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1.
Org Lett ; 26(10): 2103-2107, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38443201

RESUMO

A chemical synthesis of a unique nanosaccharide fragment from Helicobacter pylori lipopolysaccharide was achieved via a convergent glycosylation method. Challenges involved in the synthesis include the highly stereoselective construction of ß-3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) and two 1,2-cis-glycosidic linkages, as well as the formation of a branched 2,7-disubstituted heptose subunit. Hydrogen-bond mediated aglycone delivery strategy and benzoyl-directing remote participation effect were employed, respectively, for the efficient generation of the desired ß-Kdo glycoside and 1,2-cis-α-l-fucoside/d-glucoside. Moreover, the key branched framework was successfully established through a [(7 + 1) + 1] assembly approach involving the stepwise glycosylation of the heptasaccharide alcohol with two monosaccharide donors. The synthesized 1 containing a propylamine linker at the reducing end can be covalently bound to a carrier protein for further immunological studies.


Assuntos
Glicosídeos , Lipopolissacarídeos , Lipopolissacarídeos/química , Glicosídeos/química
2.
Orthop Surg ; 15(8): 2091-2101, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37076437

RESUMO

OBJECTIVE: Complications related to triceps after total elbow arthroplasty (TEA) have become a major surgical concern. The triceps-preserving approach has the advantage of not disturbing the insertion of triceps but is disadvantaged by the reduced exposure of the elbow joint. The aim of this study was to investigate the clinical and radiological outcomes of TEA with a triceps-preserving approach and to compare the outcomes of TEA to treat arthropathy with that of TEA to treat acute distal humerus fracture. METHODS: From January 2010 to December 2018, 23 patients undergoing primary TEAs were retrospectively reviewed with a mean follow-up time of 92.6 months (range, 52-136 months). Each TEA was performed using the triceps-preserving approach with a semi-constrained Coonrad-Morrey prosthesis. Patient demographics, range of motion (ROM), pain visual analogue scale (VAS), and triceps strength (Medical Research Council [MRC] scale) were compared before and after surgery. The Mayo Elbow Performance Score (MEPS), Disabilities of the Arm, Shoulder, and Hand (DASH) score, radiographic outcome, and complications were evaluated at follow-up. RESULTS: In total, seven males and 16 females were included in this study, with a mean age of 66.1 years (range:46-85 years). By the last follow-up, pain had been significantly relieved in all patients. The average MEPS in the arthropathy group and fracture group were 90.8 ± 10.3 points (range: 68-98 points) and 91.7 ± 0.4 (range: 76-100 points), respectively. The average DASH of the arthropathy group and fracture group was 37.3 ± 18.8 points (range: 18-52 points) and 38.4 ± 20.1 (range: 16-60 points). At the last follow-up after surgery, the mean flexion arcs in the arthropathy group and fracture group were 100.4° ± 24.1° and 97.8° ± 28.1°, respectively. The mean pro-supination arcs in the arthropathy group and fracture group were 142.4° ± 15.2° and 139.2° ± 17.5°, respectively. There were no significant differences in clinical outcomes between the two groups (P ≥ 0.05). Triceps strength was normal (MRC grade V) in 15 elbows and good in eight elbows. None of the cases experienced weakness of the triceps strength, infection, periprosthetic fractures, or prosthesis breakage. CONCLUSIONS: The clinical and radiographical outcomes of TEA with the triceps-preserving approach were satisfactory in patients with distal humerus fracture, osteoarthritis and rheumatoid arthritis.


Assuntos
Artrite Reumatoide , Artroplastia de Substituição do Cotovelo , Articulação do Cotovelo , Idoso , Feminino , Humanos , Masculino , Braço/cirurgia , Artrite Reumatoide/cirurgia , Cotovelo/cirurgia , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/cirurgia , Seguimentos , Próteses e Implantes , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais
3.
Org Lett ; 24(39): 7088-7094, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36169189

RESUMO

An expedient synthesis of the nonreducing hexasaccharide fragment of axinelloside A has been completed via a linear stepwise glycosylation approach. Challenges involved in the synthesis include the highly stereoselective construction of five consecutive 1,2-cis-glycosidic linkages and the formation of a sterically crowded 2,3-disubstituted l-fucoside subunit. Protecting group-directing glycosylation strategies such as the remote participation effect of the benzoyl substituent and the stereocontrolling effect of the 4,6-O-benzylidene group were employed for the synthesis of the desired 1,2-cis-glycosidic linkages. Moreover, the 2,3-branched l-fucoside framework was established through a 3-O and then 2-O glycosylation sequence in which the 3-hydroxyl group of the core l-fucose unit was glycosylated first and then the 2-hydroxyl. The synthetic hexasaccharide is properly protected, so it can be employed as a precursor to synthesize its natural form.


Assuntos
Fucose , Glicosídeos , Glicosilação , Lipopolissacarídeos , Oligossacarídeos
4.
Angew Chem Int Ed Engl ; 61(29): e202204420, 2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35543248

RESUMO

Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo-containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2→5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α-stereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2-deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.


Assuntos
Acinetobacter baumannii , Lipopolissacarídeos , Carboidratos , Dissacarídeos/química , Humanos , Lipopolissacarídeos/química , Oligossacarídeos/química , Polissacarídeos
5.
Oncol Res Treat ; 45(5): 281-290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35114663

RESUMO

BACKGROUND: A previous meta-analysis suggested that use of bevacizumab is associated with an increased risk of infection in cancer patients. With the continuous accumulation of evidence in non-small-cell lung cancer (NSCLC), we performed a new, focused meta-analysis of randomized controlled trials (RCTs) to quantify the relative risk (RR) and incidence of infectious complications in those individuals treated with bevacizumab. METHODS: Electronic databases were searched, including PubMed, Embase, and Cochrane databases. Eligible studies were prospective randomized clinical trials of NSCLC patients treated with bevacizumab with toxicity data on infectious complications. RR, overall incidence rates, and 95% confidence intervals (CI) were calculated using fixed- or random-effects models, depending on the heterogeneity of the included studies. RESULTS: A total of 4,545 patients from 14 prospective RCTs were included in the meta-analysis. Treatment with bevacizumab was not associated with an increased risk of all-grade (RR 1.12, 95% CI: 0.84-1.49) or high-grade (RR 1.11, 95% CI: 0.86-1.41) infections, respectively. The summary incidences of all-grade and high-grade infections in patients receiving bevacizumab in the treatment group were 16.4% (95% CI: 15.7-17.2%) and 4.3% (95% CI: 3.0-6.1%), respectively. CONCLUSIONS: The use of bevacizumab is not associated with a significantly higher risk of infections in NSCLC patients. These data provide reassurance regarding the risk of infection in patients with NSCLC receiving bevacizumab.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Incidência , Neoplasias Pulmonares/tratamento farmacológico
6.
Zhongguo Gu Shang ; 34(6): 492-6, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34180164

RESUMO

OBJECTIVE: To evaluate the reliability and repeatability of three-dimensional (3D)-CT measurement of glenoid track. METHODS: Glenoid and Hill-Sachs bone defects in 60 patients with recurrent anterior dislocation of the unilateral shoulder were evaluated by 3D-CT and analyzed by three independent observers(shoulder orthopedists) according to the Di Giacomo method. These injuries were classified to formulate a surgical protocol. All the patients were repeatedly measured 1 week later. Intraclass correlation coefficient (ICC) and coefficient of variation (COV) were used for reliability analysis. RESULTS: Interobserver reliability was "very good" for both measurements of glenoid diameter and glenoid bone defects, and "good" for measurements of Hill-Sachs interval. Interobserver agreement was high on the assessment of the extent of the glenoid defect, and poor on track/off track assessment of the Hill-Sachs lesion. Intraobserver reliability for measurements of glenoid diameter, glenoid defect, and Hill-Sachs interval was "very good". The COV was 4.1% for glenoid diameter, 4.4% for glenoid defect, and 21.1% for Hill-Sachs interval. CONCLUSION: The reliability and reproducibility of 3D-CT measurements of glenoid bone defects are good, but the assessment of humeral head bone defects shows large variability with poor reliability.


Assuntos
Instabilidade Articular , Luxação do Ombro , Articulação do Ombro , Humanos , Reprodutibilidade dos Testes , Ombro , Tomografia Computadorizada por Raios X
7.
BMC Musculoskelet Disord ; 22(1): 598, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34182961

RESUMO

BACKGROUND: Bony fusion rate was significantly lower in patients with type 3 Modic change than patients with normal endplates. It is not known whether there are relevant differences in fusion efficiency among patients with type 2 sclerotic Modic change or non-sclerotic Modic change, or no Modic change. METHODS: A retrospective study contained 196 lumbar segments in 123 subjects undergoing posterior lumbar interbody fusion (PLIF) with pedicle screw instrumentation (PSI) to assess the effect of type 2 sclerotic Modic change on fusion efficiency. These endplates were allocated into groups A, B, and C, according to their Modic changes. Group A had endplates with type 2 Modic change and endplate sclerosis. Group B had type 2 Modic change without endplate sclerosis. Group C had neither Modic change nor endplate sclerosis. The presence of Modic change was determined by magnetic resonance imaging (MRI). Endplate sclerosis in type 2 Modic change was detected by computed tomography (CT) before the operation. We collected CT data 3 months to more than 24 months after operation in patients to assess bony fusion. RESULTS: Incidences of bony fusion were 58.8% in group A, 95.0% in group B, 94.3% in group C. The bony fusion rate was significantly lower in group A than in either group B or C. There was no significant difference between groups B and C. Thus, endplates with type 2 sclerotic Modic change had a lower fusion rate in patients undergoing PLIF with PSI. CONCLUSION: Type 2 sclerotic Modic change could be an important factor that affects solid bony fusion in patients undergoing PLIF with PSI. CT may help diagnose endplate sclerosis in patients with type 2 change and inform the choice of the best site for spinal fusion.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Esclerose/diagnóstico por imagem , Esclerose/patologia , Fusão Vertebral/efeitos adversos
8.
Front Oncol ; 10: 549168, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240807

RESUMO

Immune checkpoint inhibitors (ICIs) cause fewer toxicities than conventional chemotherapy. Although most of the immune-related adverse events (irAEs) are mild, reversible, and manageable, potentially severe and rare irAEs remain relevant. We present a 24-year-old man with advanced hereditary renal cancer who developed bilateral posterior uveitis and retinal detachment after systematic treatment of ICI and an anti-angiogenic drug. Axitinib and pembrolizumab were administered with a partial response and following the severe ocular irAE and systemic corticosteroid treatment was initiated. Our case indicates that ocular irAEs may occur rapidly. To the best of our knowledge, this is the first case of posterior uveitis and retinal detachment in hereditary renal cancer patients treated with ICI and anti-angiogenic drugs.

9.
Orthop Surg ; 12(5): 1405-1412, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33078582

RESUMO

OBJECTIVE: To report the clinical and radiological outcomes of arthroscopically assisted surgery for combination of glenoid and greater tuberosity fractures after traumatic shoulder dislocation. METHODS: From December 2013 to December 2018, patients with concomitant fracture of the greater tuberosity and glenoid who underwent arthroscopically assisted surgery were retrospectively reviewed. Fifteen patients were included. Preoperative computed tomography (CT) scans with 3D reconstruction were performed to evaluate the fracture configuration and associated fractures. All patients underwent arthroscopically assisted surgery under general anesthesia with brachial plexus anesthesia in the lateral position. Under the arthroscopic approach, a comprehensive inspection of the joints was firstly conducted to examine the injury of bones and other tissues. With arthroscopy support, closed reduction and internal fixation of both fractures were performed with suture anchors, with or without additional cannulated screws. At the same time, other injuries were also repaired under the arthroscope. Patients were followed up (6 weeks,8 weeks,3 months,6 months,1 year after surgery) regularly for at least 1 year. At the follow-up, clinical outcomes (Constant score, ASES score, range of motion, and VAS score) and radiological outcomes were analyzed. RESULTS: Of the 15 patients, there are seven cases of men, eight cases of women; aged 22-66 years, with an average age of 48 years; left shoulder for five cases, 10 cases of the right shoulder. The injury mechanisms were: a simple fall (n = 9), an epileptic seizure (n = 1), a high fall injury (n = 2), and a traffic accident (n = 3). Of the 15 cases of glenoid fracture, 11 cases were type Ia and four cases were type II according to the Ideberg Classification System. The mean size of the glenoid fracture fragment was 28.4% (range, 8.7%-47.2%). According to the Mutch classification system, the fractures of the greater tuberosity were divided into: five cases of avulsion, one case of compression, and nine cases of split. Average time of follow-up was 38.2 months (range, 12-70 months), and one case was lost to follow-up. With fractures healing well, almost all patients had a good joint function. At the final follow-up, mean anterior flexion was 157°; mean external rotation was 40°; mean internal rotation was T11 level; the mean Constant-Murley score was 94.6 points (range, 70-100 points); the mean ASES score was 94.6 points (range, 79-100 points); and the mean VAS score was 0.4 points (range, 0-2 points). No recurrent instability or re-dislocation occurred. No patient had revision surgery. CONCLUSION: Arthroscopic management of glenoid and greater tuberosity bipolar fractures was useful and effective with minimal injury, and it achieved satisfactory clinical and radiological outcomes at a mean follow-up time of more than 3 years.


Assuntos
Artroscopia/métodos , Fixação Interna de Fraturas/métodos , Escápula/lesões , Escápula/cirurgia , Fraturas do Ombro/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Escápula/diagnóstico por imagem , Fraturas do Ombro/diagnóstico por imagem , Adulto Jovem
10.
Oncoimmunology ; 9(1): 1781333, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32923143

RESUMO

Background: Subgroup analysis of clinical trials of PD-1/PD-L1 inhibitors have reported ethnic differences in outcomes. We systematically collected published data and performed a meta-analysis to compare therapeutic efficacy in Asian and non-Asian patients receiving PD-1/PD-L1 inhibitors. Methods: Eligible studies included phase II and III prospective clinical trials with available subgroup data on Asian versus non-Asian populations. Overall survival (OS) and progression-free survival (PFS) were used to evaluate differences in outcome between Asian versus non-Asian cancer patients. Results: A total of 11,020 cancer patients from 19 prospective randomized controlled clinical trials were included. The overall estimated HR for OS was 0.69 with 95% CI of 0.61-0.77 in Asian versus 0.82 with 95% CI of 0.77-0.88 in non-Asian patients. The estimated hazard ratio (HR) for PFS measured 0.54 (95% CI, 0.32-0.76) and 0.69 (95% CI, 0.54-0.85) in Asian and non-Asian patients, respectively. Pooled ratios of OS HRs and PFS HRs reported in Asian versus non-Asian cancer patients were 0.84 (95% CI, 0.75-0.94) and 0.78 (95% CI, 0.59-0.97), respectively. Conclusions: This meta-analysis shows for the first time that Asian cancer patients have a significantly improved survival benefit than non-Asian patients receiving PD-1/PD-L1 inhibitor-based therapy.


Assuntos
Neoplasias , Receptor de Morte Celular Programada 1 , Antígeno B7-H1/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1/uso terapêutico , Estudos Prospectivos
11.
Orthop Surg ; 12(5): 1421-1429, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32812705

RESUMO

OBJECTIVE: Based on the morphological characteristics of glenoid and greater tuberosity (GT) fractures and the relationship between them, we explored the injury mechanism of acute anterior shoulder dislocation associated with glenoid and GT fractures. METHODS: From December 2013 to December 2019, we retrospectively reviewed the clinical data of patients who were diagnosed with acute anterior shoulder dislocation associated with glenoid and GT fractures in our hospital. According to the fracture site, a glenoid fracture group and a greater tuberosity fracture (GT) group were established, and the morphological characteristics of both glenoid and GT fractures were measured and statistically analyzed. RESULTS: A total of 41 patients (43 shoulders) met the inclusion criteria (39 unilateral shoulders and 2 bilateral shoulders). The mean age was 50.21 years (range, 22-71 years). A total of 27 shoulder injuries (62.8%) were split GT fractures and 33 shoulder injuries (76.7%) were combined with rotator cuff tears. The mean size of glenoid fragments was 30.16% and the mean displacement was 8.85 mm. The mean size of GT fragments was 28.43 mm. The mean superoinferior and anteroposterior displacements of the GT fragment were 6.77 mm and 4.96 mm, respectively. There was a negative correlation between the size of glenoid and GT fracture fragments (r = -0.64, P < 0.05). The glenoid fragments in the Ideberg type Ia glenoid fracture group were smaller than those in the Ideberg type II glenoid fracture group (28.41% and 40.95%, respectively), while the size of GT fragments in the type Ia group were larger than those in the type II group (29.77 mm and 20.21 mm, respectively) (P < 0.05). The GT fragments in the split GT fracture group were larger than those in the avulsion or depression GT fracture group (33.69 mm, 19.07 mm and 21.12 mm, respectively), while the size of glenoid fragments in the split GT fracture group were smaller than those in the avulsion or depression GT fracture group (23.57%, 41.37%, and 43.42%, respectively) (P < 0.05). As for the displacement direction of GT fragments, depression fractures were mainly inferior displacements, avulsion fractures were mainly anterosuperior displacements, while split fractures were mainly posteroinferior displacements (P < 0.05). Multiple regression analysis suggested that the type and the fragment size of GT fractures have a significant influence on the size of glenoid fragments. CONCLUSION: Acute anterior shoulder dislocations associated with glenoid and GT fractures are often combined with rotator cuff tears. There is a negative correlation between the size of glenoid and GT fragments, and split GT fractures are most common. Such injuries are highly correlated to the relative spatial location between the GT and the glenoid when the shoulder dislocates.


Assuntos
Escápula/lesões , Escápula/fisiopatologia , Luxação do Ombro/classificação , Luxação do Ombro/fisiopatologia , Fraturas do Ombro/classificação , Fraturas do Ombro/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
12.
Org Biomol Chem ; 18(31): 6155-6161, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32716466

RESUMO

The aminated mimetics of 2-keto-3-deoxy-sugar acids such as the anti-influenza clinical drugs oseltamivir (Tamiflu) and zanamivir (Relenza) are important bioactive molecules. Development of synthetic methodologies for accessing such compound collections is highly desirable. Herein, we describe a simple, catalyst-free glycal diazidation protocol enabled by visible light-driven conditions. This new method requires neither acid promoters nor transition-metal catalysts and takes place at ambient temperature within 1-2 hours. Notably, the desired transformations could be promoted by thermal conditions as well, albeit with lower efficacy compared to the light-induced conditions. Different sugar acid-derived glycal templates have been converted into a range of 2,3-diazido carbohydrate analogs by harnessing this mild and scalable approach, leading to the discovery of new antiviral agents.


Assuntos
Antivirais/farmacologia , Azidas/farmacologia , Carboidratos/farmacologia , Temperatura Alta , Luz , Rhinovirus/efeitos dos fármacos , Açúcares Ácidos/farmacologia , Zika virus/efeitos dos fármacos , Antivirais/síntese química , Antivirais/química , Azidas/síntese química , Azidas/química , Configuração de Carboidratos , Carboidratos/síntese química , Carboidratos/química , Testes de Sensibilidade Microbiana , Açúcares Ácidos/química
13.
Br J Cancer ; 123(1): 7-8, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32409750

RESUMO

During the COVID-19 era, Chinese hospitals have developed a system that enables vulnerable cancer patients to continue to receive high-quality medical care, optimising their survival whilst protecting them. This includes use of digital quick codes, fever clinics and optimal scheduling. We wish to share our experiences working with patients during the pandemic.


Assuntos
Betacoronavirus/patogenicidade , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Infecções por Coronavirus/complicações , Atenção à Saúde/normas , Neoplasias/terapia , Pneumonia Viral/complicações , Guias de Prática Clínica como Assunto/normas , COVID-19 , China , Infecções por Coronavirus/virologia , Europa (Continente) , Humanos , Neoplasias/virologia , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2
15.
Chem Asian J ; 14(3): 454-461, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30516348

RESUMO

A convenient and divergent approach was developed to prepare diverse bacterial 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) oligosaccharides containing a Kdo-α-(2→4)-Kdo fragment. The orthogonal protected α-(2→4) linked Kdo-Kdo disaccharide 3, serving as a common precursor, was divergently transformed into the corresponding 8-, 8'-, and 4'-hydroxy disaccharides 5, 7, and 14, respectively. Then, these alcohols were glycosylated, respectively, with the 5,7-O-di-tert-butylsilylene (DTBS) protected Kdo thioglycoside donors 1 or 2 in an α-stereoselective and high-yielding manner to afford a range of Kdo oligosaccharides. Finally, removal of all protecting groups of the newly formed glycosides resulted in the desired free Kdo oligomer.

16.
Medicine (Baltimore) ; 97(51): e13192, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30572427

RESUMO

RATIONALE: Although lung cancer is the leading cause of cancer-related death in the world, targeted therapy plays an essential role in improving the survival of lung cancer. Next-generation sequencing (NGS) technology can dynamically monitor the genomic profiles of tumors and assist cancer diagnosis and treatment. PATIENT CONCERNS: We reported on a 55-year-old man who presented with chest tightness and wheezing for 1 month. DIAGNOSES: The patient was diagnosed with stage cT4N2M1a non-small cell lung cancer (NSCLC) and was found to have wild-type EGFR by pleural effusion cytology. INTERVENTIONS: The patient received systemic treatments, including chemotherapy, targeted therapy, and radiotherapy. During the cancer development, sequential DNA sequencing data that used circulating cell-free tumor DNA, and NGS revealed EGFR L858R and T790M mutations, MYC amplification, and other gene variations. OUTCOMES: The patient died of brain and lung metastases, and had an overall survival as long as 37 months. LESSONS: The dynamic monitoring of tumor genomic profiles has important implications for NSCLC diagnosis, treatment, and prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares/genética , Monitorização Fisiológica/métodos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Progressão da Doença , Evolução Fatal , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade
17.
Carbohydr Res ; 465: 10-15, 2018 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-29879545

RESUMO

The efficient synthesis of a linear pentasaccharide with the structure 1, ß-D-Araf-(1 → 2)-α-D-Araf-(1 → 5)-α-D-Araf-(1 → 5)-α-D-Araf-(1 → 5)-α-D-Araf-(1 â†’ 5), as its octyl glycoside has been achieved through a convergent [3 + 2] coupling strategy. The difficult-to-obtain 1,2-cis-ß-arabinofuranosidic bond at the non-reducing end of the target molecule was stereoselectively constructed by the use of a 2-quinolinecarbonyl-directed 1,2-cis glycosylation method.


Assuntos
Arabinose/síntese química , Proteínas de Bactérias/química , Mycobacterium leprae/química , Mycobacterium tuberculosis/química , Arabinose/análogos & derivados , Arabinose/química , Estrutura Molecular , Especificidade por Substrato
18.
J Am Chem Soc ; 140(10): 3574-3582, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29481074

RESUMO

The stereodirecting effect of C5-ester functions on the glycosylation stereoselectivity of 3-deoxy-d- manno-oct-2-ulosonic acid (Kdo) ethyl thioglycoside donors is presented. The coupling of 5- O-arylcarbonyl or acetyl protected Kdo thioglycosides with acceptors proceeds in an α-selective and high-yielding manner, leading to formation of α-linked Kdo glycosides products. On the other hand, the glycosylation stereoselectivity of the 5- O-2-quinolinecarbonyl (Quin) or 4-nitropicoloyl substituted Kdo thioglycoside donors is switchable: (1) The glycosylation of the 5- O-Quin carrying Kdo donors with primary glycosyl acceptors shows complete ß-stereoselectivity, furnishing the corresponding ß-glycosides in good-to-excellent yield. (2) The stereochemical outcome of the secondary acceptors with these Kdo donors is determined mainly by the stereoelectronic nature of the acceptor. Only or predominant α anomeric products are obtained when the Kdo donors couple with the disarmed or highly crowded secondary carbohydrate acceptors, while the selectivity may switch to predominant ß in the glycosylation of the 5- O-4-nitropicoloyl carrying donor with more reactive secondary alcohols. The synthetic use of the newly developed Kdo donors 1c and 7b has been demonstrated by facile preparation of a structurally unique trisaccharide motif 19 which possesses both α- and ß-Kdo glycosidic bonds.


Assuntos
Ácidos Carboxílicos/química , Glicosídeos/síntese química , Açúcares Ácidos/síntese química , Compostos de Sulfidrila/síntese química , Glicosídeos/química , Glicosilação , Estrutura Molecular , Estereoisomerismo , Açúcares Ácidos/química , Compostos de Sulfidrila/química
19.
Inflammopharmacology ; 25(4): 471-484, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28577132

RESUMO

Our aim was to investigate whether tangeretin, a citrus flavonoid, was able to prevent neuroinflammation and improve dementia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent model of Parkinson's disease (PD). MPTP-HCl was infused into the substantia nigra pars compacta of male Sprague-Dawley rats. Tangeretin (50, 100 or 200 mg/kg body weight) was administered orally starting 3 days prior to MPTP injection and was continued for 20 days following injection. MPTP-lesioned rats revealed motor dysfunction in bar test and rota rod tests. Deficits in working memory and object recognition function were also observed following MPTP induction. Tangeretin treatment significantly attenuated the memory deficits and improved motor functions and cognition. Immunohistochemical analysis reveals the protective effects of tangeretin against MPTP lesion-induced dopaminergic degeneration and hippocampal neuronal loss. Tangeretin reduced expression of inflammatory mediators-COX-2, iNOS-as well reduced the levels of cytokines-interleukins (IL)-IL-1ß, IL-6 and IL-2. The experimental data suggest tangeretin as an effective candidate drug with potential for prevention and treatment of neuroinflammation and dementia associated with PD.


Assuntos
Demência/tratamento farmacológico , Flavonas/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Intoxicação por MPTP/tratamento farmacológico , Aprendizagem em Labirinto/efeitos dos fármacos , Animais , Cognição/efeitos dos fármacos , Cognição/fisiologia , Demência/metabolismo , Demência/psicologia , Relação Dose-Resposta a Droga , Flavonas/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/psicologia , Mediadores da Inflamação/metabolismo , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/psicologia , Masculino , Aprendizagem em Labirinto/fisiologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/psicologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley
20.
Oncotarget ; 8(64): 107899-107906, 2017 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-29296211

RESUMO

PURPOSE: Lipids play roles in membrane structure, energy storage, and signal transduction as well as in human cancers. Here we adopt lipidomics to identify plasma lipid markers for early screening and detection of lung cancer. EXPERIMENTAL DESIGN: Using mass spectrometry, we profiled 390 individual lipids using training and validation strategy in a total of 346 plasma samples from 199 early NSCLC patients, including 113 adenocacinoma and 86 squamous cell cancers (SqCC), and from 147 healthy controls. RESULTS: In the training stage, we found distinct lipid groups that were significantly distributed between NSCLC cases and healthy controls. We further defined a panel of four lipid markers (LPE(18:1), ePE(40:4), C(18:2)CE and SM(22:0)) for prediction of early cancer with a accuracy of 82.3% AUC (Area under ROC curve), sensitivity of 81.9% and specificity of 70.7% at the training stage and yielded the predictive power with accuracy (AUC,80.8%), sensitivity 78.7%, specificity 69.4% and in the validation stage. CONCLUSIONS: Using lipidomics we identified several lipid markers capable of discerning early stage lung carcinoma from healthy individuals, which might be further developed as a quick, safe blood test for early diagnosis of this disease.

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