MTX ranked second in all treatment options after cyclosporine A (CsA) combined with leflunomide (LEF) and TwHF alone, followed by TwHF combined with MTX. Assessment of ACR70 response found that CsA combined with LEF ranked first, TwHF combined with LEF ranked second, TwHF combined with MTX ranked third, and TwHF used singly ranked fourth. In the safety analysis, TwHF had the least probability of adverse event occurrence, followed by TwHF combined with MTX, which ranked first and second, respectively. Conclusion: Compared with the current csDMARDs for treating RA, the efficacy of TwHF was clear, and TwHF combined with MTX performed well under various endpoints. In the future, large, rigorous, and high-quality RCTs are still needed to confirm the benefits of TwHF therapy on RA.
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BACKGROUND: Neuroblastoma (NB) is a common extracranial malignancy with high mortality in children. Recently, super-enhancers (SEs) have been reported to play a critical role in the tumorigenesis and development of NB via regulating a wide range of oncogenes Thus, the synthesis and identification of chemical inhibitors specifically targeting SEs are of great urgency for the clinical therapy of NB. This study aimed to characterize the activity of the SEs inhibitor GNE987, which targets BRD4, in NB. RESULTS: In this study, we found that nanomolar concentrations of GNE987 markedly diminished NB cell proliferation and survival via degrading BRD4. Meanwhile, GNE987 significantly induced NB cell apoptosis and cell cycle arrest. Consistent with in vitro results, GNE987 administration (0.25 mg/kg) markedly decreased the tumor size in the xenograft model, with less toxicity, and induced similar BRD4 protein degradation to that observed in vitro. Mechanically, GNE987 led to significant downregulation of hallmark genes associated with MYC and the global disruption of the SEs landscape in NB cells. Moreover, a novel candidate oncogenic transcript, FAM163A, was identified through analysis of the RNA-seq and ChIP-seq data. FAM163A is abnormally transcribed by SEs, playing an important role in NB occurrence and development. CONCLUSION: GNE987 destroyed the abnormal transcriptional regulation of oncogenes in NB by downregulating BRD4, which could be a potential therapeutic candidate for NB.
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MAP30 (Momordica antiviral protein 30kD) is a single-chain â -type ribosome inactivating protein with a variety of biological activities, including anti-tumor ability. It was reported that MAP30 would serve as a novel and relatively safe agent for prophylaxis and treatment of liver cancer. To determine whether adding two tumor targeting peptides could improve the antitumor activities of MAP30, we genetically modified MAP30 with an RGD motif and a EGFRi motif, which is a ligand with high affinity for αvß3 integrins and with high affinity for EGFR. The recombinant protein ELRL-MAP30 (rELRL-MAP30) containing a GST-tag was expressed in E. coli. The rELRL-MAP30 was highly expressed in the soluble fraction after induction with 0.15 mM IPTG for 20 h at 16 °C. The purified rELRL-MAP30 appeared as a band on SDS-PAGE. It was identified by western blotting. Cytotoxicity of recombinant protein to HepG2, MDA-MB-231, HUVEC and MCF-7 cells was detected by MTT analysis. Half maximal inhibitory concentration (IC50) values were 54.64 µg/mL, 70.13 µg/mL, 146 µg/mL, 466.4 µg/mL, respectively. Proliferation inhibition assays indicated that rELRL-MAP30 could inhibit the growth of Human liver cancer cell HepG2 effectively. We found that rELRL-MAP30 significantly induced apoptosis in liver cancer cells, as evidenced by nuclear staining of DAPI. In addition, rELRL-MAP30 induced apoptosis in human liver cancer HepG2 cells by up-regulation of Bax as well as down-regulation of Bcl-2. Migration of cell line were markedly inhibited by rELRL-MAP30 in a dose-dependent manner compared to the recombinant MAP30 (rMAP30). In summary, the fusion protein displaying extremely potent cytotoxicity might be highly effective for tumor therapy.
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Antineoplásicos Fitogénicos/farmacología , Momordica charantia/química , Péptidos/genética , Proteínas Recombinantes de Fusión/genética , Proteínas Inactivadoras de Ribosomas Tipo 2/genética , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Clonación Molecular , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Células Hep G2 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Integrina alfa5/genética , Integrina alfa5/metabolismo , Integrina beta3/genética , Integrina beta3/metabolismo , Células MCF-7 , Péptidos/metabolismo , Unión Proteica , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/farmacología , Proteínas Inactivadoras de Ribosomas Tipo 2/metabolismo , Proteínas Inactivadoras de Ribosomas Tipo 2/farmacología , Proteína X Asociada a bcl-2/agonistas , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Health effects resulting from the smoke of carbonyl compounds (aldehydes and ketones) and metal-containing incense particles at temples during incense burning periods were evaluated at temple A (without incense reduction activities) and B (with incense reduction activities), Nantou County, in 2018. The predominant size fractions of particles were PM1, PM1-2.5, and PM2.5-10 at both temples. The total particle mass at temple A was approximately 1.1 times that of temple B due to incense reduction at temple B. The most abundant metal elements in all particle size fractions at both temples were Fe, Al, and Zn. Metal species of incense smoke are divided into three groups by hierarchical cluster analysis and heatmaps, showing higher metal contents in groups PM1, PM18-10, and PM18-2.5 at temple A. In contrast, higher metal contents were observed in PM18-10 and PM2.5-1 at temple B. Most of the carbonyl species were formaldehyde and acetaldehyde, released during incense burning periods, with concentrations ranging from 6.20 to 13.05 µg/m3 at both temples. The total deposited fluxes of particle-bound metals at temples A and B were determined to be 83.00% and 84.82% using the International Commission on Radiological Protection (ICRP) model. Health-risk assessments revealed that the risk values of metals and carbonyls were above recommended guidelines (10-6) at temple A. Since worshippers and staff are exposed to incense burning environments with poor ventilation over a long period, these toxic organic compounds and metals increase health risks in the respiratory tract. Therefore, incense reduction is important to achieve healthy temple environments.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Formaldehído , Humanos , Tamaño de la Partícula , Medición de Riesgo , HumoRESUMEN
Chitosan (CTS) and mesoporous calcium silicate (MCS) have been developed for bone defect healing; however, their bone regeneration capacity still does not satisfy the patients with bone diseases. Gadolinium (Gd) is accumulated in human bones, and plays a beneficial role in regulating cell performance and bone regeneration. We firstly constructed Gd-doped MCS/CTS (Gd-MCS/CTS) scaffolds by a lyophilization technology. The interconnected arrangement of CTS films lead to forming macropores by using ice crystals as templates during the lyophilization procedure, and the Gd-MCS nanoparticles dispersed uniformly on the macropore walls. The biocompatible chemical components and hierarchical pores facilitated the attachment and spreading of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Interestingly, the Gd dopants in the scaffolds effectively activated the Wnt/ß-catenin signaling pathway, resulting in excellent cell proliferation and osteogenic differentiation capacities. The osteogenic-related genes such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and collagen type1 (COL-1) were remarkably up-regulated by Gd-MCS scaffolds as compared with MCS scaffolds, and their expression levels increased in a positive correlation with Gd doping amounts. Moreover, in vivo rat cranial defect tests further confirmed that Gd-MCS/CTS scaffolds significantly stimulated collagen deposition and new bone formation. The exciting finding suggested the beneficial effects of Gd3+ ions on osteogenic differentiation and new bone regeneration, and Gd-MCS/CTS scaffolds can be employed as a novel platform for bone defect healing.
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Regeneración Ósea/efectos de los fármacos , Compuestos de Calcio/química , Compuestos de Calcio/farmacología , Quitosano/química , Gadolinio/química , Gadolinio/farmacología , Silicatos/química , Silicatos/farmacología , Fosfatasa Alcalina/metabolismo , Animales , Materiales Biocompatibles/química , Huesos/efectos de los fármacos , Huesos/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Trace rare earth elements such as lanthanum (La) regulated effectively bone tissue performances; however, the underlying mechanism remains unknown. In order to accelerate bone defects especially in patients with osteoporosis or other metabolic diseases, we firstly constructed lanthanum-doped mesoporous calcium silicate/chitosan (La-MCS/CTS) scaffolds by freeze-drying technology. During the freeze-drying procedure, three-dimensional macropores were produced within the La-MCS/CTS scaffolds by using ice crystals as templates, and the La-MCS nanoparticles were distributed on the macropore walls. The hierarchically porous structures and biocompatible components contributed to the adhesion, spreading and proliferation of rat bone marrow-derived mesenchymal stem cells (rBMSCs), and accelerated the in-growth of new bone tissues. Particularly, the La3+ ions in the bone scaffolds remarkably induced the osteogenic differentiation of rBMSCs via the activation of the TGF signal pathway. A critical-sized calvarial-defect rat model further revealed that the La-MCS/CTS scaffolds significantly promoted new bone regeneration as compared with pure MCS/CTS scaffolds. In conclusion, the La-MCS/CTS scaffold showed the prominent ability in osteogenesis and bone regeneration, which showed its application potential for bone defect therapy.
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Huesos/efectos de los fármacos , Compuestos de Calcio/farmacología , Quitosano/farmacología , Lantano/farmacología , Silicatos/farmacología , Ingeniería de Tejidos , Animales , Compuestos de Calcio/química , Quitosano/química , Lantano/química , Tamaño de la Partícula , Porosidad , Ratas , Silicatos/química , Propiedades de SuperficieRESUMEN
Mesenchymal stem cells have been widely studied to promote local bone regeneration of osteonecrosis of the femoral head (ONFH). Previous studies observed that dimethyloxaloylglycine (DMOG) enhanced the angiogenic and osteogenic activity of mesenchymal stem cells by activating the expression of hypoxia inducible factor-1α (HIF-1α), thereby improving the bone repair capacity of mesenchymal stem cells. In the present study, it was investigated whether DMOG could increase the bone repair capacity of adipose-derived stem cells (ASCs) in the treatment of ONFH. Western blot analysis was performed to detect HIF-1α protein expression in ASCs treated with different concentrations of DMOG. The results showed DMOG enhanced HIF-1α expression in ASCs in a dose-dependent manner at least for 7 days. Furthermore, DMOG-treated ASCs were transplanted into the necrotic area of a rabbit model of ONFH to treat the disease. Four weeks later, micro-computed tomography (CT) quantitative analysis showed that 58.8±7.4% of the necrotic area was regenerated in the DMOG-treated ASCs transplantation group, 45.5±3.4% in normal ASCs transplantation group, 25.2±2.8% in only core decompression group and 10.6±2.6% in the untreated group. Histological analysis showed that transplantation of DMOG-treated ASCs clearly improved the bone regeneration of the necrotic area compared with the other three groups. Micro-CT and immunohistochemical analysis demonstrated the revasculation of the necrotic area were also increased significantly in the DMOG-treated ASC group compared with the control groups. Thus, it is hypothesized that DMOG could increase the bone repair capacity of ASCs through enhancing HIF-1α expression in the treatment of ONFH.
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OBJECTIVE: To investigate the effects of the active ingredients combined therapy on inflammatory factors interleukin 1 beta (IL-1ß) and neuropeptide Y (NPY) based on pharmacodynamics in rats. METHODS: The animal model was built by transient middle cerebral artery occlusion (MCAO). The method for evaluating the concentrations of the FA-Pr-Al components in rat plasma was established by using HPLC and the expression levels of IL-1ß and NPY were determined by ELISA. A new mathematics method of the trend of percentage rate of change (PRC) was used to assess the correlation between pharmacokinetics (PK) and pharmacodynamics (PD). RESULTS: FA-Pr-Al in combination reduced neurological deficits, decreased infarct volume and inhibited the expression levels of IL-1ß and NPY (all P<0.05) compared with the model group. FA, Pr and Al all displayed two compartment open models in rats. Clockwise hysteresis loops were obtained by time-concentration-effect curves. IL-1ß and NPY level changes in the plasma followed an opposite trend to the plasma concentration tendency after Cmax was reached. Astragaloside's PRC value was significantly higher than those of FA and puerarin between 120 to 180 min. CONCLUSIONS: The pharmacokinetics of FA-Pr-Al in combination were closely related its pharmacodynamics in treating ischemia/reperfusion injury, and the components of FA-Pr-Al may have a synergistic pharmacological effect. Astragaloside may play a more pronounced role in regulating IL-1ßand NPY levels compared with puerarin or FA.
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Simultaneous bilateral fractures of the femoral neck are rare injuries, which are reportedly induced by low-speed energy with predisposing factors including systemic diseases, medications and eclamptic seizures. Those caused by high energy are even rarer. High energy-induced bilateral fractures of the femoral neck conceive of high incidence of mortality and present great challenges in the early management. We report one case of a 52-year-old man with simultaneous bilateral fractures of the femoral neck which resulted from a motor pedestrian accident. One-stage closed reduction and internal fixation was done following the emergent resuscitation and neurosurgical management for concomitant brain injuries. The fractures united. There was no pain in the hips, and they had a normal range of motion. The treatment protocol, mechanism of the injury and possible postoperative complications were discussed to expand a comprehensive understanding about these infrequent types of fractures.
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Fracturas del Cuello Femoral/etiología , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/cirugía , Fijación Interna de Fracturas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Tomografía Computarizada por Rayos XRESUMEN
Detailed mechanisms of WhiB-like (Wbl) proteins involved in antibiotic biosynthesis and morphological differentiation are poorly understood. Here, we characterize the role of WblAch, a Streptomyces chattanoogensis L10 protein belonging to this superfamily. Based on DNA microarray data and verified by real-time quantitative PCR (qRT-PCR), the expression of wblAch was shown to be positively regulated by AdpAch. Gel retardation assays and DNase I footprinting experiments showed that AdpAch has specific DNA-binding activity for the promoter region of wblAch. Gene disruption and genetic complementation revealed that WblAch acts in a positive manner to regulate natamycin production. When wblAch was overexpressed in the wild-type strain, the natamycin yield was increased by â¼30%. This provides a strategy to generate improved strains for natamycin production. Moreover, transcriptional analysis showed that the expression levels of whi genes (including whiA, whiB, whiH, and whiI) were severely depressed in the ΔwblAch mutant, suggesting that WblAch plays a part in morphological differentiation by influencing the expression of the whi genes.
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Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Natamicina/biosíntesis , Streptomyces/enzimología , Streptomyces/crecimiento & desarrollo , Transactivadores/metabolismo , Secuencia de Aminoácidos , Proteínas Bacterianas/genética , Datos de Secuencia Molecular , Streptomyces/genética , Transactivadores/genéticaRESUMEN
OBJECTIVE: To explore the potential association between the serum levels of 25-hydroxyvitamin D [25(OH)D] and carotid atherosclerosis in patients with type 2 diabetes. MATERIAL AND METHODS: Three hundred and fifty patients with type 2 diabetes were enrolled in this study in Shanghai, China. B-mode ultrasound was used to detect carotid plaques as indicators of atherosclerosis and measure carotid artery intima-media wall thickness (C-IMT) at two sites of carotid artery. Subjects were divided into group A (patients with carotid plaques) and group B (patients without carotid plaques) and be assessed clinically. Serum levels of 25(OH)D and other clinical parameters were measured. Multivariate logistic regression was performed to find predictors of carotid atherosclerosis in the entire group. RESULTS: The levels of serum 25(OH)D were lower in group A than in group B[19.60 (13.30-25.73) vs 23.19 (18.10-30.06)ng/ml, P<0.001]. The C-IMT levels [(1.00±0.17 vs 0.88±0.20)mm, Ptrend<0.001] and proportion of people with carotid plaques(44/88 vs 20/87, Ptrend<0.001) in the lowest quartile of 25(OH)D were higher than in the highest quartile. Vitamin D concentrations were inversely associated with HbA1c in women(r=-0.194, P=0.006), and C-IMT in men(r=-0.409, P<0.001). Logistic regression analysis showed age, male sex, current smoke, history of hypertension, SBP, LDL-C and lg[25(OH)D] (OR: 0.924, 95%CI: 0.893-0.955, P<0.001) were independently associated with the presence of carotid plaques in T2DM. CONCLUSIONS: Serum vitamin D level is significantly and independently associated with carotid atherosclerosis in patients with T2DM in Shanghai, China.
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Enfermedades de las Arterias Carótidas/sangre , Diabetes Mellitus Tipo 2/sangre , Hidroxicolecalciferoles/sangre , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/complicaciones , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , China/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/sangre , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/etiología , Factores SexualesRESUMEN
The effects of hypoxia on the osteogenic potential of mesenchymal stem cells (MSCs) have been previously reported. From these studies, possible factors affecting the association between hypoxia and the osteogenic differentiation of MSCs have been suggested, including hypoxia severity, cell origin and methods of induction. The effect of the duration of hypoxia, however, remains poorly understood. The aim of the present study was to investigate the effect of continuous hypoxia on the induced osteogenesis of MSCs. Rat MSCs were isolated and cultured in vitro. Once the cells had been cultured to passage three, they were switched to 1% oxygen and cultured either with or without osteogenic medium, while cells in the control groups were cultured under normoxia in corresponding conditions. Four osteogenic differentiation biomarkers, runt-related transcription factor 2, osteopontin, osteocalcin and alkaline phosphatase, were analyzed by quantitative polymerase chain reaction and western blotting at defined intervals throughout the culture period. In addition, Alizarin Red staining was used to assess changes in mineralization. The results showed that 1% hypoxia was able to enhance and accelerate the osteogenic ability of the MSCs during the initial phases of differentiation, and the protein expression of certain associated biomarkers was upregulated. However, continuous hypoxia was shown to impair osteogenesis in the latter stages of differentiation. These findings suggest that hypoxia can regulate the osteogenesis of MSCs in a time-dependent manner.
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Hipoxia de la Célula , Células Madre Mesenquimatosas/citología , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Animales , Diferenciación Celular , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Células Madre Mesenquimatosas/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogénesis , Osteopontina/genética , Osteopontina/metabolismo , ARN Mensajero/metabolismo , RatasRESUMEN
Hypovitaminosis D is highly prevalent in type 2 diabetes. The aim of this study is to determine the serum levels of 25-hydroxyvitamin D [25(OH)D] in type 2 diabetic patients with and without mild cognitive impairment (MCI), and examine the relationship of 25(OH)D and MCI with other clinical factors. One hundred and sixty-five diabetic patients were enrolled in this study. Among whom, 95 patients were considered as MCI [Montreal Cognitive Assessment score (MoCA) < 26] and the other 70 as no MCI (MoCA ≥ 26). Subjects were assessed clinically. Diabetic patients with MCI had a longer duration of DM, fewer years of education, elevated fasting blood glucose (FBG), resistant index (RI) of carotid, and lower levels of 25(OH)D {[17.35 (13.02-25.92) vs 28.00 (19.67-34.30)] ng/ml, P < 0.001}. The MoCA score was positively correlated with log10[25(OH)D], education year, and inversely correlated with duration of DM, history of hypertension, intima-media thickness (IMT), FBG, max-RI, and min-RI. Log10[25(OH)D] was positively correlated with MoCA score, and inversely correlated with IMT, in multivariate regression analysis adjusted for age, sex, and education year, 25(OH)D (ß = 0.210, P = 0.003), history of hypertension (ß = -0.191, P = 0.007), IMT (ß = -0.194, P = 0.007), and FBG (ß = -0.157, P = 0.026) independently predicted MoCA score. In conclusion, our results suggest that levels of serum 25(OH)D are inversely associated with the cognitive impairment in diabetic patients. Vitamin D may be a potential protective factor for cognitive impairment in patients with type 2 diabetes.
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Trastornos del Conocimiento/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Vitamina D/análogos & derivados , Biomarcadores/sangre , Trastornos del Conocimiento/diagnóstico , Diabetes Mellitus Tipo 2/psicología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Análisis de Regresión , Factores de Riesgo , Índice de Severidad de la Enfermedad , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/psicologíaRESUMEN
OBJECTIVE: To explore the antimicrobial resistance of nosocomial Gram-negative bacilli across China. METHODS: A total of 1247 consecutive and non-repetitive Gram-negative bacilli were isolated from 13 Chinese teaching hospitals from March to August 2012. All isolates were sent to a central laboratory for reidentification and susceptibility testing. The minimal inhibitory concentration (MICs) of meropenem and other antibacterial agents were determined by agar dilution method. And the data were analyzed with WHONET-5.6 software. RESULTS: The activity of antimicrobial agents against Enterobacteriaceae was in the following descending order of susceptibility rate: meropenem (97.5%, 849/871) , amikacin (94.5%, 823/871) , imipenem (93.6%, 815/871) , ertapenem (92.9%, 809/871) , piperacillin/tazobactam (89.9%, 783/871) , cefoperazone/sulbactam (83.5%, 727/871) , cefepime (78.1%, 680/871) , polymyxin B (77.0%, 670/871) , cefiazidime (69.6%, 606/871) , levofloxacin (69.2%, 603/871) , ciprofloxacin (63.6%, 554/871) , minocyline (63.1%, 550/871) , ceftriaxone (55.7%, 485/871) , cefotaxime (54.2%, 472/871) and cefoxitin (51.4%, 448/871) . The prevalence of extended-spectrum beta-lactamase (ESBL) was 64.3% (117/182) in Escherichia coli (E. coli) and 32.1% (60/187) in Klebsiella pneumonia (K. pneumoniae) . The sensitivities of E. coli to meropenem and imipenem were 100%. And over 90% of E. coli was sensitive to ertapenem, amikacin, piperacillin/tazobactam and polymyxin B. However, over 60% of E. coli was resistant to ciprofloxacin, levofloxacin, ceftriaxone and cefotaxime. The susceptibility of K. pneumoniae to meropenem, imipenem, amikacin and polymyxin B maintained at over 90%. The activities of antimicrobial agents against E. cloacae, E. aerogenes and Citrobacter freundii were in the following descending order of susceptibility rate: meropenem (96.0%-100%) , imipenem (96.0%-100%) , polymyxin B (95.8%-100%) , amikacin (92.2%-100%) , ertapenem (85.6%-93.3%) , cefepime (77.8%-93.3%) , cefoperazone/sulbactam (78.4%-90.0%) and piperacillin/tazobactam (65.0%-89.8%) . The most susceptible agent against Acinetobacter baumannii (A. baumannii) was polymyxin B (100%) . The susceptibilities of A.baumannii to imipenem, meropenem and minocyline were 37.8% (65/172) , 36.0% (62/172) and 62.8% (108/172) respectively. The most active agents against Pseudomonas aeruginosa (P. aeruginosa) were polymyxin B (97.2%, 173/178) , followed by amikacin (89.3%, 159/178) and cefiazidime (83.7%, 149/178) . Clinical and Laboratory Standards Institute revised P.aeruginosa susceptibility standard in 2012. The sensitivity of piperacillin/tazobactam changed from 83.7% (149/178) to 77.5% (138/178) . The sensitivity of meropenem decreased from 78.1% ( 139/178 ) to 71.3% ( 127/178 ) while that of imipenem declined from 69.7% (124/178) to 59.6% (106/178) . The prevalence of multi-drug resistant A. baumannii and P. aeruginosa were 65.7% (113/172) and 9.0% (16/178) respectively. CONCLUSIONS: Carbapenems remain highly active against Enterobacteriaceae. Increasing resistance of A. baumannii to all antimicrobial agents is noted. New breakpoint to P.aeruginosa has obvious effects on antimicrobial sensitivity.
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Antiinfecciosos/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , China , Bacterias Gramnegativas/aislamiento & purificación , Hospitales de Enseñanza , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common and severe complication following femoral neck fractures in young adults. Despite significant advances in surgical techniques, radiological evaluation and comprehensive treatment for the prevention of ONFH, the incidence of traumatic ONFH has remained unchanged at approximately 20% in recent decades. The injury-to-surgery interval is considered as a principal factor affecting the occurrence of ONFH, and traditionally, femoral neck fractures are treated emergently. However, the relationship between the injury-to-surgery interval and ONFH occurrence is poorly understood, and previous reviews have not provided a precise explanation due to the lack of strict selection criteria for studies. METHODS: We reviewed previously published articles and included in current systematic review those studies with accurate multivariate analyses that included age, fracture type, operation method, follow-up, ONFH occurrence and injury-to-surgery interval. RESULTS: Six case studies were included and reevaluated. The studies included 263 hips for final analysis, with an overall incidence of postfracture ONFH of 17.5%. Patients were categorized into groups of less/more than 8 h, less/more than 24 h, less/more than 48 h and less/more than 3 weeks based on the individual injury-to-surgery interval. The postfracture ONFH incidence ranged from 13.3% (<8 weeks) to 21.7% (>3 weeks). Operations performed within 3 weeks of injury resulted in a lower ONFH incidence compared with operations performed after 3 weeks; however, this difference was not statistically significant. The ONFH incidence remained relatively stable when the operations were performed within 3 weeks of injury. CONCLUSIONS: The injury-to-surgery interval did not significantly affect the incidence of postoperative ONFH.
Asunto(s)
Fracturas del Fémur/complicaciones , Necrosis de la Cabeza Femoral/epidemiología , Adolescente , Adulto , Factores de Edad , Fracturas del Fémur/cirugía , Necrosis de la Cabeza Femoral/etiología , Fijación de Fractura , Humanos , Persona de Mediana Edad , Factores de Tiempo , Adulto JovenRESUMEN
To observe the effect and mechanism of Yiqi Tongluo Jiedu capsule aganist cerebral ischemia reperfusion injury, the SD rats were randomly divided into following groups: sham-operated group, model group, the group of low, medium and high dose of Yiqi Tongluo Jiedu capsule, and nimodipine group. Using focal middle cerebral artery embolization (MCAO) model, following items were observed: symptoms of neurological deficit score; infarct volume; activity of SOD, content of MDA and NO, activity of NOS of ischemic brain tissue; Bcl-2 and Bax protein expression; content of IL-1beta, IL-6 and TNFalpha in serum; IL-1beta mRNA expression of ischemic brain tissue. Results showed that Yiqi Tongluo Jiedu capsule could significantly reduce the symptoms of neurological deficits, promote the recovery symptoms of neurological deficits; narrow infarct volume of brain tissue obviously, reduce the percentage of infarct volume; raise activity of SOD, reduce content of MDA and NO, reduce activity of NOS; increase Bcl-2 protein, reduce Bax expression; reduce content of IL-1beta, IL-6 and TNFa in serum; reduce IL-1beta mRNA expression of ischemic brain tissue. Yiqi Tongluo Jiedu capsule has significant protective effects against ischemic brain injury, it has significant anti-apoptotic, antioxidant and anti-inflammatory effects.
Asunto(s)
Encéfalo , Medicamentos Herbarios Chinos/farmacología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Animales , Encéfalo/metabolismo , Encéfalo/patología , Cápsulas , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Infarto de la Arteria Cerebral Media/patología , Interleucina-1beta/sangre , Interleucina-1beta/genética , Interleucina-6/sangre , Masculino , Malondialdehído/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Plantas Medicinales/química , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/sangre , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Proteína X Asociada a bcl-2/metabolismoRESUMEN
UNLABELLED: The aim of this study was to evaluate the risk factors of mild cognitive impairment (MCI) in middle-aged patients with type 2 diabetes (T2DM). METHODS: Montreal Cognitive Assessment (MoCA) was applied as cognition assessment implement. One hundred and fifty-seven middle-aged type 2 diabetic patients were enrolled in this cross-section study (age 40~69, mean age 55 ± 7). There were 93 patients with MCI (MoCA score<26) in MCI group and 64 with normal cognitive function (MoCA score ≥ 26) in control group. Information of history of disease, family history, data of BMI, WHR, HbA1c, FINS, C-Peptide (C-P), SBP, DBP, blood lipid (TG, TC, LDL-C, HDL-C and carotid ultrasound (carotid IMT, carotid resistance index [RI]) was collected. RESULTS: There were significant differences in the rate of patients with hypertension ([40.63 vs. 58.06%], P=0.026), duration of diabetes mellitus ([3.09 ± 4.04 y vs. 4.80 ± 4.94 y], P=0.024), C-P ([2.79 ± 1.09 ng/ml vs. 2.26 ± 1.00 ng/ml], P=0.008), Max C-IMT ([0.81 ± 0.15 mm vs. 0.91 ± 0.15 mm], P<0.001), Min C-RI (0.71 ± 0.06 vs. 0.68 ± 0.06, P<0.05), and no significant differences in the duration of hypertension and hyperlipidemia, BMI, WHR, HbA1c, SBP, DBP and blood lipid between control group and MCI group. MoCA scores were positively correlated with C-P (r=0.252, P=0.005), and negatively correlated with the history of hypertension (r=-0.244, P=0.002), duration of DM (r=-0.161, P=0.044), Max C-IMT (r=-0.253, P=0.005) and Min C-RI (r=-0.183, P=0.023). Multiple regression analysis showed that history of hypertension (Beta=-0.267, P=0.002), C-P (Beta=0.281, P=0.001) and Min C-RI (Beta=-0.221, P=0.011) were significantly independent determinants for the MoCA scores. CONCLUSIONS: The longer duration of diabetes, history of hypertension, lower serum C-P levels, thickened C-IMT and higher C-RI could be risk factors of MCI in type 2 diabetic patients. This finding could have an important impact on the management of cognitive decline in diabetic patients.