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1.
RSC Adv ; 12(47): 30764-30770, 2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36349153

RESUMO

Materials with high ferroelectric polarization strength and sufficient absorption of visible light have unique advantages in photocatalysis. Based on the results of structure search, phonon frequency, and elasticity coefficient calculations, CaBiO3 has a stable R3 polar structure. First-principles calculations indicate that R3-CaBiO3 is a potentially efficient ferroelectric visible-light photocatalytic material for hydrogen production. CaBiO3 under slight strain can maintain high ferroelectric polarization strength, strong visible light absorption capacity and small effective mass. CaBiO3 under tensile strain has potentially ferroelectric photogeneration of hydrogen with a band edge position that crosses the redox potential of water. These results can expand the application of Bi-based materials in photocatalytic hydrogen production.

2.
Nephron ; : 1-10, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36349777

RESUMO

INTRODUCTION: IgA nephropathy is the most common primary glomerulonephritis among adults in clinic. Thin basement membrane nephropathy is often underestimated or even omitted if it coincides with IgA nephropathy. Therefore, it is necessary to study the epidemiological, clinical, and molecular characteristics of the concurrence of this entity. METHODS: Eight patients with concurrent IgA nephropathy and thin basement membrane nephropathy (IgA-T) were retrospectively analyzed based on their clinicopathological characteristics. Genetic analysis was performed using whole-exome sequencing and Sanger's sequencing. Data of the patients with IgA nephropathy and normal basement membrane (IgA-N) and variants in the local in-house database were used as controls. All candidate variants were assessed in silico. RESULTS: The clinical manifestations of patients with IgA-T were hematuria, proteinuria, and renal insufficiency. Histopathological analysis showed mild mesangial hyperplasia, focal segmental glomerulosclerosis, podocyte activation, and foot process fusion. Crescent was rarely seen. COL4A and/or podocyte cytoskeleton and mitochondria-related gene variants were detected in seven IgA-T patients. Three patients exhibited pathogenic variants of COL4A, including a new variant. All IgA-T and one IgA-N patient possessed ITGB4 and/or PLEC variants, but there was no corresponding genotype-phenotype relationship. Six patients possessed other podocyte cytoskeleton and mitochondria-related gene variants such as NPHS2, SRGAP1, MYO1E, MYO1C, WT1, and COQ9, which were first reported in patients with IgA-T and were not in controls. Altogether, there were no significant differences in the degrees of proteinuria, serum creatinine, and eGFR during the follow-up period of 5-10 years, but there was a significant difference in the degree of proteinuria between IgA-T patients with podocyte-related gene variants and IgA-N patients. In the IgA-T group, patients with podocyte-related gene variants seemed predisposed to progress than patients without those variants, with higher proteinuria and serum creatinine and reduced eGFR. CONCLUSION: Concurrent thin basement membrane nephropathy and/or heterozygous COL4A gene pathogenic variants do not necessarily predict the short-term progress of sporadic IgA nephropathy in adults. Predisposition factors for this disease progression should be considered for detecting the variants of COL4A and podocyte cytoskeleton and mitochondria-related genes simultaneously, which also manifests the complexity and heterogeneity of IgA nephropathy with concurrent thin basement membrane nephropathy.

3.
Front Public Health ; 10: 1014995, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420011

RESUMO

Background: The increasing incidence of carbapenem-resistant bacterial infections has become a serious public health threat. This study aimed to investigate and analyze the current regional differences in carbapenem-resistant gram-negative bacteria (CRGN) in a major Province of China, and provide suggestions for preventing hospital infections. Methods: A questionnaire survey was used to obtain the current data on CRGN from 36 hospitals in Shandong Province, China, from 2019 to 2020. The association between the detection rates and discovery rates of CRGN and the use of antibacterial drugs was analyzed using Spearman's correlation coefficient. In addition, we compared the detection rates of CRGN and antibacterial drugs using hospitals categorized according to different levels and economic areas using the Kruskal-Wallis test. Results: The average detection rates of CRGN across the 36 hospitals varied from 1.91% to 66.04%. The discovery rate of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant Acinetobacter baumannii (CRAB) remained below 5‰, and that of carbapenem-resistant Pseudomonas aeruginosa (CRPA) was below 10‰. Except for CRAB, the correlations between the detection rate and antimicrobial drug use intensity and carbapenem drug use percentage were 0.11-0.29 and 0.31-0.47, respectively. Carbapenem drug use was higher in the provincial hospital group than in the prefecture-level hospitals (P < 0.05), and that in the high-economic regional hospital group was higher than in the low-economic regional hospital group (P < 0.05). Conclusions: The detection and discovery rates of CRE were low, and those of CRAB were high in Shandong Province. Larger hospitals have higher carbapenem drug use. These results can be used as a reference for preventing CRGN infections in developing countries and provide a basis for regional carbapenem resistance prevention and control strategies.


Assuntos
Infecções Bacterianas , Infecções por Bactérias Gram-Negativas , Humanos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Hospitais
4.
RSC Adv ; 12(49): 32027-32034, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36415548

RESUMO

Ferroelectric oxides with large bandgaps have restricted applications in photovoltaic and photocatalytic fields. Based on recent experiments with the ferroelectric compound, LiSbO3, the stability and optoelectronic properties of a new ferroelectric compound, namely Li2SbBiO6, are investigated in this study. The calculated results demonstrate that Li2SbBiO6 satisfies the stability conditions of the elastic coefficients and phonon dynamics. Li2SbBiO6 maintains the ferroelectric polarization strength of LiSbO3 and significantly reduces the bandgap, and thus has been explored for applications in photovoltaic and photocatalytic fields. Li2SbBiO6 is a new potential ferroelectric oxide for harvesting visible light owing to its suitable bandgap and a large hole-electron effective mass ratio.

5.
J Med Internet Res ; 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36417585

RESUMO

BACKGROUND: The COVID-19 pandemic has imposed additional stress on population health that may result in a change of sleeping behavior. OBJECTIVE: In this study, we hypothesized that using natural language processing (NLP) to explore social media would help to assess the mental health condition of people experiencing insomnia after the outbreak of COVID-19. METHODS: We designed a retrospective study using public social media content from Twitter. We categorized insomnia-related tweets based on time into two intervals: pre-pandemic (01/01/2019 to 01/01/2020) and peri-pandemic (01/01/2020 to 01/01/2021). We performed sentiment analysis using pretrained transformers in conjunction with Dempster-Shafer theory (DST) to classify the polarity of emotions into positive, negative, and neutral. We validated the proposed pipeline on 300 annotated tweets. Additionally, we performed temporal analysis to examine the effect of time on the users' insomnia experience, using logistic regression. RESULTS: We extracted 305,321 tweets containing the word insomnia (pre-pandemic, 139,561 and peri-pandemic, 165,760). The best combination of pretrained transformers via DST yielded 84% accuracy. Next, using this pipeline, we found that the odds of negative tweets (OR, 1.39; 95% CI, 1.37-1.41, P<.001) were higher peri-pandemic compared to pre-pandemic. The likelihood of negative tweets after midnight was 21% higher than before midnight (OR, 1.21; 95%CI: 1.19-1.23, P<.001). Peri-pandemic, while the odds of negative tweets were 2% higher after midnight compared to before midnight (OR, 1.02; 95%CI: 1.00-1.07, P = .008), they were 43% higher (OR, 1.43; 95%CI: 1.40-1.46, P<.001) peri-pandemic. CONCLUSIONS: The proposed novel sentiment analysis pipeline that combines pretrained transformers by DST is capable of classifying the emotion or sentiment of insomnia-related tweets. Twitter users shared more negative tweets about insomnia peri-pandemic than pre-pandemic. Future studies using a natural language processing framework could assess tweets about other psychological distress, habit changes, weight gain due to inactivity, and the effect of viral infection on sleep.

6.
Diabetes Obes Metab ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36346108

RESUMO

AIM: To investigate the distribution of abdominal fat, particularly ectopic fat accumulation, in relation to glucose metabolism in overweight/obese patients. MATERIALS AND METHODS: This study included 257 overweight/obese subjects with body mass index ≥23 kg/m2 . All the subjects underwent an oral glucose tolerance test. Magnetic resonance imaging-proton density fat fraction was used to measure fat accumulation in the liver, pancreas and abdomen. Impaired glucose regulation (IGR) was defined as the presence of prediabetes or diabetes. RESULTS: Liver fat content (LFC) and visceral adipose tissue (VAT) were higher in overweight/obese subjects with diabetes than in those with normal glucose tolerance (NGT). No significant differences were observed in the pancreas fat content and subcutaneous fat area between subjects with NGT and IGR. LFC was an independent risk factor of IGR (odds ratio = 1.824 per standard deviation unit, 95% CI 1.242-2.679, p = .002). Compared with the lowest tertile of LFC, the multivariate-adjusted odds ratio for the prevalence of IGR in the highest tertile was 2.842 (95% CI 1.205-6.704). However, no association was observed between the VAT per standard deviation increment and tertiles after adjusting for multiple factors. For discordant visceral and liver fat phenotypes, the high LFC-low VAT and high LFC-high VAT groups had a higher prevalence of IGR than the low LFC-low VAT group. However, there was no difference in the prevalence of IGR between the low LFC-low VAT and low LFC-high VAT groups. CONCLUSION: Compared with visceral and pancreatic fat content, LFC is a superior risk biomarker for IGR in overweight/obese subjects.

7.
World J Gastroenterol ; 28(41): 5993-6001, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36405104

RESUMO

BACKGROUND: Collagenous gastritis (CG) is a rare condition whose pathogenesis may be related to immune abnormalities. We report a case of CG from China. CASE SUMMARY: A 24-year-old woman presented with recurrent abdominal distension and discomfort for 3 mo. Upper gastrointestinal endoscopy found diffuse nodular elevation-depression changes in the mucosa of the entire gastric corpus. Endoscopic ultrasound showed predominant involvement of the lamina propria and submucosa, and computed tomography imaging showed mild enhancement of the gastric wall. Pathological histology revealed that the thickness of the subepithelial collagen band was about 40 µm, and the Masson trichrome staining result was positive and the Congo red staining result was negative. This case is consistent with the child-adolescent type of CG. CONCLUSION: Serum pepsinogen I, pepsinogen II, pepsinogen I/II ratio, and gastrin-17 may be potential non-invasive monitoring markers. Currently, treatments for CG vary, and the likely prognosis is unknown. Individual cases of gastric cancer in patients with CG have been reported.


Assuntos
Gastrite , Síndromes de Malabsorção , Humanos , Adolescente , Feminino , Adulto Jovem , Adulto , Pepsinogênio A , Gastrite/patologia , Pepsinogênio C , Colágeno
8.
Sci Total Environ ; 858(Pt 2): 159774, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36334659

RESUMO

Agricultural plastic-film residues have been considered as one of the important sources of microplastics in the agroecosystem. However, limited researches were conducted on the accumulation of microplastics in long-term film-mulched paddy soil. This study aims to investigate the distribution and the weathering characteristics of filmy microplastics in a mulched paddy field (non-mulch, four years of mulched, and ten years of continuous mulched soil were investigated) in Southwest China. More than 50 % of the microplastics in the mulched soil were 1-3 mm, whereas the largest percentage of the microplastics in the non-mulched soil was <1 mm (55.3 %). Microplastic compositions in this field mainly consist of polyester (PES) and polyethylene (PE) (82.1 %). The abundance of microplastics increases with the film mulching time, which were 76.2 ± 18.4, 118.6 ± 44.8, and 159.6 ± 23.5 items kg-1 in soil with non-mulching, four years of mulching, and ten years of continuous mulching, respectively. The filmy microplastics accumulated annually in the plough layer is estimated at 18.1 million items ha-1. Weathering characteristics of filmy microplastics extracted from paddy soil were characterized using FTIR, SEM-EDS, AFM, and contact angle meter. The vinyl, carbonyl, and hydroxyl indices calculated from FTIR results showed that the degradation degree of microplastics incereased as mulching time rose; compared with commercial PE films, the oxygen-containing functional groups of soil-extracted PE films were increased. This study revealed the status of microplastic pollution in paddy soil with long-term mulching. It provided primary data and a scientific basis for further study on environmental behavior and ecological impacts of microplastics in agricultural soils.

9.
Int J Biol Macromol ; 223(Pt A): 307-315, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36336159

RESUMO

In the present study, four different combinations of gums, including carrageenan (CG), its binary blends with xanthan gum (XG) or guar gum (GG) in equal ratios, and its ternary blends with XG and GG in three equal ratios, were involved into making partially crystalline emulsions (PCEs), respectively. The freshly prepared emulsions were systematically characterized by rheological property, particle size distribution, microscopic morphology, interfacial property, and intermolecular interactions, and their emulsion stabilities were further evaluated using multiple light scattering technique and storage test. All PCEs stabilized by gum blends (CG + XG, CG + GG, and CG + XG + GG) obtained decreased apparent viscosities at 0.01 s-1 (10.12-25.32 Pa·s), particle sizes (3.12-4.06 µm), as well as interfacial protein concentrations (22.60-27.01 mg/m2), which were much lower than those with single CG (35.98 Pa·s, 6.72 µm, and 47.74 mg/m2, respectively). The microscopic morphology showed that blending CG with XG and/or GG contributed to formation of firmer three-dimensional matrix, thereby preventing the aggregation of fat droplets. Inclusion of XG and/or GG also significantly reduced contribution of hydrophobic interactions from 0.72 to 0.24-0.44 mg/mL. Both multiple light scattering and storage test revealed that emulsion instabilities were mainly manifested as a clarification at the bottom and an agglomeration at the top. PCE-CG + XG + GG exhibited superior stability with low creaming index (6.20 %) and viscosity (1180.0 mPa·s) after three months of storage. The research aims to evaluate the effects of CG and its blends with XG and GG on stability of PCEs, and the results potentially provide valuable information for manufacture of stable PCE foods.

10.
Front Public Health ; 10: 1031743, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388350

RESUMO

Exposure to environmental ionizing radiation (IR) is ubiquitous, and large-dose exposure to IR is known to cause DNA damage and genotoxicity which is associated with an increased risk of cancer. Whether such detrimental effects are caused by exposure to low-dose IR is still debated. Therefore, rapid and early estimation of absorbed doses of IR in individuals, especially at low levels, using radiation response markers is a pivotal step for early triage during radiological incidents to provide adequate and timely clinical interventions. However, there is currently a crucial shortage of methods capable of determining the extent of low-dose IR exposure to human beings. The phosphorylation of histone H2AX on serine 139 (designated γ-H2AX), a classic biological dosimeter, can be used to evaluate the DNA damage response. We have developed an estimation assay for low-level exposure to IR based on the mass spectrometry quantification of γ-H2AX in blood. Human peripheral blood lymphocytes sensitive to low-dose IR, maintaining low temperature (4°C) and adding enzyme inhibitor are proven to be key steps, possibly insuring that a stable and marked γ-H2AX signal in blood cells exposed to low-dose IR could be detected. For the first time, DNA damage at low dose exposures to IR as low as 0.01 Gy were observed using the sensitive variation of γ-H2AX with high throughput mass spectrometry quantification in human peripheral blood, which is more accurate than the previously reported methods by virtue of isotope-dilution mass spectrometry, and can observe the time effect of DNA damage. These in vitro cellular dynamic monitoring experiments show that DNA damage occurred rapidly and then was repaired slowly over the passage of post-irradiation time even after exposure to very low IR doses. This assay was also used to assess different radiation exposures at the in vitro cellular level. These results demonstrate the potential utility of this assay in radiation biodosimetry and environmental risk assessment.


Assuntos
Linfócitos , Radiação Ionizante , Humanos , Relação Dose-Resposta à Radiação , Linfócitos/efeitos da radiação , Dano ao DNA , Espectrometria de Massas
11.
Front Endocrinol (Lausanne) ; 13: 991773, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353229

RESUMO

Background: The treatment strategies and prognosis for gastroenteropancreatic neuroendocrine tumors were associated with tumor grade. Preoperative predictive grading could be of great benefit in the selection of treatment options for patients. However, there is still a lack of effective non-invasive strategies to detect gastrointestinal neuroendocrine tumors (GI-NETs) grading preoperatively. Methods: The data on 147 consecutive GI-NETs patients was retrospectively collected from January 1, 2012, to December 31, 2019. Logistic regression was used to construct a predictive model of gastrointestinal neuroendocrine tumor grading using preoperative laboratory and imaging parameters.The validity of the model was assessed by area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: The factors associated with GI-NETs grading were age, tumor size, lymph nodes, neuron-specific enolase (NSE), hemoglobin (HGB) and sex, and two models were constructed by logistic regression for prediction. Combining these 6 factors, the nomogram was constructed for model 1 to distinguish between G3 and G1/2, achieving a good AUC of 0.921 (95% CI: 0.884-0.965), and the sensitivity, specificity, accuracy were 0.9167, 0.8256, 0.8630, respectively. The model 2 was to distinguish between G1 and G2/3, and the variables were age, tumor size, lymph nodes, NSE, with an AUC of 0.847 (95% CI: 0.799-0.915), and the sensitivity, specificity, accuracy were 0.7882, 0.8710, 0.8231, respectively. Two online web servers were established on the basis of the proposed nomogram to facilitate clinical use. Both models showed an excellent calibration curve through 1000 times bootstrapped dataset and the clinical usefulness were confirmed using decision curve analysis. Conclusion: The model served as a valuable non-invasive tool for differentiating between different grades of GI-NETs, personalizing the calculation which can lead to a rational treatment choice.


Assuntos
Neoplasias Gastrointestinais , Tumores Neuroendócrinos , Humanos , Nomogramas , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Gradação de Tumores , Estudos Retrospectivos , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/cirurgia
12.
Ther Adv Med Oncol ; 14: 17588359221133546, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339926

RESUMO

Background: Savolitinib, a selective MET inhibitor, showed efficacy in patients with non-small cell lung cancer (NSCLC), including pulmonary sarcomatoid carcinoma (PSC), harbouring MET exon 14 skipping alteration (METex14). Objective: To analyse post hoc, the association between circulating tumour DNA (ctDNA) biomarkers and clinical outcomes, including resistance, with savolitinib. Design: A multicentre, single-arm, open-label phase 2 study. Methods: All enrolled patients with baseline plasma samples were included. Outcomes were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) by baseline METex14 and post-treatment clearance, coexisting gene alterations at baseline and disease progression. Results: Among 66 patients with baseline ctDNA sequencing, 46 (70%) had detectable METex14. Frequent coexisting baseline gene alterations included TP53 and POT1 mutations. Patients with detectable baseline METex14 exhibited worse PFS [hazard ratio (HR), 1.77; 95% confidence interval (CI), 0.88-3.57; p = 0.108] and OS (HR, 3.26; 95% CI, 1.35-7.89; p = 0.006) than those without, despite showing a numerically higher ORR. Among 24 patients with baseline detectable METex14 and evaluable postbaseline samples, 13 achieved METex14 clearance post-treatment. Median time to first clearance was 1.3 months (range, 0.7-1.5). METex14 post-treatment clearance was associated with better ORR (92.3%; 95% CI, 64.0-99.8 versus 36.4%; 95% CI, 10.9-69.2; p = 0.0078), PFS (HR, 0.44; 95% CI, 0.2-1.3; p = 0.1225) and OS (HR, 0.31; 95% CI, 0.1-1.0; p = 0.0397) versus non-clearance. Among 22 patients with disease progression, 10 acquired pathway alterations (e.g. in RAS/RAF and PI3K/PTEN) alone or with secondary MET mutations (D1228H/N and Y1230C/H/S). Conclusion: ctDNA biomarkers may allow for longitudinal monitoring of clinical outcomes with savolitinib in patients with METex14-positive PSC and other NSCLC subtypes. Specifically, undetectable baseline METex14 or post-treatment clearance may predict favourable clinical outcomes, while secondary MET mutations and other acquired gene alterations may explain resistance to savolitinib. Registration: The trial was registered with ClinicalTrials.gov (NCT02897479) on 13 September 2016.

13.
Phys Chem Chem Phys ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36448558

RESUMO

Polarized structured nitride semiconductors are attractive due to their unique and environment-friendly electronic properties. The stability, ferroelectricity and photocatalytic and photovoltaic properties of super-wurtzite Mg2XN3 (X = Bi, Mo, Nb, Sb, Ta, Tc and W) were determined based on first principles calculations in this study. The calculated results indicate that Mg2XN3 (X = Sb, Ta, Bi and Nb) are stable polar nitrides by phonon frequencies, elastic coefficients and ferroelectric analysis. Mg2XN3 (X = Sb, Ta and Nb) with large ferroelectric polarization strength could absorb ultraviolet light to promote photocatalytic water splitting for hydrogen production. Mg2BiN3 is a new excellent photovoltaic candidate due to its ideal energy band, high electron mobility, high absorption coefficient and large ferroelectric polarization strength.

15.
J Opt Soc Am A Opt Image Sci Vis ; 39(8): 1385-1392, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36215582

RESUMO

We first introduce a class of a superimposed Hermite-Gaussian-correlated Schell model with a multiple off-axis vortices beam, with the side lobe of the beam carrying one to four vortex singularities at the source plane. Subsequently, the variation laws of this beam after being focused by a thin lens are studied theoretically to obtain the optimal beam parameters. The numerical simulation results show that the beam possesses a unique multiple vortex structure, phase structure, and orbital angular momentum. Its intensity resembles a spiral staircase rotating around the axes. The rotational symmetry property of the transverse energy flow along the z axis was broken by the vortices. The hot spot position can be adjusted flexibly by changing the off-axis distance of vortices. This study is of great significance for nondestructive capture and manipulation of multiple particles or cells.

16.
JTO Clin Res Rep ; 3(10): 100407, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36217329

RESUMO

Introduction: Savolitinib has been found to have encouraging antitumor activity and a favorable safety profile in Chinese patients with pulmonary sarcomatoid carcinoma and other NSCLCs with MET exon 14 skipping alterations (MET ex14 positive) at the primary analysis of a phase 2 study. Here, we present the long-term efficacy and safety data of savolitinib, including subgroup analyses. Methods: This multicenter, single-arm, open-label, phase 2 study in the People's Republic of China enrolled MET inhibitor-naive adults with locally advanced or metastatic METex14-positive NSCLC (NCT02897479). Oral savolitinib at a dose of 400 or 600 mg was administered once daily (body weight dependent). The primary objectives of the final analysis were long-term overall survival (OS) and subgroup analyses by previous systemic treatment, NSCLC subtypes, and brain metastases. Results: At the final analysis cutoff date (June 28, 2021), a total of 70 patients were enrolled and receiving savolitinib, and median follow-up was 28.4 (interquartile range: 26.2-36.3) months. The median OS was 12.5 months (95% confidence interval [CI]: 10.5-21.4 [18- and 24-mo OS rates, 42.1% and 31.5%, respectively]). Median OS in pretreated or treatment-naive patients was 19.4 (95% CI: 10.5-31.3) and 10.9 (95% CI: 7.5-14.0) months, respectively; it was 10.6 months (95% CI: 4.6-14.0) in patients with pulmonary sarcomatoid carcinoma, 17.3 months (95% CI: 10.6-23.6) in other NSCLC subtypes, and 17.7 months (95% CI: 10.5-not evaluable) in patients with brain metastases. No new safety signals emerged with prolonged follow-up and exposure. Conclusions: The updated results further confirm the favorable benefit and acceptable safety of savolitinib in Chinese patients with METex14-positive NSCLC.

17.
Eur Radiol ; 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36255486

RESUMO

OBJECTIVES: The relative incremental predictive value of myocardial deformation over ventricular volume for future adverse events in patients with repaired tetralogy of Fallot (rTOF) remains unknown. We aimed to determine the incremental prognostic value of myocardial deformation over ventricular volume to predict adverse events in patients with rToF. METHODS: We retrospectively included patients with rTOF who completed cardiac magnetic resonance (CMR) and follow-up in our hospital from January 2014 to October 2020, and stratified according to the presence or absence of adverse events during follow-up. The strain parameters of the right ventricular (RV) and left ventricular (LV) were obtained from CMR-derived feature tracking. Multivariable Cox proportional hazard models and net reclassification improvement analysis were used to analyze the prognostic information of biventricular strain and volume parameters in rTOF patients. RESULTS: Among 98 patients with rTOF, 54 (55.1%) experienced primary and/or secondary events during a median follow-up period of 27.0 months. Univariable analysis indicated that RV volume and strain were significantly associated with both primary events and all adverse events (all p < .01). Multivariable Cox regression and net reclassification improvement analyses achieved incremental global χ2 (all p < .001), C index (all p < .001), and overall correct reclassification by sequentially adding CMR-derived RV volume, RV strain and LV strain parameters to preexisting clinical factors in adverse events model analyses. CONCLUSIONS: RV and LV myocardial deformation provided incremental prognostic information and significant improvement for risk stratification over RV size and clinical variables and therefore can be combined to further enhance prognostication. KEY POINTS: • RV volume and strain were significantly associated with both primary events and all adverse events, whereas LV volume and strain were associated with primary events. • Ventricular myocardial deformation is a strong predictor of adverse outcomes of patients with repaired tetralogy of Fallot, providing increased prognostic information and significantly improved risk stratification over ventricular size.

18.
J Org Chem ; 87(21): 14879-14888, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36223839

RESUMO

The versions of Miyaura borylation and protoboration of alkynes catalyzed by low loadings of palladium (400 mol ppm = 0.04 mol %) have been developed. These transformations have a broad substrate scope, good functional-group compatibility, and gram-scale synthetic ability.


Assuntos
Alcinos , Paládio , Catálise
19.
Biomaterials ; 290: 121833, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36201945

RESUMO

Photodynamic therapy (PDT) has recently emerged as a promising, targeted treatment modality for glioblastoma (GBM) which is the most vicious type of brain tumor. Successful GBM-PDT hinges upon light activation of a photosensitizer accumulated in the tumor. However, inadequate tumor accumulation of photosensitizer severely limits the success of PDT of GBM. To tackle this difficulty, we herein propose a drug delivery strategy of "platelets with photo-controlled release property". This strategy exploits platelets as carriers to deliver a photosensitizer which, in the current study, is a nano-composite (BNPD-Ce6) comprised of chlorine e6 (Ce6) loaded to boron nitride nanoparticles with a surface coating of polyglycerol and doxorubicin. To demonstrate the working mechanism and therapeutic advantage of this strategy, we loaded mouse platelets with BNPD-Ce6 to yield the nano-device BNPD-Ce6@Plt. In vitro experiments showed BNPD-Ce6@Plt to have a high loading capacity and efficiency. Laser irradiation (LI) at a wavelength of 808 nm induced ROS generation in BNPD-Ce6@Plt which displayed rapid activation, aggregation, and speedy discharge of BNPD-Ce6 into co-cultured GL261 mouse GBM cells which in turn, after LI, exhibited marked ROS generation, DNA damage, reduced viability, and cell death. In vivo animal experiments, mice that were intravenously injected with BNPD-Ce6@Plt exhibited rapid and extensive BNPD-Ce6 accumulation in both subcutaneous and intra-brain GL261 tumors shortly after LI of the tumors and the tumors displayed massive tissue necrosis after LI for a second time. Finally, a PDT regimen of two intravenous BNPD-Ce6@Plt injections each followed by multiple times of extracranial LI at the tumor site significantly inhibited the growth of intra-brain GL261 tumors and markedly increased the survival of the host animals. No apparent tissue damage was found in vital organs. Our findings make a compelling case for the notion that platelets are efficient carriers that can photo-controllably deliver nano-photosensitizers to achieve highly targeted and efficacious PDT of GBM. This work presents a novel approach to GBM-PDT with great translational potential.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Fotoquimioterapia , Porfirinas , Camundongos , Animais , Glioblastoma/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Preparações de Ação Retardada , Linhagem Celular Tumoral , Porfirinas/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Neoplasias Encefálicas/tratamento farmacológico
20.
Nat Commun ; 13(1): 6244, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36271048

RESUMO

The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms underlying such opposing behaviors remain elusive. Here, using the recently developed AAV1-mediated anterograde transsynaptic tagging technique in mice, we show that NAc neurons receiving basolateral amygdala inputs (NAcBLA) promote positive reinforcement via disinhibiting dopamine neurons in the ventral tegmental area (VTA). In contrast, NAc neurons receiving paraventricular thalamic inputs (NAcPVT) innervate GABAergic neurons in the lateral hypothalamus (LH) and mediate aversion. Silencing the synaptic output of NAcBLA neurons impairs reward seeking behavior, while silencing of NAcPVT or NAcPVT→LH pathway abolishes aversive symptoms of opiate withdrawal. Our results elucidate the afferent-specific circuit architecture of the NAc in controlling reward and aversion.


Assuntos
Núcleo Accumbens , Alcaloides Opiáceos , Camundongos , Animais , Núcleo Accumbens/metabolismo , Recompensa , Área Tegmentar Ventral/fisiologia , Neurônios Dopaminérgicos
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