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1.
Chemistry ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125735

RESUMO

Known for excellent stability, porosity and functionality, the high-valent Zr4+ metal-organic frameworks (Zr-MOFs) still meets synthetic challenge in modulating the strength of Zr-Ocarboxylate linkage. Herein we explore the unusual coordination dynamics of fluorinated Zr-MOFs by designing two trifluoromethyl modified ligands with distinct geometry preference to form a family of thermodynamic and kinetic products. The low-connecting kinetic Zr-MOFs possess substitutable coordination sites to endow Zr6-cluster with extra dynamic behaviors, thus opening a post-synthetic pathway to sequential reassembly/disassembly processes. Comprehensive factors, including ligand geometry, Zr6-cluster connectivity, acid modulator and reaction temperature/concentration, have been studied for controllable syntheses. The stability, hydrophobicity and gas adsorption/separation properties of obtained Zr-MOFs are explored. This work sheds light on the understanding of the dynamic coordination chemistry of Zr-MOFs beyond strong Zr-O bond, which poses a versatile platform for modification and functionalization of Zr-MOFs.

2.
Clin Ther ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32178858

RESUMO

PURPOSE: Remimazolam tosylate (HR-7056) is a novel ester-type benzodiazepine with ultrafast onset of effect. The compound is being developed for sedation induction and maintenance during anesthesia. It was approved for procedural anesthesia in December 2019 by the National Medical Products Administration of China. Previous studies have reported on remimazolam's effects on consciousness and cognition. Although the time to full psychomotor recovery after remimazolam-mediated sedation is critical for decisions regarding hospital discharge, relevant clinical evidence is still lacking. This study investigated the residual psychomotor effects of remimazolam and their recovery from sedating treatment in 2 simulated clinical settings: (1) single-dose administration for sedation initiation; and (2) constant rate infusion for sedation maintenance. METHODS: A single-ascending-dose, parallel-group, midazolam-controlled study and a 2-way crossover study evaluating the reversal effect of flumazenil versus placebo after a 2-h constant rate infusion were conducted with HR-7056 in 87 Chinese healthy volunteers; the studies used a double-blind, randomized trial design. A battery of psychomotor tests was administered before dosing and several times postdose over 4-6 h. Pharmacokinetic, sedation, and safety assessments were performed throughout the studies. FINDINGS: After bolus infusion, the Bispectral Index score decreased in a concentration-dependent manner with HR-7056, accompanied by a sharp drop of Modified Observer's Assessment of Alertness/Sedation score. The recovery of consciousness was much faster with HR-7056 than with midazolam. During the constant rate infusion, the Bispectral Index score was maintained between 40 and 60 with an average plasma remimazolam concentration of ~1000 ng/mL. Subjects' performance in saccadic and smooth pursuit eye movement, body sway, test of choice reaction time, and word recall was significantly impaired after single-dose midazolam and after constant rate infusion of remimazolam. The end-of-infusion injection of flumazenil shortened the median time to full alertness to 3.5 min and effectively reversed psychomotor and cardiovascular dysfunction. IMPLICATIONS: The study results showed quicker psychomotor recovery from sedation in the remimazolam-treated group. The moderate and short-lasting residual effect of remimazolam after 2-h conscious sedation proposes a need for psychomotor assessment(s) before hospital discharge. ClinicalTrials.gov identifiers: NCT01970072 and NCT03444480.

3.
Abdom Radiol (NY) ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32185444

RESUMO

OBJECTIVES: This study aimed to evaluate the feasibility of using the hepatocyte enhancement fraction (HEF) based on gadoxetic acid-enhanced magnetic resonance imaging (MRI) for assessing the liver function in patients with chronic hepatitis B. METHODS: Sixty patients with Child-Pugh grade A (CP-A), 18 with Child-Pugh grade B (CP-B), 2 with Child-Pugh grade C (CP-C), and 20 with normal liver function (NLF) were enrolled. Gadolinium ethoxybenzyldiethy-lenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI was conducted. T1 mapping imaging was performed before and 20 min after Gd-EOB-DTPA administration. The pre- and post-contrast T1 values of the liver (T1pre and T1post), increase in the T1 relaxation rate (ΔR1), rate of decrease in the T1 relaxation time (ΔT1), HEF, and uptake coefficient (K) parameters in the NLF, CP-A, and CP-B + CP-C groups were compared using one-way analysis of variance. The effectiveness of each parameter in differentiating the NLF + CP-A group from the CP-B + CP-C group was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: The HEF, K, ΔT1, and ΔR1 values decreased, while the T1post and T1pre values increased, with the increase in liver function damage. Significant differences in T1post, ΔT1, ΔR1, and HEF were found between different groups, except for the CP-A and NLF groups. However, no significant difference was observed in the T1pre among the three groups. HEF exhibited the largest area under the ROC curve. CONCLUSION: The HEF is an effective method for evaluating liver function in patients with hepatitis B.

4.
Eur J Pharm Sci ; 147: 105281, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32126254

RESUMO

AIM: Janagliflozin is an orally selective SGLT2 inhibitor. To predict human pharmacokinetics/pharmacodynamics (PK/PD) characteristics of janagliflozin. To design optimal starting dose and effective dose for janagliflozin first-in-human (FIH) study. METHODS: Animal PK/PD properties of janagliflozin were obtained from preclinical in vivo and in vitro study. Pharmacologically effective level of same class SGLT2 inhibitors were assessed through preclinical and clinical efficacy data of dapagliflozin, empagliflozin and canagliflozin. Human PK parameters and profiles of janagliflozin were predicted by various methods such as allometric scaling (AS), dedrick and PK/PD modeling analysis. Mechanistic PK/PD model was developed to describe janagliflozin-mediated impact on urinary glucose excretion (UGE). Human IC50 was scaled from rat model-estimated IC50 by correcting interspecies difference of in vitro IC50 and plasma fu of rat and human. The quantitative PK/PD prediction of janagliflozin was evaluated via observed PK/PD profiles of healthy subjects. Predicted PK/PD characteristics of janagliflozin were applied in FIH dose design. Optimal starting dose was suggested by considering preclinical PD and toxicity data of janagliflozin. Effective dose was suggested by considering pharmacologically effective level of same class drugs. RESULTS: PK/PD characteristics of janagliflozin in preclinical species were summarized. Pharmacologically effective level for SGLT2 inhibitors was defined as 25~30% ΔUGE (ΔUGE=--(PG*GFR)within24h) based on efficacy data of three same class drugs. Human predicted CL, Vss and F were 1.04 L/h, 77.5 L and 0.80. Predicted AUC and Cmax of janagliflozin of 10 and 50 mg were within 0.47~2.08 fold of observed values. Predicted human UGE0-24 h and UGE0-144 h of 10 and 50 mg dose range were within 0.66~1.41 fold of observed values. Optimal starting dose and pharmacologically active dose (PAD) were suggested as 10 mg and 50 mg. Dose range for FIH study was designed as 10-450 mg. CONCLUSIONS: This study predicted human PK/PD characteristics of janagliflozin based on preclinical data and provide optimal dose design for janagliflozin FIH study based on pharmacologically effective level of same class drugs.

5.
BMC Complement Med Ther ; 20(1): 16, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-32020888

RESUMO

BACKGROUND: Quantitation analysis and chromatographic fingerprint of multi-components are frequently used to evaluate quality of herbal medicines but fail to reveal activity of the components. It is necessary to develop a rational approach of chromatography coupled with activity detection for quality assessment of herbal medicines. METHODS: An on-line HPLC-ultraviolet detection-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) free radical scavenging (HPLC-UV-ABTS) method was developed to obtain the chromatographic fingerprints and ABTS+• inhibition profiles (active fingerprints) of Rehmanniae Radix (Dihuang) and Rehmannia Radix Praeparata (Shu Dihuang). Eighteen compounds showing ABTS+• inhibition activity were identified by HPLC-fourier-transform mass spectrometry (HPLC-FTMS). Verbascoside was used as a positive control to evaluate the total activities of the samples and the contribution rate of each compound. The similarities of the chromatographic and active fingerprints were estimated by the vectorial angle cosine method. RESULTS: The results showed that the HPLC-UV-ABTS method could efficiently detect antioxidant activity of the herbal medicine samples. The antioxidants were different between the two herbs and several new antioxidants were identified in Shu Dihuang. A function equation was generated in terms of the negative peak area (x) and the concentrations of verbascoside (y, µg/mL), y = 2E-07 × 4 - 8E-05 × 3 + 0.0079 × 2 + 0.5755x + 1.4754, R2 = 1. Iridoid glycosides were identified as main antioxidants and showed their higher contributions to the total activity of the samples. The total contributions of the three main active components in the Dihuang and Shu Dihuang samples to the total activity, such as echinacoside, verbascoside and an unknown compound, were 39.2-58.1% and 55.9-69.4%, respectively. The potencies of the main active components in the Shu Dihuang samples were two to ten times those in the Dihuang samples. Similarity values for S12 in the chromatographic fingerprints and S03, S12 and P03 in the active fingerprints were less than 0.9. The three batches of samples might show their different quality with the other samples. CONCLUSIONS: The results suggested that the combination of "quantity-effect" research strategy and the HPLC-UV-ABTS analysis method could comprehensively evaluate the active components and quality of Dihuang and Shu Dhuang.

6.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(1): 37-41, 2020 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-32037764

RESUMO

OBJECTIVE: To propose and evaluate the clinical effect of midpiece facial nerve dissection through transparotid approach in regional parotidectomy. METHODS: A total of 136 patients with benign parotid tumors were categorized into three groups according to the way of facial nerve dissection: anterograde dissection from main trunk (anterograde, n=70), retrograde dissection from distal branches (retrograde, n=34), and midpiece dissection through transparotid approach (middle dissection, n=32). Surgery duration, facial nerve injury, salivary fistula, earlobe sensation, Frey's syndrome, and aesthetic evaluation were compared. RESULTS: The surgery duration in the middle dissection group was significantly shorter than that in the other two groups. The proportion of salivary fistula was higher in the anterograde group (9 cases, 12.9%; P<0.05) compared with that in the other groups. Postoperative facial nerve injury was similar between the middle dissection (1 case, 3.1%) and anterograde groups (3 cases, 4.3%) with lower injury rate compared with the retrograde group (7 cases, 20.6%). The anterograde group had more cases of hypoesthesia of the earlobe (12 cases, 17.1%; P<0.05) than the other two groups. Aesthetic score was higher in the anterograde and middle dissection groups compared with that in the retrograde group (P<0.05). CONCLUSIONS: Midpiece facial nerve dissection is technically feasible and clinically viable in regional parotidectomy.


Assuntos
Neoplasias Parotídeas , Sudorese Gustativa , Estética Dentária , Nervo Facial , Humanos , Glândula Parótida , Complicações Pós-Operatórias , Estudos Retrospectivos
7.
Colloids Surf B Biointerfaces ; 188: 110798, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31955020

RESUMO

Gelatin microspheres have been commonly used in tissue engineering, but their application is often limited by the uncontrollability and potential cytotoxicity of traditional chemical cross-linking method. Methylacrylamide modification and photocrosslinking provide a controllable and cytocompatible cross-linking method for gelatin hydrogels, however, microspheres fabricated by this single photopolymerization process is uncontrollable. In this study, we show that increasing the gelling ability of gelatin methacrylamide (GMA) at low temperatures is vital to prepare photocrosslinked gelatin microspheres, which in turn improves the controllability and compatibility of conventional chemical cross-linking methods. We detailed characterized the rheological performance with varying temperature and demonstrated that the gelling capability of GMA could be improved by increasing GMA solution concentration and reducing methacrylate substitution. The physicochemical properties of the photocrosslinked microspheres can be modulated via methacrylamide modification, as evidenced by the positive correlation between the physicochemical optimization of the hydrogel bulk and the degree of methacrylate substitution. Next, we successfully fabricated GMA spheres by a two-step process of low-temperature gelation followed by photopolymerization crosslinking. Finally, we show that the microcarriers exhibited favorable supporting for MC3T3-E1 cell proliferation, spreading, and osteogenic differentiation. This study provided a controllable and cytocompatible photocrosslinking procedure for GMA microspheres with broad application prospects, of course, not limited to cell microcarriers.

8.
Sci Rep ; 10(1): 102, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919462

RESUMO

Basidioradulum was morphologically considered to be a synonym of Xylodon. Here, its independence within Hymenochaetales is confirmed from a phylogenetic perspective. Basidioradulum radula, the generic type, is widely distributed in Northern Hemisphere. Two Southern Hemisphere species close to B. radula are newly described as B. mayi and B. tasmanicum, respectively, from Victoria and Tasmania, Australia. Basidioradulum mayi differs from B. radula by lack of cystidia. Moreover, the hymenial surface of B. radula is normally much more strongly hydnoid than that of B. mayi. Basidioradulum tasmanicum is distinct from B. radula and B. mayi by having capitate cystidia, ellipsoid to subglobose basidiospores, and crystal-covered hyphae. Although morphologically distinct, the two new species isolated by Bass Strait have an almost identical ITS region, and could not be differentiated by nLSU- and ITS-based phylogenetic analyses. This case reminds us that basing phylogeny simply on the ITS as a barcode region may underestimate fungal species diversity.

9.
J Med Chem ; 63(4): 1660-1670, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-31990537

RESUMO

Endothelial lipase (EL) hydrolyzes phospholipids in high-density lipoprotein (HDL) resulting in reduction in plasma HDL levels. Studies with murine transgenic, KO, or loss-of-function variants strongly suggest that inhibition of EL will lead to sustained plasma high-density lipoprotein cholesterol (HDL-C) increase and, potentially, a reduced cardiovascular disease (CVD) risk. Herein, we describe the discovery of a series of oxadiazole ketones, which upon optimization, led to the identification of compound 12. Compound 12 was evaluated in a mouse pharmacodynamics (PD) model and demonstrated a 56% increase in plasma HDL-C. In a mouse reverse cholesterol transport study, compound 12 stimulated cholesterol efflux by 53% demonstrating HDL-C functionality.

10.
JAMA Pediatr ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904798

RESUMO

Importance: The number of children who were born to mothers with Zika virus (ZIKV) infection during pregnancy but who did not have apparent disability at birth is large, warranting the study of the risk for neurodevelopmental impairment in this population without congenital Zika syndrome (CZS). Objective: To investigate whether infants without CZS but who were exposed to ZIKV in utero have normal neurodevelopmental outcomes until 18 months of age. Design, Setting, and Participants: This cohort study prospectively enrolled a group of pregnant women with ZIKV in Atlántico Department, Colombia, and in Washington, DC. With this cohort, we performed a longitudinal study of infant neurodevelopment. Infants born between August 1, 2016, and November 30, 2017, were included if they were live born, had normal fetal brain findings on magnetic resonance imaging and ultrasonography, were normocephalic at birth, and had normal examination results without clinical evidence of CZS. Seventy-seven infants born in Colombia, but 0 infants born in the United States, met the inclusion criteria. Exposures: Prenatal ZIKV exposure. Main Outcomes and Measures: Infant development was assessed by the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) and the Alberta Infant Motor Scale (AIMS) at 1 or 2 time points between 4 and 18 months of age. The WIDEA and AIMS scores were converted to z scores compared with normative samples. Longitudinal mixed-effects regression models based on bootstrap resampling methods estimated scores over time, accounting for gestational age at maternal ZIKV infection and infant age at assessment. Results were presented as slope coefficients with 2-tailed P values based on z statistics that tested whether the coefficient differed from 0 (no change). Results: Of the 77 Colombian infants included in this cohort study, 70 (91%) had no CZS and underwent neurodevelopmental assessments. Forty infants (57%) were evaluated between 4 and 8 months of age at a median (interquartile range [IQR]) age of 5.9 (5.3-6.5) months, and 60 (86%) underwent assessment between 9 and 18 months of age at a median (IQR) age of 13.0 (11.2-16.4) months. The WIDEA total score (coefficients: age = -0.227 vs age2 = 0.006; P < .003) and self-care domain score (coefficients: age = -0.238 vs age2 = 0.01; P < .008) showed curvilinear associations with age. Other domain scores showed linear declines with increasing age based on coefficients for communication (-0.036; P = .001), social cognition (-0.10; P < .001), and mobility (-0.14; P < .001). The AIMS scores were similar to the normative sample over time (95% CI, -0.107 to 0.037; P = .34). Nineteen of 57 infants (33%) who underwent postnatal cranial ultrasonography had a nonspecific, mild finding. No difference was found in the decline of WIDEA z scores between infants with and those without cranial ultrasonography findings except for a complex interactive relationship involving the social cognition domain (P < .049). The AIMS z scores were lower in infants with nonspecific cranial ultrasonography findings (-0.49; P = .07). Conclusions and Relevance: This study found that infants with in utero ZIKV exposure without CZS appeared at risk for abnormal neurodevelopmental outcomes in the first 18 months of life. Long-term neurodevelopmental surveillance of all newborns with ZIKV exposure is recommended.

11.
Biomed Chromatogr ; 34(2): e4704, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629371

RESUMO

Abivertinib represents a highly selective irreversible epidermal growth factor receptor tyrosine kinase inhibitor. Two major metabolites of abivertinib, M7 and MII-6, were detected in human plasma, which are recommended to be monitored for safety reasons in clinical trial. A high-throughput quantification method utilizing liquid chromatography-tandem mass spectrometry was designed and verified to quantify abivertinib's primary metabolites in human plasma. Solid-phase extraction was used to process the plasma, and then the analytes underwent a gradient elution separation in an Aquity UPLC BEH C18 column (1.7 µm, 2.1 × 50 mm) with mobile phase A (10 mm ammonium acetate containing 0.1% formic acid) and mobile phase B (methanol-acetonitrile, 2:8, v/v, with 0.1% formic acid). Ion transitions of M7 (m/z 490.2 → 405.1) and MII-6 (m/z 476.2 → 391.1) were monitored under multiple reaction monitoring mode and electrospray ionization in positive ion mode. This simultaneous determination method was found to have acceptable precision, accuracy and linearity in the 0.5-500 ng/mL range for M7 and the 0.5-500 ng/mL range for MII-6, accompanied by a mild matrix effect but high recovery. Further stability assessments indicated that both analytes remained stable throughout the entire experimental process from harvesting whole blood to plasma extraction and analysis.


Assuntos
Antineoplásicos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Pirimidinas/sangue , Espectrometria de Massas em Tandem/métodos , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estabilidade de Medicamentos , Ensaios de Triagem em Larga Escala , Humanos , Limite de Detecção , Modelos Lineares , Neoplasias Pulmonares/tratamento farmacológico , Pirimidinas/farmacocinética , Pirimidinas/uso terapêutico , Reprodutibilidade dos Testes , Extração em Fase Sólida
13.
J Neurotrauma ; 37(1): 43-54, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31397209

RESUMO

Microglia are the primary immune cells in the central nervous system and undergo significant morphological and transcriptional changes after traumatic brain injury (TBI). However, their exact contribution to the pathogenesis of TBI is still debated and remains to be elucidated. In the present study, thy-1 GFP mice received a colony-stimulating factor 1 receptor inhibitor (PLX3397) for 21 consecutive days, then were subjected to moderate fluid percussion injury (FPI). Brain samples were collected at 1 day and 3 days after FPI for flow cytometry analysis, immunofluorescence, dendrite spine quantification, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and Western blot. We found that PLX3397 treatment significantly attenuated the percentages of resident microglia and infiltrated immune cells. Depletion of microglia promoted neurite outgrowth, preserved dendritic spines and reduced total brain cell and neuronal apoptosis after FPI, which was accompanied by decreased the protein levels of endoplasmic reticulum stress marker proteins, C/EBP-homologous protein and inositol-requiring kinase 1α. Taken together, these findings suggest that microglial depletion may exert beneficial effects in the acute stage of FPI.

14.
Food Chem ; 309: 125745, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31678670

RESUMO

Simultaneous determination of multiclass illegal dyes possessing different chemical properties is difficult. By using LC-MS/MS via negative/positive ion switching mode, an efficient and fast multi-residual method for simultaneous determination of multiclass 52 illegal dyes with different acidic-basic properties in foodstuffs was developed and validated during one single run, including 23 fat-soluble neutral azo dyes, 8 acidic sulfonated azo dyes, 12 triphenylmethane basic dyes, three basic indole dyes, three xanthene dyes, one quinoline dye, and two anthraquinones dyes. The illegal dyes were extracted with methanol-acetonitrile and further purified with d-SPE procedure to reduce interference. Sample dilution with 100-fold was used for the elimination of matrix effects of the quantitation of LC-MS/MS analysis. Validation data showed the good recoveries in the range of 71.2-111.2%, with relative standard deviations less than 20%, suggesting the developed method is suitable for the identification and quantitation of multiclass illegal dyes at trace levels in foods.


Assuntos
Cromatografia Líquida/métodos , Corantes/análise , Contaminação de Alimentos/análise , Espectrometria de Massas em Tandem/métodos
15.
Zhongguo Gu Shang ; 32(11): 1057-1062, 2019 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-31870057

RESUMO

OBJECTIVE: To explore CT imaging features and reason for missed diagnosis of clinical practice of occult anterior calcaneal process fracture. METHODS: From July 2013 to November 2018, the clinical data of 13 patients with occult an anterior calcaneal process fracture were retrospectively analyzed, including 2 males and 11 females, aged from 22 to 54 years old. Classification of fracture, displacement of fracture, direction of fracture line, size of fracture, with or without tarsal coalition, other fractures and misdiagnosis, the time from injury to diagnosis, condition of treatment and fracture healing were observed according to case history, data of X-ray and CT. RESULTS: Thirteen patients were diagnosed as occult anterior calcaneal process fracture after CT examination. According to Degan classification, 9 patients were type I, 4 patients were typeII; 4 patients were occurred displacement, and 9 patients did not occurred displacement. On the horizontally CT, fracture line of 12 patients showed transverse, 1 patient oblique, and the size of fracture ranged from 0.40 to 1.72 cm; while on the sagittal view, fracture line of 12 patients showed vertical, 1 patient oblique, and the size of fracture ranged from 0.10 to 0.59 cm. No patients combined with talocalcaneal and scaphoid bridge. Six patients were simple anterior calcaneal process fracture, 7 patients combined with other fractures. Eight patients were misdiagnosed. The time from injury to diagnose ranged from 0 to 21 days. Nine patients with type Iwere performed conservative treatment, 6 patients healed well and 3 patients with fracture line less than 1 cm on horizontally view occurred fracture nonunion. Four patients with type II did not perform operation, and fracture were not union, regardless of fracture size. CONCLUSIONS: Occult anterior calcaneal process fracture have high rate of missed diagnosis in clinical practice. CT imaging features of fracture showed that most fracture line were transverse on CT horizontal plane while vertical on CT sagittal plane, as well as small side of fragment on CT sagittal plane with differernt sizes of fragment on CT horizontal plane; type Ifracture with fragment less than 1 cm on CT horizontal plane and type II both have high rate of nonunion while treated with conservative treatment.


Assuntos
Calcâneo , Fraturas Ósseas , Fraturas Fechadas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
16.
Zookeys ; 884: 23-42, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31723324

RESUMO

Three new species and one subspecies of the genus Amynthas are described from Guangxi Zhuang Autonomous Region, China: The new species are: Amynthas maximus Qiu & Dong, sp. nov. and Amynthas tortuosus Qiu & Dong, sp. nov., and Amynthas shengtangmontis Dong & Jiang, sp. nov., the subspecies is Amynthas shengtangmontis minusculus subsp. nov. All have four pairs of spermathecal pores in 5/6-8/9, which indicates that they should belong to the corticis-group. Their morphological characteristics are compared to other similar species in the corticis-group from China and other Asian countries, such as Amynthas pulvinus Sun & Jiang, 2013, Amynthas homosetus (Chen, 1938), Amynthas corticis (Kinberg, 1867), Amynthas dorsualis Sun & Qiu, 2013, and Amynthas carnosus (Goto & Hatai, 1899). In addition, the results presented are confirmed by the pairwise comparison of COI barcode sequences. The pairwise distances between each new species and the other eighteen corticis-group species are greater than 14.7% on average. Furthermore, the pairwise distance between A. shengtangmontis shengtangmontis and A. shengtangmontis minusculus is 10.7-11.4%.

17.
Medicine (Baltimore) ; 98(47): e17982, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764808

RESUMO

RATIONALE: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is an infection-associated encephalitis/encephalopathy syndrome that is predominately caused by a virus. MERS has no direct association with central nervous system (CNS) infections or inflammation. Non-CNS infections may cause reversible lesion in the splenium of corpus callosum. Recently, there have been reports of many patients with hyponatremia related MERS. Interleukin-6 (IL-6) was also found elevated in serum and in cerebrospinal fluid (CSF) in patients with MERS. The role of IL-6 in the non-osmotic release of vasopressin is crucial. Persistent hyponatremia may be linked to this effect. The following is a case report of MERS secondary to encephalitis, complicated by hyponatremia. We will summarize the latest research and progress regarding MERS. PATIENT CONCERNS: A 31-year-old man was admitted to our department with a 5-day history of fever and headache. His initial diagnosis was encephalitis and hyponatremia; during this period the patient also developed MERS secondary to the encephalitis. DIAGNOSES: Encephalitis was diagnosed by reviewing the history of fever, headache, neck rigidity and Kerning sign (+) on clinical examination. Lab tests revealed: serum VCA IgG (+), EBNA-1 IgG (-), EBV IgM (-), and inflammation in the analysis of CSF. Cranial MRI+C showed that the blood vessels on the surface of the brain were obviously increasing and thickening and diffuse slow waves were detected on the electroencephalogram (EEG). The patient's hyponatremia aggravated on the third day of hospitalization. On the fourth day of hospitalization, the patient was somnolent, apathetic, and slow. Magnetic resonance imaging (MRI) of the brain, with a T2-weighted fluid attenuated inversion recovery image, showed high-signal intensity in the splenium of the corpus callosum (SCC) on the fifth day of hospitalization. Diffusion-weighted imaging (DWI) showed splenial hyperintensity as a "boomerang sign" and reduced diffusion on apparent diffusion coefficient (ADC) maps. Cranial MRI findings returned to normal after 1 month. The diagnosis of MERS was confirmed. INTERVENTIONS: We administered an intravenous drip infusion of acyclovir and prescribed oral sodium supplementation. OUTCOMES: The patient's neurological symptoms gradually improved. The MRI lesion in the SCC disappeared on the 30th day. LESSONS: In patients with encephalitis accompanied by hyponatremia, elevated IL-6 or urinary ß2-microglobulin (ß2MG), and exacerbations such as sudden somnolence, delirium, confusion, and seizures, the possibility of secondary MERS should be investigated, in addition to the progression of encephalitis.


Assuntos
Corpo Caloso/patologia , Encefalite/complicações , Hiponatremia/etiologia , Adulto , Encefalite/diagnóstico , Humanos , Masculino , Índice de Gravidade de Doença
18.
Angew Chem Int Ed Engl ; 58(47): 17033-17040, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31507037

RESUMO

We transformed the hydrophilic metal-organic framework (MOF) UiO-67 into hydrophobic UiO-67-Rs (R=alkyl) by introducing alkyl chains into organic linkers, which not only protected hydrophilic Zr6 O8 clusters to make the MOF interspace superoleophilic, but also led to a rough crystal surface beneficial for superhydrophobicity. The UiO-67-Rs displayed high acid, base, and water stability, and long alkyl chains offered better hydrophobicity. Good hydrophobicity/oleophilicity were also possible with mixed-ligand MOFs containing metal-binding ligands. Thus, a (super)hydrophobic MOF catalyst loaded with Pd centers efficiently catalyzed Sonogashira reactions in water at ambient temperature. Studies of the hydrophobic effects of the coordination interspace and the outer surface suggest a simple de novo strategy for the synthesis of superhydrophobic MOFs that combine surface roughness and low surface energy. Such MOFs have potential for environmentally friendly catalysis and water purification.

19.
Aging (Albany NY) ; 11(18): 7830-7846, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31553952

RESUMO

LncRNA-XIST participated in the regulation of Non-small cell lung cancer (NSCLC) progression, but the underlying mechanisms are still unclear. This study showed that LncRNA-XIST aberrantly overexpressed in either NSCLC tissues or cell lines comparing to their paired control groups. Knock-down of LncRNA-XIST promoted NSCLC cell apoptosis and inhibited cell proliferation, which were reversed by synergistically treating cells with pyroptosis inhibitor Necrosulfonamide (NSA). In addition, knock-down of LncRNA-XIST also promoted reactive oxygen species (ROS) production and NLRP3 inflammasome activation. In parallel, ROS scavenger N-acetyl cysteine (NAC) abrogated the effects of downregulated LncRNA-XIST on NSCLC cell pyroptosis. Furthermore, miR-335 was the downstream target of LncRNA-XIST and overexpressed LncRNA-XIST increased SOD2 expression levels by sponging miR-335. Mechanistically, miR-335 inhibitor reversed the effects of downregulated LncRNA-XIST on ROS levels and cell pyroptosis, which were abrogated by synergistically knocking down SOD2. Taken together, knock-down of LncRNA-XIST inhibited NSCLC progression by triggering miR-335/SOD2/ROS signal pathway mediated pyroptotic cell death.

20.
Bioanalysis ; 11(16): 1483-1493, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31478754

RESUMO

Aim: CX1003 is a novel multitargeted receptor tyrosine kinase inhibitor targeting cancer patients with relapsed or metastatic malignant solid tumors. The study aimed to develop a robust and rapid assay approach to quantify CX1003 in human plasma. Methodology & results: Samples of plasma were purified by SPE where the diluted eluates were then separated by a Waters Acquity CSH C18 column and thereafter detected using positive electrospray ionization via an ultra performance LC-MS/MS. Conclusion: The method to quantify CX1003 in human plasma was first exploited and validated with good sensitivity and specificity, and successfully fulfilled the requirement of the first-in-human clinical pharmacokinetic study of CX1003 in Chinese patients with relapsed or metastatic malignant solid tumors.


Assuntos
Análise Química do Sangue/métodos , Cromatografia Líquida/métodos , Neoplasias/sangue , Neoplasias/metabolismo , Espectrometria de Massas em Tandem/métodos , Humanos , Modelos Lineares
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