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1.
Transl Vis Sci Technol ; 10(13): 30, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34817575

RESUMO

Purpose: To investigate the effects of indocyanine green (ICG) solution on the viability and cytolysis of human lens epithelial cells ex vivo. Methods: A total of 200 pieces of anterior capsules were obtained during cataract surgery, and 110 pieces of the anterior capsules were randomly divided into five groups and treated by immersion in different concentrations of ICG solution. The remaining 90 anterior capsules were also divided into five groups and treated with a combination of drug immersion and washing in balanced salt solution. Electron microscopy and trypan blue and eosin stains were used to analyze the cells. Percentage of dead, shedding, or living lens epithelial cells was estimated and used to demonstrate effects of the ICG on viability and cytolysis. Results: Compared with the control group, the percentage of dead and shedding lens epithelial cells increased while the percentage of living lens epithelial cells decreased in all the immersion groups. In the washing groups, the percentage of the living lens epithelial cells was 63.42% ± 2.49%, 54.04% ± 1.84%, 43.51% ± 2.63%, 29.21% ± 2.40%, and 15.73% ± 1.61% for the five groups and reflected a concentration-effect relationship. Electron microscopy showed that the higher the concentration of the ICG solution, the more severe the destruction of the lens epithelial cell structure. Conclusions: ICG could reduce the viability of the lens epithelial cells and promote cell cytolysis. Translational Relevance: Our study showed that ICG could directly reduce the viability of the lens epithelial cells in a concentration-dependent fashion, which can theoretically reduce the incidence of posterior capsule opacification.

2.
World J Pediatr ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34767193

RESUMO

BACKGROUND: There is a paucity of studies conducted in China on the outcomes of all live-birth extremely premature infants (EPIs) and there is no unified recommendation on the active treatment of the minimum gestational age in the field of perinatal medicine in China. We aimed to investigate the current treatment situation of EPIs and to provide evidence for formulating reasonable treatment recommendations. METHODS: We established a real-world ambispective cohort study of all live births in delivery rooms with gestational age (GA) between 24+0 and 27+6 weeks from 2010 to 2019. RESULTS: Of the 1163 EPIs included in our study, 241 (20.7%) survived, while 849 (73.0%) died in the delivery room and 73 (6.3%) died in the neonatal intensive care unit. Among all included EPIs, 862 (74.1%) died from withholding or withdrawal of care. Regardless of stratification according to GA or birth weight, the proportion of total mortality attributable to withdrawal of care is high. For infants with the GA of 24 weeks, active treatment did not extend their survival time (P = 0.224). The survival time without severe morbidity of the active treatment was significantly longer than that of withdrawing care for infants older than 25 weeks (P < 0.001). Over time, the survival rate improved, and the withdrawal of care caused by socioeconomic factors and primary nonintervention were reduced significantly (P < 0.001). CONCLUSIONS: The mortality rate of EPIs is still high. Withdrawal of care is common for EPIs with smaller GA, especially in the delivery room. It is necessary to use a multi-center, large sample of real-world data to find the survival limit of active treatment based on our treatment capabilities.

3.
J Am Chem Soc ; 143(35): 14025-14040, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34432467

RESUMO

Transition-metal-catalyzed enantioselective C-H functionalization has become a powerful strategy for the formation of C-C or C-X bonds, enabling the highly asymmetric synthesis of a wide range of enantioenriched compounds. Atropisomers are widely found in natural products and pharmaceutically relevant molecules, and have also found applications as privileged frameworks for chiral ligands and catalysts. Thus, research into asymmetric routes for the synthesis of atropisomers has garnered great interest in recent years. In this regard, transition-metal-catalyzed enantioselective C-H functionalization has emerged as an atom-economic and efficient strategy toward their synthesis. In this Perspective, the approaches for the synthesis of atropisomers by transition-metal-catalyzed asymmetric C-H functionalization reactions are summarized. The main focus here is on asymmetric catalysis via Pd, Rh, and Ir complexes, which have been the most frequently utilized catalysts among reported enantioselective C-H functionalization reactions. Finally, we discuss limitations on available protocols and give an outlook on possible future avenues of research.

4.
Bioresour Technol ; 339: 125502, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34304097

RESUMO

Septic tank effluent from rural areas was an ideal medium for cultivating oleaginous microalgae. However, the characteristics of septic tank effluents varied greatly due to the different incoming wastewater, and bring uncertain risks for algal growth. In this study, an oleaginous microalgae was cultivated in septic effluents from different mixed wastewater. The results showed that the effluent from pure toilet wastewater was the best medium to achieve the highest biomass yield (1.68 g·L-1) and productivity (154.6 mg·L-1·d-1). In contrast, the discharge of kitchen or laundry wastewater reduced the biomass production by 50.5-79.1%. That caused much lower lipids production in effluents from mixed wastewater regardless of its high lipids content and saturation degree. The results suggest that the discharge of kitchen or laundry wastewater bring risks for biomass and lipids production, and should be separated from the toilet wastewater before entering into septic tank.


Assuntos
Chlorella , Poluentes Ambientais , Microalgas , Lipídeos , Águas Residuárias
5.
BMC Cancer ; 21(1): 677, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34102999

RESUMO

BACKGROUND: Malignant melanoma of the female genital tract is relatively uncommon and accounts for 3-7% of all melanoma localizations. This study aimed to identify driver genes in melanoma of the female genital tract with the purpose of enhancing understanding of disease pathogenesis and identifying potential new therapeutic targets to develop effective therapies. METHODS: KIT (CD117) and BRAF expression were detected immunohistochemically. Polymerase Chain Reaction (PCR) and Sanger sequencing techniques were performed to identify the mutational status of BRAF, NRAS, KRAS, NF1, KIT, PDGFRA and SF3B1 on 19 melanomas of the female genital tract, paired with 25 cutaneous melanomas, 18 acral melanomas and 11 melanomas of nasal cavity. RESULTS: Somatic variant analysis identified KRAS (6/19; 32%) as the most commonly mutated gene, followed by KIT (4/19; 21%), SF3B1 (3/19; 16%) and NRAS (1/19; 5%). None of the cases were found to harbor BRAF, NF1 and PDGFRA mutations in melanomas of the female genital tract. However, none of the cases were found to harbor SF3B1 and KIT mutations in cutaneous melanomas, acral melanomas and melanomas of nasal cavity. Recurrent KIT mutations, as well as mutations in the less frequently mutated genes NRAS and SF3B1, were exclusively detected in vulvovaginal melanomas, but not in tumors arising in the cervix. However, recurrent KRAS mutations were detected in similar frequencies in tumors of the vulva, vagina, and cervix. Additionally, recurrent KRAS and KIT mutations occurred predominantly in polygonal and epithelioid cell types of melanoma in the female genital tract. Immunohistochemistry revealed moderate or strong cytoplasmic CD117 expression in 6 of the 19 cases (31.6%). CONCLUSIONS: We observed that gynecologic melanoma harbored distinct mutation rates in the KIT, BRAF, SF3B1, KRAS, and NRAS genes. Our findings support the notion that gynecologic melanoma is a distinct entity from non-gynecologic melanoma, and these findings offer insights into future therapeutic options for these patients.


Assuntos
Neoplasias dos Genitais Femininos/genética , Melanoma/genética , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Fatores de Processamento de RNA/metabolismo , Adulto , Idoso , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Melanoma/patologia , Pessoa de Meia-Idade , Mutação
6.
Neurosci Bull ; 37(9): 1289-1302, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34076854

RESUMO

Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-ß superfamily. It is widely distributed in the central and peripheral nervous systems. Whether and how GDF-15 modulates nociceptive signaling remains unclear. Behaviorally, we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats. Electrophysiologically, we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia (DRG) neurons. Furthermore, GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents, and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction. GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels, suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel. Immunohistochemistry results showed that activin receptor-like kinase-2 (ALK2) was widely expressed in DRG medium- and small-diameter neurons, and some of them were Nav1.8-positive. Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors. Inhibition of PKA and ERK, but not PKC, blocked the inhibitory effect of GDF-15 on Nav1.8 currents. These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK, which mediate the peripheral analgesia of GDF-15.


Assuntos
Analgesia , Canal de Sódio Disparado por Voltagem NAV1.8 , Animais , Gânglios Espinais , Fator 15 de Diferenciação de Crescimento , Ratos , Células Receptoras Sensoriais , Canais de Sódio , Tetrodotoxina/farmacologia
7.
J Am Chem Soc ; 143(25): 9639-9647, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34152752

RESUMO

The stereoselective construction of all-carbon quaternary stereocenters, especially acyclic ones, represents an important challenge in organic synthesis. In particular, homopropargyl amides with a quaternary stereocenter ß to a nitrogen atom are valuable synthetic intermediates, which could be transformed to diverse chiral structures through alkyne transformations. However, highly enantioselective synthetic methods for homopropargyl amides with a ß quaternary stereocenter are extremely rare. We report here unprecedented substrate-directed, iridium-catalyzed enantioselective hydroalkynylations of trisubstituted alkenes to form an acyclic all-carbon quaternary stereocenter ß to a nitrogen atom. The hydroalkynylation of enamide occurred with unconventional selectivity, favoring the more hindered reaction site. Homopropargyl amides with ß-stereocenters were prepared in high regio- and enantioselectivities. Combined experimental and computational studies revealed the origin of the regio- and enantioselectivities.

8.
BMC Ophthalmol ; 21(1): 222, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001069

RESUMO

BACKGROUND: Ocular toxoplasmosis caused by Toxoplasma gondii is an infectious disease which is widely distributed around the world and can present with various clinic manifestations. We are here reporting an unusual case presented with epiretinal membrane (ERM), i.e., macular pucker. CASE PRESENTATION: A 16-year old male patient visited our outpatient clinic complaining of decreased vision for about 8 years in his left eye. The best-corrected visual acuity (BCVA) was 20/20 OD and 20/400 OS. There was sensory exotropia in his left eye. No inflammatory cells or flare were found in his anterior chamber or vitreous cavity OU. An ERM involving his left macular area was found on his dilated fundus exam, which was confirmed by Optical Coherence Tomography (OCT). The ERM was found to involve his left macular area with his foveal ellipsoid zone absent. The right eye was found to be within normal limit. After a thorough discussion with the patient and his parents about treatment options and surgical benefits, risks and alternatives, we performed vitrectomy, peeled off the ERM and collected the vitreous sample for parasite testing during the procedure. Patient's blood also was drawn for serological testing. Vitreous sample analysis and serological tests confirmed ocular toxoplasmosis OS as his final diagnosis. Unfortunately, the BCVA of this patient was not improved after the surgery, but the exotropia disappeared. CONCLUSION: ERM is an unusual clinical presentation of ocular toxoplasmosis. We may add Toxoplasma gondii infection as a differential diagnosis when encountering ERM cases.


Assuntos
Membrana Epirretiniana , Toxoplasmose Ocular , Adolescente , Membrana Epirretiniana/cirurgia , Humanos , Masculino , Tomografia de Coerência Óptica , Toxoplasmose Ocular/diagnóstico , Acuidade Visual , Vitrectomia
9.
J Ethnopharmacol ; 275: 114045, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33831463

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Dang-Gui-Si-Ni (DGSN) decoction as a classic prescription has been widely used for thousands of years in the clinical practice of traditional Chinese medicine (TCM). Especially in recent years, the potential efficacy of TCM for the treatment of Raynaud's syndrome has attracted great attention as there are still no specific remedies for this disease. However, the active constituents and underlying mechanisms responsible for the therapeutic benefits are not well understood, which makes it difficult to ensure quality control or to design research and drug development strategies. To identify the potential pharmacodynamic ingredients (PPIs) of TCM will help to achieve suitable process control procedures for industrial production and large-scale manufacturing. AIM OF THE STUDY: In the present study, we propose a multi-dimensional qualitative analysis method combining water-decoction spectra, in-vitro intestinal absorption spectra, in-vivo plasma spectra, and molecular docking of components to quickly identify the PPIs for the DGSN decoction of TCM. MATERIALS AND METHODS: Water-based decoctions of DGSN were prepared in accordance with the clinical use registered in ancient books. Ultra-high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q/TOF-MS) coupled with computerized modelling activity screening was used to quickly identify the PPIs of the DGSN decoction. Bioactive compounds absorbed in vitro were identified using the everted intestinal sac model from rats and compounds absorbed in vivo were confirmed in portal vein blood samples obtained following oral administration in rats. Molecular docking validation experiments were adopted to predict the binding activity to coagulation factors I, II, VII, X, and IX. The active components were further confirmed by pharmacodynamics analysis. The anticoagulant activity of the DGSN decoction was verified using rat models. RESULTS: Thirty-one compounds were identified in the DGSN decoction. According to the in vivo experiments, 22 compounds that could be absorbed in vivo were detected by the everted intestinal sac model in rats. This model greatly reduces the scope of PPIs and is easy to perform. Ten compounds were detected in the portal vein blood in rats. The compounds detected in plasma provide stronger evidence supporting the PPIs. Molecular docking in vitro experiments indicated that 7 compounds exhibited better binding activity with coagulation factors I, II, VII, X, and IX. The animal experiments confirmed that the DGSN decoction could improve the microcirculation, providing indirect proof of anticoagulant activity suggested by the molecular docking studies. Finally, based on the multi-dimensional methods, 9 potential compounds present in the DGSN decoction were identified as PPIs (i.e., ferulic acid, paeoniflorin, albiflorin, chlorogenic acid, cryptochlorogenic acid, liquiritin, liquiritin apioside, cinnamaldehyde and glycyrrhizic acid). CONCLUSION: Overall, this study combined the water-decoction spectra, intestinal absorption spectra in vitro, plasma spectra in vivo, and molecular docking studies to establish a multi-dimensional qualitative analysis method of the DGSN decoction. Meanwhile, 9 compounds in DGSN decoction were identified as PPIs using this method, and are proposed for application as quality standards for complex TCM prescriptions.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Administração Oral , Animais , Fatores de Coagulação Sanguínea/química , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Flavonoides/análise , Flavonoides/química , Hidroxibenzoatos/análise , Hidroxibenzoatos/química , Absorção Intestinal , Masculino , Medicina Tradicional Chinesa , Microcirculação/efeitos dos fármacos , Simulação de Acoplamento Molecular , Nucleosídeos/análise , Nucleosídeos/química , Plasma/química , Ratos Sprague-Dawley , Doença de Raynaud/tratamento farmacológico , Terpenos/análise , Terpenos/química
10.
Food Chem ; 356: 129678, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33812185

RESUMO

This study investigated the effect of frozen storage periods (0, 2, 4, 6, or 8 weeks) of raw meat and stewing on the flavor of chicken broth. With the increased storage duration of frozen raw material, the contents of the free amino acids, nucleotides and mineral elements in the broth decreased significantly, especially within the first 4 weeks, and then increased significantly. Meanwhile, the volatile compounds showed the reverse trend. The results from the E-nose, E-tongue and sensory evaluation indicated a progressive difference in overall flavor profiles between the samples. The sensory scores of the meaty and fatty traits reached a maximum as raw chicken meat was stored for 4 weeks at -18 °C, which should be related to the increased contents of aldehydes and 2-pentyl furan. Overall, the limited storage duration of frozen raw meat can enhance the flavor of chicken broth.


Assuntos
Culinária/métodos , Carne/análise , Aminoácidos/análise , Animais , Galinhas , Cromatografia Líquida de Alta Pressão , Nariz Eletrônico , Congelamento , Cromatografia Gasosa-Espectrometria de Massas , Paladar , Fatores de Tempo , Compostos Orgânicos Voláteis/análise
11.
Artigo em Inglês | MEDLINE | ID: mdl-33929794

RESUMO

Implantation of intraocular lens after combined procedure of vitrectomy and cataract surgery is usually required to reduce the postoperative refraction errors. However, because of the severe fibrosis of the anterior capsule and the adhesion between the anterior and posterior capsules, it is difficult to reopen the capsular bag to complete the secondary IOL implantation. We describe here a surgical approach for reopening the severe adhesion between capsules and removing the significant fibro-proliferative membranous material by injecting viscoelastic agent into the periphery of the capsular bag to separate the anterior and posterior capsules. The IOL was implanted into the capsular bag without any zonular rupture or posterior capsule tear. The position of the intraocular lens was stable during postoperative follow-ups up to 3 months. Our procedure to open a severely fibrosis capsule is safe and effective, and may be used as a preferred method.

12.
J Surg Oncol ; 123(4): 1134-1143, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33497476

RESUMO

BACKGROUND AND OBJECTIVES: To construct a prediction model of solitary pulmonary nodules (SPNs), to predict the possibility of malignant SPNs in patients aged 15-85 years in northwest China for clinical diagnostic and therapeutic decision-making. METHODS: The features of SPNs were assessed by multivariate logistic regression, followed by visualization using a nomogram. Hosmer lemeshow was applied to evaluate the fitting degree of the model. The area under the receiver operating characteristic (ROC) curve was identified to determine the discriminative ability of the model. RESULTS: Lobulation, spiculation, pleural-tag, carcinoembryonic antigen, neuron-specific enolase, and total serum protein were independent predictors of malignant pulmonary nodules (p < .05). Lobulation (100 points) scored the highest in the nomogram, and the Hosmer-Lemeshow goodness-of-fit statistic was 0.805 (p > .05). The area under curve (AUC) of the modeling and validation groups using logistic regression were 0.859 (95% CI, 0.805-0.903) and 0.823 (95% CI, 0.738-0.890), respectively. Moreover, the AUC of our model was higher than that of the Mayo model, VA model, and Peking University (AUC 0.823 vs. 0.655 vs. 0.603 vs. 0.521). CONCLUSION: Our prediction model is more suitable for predicting the possibility of malignant SPNs in northwest China, and can be calculated using a nomogram to determine further treatments.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/diagnóstico , Modelos Estatísticos , Nomogramas , Nódulo Pulmonar Solitário/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Fatores de Risco , Nódulo Pulmonar Solitário/sangue , Nódulo Pulmonar Solitário/cirurgia , Adulto Jovem
13.
J Am Chem Soc ; 143(1): 114-120, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33356232

RESUMO

A rhodium(III)-catalyzed enantioselective C-H activation/annulation process is disclosed. With a catalyst derived from a chiral CpRh(III) complex and a chiral acid, the direct annulation reactions between 1-aryl isoquinoline derivatives and alkynes take place smoothly to afford a series of chiral azoniahelicenes in excellent yields and enantioselectivity (up to 99% yield and 96% ee). Mechanistic studies suggest that C-H bond cleavage may be the turnover-limiting step.

14.
Breast ; 54: 319-327, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33278648

RESUMO

PURPOSE: To evaluate the effect of the 21-gene recurrence score (RS) assay in breast cancer-specific mortality (BCSM) and decision-making for chemotherapy in older (aged ≥65 years) breast cancer. METHODS: We retrospectively included older patients with T1-2N0 and estrogen receptor-positive breast cancer in the Surveillance, Epidemiology, and End Results database. Cox regression model and competing-risks model were used for data analysis. RESULTS: This study included 8524 patients, 1987 (23.3%) had low RS, 5059 (59.4%) had intermediate RS, and 1478 (17.3%) had high RS. Chemotherapy was administrated in 2.0%, 8.6%, and 51.2% for low, intermediate, and high RS cohorts, respectively (P < 0.001). A total of 597 deaths were recorded, including one-quarter of breast cancer-related deaths and three-quarters as competing causes of death. The 5-year BCSM was 5.4%, 4.7%, and 9.1% for low, intermediate, and high RS cohorts, respectively (P < 0.001), using the Cox regression model, and was 0.8%, 0.9%, and 5.2% for low, intermediate, and high RS cohorts using the competing-risks regression, respectively (P < 0.001). RS was independently correlated with BCSM in both prognostic models. The stratified analysis demonstrated that chemotherapy was not correlated with a lower risk of BCSM in intermediate and high RS cohorts in both prognostic models. Sensitivity analyses replicated similar findings after stratification by the year of diagnosis and patients' age. CONCLUSIONS: The competing-risks model is useful in dealing with multiple end events for older breast cancer patients. 21-gene RS was independently associated with BCSM. However, chemotherapy did not significantly decrease the risk of BCSM in intermediate and high RS cohorts.


Assuntos
Neoplasias da Mama/genética , Tomada de Decisão Clínica/métodos , Testes Genéticos/estatística & dados numéricos , Recidiva Local de Neoplasia/etiologia , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Feminino , Testes Genéticos/métodos , Humanos , Recidiva Local de Neoplasia/genética , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER
15.
Sci Rep ; 10(1): 22070, 2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33328559

RESUMO

The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p < 0.001). There were significant differences in the hazard curve between IDC and MBC. The hazard curve for breast cancer mortality in the IDC cohort peaked at 3 years (2%), and then changed to a slowly decreasing plateau after prolonged follow up. However, the hazard curve for breast cancer mortality in the MBC cohort peaked at 2 years (7%), then declined sharply between 3 and 6 years, and changed to a low death rate after a follow-up time exceeding 6 years. Subgroup analyses revealed that the hazard curves significantly differed between IDC and MBC after stratifying by tumor stage and hormone receptor status. Our study suggests that patients with MBC should receive more effective systemic agents and intensive follow-up because of their significantly augmented risk of death compared to IDC patients.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Invasividade Neoplásica , Fatores de Risco , Taxa de Sobrevida
16.
BMC Cancer ; 20(1): 1146, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238939

RESUMO

BACKGROUND: The value of postmastectomy radiotherapy (PMRT) for pathological node-positive triple-negative breast cancers (TNBC) remains debatable. The aim of this population-based retrospective study was to evaluate the effect of PMRT on survival outcomes in this population. METHODS: Patients diagnosed with stage T1-4N1-N3M0 TNBC between 2010 and 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We used univariate and multivariate Cox regression hazards method to determine the independent prognostic factors associated with 3-year breast cancer-specific survival (BCSS). The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. RESULTS: Of the 4398 patients included in this study, 2649 (60.2%) received PMRT. Younger age, black ethnicity, and advanced tumor (T) and nodal (N) stage were the independent predictors associated with PMRT receipt (all P < 0.05). Patients who received PMRT showed better 3-year BCSS (OR = 0.720, 95% CI = 0.642-0.808, P < 0.001) than those that did not. The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. The results showed that PMRT was associated with better 3-year BCSS in patients with stage T3-4N1 (P = 0.042), T1-4N2 (P < 0.001), and T1-4N3 (P < 0.001), while comparable 3-year BCSS was found between the PMRT and non-PMRT cohorts with T1-2N1 disease (P = 0.191). CONCLUSIONS: Radiotherapy achieved better 3-year BCSS in TNBC patients with stage T3-4N1 and T1-4N2-3 disease. However, no survival benefit was found with the addition of PMRT in patients with T1-2N1 TNBC.


Assuntos
Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Radioterapia Adjuvante/mortalidade , Neoplasias de Mama Triplo Negativas/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Lobular/patologia , Carcinoma Lobular/radioterapia , Feminino , Seguimentos , Humanos , Mastectomia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/radioterapia
17.
Neurosci Bull ; 36(12): 1484-1499, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33067780

RESUMO

Trigeminal neuralgia is a debilitating condition, and the pain easily spreads to other parts of the face. Here, we established a mouse model of partial transection of the infraorbital nerve (pT-ION) and found that the Connexin 36 (Cx36) inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia. Mefloquine reversed the pT-ION-induced upregulation of Cx36, glutamate receptor ionotropic kainate 2 (GluK2), transient receptor potential ankyrin 1 (TRPA1), and phosphorylated extracellular signal regulated kinase (p-ERK) in the trigeminal ganglion. Cold allodynia but not mechanical allodynia induced by pT-ION or by virus-mediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS102, and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanical allodynia. In conclusion, we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2, TRPA1, and p-ERK signaling.


Assuntos
Conexinas/metabolismo , Dor Facial , Hiperalgesia , Receptores de Ácido Caínico/metabolismo , Canal de Cátion TRPA1/metabolismo , Gânglio Trigeminal , Animais , China , Temperatura Baixa , Conexinas/antagonistas & inibidores , Dor Facial/metabolismo , Indóis , Masculino , Mefloquina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Oximas
18.
ACS Chem Neurosci ; 11(19): 2935-2943, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-32926772

RESUMO

The Tacr3 gene encodes tachykinin receptor 3 (NK3R), which belongs to the tachykinin receptor family. This family of proteins includes typical G protein-coupled receptors and belongs to the rhodopsin subfamily. NK3R functions by binding to its high-affinity ligand, neurokinin B(NKB). The role of Tacr3/NK3R in growth and reproduction has been extensively studied, but Tacr3/NK3R is also widely expressed in the nervous system from the spinal cord to the brain and is involved in both physiological and pathological processes in the nervous system, including mood disorders, chronic pain, learning and memory deficiencies, Alzheimer's disease, Parkinson's disease, addiction-related processes, hypoxic-ischemic encephalopathy, body fluid management, neural development, and schizophrenia. Here, we summarize the structure of NK3R/NKB and its cellular signaling as well as the expression of Tacr3/NK3R in the nervous system, and we provide a comprehensive summary of the role of Tacr3/NK3R in neurological diseases, including reproduction-related disorders and other neurological diseases. At the end of this review, we propose the hypothesis that Tacr3/NK3R mediates a variety of brain functions by affecting the excitability of different neurons with specific functions. On the basis of this "excited or not" hypothesis, more studies related to Tacr3 should be carried out in other nervous system diseases in order to better understand the biological roles of Tacr3.


Assuntos
Neurocinina B , Receptores da Neurocinina-3 , Reprodução , Animais , Humanos , Neurônios , Receptores Acoplados a Proteínas G
19.
J Am Chem Soc ; 142(37): 15678-15685, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32865413

RESUMO

Rhodium(III)-catalyzed enantioselective oxidative C-H/C-H cross-coupling reaction between two arenes is disclosed. With the combination of a chiral CpRh(III) complex and a chiral carboxylic acid additive, the direct coupling reactions between 1-aryl isoquinoline derivatives and electron-rich heteroarenes such as thiophenes, furans, benzothiophenes, and benzofurans are realized via a double C-H functionalization process. A series of axially chiral compounds are obtained in excellent yields and enantioselectivities (up to 99% yield and 99% ee). Mechanistic studies suggest that both C-H bond cleavages may not be the turnover-limiting step.

20.
J Ophthalmol ; 2020: 8956275, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908687

RESUMO

The ultimate goal of cataract surgery is to restore the accommodation while restoring distance visual acuity. Different kinds of accommodative intraocular lens (IOLs) and surgical techniques have been suggested to apply during the surgery, but they showed poor postoperative accommodation. It is possible to achieve this goal by refilling the lens with an injectable polymer. We present a summary of the existing materials, methods, results, and some obstacles in clinical application that remain of lens refilling for restoration of accommodation. Two main problems have restricted the clinical application of this technique. One was the formation of postoperative secondary capsule opacification and the other was the different accommodative power after surgery.

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