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1.
Med Clin (Barc) ; 2020 Mar 17.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32197859

RESUMO

Ventilator-associated pneumonia (VAP) is a major complication among critically ill patients who depend on mechanical ventilation. Few reports have focused on intracerebral hemorrhage patients with VAP. Our main objective was to investigate the bacteria distribution characteristics and the impact of ventilator-associated pneumonia mortality in critical cerebral hemorrhage patients. This retrospective study included 89 cases of cerebral hemorrhage patients with VAP admitted to the ICU of Huashan Hospital. We used the chi-square test to compare qualitative variables and Student's t-test to compare means between groups of normally distributed quantitative variables. Multiple logistic regression analysis was used to assess mortality-independent predictors in the ICU. A total of 42% patients with cerebral hemorrhage were diagnosed with VAP in the ICU during the study period, and the mortality rate was 18%. Acinetobacter baumannii (n=58), Klebsiella pneumoniae (n=52), and Pseudomonas aeruginosa (n=21) were the most common pathogenic bacteria. Blood volume >30ml, tracheal ventilation mode and head of bed elevation were independent factors associated with increased mortality. Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the time from bleeding to intubation were other potentially important factors. While the number of infecting bacteria may not be directly related to death, it can increase antibiotic consumption and length of intensive care unit (ICU) stays. Blood volume >30ml, tracheal ventilation mode and head of bed elevation were directly related to the death of critical cerebral hemorrhage patients with ventilator-associated pneumonia.

2.
Int J Biol Macromol ; 151: 576-583, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32061692

RESUMO

Three polysaccharides of uniform molecular weight designated as SJP1-1, SJP2-1, and SJP3-1 from Smilacina japonica were studied in this paper. Respectively, their specific optical rotations were -45°, -75°, and -35°, their polysaccharide contents were 89.22%, 93.05%, and 59.83%, their relative average molecular weights were 1.87 × 105 Da, 1.04 × 105 Da, and 1.36 × 104 Da. Three polysaccharides were all composed mainly of the three monosaccharides mannose, glucose, and galactose, which together in SJP1-1, SJP2-1, and SJP3-1 respectively made up 96.34%, 98.23%, and 91.67% of the total polysaccharide. The polysaccharide structure was maintained mostly by ß-glucose (1 → 3), ß-glucose (1 → 4), α-mannose (1 → 3), and α-galactose (1 → 4) glycosidic linkages. Scanning electron microscopy showed that SJP1-1, SJP2-1, and SJP3-1 were smooth uniform microspheres with diameters of 10-20 µm that combined to form both uniformly dispersed particles and blocky structures. Finally, antioxidant assay showed that these polysaccharides all had a strong ability to scavenge ·OH and DPPH· radicals, with the effects of purified polysaccharides being greater than those of crude polysaccharides. This first report on the properties of these polysaccharides provides a basis for further studies to shed light on the medical properties of Smilacina japonica.

3.
Medicine (Baltimore) ; 99(5): e19002, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000441

RESUMO

Laparoscopic gastrectomy (LG) using intracorporeal anastomosis has recently become more prevalent due to the advancements of laparoscopic surgical instruments. However, intracorporeally hand-sewn anastomosis (IHSA) is still uncommon because of technical difficulties. In this study, we evaluated various types of IHSA following LG with respect to the technical aspects and postoperative outcomes.Seventy-six patients who underwent LG using IHSA for treatment of gastric cancer between September 2014 and June 2018 were enrolled in this study. We described the details of IHSA in step-by-step manner, evaluated the clinicopathological data and surgical outcomes, and summarized the clinical experiences.Four types of IHSA have been described: one for total gastrectomy (Roux-en-Y) and 3 for distal gastrectomy (Roux-en-Y, Billroth I, and Billroth II). The mean operation time and anastomotic time was 288.7 minutes and 54.3 minutes, respectively. Postoperative complications were observed in 13 patients. All of the patients recovered well with conservative surgical management. There was no case of conversion to open surgery, anastomotic leakage, or mortality.LG using IHSA was safe and feasible and had several advantages compared to mechanical anastomosis. The technique lengthened operating time, but this could be mitigated by increased surgical training and experience.


Assuntos
Anastomose Cirúrgica/métodos , Gastrectomia/métodos , Derivação Gástrica/métodos , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Duração da Cirurgia , Complicações Pós-Operatórias , Neoplasias Gástricas/patologia
4.
Drug Des Devel Ther ; 14: 285-296, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021111

RESUMO

Ivermectin, a dihydro derivative of avermectin (AVM), was introduced into the veterinary, agricultural and aquaculture markets for animal health in 1981. Ivermectin was soon adopted in 1987 as a human medicine that was originally used for the treatment of onchocerciasis, a parasitic infection. Since then, ivermectin has also been used to control other human diseases and has exerted a significant effect on human health and welfare. In the past decade, many published studies have attempted to determine the role of ivermectin in cancer. In this review, we summarize the published studies to define the current progress in the characterization of ivermectin. Ivermectin causes cell death in cancer cell lines by inducing PAK1-mediated cytostatic autophagy, caspase-dependent apoptosis and immunogenic cell death (ICD) through the modulation of some pathways, including the WNT-T cell factor (TCF), Hippo and Akt/mTOR pathways. Ivermectin can affect the growth and proliferation of cancer cells and plays several different roles, such as its functions as an RNA helicase, a small-molecule mimetic of the surface-induced dissociation (SID) peptide, an activator of chloride channel receptors, and an inducer of mitochondrial dysfunction and oxidative stress. In addition, ivermectin induces the multidrug resistance protein (MDR), has potent anti-mitotic activity, targets angiogenesis and inhibits cancer stem-like cells (CSCs). Many studies have proven that ivermectin exerts antitumour effects and might thus benefit patients with cancer after sufficient clinical trials.

5.
Adv Mater ; : e1905295, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32077160

RESUMO

Developing advanced high-rate electrode materials has been a crucial aspect for next-generation lithium ion batteries (LIBs). A conventional nanoarchitecturing strategy is suggested to improve the rate performance of materials but inevitably brings about compromise in volumetric energy density, cost, safety, and so on. Here, micro-size Nb14 W3 O44 is synthesized as a durable high-rate anode material based on a facile and scalable solution combustion method. Aberration-corrected scanning transmission electron microscopy reveals the existence of open and interconnected tunnels in the highly crystalline Nb14 W3 O44 , which ensures facile Li+ diffusion even within micro-size particles. In situ high-energy synchrotron XRD and XANES combined with Raman spectroscopy and computational simulations clearly reveal a single-phase solid-solution reaction with reversible cationic redox process occurring in the NWO framework due to the low-barrier Li+ intercalation. Therefore, the micro-size Nb14 W3 O44 exhibits durable and ultrahigh rate capability, i.e., ≈130 mAh g-1 at 10 C, after 4000 cycles. Most importantly, the micro-size Nb14 W3 O44 anode proves its highest practical applicability by the fabrication of a full cell incorporating with a high-safety LiFePO4 cathode. Such a battery shows a long calendar life of over 1000 cycles and an enhanced thermal stability, which is superior than the current commercial anodes such as Li4 Ti5 O12 .

6.
Hepatology ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31903610

RESUMO

Transforming growth factor beta (TGF-ß) suppresses early stages of tumorigenesis, but contributes to migration and metastasis of cancer cells. However, the role of TGF-ß signaling in invasive prometastatic hepatocellular carcinoma (HCC) is poorly understood. In this study, we investigated the roles of canonical TGF-ß/SMAD3 signaling and identified downstream effectors on HCC migration and metastasis. By using in vitro trans-well migration and invasion assays and in vivo metastasis models, we demonstrated that SMAD3 and Protein Tyrosine Phosphatase Receptor Epsilon (PTPRε) promotes migration, invasion and metastasis of HCC cells in vitro and in vivo. Further mechanistic studies revealed that, upon TGF-ß stimulation, SMAD3 binds directly to PTPRε promoters to activate its expression. PTPRε interacts with TGFBR1/SMAD3 and facilitates recruitment of SMAD3 to TGFBR1, resulting a sustained SMAD3 activation status. The tyrosine phosphatase activity of PTPRε is important for binding with TGFBR1, recruitment and activation of SMAD3, and its prometastatic role in vitro. A positive correlation between pSMAD3/SMAD3 and PTPRε expression were determined in HCC samples, and high expression of SMAD3 or PTPRε was associated with poor prognosis of HCC patients. Conclusion PTPRε positively feedback regulates TGF-ß/SMAD3 signaling to promote HCC metastasis.

7.
Chemistry ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919969

RESUMO

Controlled synthesis of metal-organic framework (MOF)-based materials with multiple levels of porous structures across different length scales is of great interest in various applications but it still remains challenging. Most of the current strategies are time consuming and labor intensive, and not readily scaled-up. In this work, we introduce a straightforward one-pot fabrication strategy to prepare a robust and flexible hierarchically macro-meso-micro porous HKUST-1/polyvinylidene fluoride (PVDF) composite through solvent evaporation, in which MOF crystallization and polymer precipitation are combined together. The effect of the MOF precursor and the polymer initial amount on the morphology of the final composite was thoroughly studied. The interaction between the MOF and the polymer during the evaporation process is the key factor, which would limit the mobility of the polymer chains and cause instability in the MOF growth, thus endowing the composite with a hierarchically macro-meso-micro porous structure. This "all-in-one" porous structure could enhance the mass transport property of molecules within the composite. The obtained HKUST-1/PVDF composite showed an enhanced CO2 adsorption rate constant of 0.821 min-1 (298 K, 1 bar), which was 3.5 times higher than that of the pristine MOF. In addition, the composite showed an equivalent gas adsorption capacity under all tested pressures and greatly improved water stability.

8.
Nat Commun ; 11(1): 132, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919355

RESUMO

Exploring advanced battery materials with fast charging/discharging capability is of great significance to the development of modern electric transportation. Herein we report a powerful synergistic engineering of carbon and deficiency to construct high-quality three/two-dimensional cross-linked Ti2Nb10O29-x@C composites at primary grain level with conformal and thickness-adjustable boundary carbon. Such exquisite boundary architecture is demonstrated to be capable of regulating the mechanical stress and concentration of oxygen deficiency for desired performance. Consequently, significantly improved electronic conductivity and enlarged lithium ion diffusion path, shortened activation process and better structural stability are realized in the designed Ti2Nb10O29-x@C composites. The optimized Ti2Nb10O29-x@C composite electrode shows fast charging/discharging capability with a high capacity of 197 mA h g-1 at 20 C (∼3 min) and excellent long-term durability with 98.7% electron and Li capacity retention over 500 cycles. Most importantly, the greatest applicability of our approach has been demonstrated by various other metal oxides, with tunable morphology, structure and composition.

9.
J Pharm Biomed Anal ; 179: 112974, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31767224

RESUMO

Cicadae Periostracum, which is derived from the slough of Cicadidae insects, is a commonly used crude drug in traditional Chinese medicine (TCM). As specified in Chinese Pharmacopoeia, Cryptotympana atrata (CA) is the only official species of this crude drug. However, the slough of other three species, i.e., Auritibicen flammatus (AF), Cryptotympana mandrina (CM) and Platypleura kaempferi (PK), have been also used as the origins of Cicadae Periostracum in Chinese herbal market, although whether the quality of these four origins is consistent or not is still unknown. In present study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was employed to qualitatively and quantitatively compare the chemical profiles of the four origins. Totally, 34 N-acetyldopamine polymers were identified from the four origins, including 4 N-acetyldopamine dimers, 11 N-acetyldopamine trimers, 10 N-acetyldopamine tetramers, and 9 N-acetyldopamine pentamers. AF, CM and PK had similar chemical profiles with that of CA. The contents and compositional ratio of the four types of polymers in CA, AF and CM were consistent with each other, but significantly lower or different in PK. All these results suggested that AF and CM might be considered as the potential resources of Cicadae Periostracum concerning their consistent holistic quality, whereas whether PK could be used as potential origin of Cicadae Periostracum or not need further evaluation for their different compositional ratios and contents of the four types of N-acetyldopamine polymers. This is the first study on chemical profiling and comparison of N-acetyldopamine polymers in four origins of Cicadae Periostracum, which is beneficial for potential resources utilization and quality standard improvement of Cicadae Periostracum.

10.
J Photochem Photobiol B ; 202: 111671, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731076

RESUMO

As a molecular chaperone, ß-casein is difficult to form amyloid fibrils under physiological conditions due to its chaperone activity. Heparan sulfate (HS) has drawn attention of technologists all over the word because of its relation to amyloid deposits in some amyloidosis diseases. For better understanding the relationship between the ß-casein and HS, the multi-spectroscopic studies were employed. The data of thioflavin T (ThT) binding assay, transmission electron microscopy (TEM) and circular dichroism (CD) demonstrated that HS promoted fibril formation by ß-casein in the amount and the growth speed. The results of steady-state UV-vis absorption spectra, fluorescence spectroscopy and fluorescence lifetime revealed that the ß-casein-HS complexes were formed and HS quenched the fluorescence of ß-casein by a static quenching mechanism. On the basis of fluorescence analysis, the value of binding constant was equal to 1.17 × 107 L mol-1 at 338.15 K and there was about one binding site between them. According to thermodynamic parameters obtained, it was deduced that a spontaneous reaction happened, and protein-ligand complex was stabilized by hydrogen bonds and hydrophobic interaction. Furthermore, using fluorescence resonance energy transfer (FRET) assay, the value of binding distance between HS and Trp143 of ß-casein was calculated to be 0.93 nm. Finally, on the basis of synchronous fluorescence experiment, the polarity increasing and hydrophobicity decreasing around Trp143 occurred during the period of fibril formation by ß-casein.


Assuntos
Amiloide/metabolismo , Caseínas/química , Heparitina Sulfato/química , Amiloide/química , Animais , Sítios de Ligação , Caseínas/metabolismo , Bovinos , Dicroísmo Circular , Transferência Ressonante de Energia de Fluorescência , Heparitina Sulfato/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Transmissão , Ligação Proteica , Termodinâmica
11.
Br J Radiol ; 93(1105): 20190240, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31651188

RESUMO

OBJECTIVE: To compare the participation rate between CT colonography (CTC) and colonoscopy in screening population in randomized controlled trials (RCTs). METHODS: A search was performed using the PubMed, Web of Science, and Cochrane databases. RCTs that included screening populations and reported participation number were assessed. Cochrane risk of bias tool was used to assess the bias and quality. Risk ratio (RR) was used to present the results. The non-participation rate was analyzed to verify the results of participation rate. RESULTS: Five of 760 studies, with a total of 15,974 invitees, were included. The participation rate was higher at CTC (28.8%) than colonoscopy (20.8%), although the difference did not reach statistical significance (RR = 1.26; p = 0.070; I2 = 90.3%). The non-participation rate at CTC was significantly lower than colonoscopy (RR = 0.92; p = 0.012; I2 = 86.7%). Subgroup analysis suggested both the participation and non-participation rate were with significant difference between reduced/no cathartic preparation CTC and colonoscopy. Cumulative meta-analysis showed both the participation rate and non-participation rate exhibited a trend over time and sample size. CONCLUSION: The participation rate was higher at CTC than colonoscopy, although the difference did not reach statistical significance. But the non-participation rate was with statistical difference. Screening population seemed more likely to participate the reduced/no cathartic preparation CTC. Statistical evidence was provided for more large RCTs are needed in the future. ADVANCES IN KNOWLEDGE: The screening populations seem more likely to participate in the CTC, especially the reduced/no cathartic preparation CTC. The statistical evidence was provided for more large RCTs are needed in the future.


Assuntos
Colonografia Tomográfica Computadorizada/estatística & dados numéricos , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico por imagem , Programas de Rastreamento/métodos , Participação do Paciente/estatística & dados numéricos , Detecção Precoce de Câncer , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
J Nanosci Nanotechnol ; 20(4): 2138-2143, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492222

RESUMO

With the higher and higher application level of medical technology, more and more genetic diseases have been diagnosed. Nucleic acid, as an important genetic material, has been found to have important functions in the storage and transmission of the genetic information in the replication and synthesis of proteins. As the first step in nucleic acid detection experiments, nucleic acid extraction performance is associated with the purity of target nucleic acid samples, which is very important for the downstream steps. In this paper, we employed the magnetic bead for extracting nucleic acids based on the platform of large liquid handling workstation and designed a matching magnetic separation module. It was shown that the temperature control block designed in this paper has reliable stability, high accuracy by using the incremental PID algorithm, with the control accuracy up to ±0.5 °C, and the control stabilization time is about 90 s, which can satisfy the experimental requirements. Besides, the average magnetic bead transfer rate of this module was further verified by mimicking the manual magnetic bead nucleic acid extraction process. The results proved that the module has an excellent performance with the average magnetic bead transfer rate greater than 95% and the magnetic bead transfer rate in each well greater than 90%, which could be consistent with the experimental indictors of nucleic acid extraction.

13.
J Nanosci Nanotechnol ; 20(4): 2165-2170, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492225

RESUMO

The high-throughput nucleic acid detection system provides a good solution for detecting nucleic acids more safely, rapidly and accurately, which greatly improves the detection efficiency. Highthroughput nucleic acid detection mainly includes three steps: signal acquisition, signal amplification and signal processing. Therefore, obtaining the purified nucleic acid is the primary task of the nucleic acid detection, and the quality of the nucleic acid has a significant impact on results. In this paper, we employed the magnetic nanoparticle technology for extracting nucleic acids based on the platform of large liquid handling workstation and designed a matching vibrating module. The involved steps of core method, magnetic bead nucleic acid extraction technology, are mainly concerned with the cell lysis, nucleic acid binding, nucleic acid purification and magnetic particles elution. During the extraction process, specific temperature is required for the lysis and elution. It was shown that the temperature control part designed in this paper has the reliable stability, high accuracy by using the incremental proportion-integration-differentiation (PID) algorithm, with the control accuracy up to ±0.5 °C. The temperature regulating time is about 90 s, which can meet the experimental requirements. Besides, the vibrating uniformity of this module was further verified by protein concentration test, which proved that the module has the excellent performance and can be consistent with the experimental indictors of the nucleic acid extraction.

14.
J Nanosci Nanotechnol ; 20(3): 1401-1408, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492300

RESUMO

In the automated high-throughput nucleic acid detection system, we need to grip and transfer consumables frequently when carrying out multichannel nucleic acid detection. In order to ensure the efficiency of experiments and solve problems of the deflection and drop when transferring microplates, we design a self-locking mechanical gripper which consists of a rotary positioning module and a gripping module. The absolute position encoder fixed on the top of the stepper motor can collect the position data of the mechanical gripper in real time and send them to the master control board based on STM32 for processing, which ensures the accuracy of the movement of the mechanical gripper. We used SolidWorks to build models of the mechanical gripper and different microplates, and we carried on finite element analysis of microplates to find the suitable gripping position. Through the force analysis, we obtained the pressure distribution and the deformation of different microplates, and defined the effective gripping areas, which is important to the grip and transfer of microplates.

15.
Prep Biochem Biotechnol ; : 1-8, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31799894

RESUMO

Targeting the interaction interface is an effective strategy to obtain programmed death receptor 1 (PD-1)/PD-1 ligand 1 (PD-L1) nanobody blockers. To validate this strategy, the interaction interface between PD-1 and the PD-L1 extracellular domain were analyzed using Cn3D 4.1. The peptide PD-1125-136 located at the interface of PD-1 was selected as the antigen to screen nanobodies from a humanized nanobody phage display library. Six different nanobodies were screened, with molecular weights of 12 ∼ 13 kDa, excluding a single basic protein. The nanobody with the longest CDR3 region, termed PD-1-Nb-B20, was selected for further analysis. For mass production, the C-terminal His6-tagged nanobody coding sequence was optimized and cloned into pET-21b for over-expression under the T7 promoter in Escherichia coli BL21 (DE3). PD-1-Nb-B20 was expressed and pancreatic adenocarcinoma cells BxPC-3 over-expressing PD-L1 were selected for nanobody competitive inhibition assays. The purified nanobodies significantly inhibited PD-1 binding to the surface of target cells, indicating their ability to block the PD-1/PD-L1 interaction.

16.
Huan Jing Ke Xue ; 40(12): 5265-5271, 2019 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854597

RESUMO

To study the pollution characteristics and exposure health risk of perfluoroalkyl substances (PFASs) in road dust, 12 PFASs were analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) in this study. PFAS concentrations in road dust ranged from 0.95 to 111 ng·g-1, with an average concentration of (25.6±37.2) ng·g-1, suggesting large spatial differences between PFASs in road dust. PFAS concentrations on the main roads were significantly higher than on minor roads, and the minor roads downtown displayed higher concentration levels than suburban minor roads. Perfluorobutanoic acid (PFBA) was the predominant compound in Section 1 of Jie-fang Road, Jin-niu-ba Road and Shui-nian-he Road, while perfluroroocantanoic acid (PFOA, 24.8%) and perfluorooctane sulfonate (PFOS, 24.1%) were the main PFASs on other roads, indicating different sources of PFASs in these areas. The total daily dose of PFASs in road dust for children and adults were 0.168 ng·(kg·d)-1 and 0.028 ng·(kg·d)-1, respectively, suggesting higher exposure risk for children than adults. Therefore, more attention should be paid to children's health risk assessment. Daily doses of PFOA and PFOS in road dust for Chengdu residents were lower than the maximum daily intakes recommended by the European Authority, indicating that there was no immediate health risk to local residents.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Medição de Risco , Adulto , Criança , Cromatografia Líquida , Poeira , Humanos , Espectrometria de Massas em Tandem
17.
Front Behav Neurosci ; 13: 239, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31680895

RESUMO

Tourette syndrome (TS), a developmental neurobehavioral disorder, is characterized by involuntary behavioral stereotypies. Clinical studies have confirmed the positive effect of acupuncture on treating TS, but the underlying mechanisms are not fully understood. In the present study, we used behavioral tests, Western blotting, double-immunofluorescence labeling, and fluorescence spectrophotometry to investigate whether acupuncture performed at acupoints "Baihui" (GV20) and "Yintang" (GV29) affected behavioral stereotypies and regulated the dopamine (DA) system in three different brain regions in Balb/c mice injected with 3,3'-iminodipropionitrile (IDPN) as a model for TS. We found that acupuncture alleviated behavioral stereotypies, down-regulated the expression of D1R and D2R in the striatum (STR) and substantia nigra pars compacta (SNpc), and decreased the concentration of DA in the STR, SNpc, and prefrontal cortex (PFC) as well. Moreover, acupuncture reduced the expression of tyrosine hydroxylase (TH) in the SNpc. Conclusively, acupuncture ameliorated behavioral stereotypies by regulating the DA system in the STR, SNpc, and PFC. Our findings provide novel evidence for the therapeutic effect of acupuncture on TS.

18.
Aging (Albany NY) ; 11(21): 9556-9568, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31682592

RESUMO

Dexmedetomidine is known to alleviate cerebral ischemia-reperfusion injury (CIRI). We established a rat model of CIRI, which exhibited higher neurological deficit scores and a greater number of apoptotic cells in the cerebral ischemic penumbra than controls. Dexmedetomidine reversed the neuronal apoptosis and improved neurological function in this model. We then examined Sigma-1 receptor (Sig-1R) expression on the endoplasmic reticulum (ER) in brain tissues at different reperfusion time points. Sig-1R expression increased with CIRI and decreased with increasing reperfusion times. After 24 hours of reperfusion, dexmedetomidine upregulated Sig-1R expression, and ER stress proteins (GRP78, CHOP, JNK and Caspase-3) were detected in brain tissues with Western blotting. Moreover, GRP78 expression followed a pattern similar to Sig-1R. Dexmedetomidine induced GRP78 expression but inhibited CHOP, Caspase-3 and phosphorylated-JNK expression in brain tissues. A Sig-1R-specific inhibitor reduced GRP78 expression and partially inhibited the upregulation of GRP78 by dexmedetomidine. The inhibitor also increased CHOP and Caspase-3 expression and partially reversed the inhibitory effects of dexmedetomidine on these pro-apoptotic ER stress proteins. These results suggest that dexmedetomidine at least partially inhibits ER stress-induced apoptosis by activating Sig-1R, thereby attenuating brain damage after 24 hours of ischemia-reperfusion.

19.
BMC Urol ; 19(1): 107, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684917

RESUMO

BACKGROUND: To report a new standardized cognitive fusion technique on transperineal targeted biopsy (TB) of prostate, and to evaluate its efficacy for cancer detection combined with systematic biopsy (SB) . METHODS: We present a retrospective review of consecutive patients undergoing multiparametric magnetic resonance (mpMRI) imaging of the prostate with subsequent transperineal prostate biopsy from January 2016 to December 2018. A free-hand 12-core SB was performed for each patient. PI-RADS 3-5 lesions were further targeted for biopsy with our TB technique. Firstly, a central point of suspicious lesion (B') was registered cognitively on a transverse section of transrectal ultrasound (TRUS). Then, biopsy gun punctured vertically through a fixed pioneer site (A) on skin of perineum, and deep into the TRUS section to get A'. Next, targeted site (B), the surface-projection of B', would be determined on skin of perineum by A and distance from B' to A'. Finally, puncture through B to reach B'. Pathological findings of SB and TB were analyzed. RESULTS: A total of 126 patients underwent transperineal prostate biopsy (47 SB only, 79 SB + TB). The age of the patients was 68.7 ± 9.2 years. The median preoperative PSA value was 11.8 ng/mL. Preoperative prostate volume was 60.5 ± 50.0 mL. The numbers of patients with PI-RADS scores of 1 through 5 were 4, 43, 27, 21 and 31, respectively. The overall detection rate of cancer was 61/126 (48.4%), and it was significantly higher in the combination cohort (56/79, 70.9%) compared with the SB only cohort (5/47, 10.6%, p<0.001). When focused on the combination cohort, TB detected a similar overall rate of PCa (53/79, 67.1% vs 52/79, 65.8%; p = 0.87) compared with SB. The clinically significant PCa (csPC) detection rate was 52/79 (65.8%), while for TB and SB the csPC/PC rate was 51/53 (96.2%) and 48/52 (92.3%), respectively(p = 0.44). TB demonstrated a better sampling performance (positive rate for each core) compared with SB (51.0% vs 31.3%, p < 0.001). CONCLUSIONS: Surface-projection-based transperineal cognitive fusion targeted biopsy of the prostate has a good efficacy in detecting PCa.

20.
Cell Death Dis ; 10(12): 892, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31767832

RESUMO

Type 1 diabetes (T1D) is characterized by the selective autoimmune destruction of the islet ß cells, and macrophages play a significant role in this process. Small ubiquitin-like modification (SUMOylation) is an important posttranslational modification involved in T1D pathogenesis, but its function in macrophages remains unexplored. We presently developed and used macrophage-specific ubiquitin-conjugating enzyme E2 (Ubc9) knockout (LyzM-Cre-Ubc9fl/fl, KO) mice to address the impact of SUMOylation on macrophage function in a T1D model. We observed that blocking Ubc9 in macrophages exacerbated multiple-low dose streptozotocin (MLD-STZ)-induced diabetes. Specifically, after STZ treatment, blood glucose levels were consistently elevated in the KO mice. The KO mice exhibited a higher diabetes incidence than WT controls (85% vs. 55%, P < 0.01) along with a higher insulitis severity. The loss of Ubc9 impaired macrophage energy metabolism and attenuated macrophage M2 program, thereby enhancing T cell activation. Pancreas-resident macrophages, rather than migrant macrophages, played a predominant role in MLD-STZ-induced diabetes. Mechanistically, Ubc9-mediated SUMOylation of interferon regulator factor 4 (IRF4) enhanced its nuclear localization and stability, thereby transcribing IL-4 and arginase 1 (Arg1) to promote the macrophage M2 program. Ubc9-mediated SUMOylation modulates T1D risk at least in part by regulating macrophage function. Modulation of disturbed SUMOylation process in macrophages, either through cell adoptive transfer or targeted drug-delivery, could help to establish a tolerant pancreatic microenvironment and promote inflammation resolution in early insulitis stage, thus hindering T1D progression.

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