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1.
J Med Case Rep ; 15(1): 265, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33975638

RESUMO

BACKGROUND: Primary lung cancer is one of the most frequently diagnosed cancers. The common metastatic sites are the liver, bones, brain, adrenal glands and central nervous system. However, gastrointestinal metastases, particularly esophageal metastases, from lung cancer are rare. There are no cases of esophageal metastases from lung cancer which refer to its particular treatment. CASE PRESENTATION: We report a case of esophageal metastases from lung cancer. The patient was a 55-year-old Han Chinese man who first attended our hospital due to dry cough and was diagnosed with late-stage lung cancer. Three months later, the patient complained of dysphagia. Endoscopic ultrasonography (EUS) and pathological examination of the biopsy specimen was performed to confirm the lesion was metastases from lung cancer. Thyroid transcription factor 1 (TTF-1), cytokeratin 7 (CK-7) and napsin A were positive by immunohistochemistry examination. These results reconfirmed the diagnosis of esophageal metastases from lung cancer. CONCLUSIONS: Esophageal metastasis from lung cancer is very rare. It may be alleviated with personalized chemotherapy. In addition, molecular targeted therapy for patients with epidermal growth factor receptor (EGFR) mutations may be reasonable.

2.
Biomater Sci ; 9(9): 3445-3452, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33949456

RESUMO

Multidrug resistance (MDR) is one of the prime reasons for the failure of cancer chemotherapy, which continues to be a great challenge to be solved. In this work, α-tocopherol succinate (α-TOS) and doxorubicin (DOX)-based self-delivery nanomedicine (designated as α-TD) is prepared to combat drug resistance for cancer synergistic chemotherapy. Carrier-free α-TD possesses a fairly high drug loading rate and improves the cellular uptake via the endocytosis pathway. More importantly, the apoptotic inducer α-TOS could elevate the reactive oxygen species (ROS) generation, disrupt mitochondrial function and reduce adenosine 5'-triphosphate (ATP) production, which facilitate the intracellular drug retention while decreasing its efflux. As a result, α-TD achieves a considerable synergistic chemotherapeutic effect against drug resistant cancer cells. Moreover, it also exhibits a preferable inhibitory effect on tumor growth with a low system toxicity in vivo. This synergistic drug self-delivery strategy would open a new window for developing carrier-free nanomedicine for overcoming drug resistance in cancer therapy.

3.
Environ Sci Technol ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955214

RESUMO

In this work, the commercial selective catalytic reduction (SCR) catalyst V2O5-MoO3/TiO2 was sulfureted with H2S to improve both its capability for elemental mercury (Hg0) removal at low temperatures and its resistance to SO2 and H2O. Hg0 removal over both V2O5-MoO3/TiO2 and sulfureted V2O5-MoO3/TiO2 involved the catalytic oxidation of Hg0 to HgCl2 and the chemical adsorption of gaseous Hg0; therefore, the effect of sulfuration on Hg0 chemical adsorption and the catalytic oxidation of Hg0 to HgCl2 over V2O5-MoO3/TiO2 and its resistance to SO2 and H2O were investigated using Hg balance analysis. Kinetic analysis showed that the rates of the chemical adsorption and oxidation of Hg0 were both in direct proportion to the concentration of physically adsorbed Hg0. The physical adsorption of gaseous Hg0 on V2O5-MoO3/TiO2 was remarkably promoted after sulfuration, and the physical adsorption of gaseous Hg0 over sulfureted V2O5-MoO3/TiO2 was scarcely inhibited by SO2 and H2O. Therefore, the performance of V2O5-MoO3/TiO2 for Hg0 removal and its resistance to SO2 and H2O were both improved after sulfuration. Even more remarkably, sulfureted V2O5-MoO3/TiO2 can adsorb gaseous HgCl2, which resulted from Hg0 oxidation. Therefore, sulfureted V2O5-MoO3/TiO2 showed an excellent performance to recover Hg0 from coal-fired power plants, which can then be converted to liquid Hg.

4.
Environ Sci Technol ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955737

RESUMO

Capturing gaseous Hg0 using regenerable metal sulfides is a promising technology to recover gaseous Hg0 from both coal-fired flue gas (CFG) and smelting flue gas (SFG) for the centralized control. Gaseous Hg0 concentration in SFG is 2-3 orders of magnitude higher than that in CFG; therefore, the design strategy of metal sulfides for capturing gaseous Hg0 from CFG is quite different from that from SGF. In this work, the structure-activity relationship of metal sulfides to capture Hg0 was investigated according to the remarkable difference in MoO3 loading on sulfureted FeTiOx to capture low/high concentrations of gaseous Hg0. The rate of Hg0 adsorption onto metal sulfides was mainly related to the amounts of adsorption sites and S22- on the surface, the affinity of adsorption sites to gaseous Hg0, and the gaseous Hg0 concentration. Meanwhile, the capacity for Hg0 adsorption was approximately equal to the less of the amount of adsorption sites and S22- on the surface. Furthermore, capturing low concentrations of gaseous Hg0 from CFG required the metal sulfide sorbents having more adsorption sites with strong affinity to gaseous Hg0, while capturing high concentrations of gaseous Hg0 from SFG required the sorbents with enough adsorption sites.

5.
Mol Psychiatry ; 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33963282

RESUMO

It is of great clinical importance to explore more efficacious treatments for OCD. Recently, cognitive-coping therapy (CCT), mainly focusing on recognizing and coping with a fear of negative events, has been reported as an efficacious psychotherapy. However, the underlying neurophysiological mechanism remains unknown. This study of 79 OCD patients collected Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after four weeks of CCT, pharmacotherapy plus CCT (pCCT), or pharmacotherapy. Amygdala seed-based functional connectivity (FC) analysis was performed. Compared post- to pretreatment, pCCT-treated patients showed decreased left amygdala (LA) FC with the right anterior cingulate gyrus (cluster 1) and with the left paracentral lobule/the parietal lobe (cluster 2), while CCT-treated patients showed decreased LA-FC with the left middle occipital gyrus/the left superior parietal/left inferior parietal (cluster 3). The z-values of LA-FC with the three clusters were significantly lower after pCCT or CCT than pretreatment in comparisons of covert vs. overt and of non-remission vs. remission patients, except the z-value of cluster 2 in covert OCD. CCT and pCCT significantly reduced the Y-BOCS score. The reduction in the Y-BOCS score was positively correlated with the z-value of cluster 1. Our findings demonstrate that both pCCT and CCT with large effect sizes lowered LA-FC, indicating that FCs were involved in OCD. Additionally, decreased LA-FC with the anterior cingulate cortex (ACC) or paracentral/parietal cortex may be a marker for pCCT response or a marker for distinguishing OCD subtypes. Decreased LA-FC with the parietal region may be a common pathway of pCCT and CCT. Trial registration: ChiCTR-IPC-15005969.

6.
IEEE Trans Cybern ; PP2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33961570

RESUMO

The rapid emergence of high-dimensional data in various areas has brought new challenges to current ensemble clustering research. To deal with the curse of dimensionality, recently considerable efforts in ensemble clustering have been made by means of different subspace-based techniques. However, besides the emphasis on subspaces, rather limited attention has been paid to the potential diversity in similarity/dissimilarity metrics. It remains a surprisingly open problem in ensemble clustering how to create and aggregate a large population of diversified metrics, and furthermore, how to jointly investigate the multilevel diversity in the large populations of metrics, subspaces, and clusters in a unified framework. To tackle this problem, this article proposes a novel multidiversified ensemble clustering approach. In particular, we create a large number of diversified metrics by randomizing a scaled exponential similarity kernel, which are then coupled with random subspaces to form a large set of metric-subspace pairs. Based on the similarity matrices derived from these metric-subspace pairs, an ensemble of diversified base clusterings can be thereby constructed. Furthermore, an entropy-based criterion is utilized to explore the cluster wise diversity in ensembles, based on which three specific ensemble clustering algorithms are presented by incorporating three types of consensus functions. Extensive experiments are conducted on 30 high-dimensional datasets, including 18 cancer gene expression datasets and 12 image/speech datasets, which demonstrate the superiority of our algorithms over the state of the art. The source code is available at https://github.com/huangdonghere/MDEC.

7.
ESC Heart Fail ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33931949

RESUMO

AIMS: Heart failure with preserved ejection fraction (HFpEF) develops in response to hypertensive left ventricular (LV) hypertrophy and is associated with increased cardiovascular events. Although the progression to systolic heart failure is a known consequence of LV hypertrophy and HFpEF, few data are available on the LV geometry change and frequency of deterioration to systolic dysfunction in this population. METHODS AND RESULTS: We evaluated the baseline and follow-up characteristics in 680 patients with LV hypertrophy and HFpEF in this prospective cohort study. The primary endpoint was 5 year all-cause mortality. The changes of LV geometry and heart failure transition were analysed. Systolic dysfunction [left ventricular ejection fraction (LVEF) < 50%] occurred in 182 patients (26.8%) during a 5 year follow-up. Patients with LVEF deterioration were associated with a lower survival rate. Beta-blocker prescription was a protective factor for preserved LVEF. And concentric LV geometry shifted to eccentric hypertrophy was uncommon (10.6%) during a 5 year follow-up. CONCLUSIONS: A quarter of patients with hypertensive LV hypertrophy and HFpEF progresses to systolic dysfunction during a 5 year follow-up, which was accompanied by poor clinical outcomes. And beta-blocker therapy might play a protective role for preserved LVEF in this population.

8.
Phys Rev Lett ; 126(15): 155701, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33929239

RESUMO

The layered crystal of EuSn_{2}As_{2} has a Bi_{2}Te_{3}-type structure in rhombohedral (R3[over ¯]m) symmetry and has been confirmed to be an intrinsic magnetic topological insulator at ambient conditions. Combining ab initio calculations and in situ x-ray diffraction measurements, we identify a new monoclinic EuSn_{2}As_{2} structure in C2/m symmetry above ∼14 GPa. It has a three-dimensional network made up of honeycomblike Sn sheets and zigzag As chains, transformed from the layered EuSn_{2}As_{2} via a two-stage reconstruction mechanism with the connecting of Sn-Sn and As-As atoms successively between the buckled SnAs layers. Its dynamic structural stability has been verified by phonon mode analysis. Electrical resistance measurements reveal an insulator-metal-superconductor transition at low temperature around 5 and 15 GPa, respectively, according to the structural conversion, and the superconductivity with a T_{C} value of ∼4 K is observed up to 30.8 GPa. These results establish a high-pressure EuSn_{2}As_{2} phase with intriguing structural and electronic properties and expand our understandings about the layered magnetic topological insulators.

9.
Chem Commun (Camb) ; 57(32): 3929-3932, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33871531

RESUMO

In this paper, we developed a rhodium-catalyzed annulation of vinylene carbonate with amidines, leading to 4-methylquinazolines with moderate to excellent yields. This procedure proceeded by sequential ortho-acylation and annulation, where vinylene carbonate served as the acetylation reagent rather than the ethyne surrogate.

10.
Chem Commun (Camb) ; 57(34): 4134-4137, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33908446

RESUMO

A porphysome-based photodynamic O2 economizer (P-PAT) is prepared for hypoxic tumor therapy. The self-assembled porphyrin bilayers of P-PAT possess high loading capacity to atovaquone (ATO) (nearly 70%), which could restrain mitochondrial respiration to relieve hypoxia and enhance photodynamic therapy.

11.
BMC Vet Res ; 17(1): 159, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33853603

RESUMO

BACKGROUND: Immunoglobulins (Igs) distributed among systemic immune tissues and mucosal immune tissues play important roles in protecting teleosts from infections in the pathogen-rich aquatic environment. Teleost IgZ/IgT subclasses with different tissue expression patterns may have different immune functions. RESULTS: In the present study, a novel secreted IgZ heavy chain gene was cloned and characterized in common carp (Cyprinus carpio). This gene exhibited a different tissue-specific expression profile than the reported genes IgZ1 and IgZ2. The obtained IgZ-like subclass gene designated CcIgZ3, had a complete open reading frame contained 1650 bp encoding a protein of 549 amino acid residues. Phylogenetic analysis revealed that CcIgZ3 was grouped with carp IgZ2 and was in the same branch as IgZ/IgT genes of other teleosts. Basal expression detection of the immunoglobulin heavy chain (IgH) in healthy adult common carp showed that CcIgZ3 transcripts were widely expressed in systemic immune tissues and mucosal-associated lymphoid tissues. CcIgZ3 was expressed at the highest levels in the head kidneys, gills, and gonads, followed by the spleen, hindgut, oral epithelium, liver, brain, muscle, foregut, and blood; it was expressed at a very low level in the skin. The transcript expression of CcIgZ3 in leukocytes isolated from peripheral blood cells was significantly higher than that in leukocytes isolated from the spleen. Different groups of common carp were infected with Aeromonas hydrophila via intraperitoneal injection or immersion. RT-qPCR analysis demonstrated that significant differences in CcIgZ3 mRNA levels existed between the immersion and injection groups in all the examined tissues, including the head kidney, spleen, liver, and hindgut; in particular, the CcIgZ3 mRNA level in the hindgut was higher in the immersion group than in the injection group. The different routes of A. hydrophila exposure in common carp had milder effects on the IgM response than on the CcIgZ3 response. Further study of the relative expression of the IgH gene during the development of common carp showed that the tissue-specific expression profile of CcIgZ3 was very different from those of other genes. RT-qPCR analysis demonstrated that the CcIgZ3 mRNA level increased gradually in common carp during the early larval development stage from 1 day post fertilization (dpf) to 31 dpf with a dynamic tendency similar to those of IgZ1 and IgZ2, and IgM was the dominant Ig with obviously elevated abundance. Analyses of the tissue-specific expression of IgHs in common carp at 65 dpf showed that CcIgZ3 was expressed at mucosal sites, including both the hindgut and gill; in contrast, IgZ1 was preferentially expressed in the hindgut, and IgZ2 was preferentially expressed in the gill. In addition to RT-qPCR analysis, in situ hybridization was performed to detect CcIgZ3-expressing cells and IgM-expressing cells. The results showed that CcIgZ3 and IgM transcripts were detectable in the spleens, gills, and hindguts of common carp at 65 dpf. CONCLUSIONS: These results reveal that CcIgZ3 gene transcripts are expressed in common carp during developmental stage not only in systemic tissues but also in mucosal tissues. CcIgZ3 expression can be induced in immune tissues by A. hydrophila challenge via immersion and intraperitoneal injection with significantly different expression profiles, which indicates that CcIgZ3 is involved in the antimicrobial immune response and might play an important role in gut mucosal immunity.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33913222

RESUMO

INTRODUCTION: To assess the efficacy of adjuvant chemotherapy, radiotherapy, or both following the primary surgery on the progression-free survival and 5-year overall survival in patients with stage I/II uterine carcinosarcoma. METHODS: A preliminary investigation was conducted using PubMed and Embase databases to identify relevant studies published up to March, 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by Revman 5.3 software to analysis outcomes. RESULTS: Six retrospective cohort studies were involved in the analysis, including 1516 patients in observation group, 956 patients in chemotherapy group, 750 patients in radiotherapy group, and 1082 patients in raidochemotherapy group. The results indicated that chemotherapy alone (HR = 0.59, 95% CI = 0.38-0.91, p < 0.05) and radiochemotherapy (HR = 0.35, 95% CI: 0.24-0.53, p < 0.001) were associated with improved progression-free survival in patients. Similarly, pooled results suggested chemotherapy (HR = 0.49, 95% CI = 0.34-0.71, p < 0.001) and radiochemotherapy (HR = 0.46, 95% CI = 0.29-0.72, p < 0.001) promoted the 5-year overall survival compared with observation. However, radiotherapy alone had no statistical significance in improving progression-free survival (HR = 0.80, 95% CI = 0.49-1.29, p = 0.36) and 5-year overall survival (HR = 0.65, 95% CI = 0.38-1.12, p = 0.12). DISCUSSION: Chemotherapy and radiochemotherapy appeared to be prognostic beneficial to early-stage uterine carcinosarcoma.

13.
J Virol ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789997

RESUMO

Enteroviruses belong to the genus Enterovirus of the family Picornaviridae and include four human enterovirus groups (EV A-D), and the epidemic of enteroviruses such as human enterovirus A71 (EV-A71) and Coxsackievirus-A16 (CVA16) is a threat to global public health. Enteroviral 2C is the most conserved nonstructural protein among all enteroviruses and possesses the RNA helicase activity that plays pivotal roles during enteroviral life cycles, which makes 2C an attractive target for developing the anti-enteroviral drugs. In this study, we designed a peptide, named 2CL, based on the structure of EV-A71 2C. This peptide effectively impaired the oligomerization of EV-A71 2C protein, and inhibited the RNA helicase activities of 2C proteins encoded by EV-A71 and CVA16, and both of which belong to EV-A, and showed potent antiviral efficacy against EV-A71 and CVA16 in cells. Moreover, the 2CL treatment elicited a strong in vivo protective efficacy against lethal EV-A71 challenge. Besides, the antiviral strategy of targeting the 2C helicase activity can be applied to inhibit the replication of EV-B. Either 2CL or B-2CL, the peptide redesigned based on the 2CL-corresponding sequence of EV-Bs, exerted effective antiviral activity against two important EV-Bs, Coxsackievirus B3 and Echovirus 11. Together, our findings demonstrated that targeting the helicase activity of 2C by rationally designed peptide is an efficient antiviral strategy against enteroviruses, and the 2CL and B-2CL showed promising clinical potentials to be further developed as broad-spectrum anti-enteroviral drugs.ImportanceEnteroviruses are a large group of positive-sense single-stranded RNA viruses, and include numerous human pathogens, such as enterovirus A71 (EV-A71), coxsackieviruses, and echoviruses. However, no approved antiviral drug is available. Enteroviral 2C is the most conserved nonstructural protein among all enteroviruses and contains the RNA helicase activity critical for the viral life cycle. Herein, according to the structure of EV-A71 2C, we designed a peptide that effectively inhibited the RNA helicase activities of EV-A71-and coxsackievirus A16 (CVA16)-encoded 2C proteins. Moreover, this peptide exerted potent antiviral effects against EV-A71 and CVA16 in cells and elicited therapeutic efficacy against lethal EV-A71 challenge in vivo Furthermore, we demonstrated that the strategy of targeting the 2C helicase activity can be used to other relevant enteroviruses, including coxsackievirus B3 and echovirus 11. In summary, our findings provide compelling evidence that the designed peptides targeting the helicase activity of 2C could be broad-spectrum antiviral for enteroviruses.

14.
Europace ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33723602

RESUMO

AIMS: Single oral dose anti-arrhythmic drugs (AADs) are used to cardiovert recent-onset atrial fibrillation (AF); however, the optimal agent is uncertain. METHODS: We performed a systematic review and network meta-analysis of randomized trials testing single oral dose AADs vs. any comparator to cardiovert AF <7 days duration. We searched MEDLINE, Embase, and CENTRAL to April 2020. The primary outcome was successful cardioversion at timepoint nearest 8 h after administration. RESULTS: From 12 712 citations, 22 trials (2320 patients) were included. Thirteen trials included patients with some degree of heart failure; 19 included patients with some degree of ischaemic heart disease vs. placebo or rate-control (32% success) at 8 h, flecainide [73%, network odds ratio (OR) 7.6, 95% credible interval (CrI) 4.4-14.0], propafenone (70%, OR 4.6, CrI 2.9-7.3), and pilsicainide (59%, OR 10.0, CrI 1.8-69.0), but not amiodarone (28%, OR 1.0, CrI 0.4-2.8) were superior. Flecainide (OR 7.5, CrI 2.6-24.0) and propafenone (OR 4.5, CrI 1.6-13.0) were superior to amiodarone; propafenone vs. flecainide did not statistically differ (OR 0.6, CrI 0.3-1.1). At longest follow-up, amiodarone was superior to placebo (OR 11.0, CrI 3.2-41.0), flecainide vs. amiodarone (OR 0.79, CrI 0.19-3.1), and propafenone vs. amiodarone (OR 0.36, CrI 0.092-1.4) were not statistically different, and flecainide was superior to propafenone (OR 2.2, CrI 1.1-4.8). Atrial and ventricular tachyarrhythmias, bradyarrhythmias, and hypotension were rare with PO AADs. CONCLUSION: Single oral dose Class 1C AADs are effective and safe for cardioversion of recent-onset AF. Flecainide may be superior to propafenone. Amiodarone is a slower acting alternative.

15.
J Nat Prod ; 84(4): 1353-1358, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33765387

RESUMO

Under the guidance of MS/MS-based molecular networking and HPLC-UV, two new alkaloid racemates, (±)-17-hydroxybrevianamide N (1) and (±)-N1-methyl-17-hydroxybrevianamide N (2), featuring a rare o-hydroxyphenylalanine residue and an imide subunit, were isolated from a soft-coral-derived Aspergillus sp. fungus. The true natural products (+)-1 and (+)-2 were further monitored and obtained from the freshly prepared EtOAc extracts, while (-)-1 and (-)-2 are artifacts generated during extraction and purification processes. Simultaneously, the structures including absolute configurations of (+)-13S-1, (-)-13R-1, (+)-13S-2, and (-)-13R-2 were elucidated on the basis of comprehensive spectroscopic analysis, ECD calculations, and X-ray diffraction data. Interestingly, basic solution promotes the racemization of (+)-1 and (-)-1, whereas acidic solution suppresses the transformation. The current research was concerned with the true natural products and their artifacts, providing critical insight into the isolation and identification of natural products.

16.
EMBO Rep ; 22(5): e52141, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33764618

RESUMO

Tyrosine phosphorylation of secretion machinery proteins is a crucial regulatory mechanism for exocytosis. However, the participation of protein tyrosine phosphatases (PTPs) in different exocytosis stages has not been defined. Here we demonstrate that PTP-MEG2 controls multiple steps of catecholamine secretion. Biochemical and crystallographic analyses reveal key residues that govern the interaction between PTP-MEG2 and its substrate, a peptide containing the phosphorylated NSF-pY83 site, specify PTP-MEG2 substrate selectivity, and modulate the fusion of catecholamine-containing vesicles. Unexpectedly, delineation of PTP-MEG2 mutants along with the NSF binding interface reveals that PTP-MEG2 controls the fusion pore opening through NSF independent mechanisms. Utilizing bioinformatics search and biochemical and electrochemical screening approaches, we uncover that PTP-MEG2 regulates the opening and extension of the fusion pore by dephosphorylating the DYNAMIN2-pY125 and MUNC18-1-pY145 sites. Further structural and biochemical analyses confirmed the interaction of PTP-MEG2 with MUNC18-1-pY145 or DYNAMIN2-pY125 through a distinct structural basis compared with that of the NSF-pY83 site. Our studies thus provide mechanistic insights in complex exocytosis processes.


Assuntos
Proteínas Tirosina Fosfatases não Receptoras , Proteínas Tirosina Fosfatases , Peptídeos , Fosforilação , Proteínas Tirosina Fosfatases/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/metabolismo
17.
Thorac Cancer ; 12(9): 1469-1488, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33787090

RESUMO

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

18.
Life Sci ; 273: 119302, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33662427

RESUMO

Src homolog and collagen homolog (SHC) proteins are adaptor proteins bound to cell surface receptors that play an important role in signal transduction and related diseases. As an important member of the SHC protein family, SHC1 regulates cell proliferation and apoptosis, reactive oxygen species (ROS) production, and oxidative stress. Three isomeric proteins namely, p46shc, p52shc, and p66shc, are produced from the same SHC1 gene locus. All the three proteins are found in the liver, and are widely expressed in various hepatic cells. SHC1 has been proven to be associated with acute and chronic liver injuries of different etiologies, and plays important roles in liver fibrosis and hepatocellular carcinoma (HCC). Therefore, this review summarizes recent studies that discuss and explore the role of SHC1 in the occurrence and progression of liver diseases. We also provide a theoretical basis for future studies.


Assuntos
Lesão Pulmonar Aguda/patologia , Lesão Pulmonar/patologia , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo , Lesão Pulmonar Aguda/metabolismo , Animais , Humanos , Lesão Pulmonar/metabolismo , Isoformas de Proteínas , Transdução de Sinais
19.
Catheter Cardiovasc Interv ; 97 Suppl 2: 1072-1079, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33764682

RESUMO

OBJECTIVES: To investigate a strategy for ultra-low volume contrast percutaneous coronary intervention (PCI) with the aims of preserving renal function and observing the 90-day clinical endpoint in patients with non-ST-elevated myocardial infarction (non-STEMI) and chronic kidney disease (CKD). BACKGROUND: The feasibility, safety, and clinical utility of PCI with ultra-low radio-contrast medium in patients with non-STEMI and CKD are unknown. METHODS: A total of 29 patients with non-STEMI and CKD (estimated glomerular filtration rate [eGFR] of ≤60 ml/min/1.73 m2 ) were included. Ultra-low volume contrast PCI was performed after minimal contrast coronary angiography using zero contrast optical coherence tomography (OCT) guidance. Pre- and post-PCI angiographic measurements were performed using quantitative flow ratio (QFR) for pre-perfusion assessment and verifying improvement. RESULTS: The median creatinine level was 2.1 (inter-quartile range 1.8-3.3), and mean eGFR was 48 ± 8 ml/min/1.73 m2 pre-PCI. During the PCI procedure, OCT revealed 15 (52%) cases of abnormalities post-dilation. There was no significant change in the creatinine level and eGFR in the short- or long-term, and no major adverse events were observed. CONCLUSION: In non-STEMI patients with high-risk CKD who require revascularization, QFR and no contrast OCT-guided ultra-low contrast PCI may be performed safely without major adverse events.

20.
Zhongguo Zhong Yao Za Zhi ; 46(1): 155-161, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645065

RESUMO

The aim of this paper was to investigate the effect of berberine hydrochloride on the cell wall integrity of Candida albicans hypha. The minimal inhibitory concentration(MIC) of berberine hydrochloride against clinical and standard C. albicans strains was detected by micro liquid-based dilution method; the effect of berberine hydrochloride on the colony formation of C. albicans SC5314 was investigated by spot assay; the effect of berberine hydrochloride on the metabolism of C. albicans SC5314 hypha was checked by XTT reduction assay, and the viability of C. albicans SC5314 hypha was tested by fluorescent staining assay. The effect of berberine hydrochloride on the morphology of C. albicans SC5314 hypha was examined by scanning electron microscope. The changes in the cell wall of C. albicans SC5314 hypha after berberine hydrochloride treatment were detected by transmission electron microscopy. The effect of berberine hydrochloride on ß-glucan from C. albicans SC5314 was detected by flow cytometry. The effect of berberine hydrochloride on hypha-specific gene ECE1 and ß-glucan synthase genes FKS1 and FKS2 in C. albicans was examined by qRT-PCR. The results showed that berberine hydrochloride showed a strong inhibitory effect on both clinical and standard strains of C. albicans, and the MIC was 64-128 µg·mL~(-1). Spot assay, XTT redunction assay and fluorescent staining assay showed that with the increase of berberine hydrochloride concentration, the viability of C. albicans SC5314 gradually decreased. The transmission electron microscopy scanning assay showed that this compound could cause cell wall damage of C. albicans. The flow cytometry analysis showed the exposure degree of C. albicans ß-glucan. The qRT-PCR further showed that berberine hydrochloride could significantly down-regulate hypha-specific gene ECE1 and ß-glucan synthase-related gene FKS1 and FKS2. In conclusion, this compound can down-regulate C. albicans and ß-glucan synthase-related gene expressions, so as to destroy the cell wall structure of C. albicans, expose ß-glucan and damage the integrity of the wall.


Assuntos
Berberina , Candida albicans , Antifúngicos/farmacologia , Berberina/farmacologia , Candida albicans/genética , Parede Celular , Hifas , Testes de Sensibilidade Microbiana
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