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1.
Food Chem ; 398: 133874, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35964567

RESUMO

The influence of ultrasound-assisted immersion freezing (UF), immersion freezing (IF), and air freezing (AF) on the protein oxidation, structure, and thermal stability of chicken breast during frozen storage was evaluated in this study. Compared to IF and AF samples, the UF samples had a lower carbonyl content, dityrosine content, and surface hydrophobicity of myofibrillar protein (MP) (P < 0.05), as well as a higher free amino group content and total and reactive sulfhydryl content (P < 0.05). Moreover, UF significantly delayed the deterioration of protein secondary and tertiary structures and the decrease in protein thermal stability during frozen storage (P < 0.05). Additionally, the UF samples at 180 days had similar protein structures and quality characteristics to the IF samples at 90 days or the AF samples at 60 days. Overall, UF treatment can effectively retard protein oxidation, protein structure deterioration, and protein thermal stability loss caused by frozen storage.


Assuntos
Galinhas , Proteínas , Animais , Congelamento , Interações Hidrofóbicas e Hidrofílicas , Estabilidade Proteica
2.
Cell Discov ; 8(1): 94, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127333

RESUMO

Skull base chordoma (SBC) is a bone cancer with a high recurrence rate, high radioresistance rate, and poorly understood mechanism. Here, we profiled the transcriptomes of 90,691 single cells, revealed the SBC cellular hierarchies, and explored novel treatment targets. We identified a cluster of stem-like SBC cells that tended to be distributed in the inferior part of the tumor. Combining radiated UM-Chor1 RNA-seq data and in vitro validation, we further found that this stem-like cell cluster is marked by cathepsin L (CTSL), a gene involved in the packaging of telomere ends, and may be responsible for radioresistance. Moreover, signatures related to partial epithelial-mesenchymal transition (p-EMT) were found to be significant in malignant cells and were related to the invasion and poor prognosis of SBC. Furthermore, YL-13027, a p-EMT inhibitor that acts through the TGF-ß signaling pathway, demonstrated remarkable potency in inhibiting the invasiveness of SBC in preclinical models and was subsequently applied in a phase I clinical trial that enrolled three SBC patients. Encouragingly, YL-13027 attenuated the growth of SBC and achieved stable disease with no serious adverse events, underscoring the clinical potential for the precision treatment of SBC with this therapy. In summary, we conducted the first single-cell RNA sequencing of SBC and identified several targets that could be translated to the treatment of SBC.

3.
Chemosphere ; 308(Pt 2): 136276, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36058375

RESUMO

Visible-light (VL) photocatalysis has been regarded as an intriguing technology for the control of persistent environmental pollutants. In this study, the novel homogeneous Co doped-Bi/BiOBr nanocomposites (CB-X) were prepared via a facile one-step hydrothermal method, featured with a uniform 0D Bi nanodots distribution on 2D Co-doped BiOBr nanosheets, and the photocatalytic performance was evaluated by decomposing the BPA as a prototype contaminant. The degradation experiment indicated that the optimal CB-2 nanocomposite exhibited the best photocatalytic activity with a 94% removal efficiency of BPA under the VL irradiation of 30 min; And the corresponding apparent rate constant (k) was as high as 0.107 min-1, which was 10.7 times greater than that of Bi/BiOBr (0.010 min-1). Benefiting from the modulation effect of Co-doping on the intrinsic electron configuration of Bi/BiOBr, the elevated VL adsorption capacity and accelerated h+/e- pairs separation rate were achieved, which were evidenced by photoluminescence (PL) spectroscopy, photo-electrochemical measurements and density functional theory (DFT) calculation. Moreover, the major reactive species in CB-X/VL system were uncovered to be •O2- and 1O2, whereas •OH and h+ presented a secondary contribution in the BPA elimination. Finally, the possible photocatalytic mechanism involved in CB-X nanocomposites and BPA degradation pathways were proposed on the basis of the various intermediates and products detected by LC-MS/MS.

4.
Eur J Med Genet ; 65(11): 104608, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36100157

RESUMO

Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative disorders, which is characterized by the presence of progressive spasticity and weakness in bilateral lower limbs. Spastic paraplegia 62 (SPG62) caused by the endoplasmic reticulum lipid raft associated 1 (ERLIN1) gene mutation is a rare subtype of HSP. Herein, we report the case of the first Chinese SPG62 patient, explore the potential pathogenic mechanism and review ERLIN1-related HSP patients. A 23-year-old man had progressive difficulty in walking and gait abnormalities for more than 11 years. Physical examination showed slightly reduced muscle strength (5-/5) and elevated muscle tone in the lower limbs and hyperreflexia in four limbs. Genetic analysis identified a novel splicing site mutation in ERLIN1 gene (c.504+1G > A), which was predicted to disturb the normal splicing process of mRNA by bioinformatic tools. Minigene experiment further confirmed the mutation c.504+1G > A could cause erroneous deletion of Exon 7 in the mRNA, which may change the conserved prohibitin (PHB) domain of erlin-1 and affect the function of erlin1/2 complex. Thus, we identified a pathogenic mutation of ERLIN1 splicing site causing delayed-onset pure HSP. This study widened the genetic and phenotypic spectrum of SPG62.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36103368

RESUMO

BACKGROUND: Demographic factors have been implicated in THA and TKA outcome disparities. Specifically, patients' racial backgrounds have been reported to influence outcomes after surgery, including length of stay, discharge disposition, and inpatient readmissions. However, in the United States, health-impacting socioeconomic disadvantage is sometimes associated with racial differences in ways that can result in important confounding, thereby raising the question of whether race-associated post-THA/TKA adverse outcomes are an independent function of race or a byproduct of confounding from socioeconomic deprivation, which is potentially addressable. To explore this, we used the Area Deprivation Index (ADI) as a proxy for socioeconomic disadvantage, since it is a socioeconomic parameter that estimates the likely deprivation associated with a patient's home address. QUESTIONS/PURPOSES: The goal of this study was to investigate (1) whether race (in this study, Black versus White) was independently associated with adverse outcomes, including prolonged length of stay (LOS > 3 days), nonhome discharge, 90-day readmission, and emergency department (ED) visits while controlling for age, gender, BMI, smoking, Charlson comorbidity index (CCI), and insurance; and (2) whether socioeconomic disadvantage, measured by ADI, substantially mediated any association between race and any of the aforementioned measured outcomes. METHODS: Between November 2018 and December 2019, 2638 underwent elective primary THA and 4915 patients underwent elective primary TKA for osteoarthritis at one of seven hospitals within a single academic center. Overall, 12% (742 of 5948) of patients were Black and 88% (5206 of 5948) were White. We included patients with complete demographic data, ADI data, and who were of Black or White race; with these criteria, 11% (293 of 2638) were excluded in the THA group, and 27% (1312 of 4915) of patients were excluded in the TKA group. In this retrospective, comparative study, patient follow-up was obtained using a longitudinally maintained database, leaving 89% (2345 of 2638) and 73% (3603 of 4915) for analysis in the THA and TKA groups, respectively. For both THA and TKA, Black patients had higher ADI scores, slightly higher BMIs, and were more likely to be current smokers at baseline. Furthermore, within the TKA cohort there was a higher proportion of Black women compared with White women. Multivariable regression analysis was utilized to assess associations between race and LOS of 3 or more days, nonhome discharge disposition, 90-day inpatient readmission, and 90-day ED admission, while adjusting for age, gender, BMI, smoking, CCI, and insurance. This was followed by a mediation analysis that explored whether the association between race (the independent variable) and measured outcomes (the dependent variables) could be partially or completely attributable to confounding from the ADI (the mediator, in this model). The mediation effect was measured as a percentage of the total effect of race on the outcomes of interest that was mediated by ADI. RESULTS: In the THA group, after adjusting for age, gender, BMI, smoking, CCI, and insurance, White patients had lower odds of experiencing an LOS of 3 days or more (OR 0.43 [95% confidence interval (CI) 0.31 to 0.59]; p < 0.001) and nonhome discharge (OR 0.39 [95% CI 0.27 to 0.56]; p < 0.001). In mediation analysis, ADI partially explained (or mediated) 37% of the association between race and LOS of 3 days or more (-0.043 [95% CI -0.063 to -0.026]; p < 0.001) and 40% of the association between race and nonhome discharge (0.041 [95% CI 0.024 to 0.059]; p < 0.001). However, a smaller direct association between race and both outcomes was observed (LOS 3 days or more: -0.075 [95% CI -0.13 to -0.024]; p = 0.004; nonhome discharge: 0.060 [95% CI 0.016 to 0.11]; p = 0.004). No association was observed between race and 90-day readmission or ED admission in the THA group. In the TKA group, after adjusting for age, gender, BMI, smoking, CCI, and insurance, White patients had lower odds of experiencing an LOS of 3 days or more (OR 0.41 [95% CI 0.32 to 0.54]; p < 0.001), nonhome discharge (OR 0.44 [95% CI 0.33 to 0.60]; p < 0.001), 90-day readmission (OR 0.54 [95% CI 0.39 to 0.77]; p < 0.001), and 90-day ED admission (OR 0.60 [95% CI 0.45 to 0.79]; p < 0.001). In mediation analysis, ADI mediated 19% of the association between race and LOS of 3 days or more (-0.021 [95% CI -0.035 to -0.007]; p = 0.004) and 38% of the association between race and nonhome discharge (0.029 [95% CI -0.016 to 0.040]; p < 0.001), but there was also a direct association between race and these outcomes (LOS 3 days or more: -0.088 [95% CI -0.13 to -0.049]; p < 0.001; nonhome discharge: 0.046 [95% CI 0.014 to 0.078]; p = 0.006). ADI did not mediate the associations observed between race and 90-day readmission and ED admission in the TKA group. CONCLUSION: Our findings suggest that socioeconomic disadvantage may be implicated in a substantial proportion of the previously assumed race-driven disparity in healthcare utilization parameters after primary total joint arthroplasty. Orthopaedic surgeons should attempt to identify potentially modifiable socioeconomic disadvantage indicators. This serves as a call to action for the orthopaedic community to consider specific interventions to support patients from vulnerable areas or whose incomes are lower, such as supporting applications for nonemergent medical transportation or referring patients to local care coordination agencies. Future studies should seek to identify which specific resources or approaches improve outcomes after TJA in patients with socioeconomic disadvantage. LEVEL OF EVIDENCE: Level III, therapeutic study.

6.
Biomolecules ; 12(9)2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36139159

RESUMO

Circular RNA (circRNA) is often regarded as a special kind of non-coding RNA, involved in the regulation mechanism of various diseases, such as tumors, neurological diseases, and inflammation. In a broad spectrum of biological processes, the modification of the 76-amino acid ubiquitin protein generates a large number of signals with different cellular results. Each modification may change the result of signal transduction and participate in the occurrence and development of diseases. Studies have found that circRNA-mediated ubiquitination plays an important role in a variety of diseases. This review first introduces the characteristics of circRNA and ubiquitination and summarizes the mechanism of circRNA in the regulation of ubiquitination in various diseases. It is hoped that the emergence of circRNA-mediated ubiquitination can broaden the diagnosis and prognosis of the disease.

7.
Cancers (Basel) ; 14(18)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36139591

RESUMO

We compared perioperative outcomes after on-clamp versus off-clamp robot-assisted partial nephrectomy (RAPN) for >7 cm renal masses. A multicenter dataset was queried for patients who had undergone RAPN for a cT2cN0cM0 kidney tumor from July 2007 to February 2022. The Trifecta achievement (negative surgical margins, no severe complications, and ≤ 30% postoperative estimated glomerular filtration rate (eGFR) reduction) was considered a surrogate of surgical quality. Overall, 316 cases were included in the analysis, and 58% achieved the Trifecta. A propensity-score-matched analysis generated two cohorts of 89 patients homogeneous for age, ASA score, preoperative eGFR, and RENAL score (all p > 0.21). Compared to the on-clamp approach, OT was significantly shorter in the off-clamp group (80 vs. 190 min; p < 0.001), the incidence of sRFD was lower (22% vs. 40%; p = 0.01), and the Trifecta rate higher (66% vs. 46%; p = 0.01). In a crude analysis, >20 min of hilar clamping was associated with a significantly higher risk of sRFD (OR: 2.30; 95%CI: 1.13-4.64; p = 0.02) and with reduced probabilities of achieving the Trifecta (OR: 0.46; 95%CI: 0.27-0.79; p = 0.004). Purely off-clamp RAPN seems to be a safe and viable option to treat cT2 renal masses and may outperform the on-clamp approach regarding perioperative surgical outcomes.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36117401

RESUMO

BACKGROUND: Empathy is the ability to understand and share the feelings of others. It is fundamental to emotional intelligence and social iterations. Neuroimaging studies have demonstrated that empathy activates brain regions associated with the social cognition network. AIM: To explore the neural underpinnings of empathy revealed by stereoelectroencephalography (SEEG) utilizing recurrence quantification analysis (RQA). METHODS: This retrospective cohort included 38 epilepsy patients with SEEG implantation. RQA metrics were applied to parameterize the network organization of default mode network (DMN) brain regions. The relationships between DMN, seizure burden activity and empathy, as measured using the Interpersonal Reactivity Index were examined using partial least-square regression and mediation analysis. RESULTS: RQA metrics with DMN (R2 = 0.75, PBonferroni < 0.001) and its subsystems (medial temporal subsystem: R2 = 0.53, PBonferroni < 0.001; Core subsystem: R2 = 0.70, PBonferroni < 0.001; dorsal medial subsystem: R2 = 0.48, PBonferroni < 0.001) were positively correlated with empathy scores. Out of 13 RQA metrics, the mean diagonal line length, entropy of the diagonal line lengths, trapping time, maximal vertical line length and recurrence time of 2nd type, were found to be statistically higher in patient cohorts with reportedly high empathy. Furthermore, DMN characteristics (b path: F = 3.69, P = 0.04), rather than seizure burdens (direct effect: t = 0.33, P = 0.74, c' = - 0.007) mediated empathy status. CONCLUSION: The present study used various RQA metrics to parameterize the network organization of DMN, and determine the neural underpinning of DMN for empathy modulation. This article is protected by copyright. All rights reserved.

9.
Org Lett ; 24(36): 6588-6593, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36053071

RESUMO

The enantioselective organocatalytic conjugate alkenylation of ß-substituted alkenyl benzimidazoles afforded ß-stereogenic 2-alkyl benzimidazole derivatives in excellent enantioselectivities. Chiral binaphthols were effective catalysts for promoting the nucleophilic addition of bench-stable alkenyl trifluoroborate salts under mild conditions, expanding their applications by utilizing C=N-containing azaarenes as activating groups. The synthetic utility of this strategy is demonstrated by conversions into several useful enantiomerically enriched benzimidazole building blocks.


Assuntos
Benzimidazóis , Sais , Catálise , Estrutura Molecular , Estereoisomerismo
10.
J Ethnopharmacol ; 299: 115696, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36087845

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Pinellia ternata (Thunb.) Breit, called Pinelliae Rhizoma (PR) and Banxia in Chinese, is a well-known traditional Chinese medicine (TCM) with the functions of "removing dampness-phlegm" and "downbear counterflow and check vomiting". PR has potential toxic effects that can be detoxified by Fuzhi processing (repeated processing using one or multiple adjuvants) with specific adjuvants. AIM OF THE STUDY: This paper aims to provide a summary of traditional and current processing methods used to detoxify PR. MATERIALS AND METHODS: The available references of the processing methods of PR from the classic books of Materia Medica, literature, online databases and masters or doctoral theses are collected and summarized. We also discussed the possible processing mechanisms of how we can achieve a safer and effective application of PR via these processing methods. RESULTS: PR cannot be administered orally before processing. PR contains nucleoside alkaloids, cerebrosides, fatty acids, lectin, polysaccharides, and calcium oxalate crystals. To date, although the active substances of PR are still unclear, the toxic components are almost completely clarified as needle-like calcium oxalate crystals (NCOCs) and lectin proteins. Furthermore, the toxic effects of PR include causing death in animals, inflammation, conjunctival irritation, pregnancy toxicity, teratogenicity, visceral toxicity, aphonia and vomiting. From ancient times to now, Fuzhi methods have remained the predominant method for PR processing, and the main adjuvants used are ginger juice, alum, licorice and lime. In addition, detoxification mechanisms are related to removing or damaging the NCOC and lectin in PR based on processing with adjuvants. Currently, Fuzhi processing has been greatly improved, and novel processing technologies with novel adjuvants have been used for PR processing. However, there are still some flaws in PR processing, which should be urgently solved in the future, and clarifying the characteristic bioactive compounds in PR corresponding to its function or effects is the most important step for PR processing. CONCLUSION: Our present paper reviewed the previous literature regarding all aspects of the processing of PR, and this paper will be helpful for achieving a safer and effective application of PR and its processed products and will also be beneficial for the further optimization of processing technology and clinical medication safety of PR.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Materia Medica , Pinellia , Adjuvantes Farmacêuticos , Alcaloides/análise , Animais , Oxalato de Cálcio , Cerebrosídeos/análise , Medicamentos de Ervas Chinesas/química , Ácidos Graxos/análise , Lectinas/análise , Materia Medica/análise , Medicina Tradicional Chinesa , Nucleosídeos/análise , Pinellia/química , Rizoma/química , Tecnologia Farmacêutica/métodos , Vômito
11.
J Phys Chem Lett ; : 8864-8871, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36125003

RESUMO

The relatively weak Raman enhanced factors of semiconductor-based substrate limit its further application in surface-enhanced Raman scattering (SERS). Here, a kind of two-dimensional (2D) semimetal material, molybdenum carbide (Mo2C) film, is prepared via a chemical vapor deposition (CVD) method, and the origin of SERS is investigated for the first time. The detection limits of the prepared Mo2C films for crystal violet (CV) and rhodamine 6G (R6G) molecules are low at 10-6 M and 10-8 M, respectively. Our detailed theoretical analysis, based on density functional theory and the finite element method, demonstrates that the enhancement of the 2D Mo2C film is indeed CM in nature rather than the EM effects. Besides, the basic doping strategies are proposed to further optimize the SERS sensitivity of Mo2C for Fermi level regulation. We believe this work will provide a helpful guide for developing a highly sensitive semimetal SERS substrate.

12.
NanoImpact ; : 100428, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36126900

RESUMO

BACKGROUND: Nanoparticles have been employed as nanopesticides for pest control in agriculture. However, the harmful effects of their chemical synthesis on human and environmental health have resulted in increased use of green synthetic approaches, including the use of plant extracts. The brown planthopper, Nilaparvata lugens (Stål) (BPH), is a severe pest of rice plants (Oryza sativa L.), especially in Asia. It is usually controlled chemically but has developed resistance against many insecticides. RESULTS: In this study, we synthesized metallic silver (Ag-NPs) and copper-oxide (CuO-NPs) nanoparticles using the exogenous phytohormone, gibberellic acid (GA3), as a reducing agent. We then sprayed them separately on rice plants and BPH together and evaluated their effects on the plants and insects. SEM and TEM images showed that the synthesis was successful, indicated by the sizes (25-60 nm), uniform shape and spherical and cubical structures of Ag-NPs, as well as by the rugby sheet-like of CuO-NPs with lateral sizes of 150-340 nm and thickness of 30-70 nm. Independent applications of the nanoparticles and GA3 on rice plants induced different volatile profiles, of which the highest number emitted was under Ag-NPs, including the highest emission of linalool. Transcriptome analysis showed that Ag-NPs-treated rice plants showed different transcriptome profiles compared to the control, 24 h after treatment, including the upregulation of the linalool synthase gene, genes of plants transcription factors such as WRKY, bHLH and NAC and other genes involved in plant defense responses. In all treatments, the mortality rate of BPH increased with an increase in NPs concentrations over time but was prominent under Ag-NPs treatment. The LC50 values for Ag-NPs and CuO-NPs decreased with an increase in time. Also, the nanoparticles increased the activities of protective enzymes (POD, SOD and CAT), inhibited that of detoxification enzymes (A-CHE, ACP and AKP), and reduced total protein concentrations in the BPH. CONCLUSIONS: These results show that synthesizing nanoparticles using phytohormones may be a safer and environmentally friendly option, which also holds promise for controlling the BPH in rice production.

13.
Bioinformatics ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094339

RESUMO

MOTIVATION: Species tree inference from multi-copy gene trees has long been a challenge in phylogenomics. The recent method ASTRAL-Pro has made large strides by enabling multi-copy gene family trees as input and has been quickly adopted. Yet, its scalability, especially memory usage, needs to improve to accommodate the ever-growing dataset size. RESULTS: We present ASTRAL-Pro 2, an ultrafast and memory efficient version of ASTRAL-Pro that adopts a placement-based optimization algorithm for significantly better scalability without sacrificing accuracy. AVAILABILITY: The source code and binary files are publicly available at https://github.com/chaoszhang/ASTER; data are available at https://github.com/chaoszhang/A-Pro2_data. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

14.
Nat Cancer ; 3(9): 1088-1104, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36138131

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Characterization of genetic alterations will improve our understanding and therapies for this disease. Here, we report that PDAC with elevated expression of METTL16, one of the 'writers' of RNA N6-methyladenosine modification, may benefit from poly-(ADP-ribose)-polymerase inhibitor (PARPi) treatment. Mechanistically, METTL16 interacts with MRE11 through RNA and this interaction inhibits MRE11's exonuclease activity in a methyltransferase-independent manner, thereby repressing DNA end resection. Upon DNA damage, ATM phosphorylates METTL16 resulting in a conformational change and autoinhibition of its RNA binding. This dissociates the METTL16-RNA-MRE11 complex and releases inhibition of MRE11. Concordantly, PDAC cells with high METTL16 expression show increased sensitivity to PARPi, especially when combined with gemcitabine. Thus, our findings reveal a role for METTL16 in homologous recombination repair and suggest that a combination of PARPi with gemcitabine could be an effective treatment strategy for PDAC with elevated METTL16 expression.

15.
Front Med (Lausanne) ; 9: 950564, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117971

RESUMO

Background: Oral dental treatment cause anxiety, fear, and physical stress. This study aimed to investigate the efficacy and safety of moderate sedation by remimazolam with alfentanil vs. propofol with alfentanil in third molar extraction. Methods: This single-center, randomized, single-blind clinical trial included 100 adults who underwent third molar ambulatory extraction. All patients had continuous infusion of Alfentanil 0.2 µg/kg/min. Group remimazolam with alfentanil (group RA) had an induction dose of 80 µg/kg and maintenance dosage of 5 µg/kg/min. In group propofol with alfentanil (PA group), propofol was infused at an initial concentration of 1.8 µg/mL under target controlled infusion (TCI) mode and a maintenance concentration of 1.5 µg/mL. The incidence rates of adverse effects were recorded and compared. Depth of sedation was assessed using the modified observer alertness/sedation assessment (MOAA/S) and entropy index. Recovery characteristics were recorded and complications observed for next 24 h. Results: The incident of adverse events 6 (12%) in the group RA was lower than the group PA 25 (50%) [Mean difference 0.136 (95%CI, 0.049-0.377); P < 0.05], with no serious adverse events during the sedation procedure. The incidence of injection pain in group RA was significantly lower than that in group PA [4 vs. 26%, mean difference 0.119 (95%CI, 0.025-0.558); P = 0.004]. Before starting local anesthesia, the mean arterial pressure, heart rate, and respiratory rate of the PA group were lower than those of the RA group. None of the patients required further treatments for a decreased heart rate, blood pressure, or low SpO2. The rate of moderate sedation success was 100% in both groups. The MOAA/S score was similar between the groups indicating that the depth of sedation was effective. Group RA had significantly shorter recovery and discharge times than those of group PA. Conclusions: Remimazolam with alfentanil is a safer and more effective alternative for ambulatory sedation and can reduce recovery and discharge time and the incidence of perioperative adverse events compare with propofol. Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier: ChiCTR2200058106.

16.
NPJ Precis Oncol ; 6(1): 66, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123526

RESUMO

Despite limited efficacy of immunotherapy for advanced non-small-cell lung cancer (NSCLC) with driver mutations, whether neoadjuvant immunotherapy could be clinically valuable in those patients warrants further investigation. We utilized 40 oncogene-mutant NSCLC treated with induction immunotherapy from a large consecutive multicenter cohort. Overall response rate was 62.5% while 2 patients had disease progression. Of 39 patients that received surgery, R0 resection rate was 97.4%. The major pathological response (MPR) rate was 37.5% and the pathological complete response (pCR) rate was 12.5%. Pre-treatment PD-L1 expression was not a predictive biomarker in these patients. Median disease-free survival for all oncogenic mutation and EGFR mutation was 28.5 months. Indirect comparison through integrating CTONG1103 cohort showed neoadjuvant immunotherapy plus chemotherapy yielded the most superior efficacy among erlotinib and chemotherapy for resectable EGFR-mutant NSCLC. No MPR patients were identified with neoadjuvant immunotherapy plus chemotherapy for uncommon EGFR insertion or point mutations. Our results indicated the potential clinical feasibility of neoadjuvant immunotherapy for resectable localized oncogene-mutant NSCLC especially for EGFR-mutant NSCLC.

17.
Front Neurol ; 13: 970111, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36062009

RESUMO

Background: Previous observational studies have supported the hypothesis that vitamin D supplementation protects against stroke. However, several current intervention studies contradict this observation. Therefore, we conducted a meta-analysis to investigate further the association between vitamin D supplementation and the risk of stroke. Methods: This meta-analysis was conducted in accordance with the PRISMA statement and included all the randomized controlled trials (RCTs) that analyzed the relationship between vitamin D supplementation and the risk of stroke. A literature search strategy was established, and the following Medical Search Terms (MeSH) were used: "vitamin D," "Calcitriol," "Calcifediol," "Cholecalciferol," "25-Hydroxyvitamin D 2," "ergocalciferols," "stroke," and stroke-derived terms. We searched for articles published before January 2022 in several databases, namely, PubMed, Web of Science, EMBASE, and The Cochrane Library. We also reviewed references included in relevant published meta-analyses and searched the http://www.ClinicalTrials.gov website for additional RCTs. The Q test and I 2 were utilized to assess the degree of heterogeneity among the studies. Review Manager 5.3 and STATA16.0 software programs were used to assess the literature quality and perform statistical analyses. Results: In total, twenty-four RCTs (86,202 participants) were included. There was no statistical heterogeneity among the RCTs (I 2 = 0.0%, P = 0.94) included in this meta-analysis. We determined that vitamin D supplementation was not associated with a reduced risk of stroke compared with the placebo (RR = 1.02, 95% CI: 0.93-1.13, P = 0.65). In total, 10 studies only included women, and 14 studies included women and men among the 24 RCTs. Therefore, we performed a subgroup analysis based on sex. After the subgroup analysis, the effect remained statistically insignificant (mixed-sex group: RR = 1.06, 95% CI: 0.93-1.22, P = 0.37, women group: RR = 0.98, 95% CI: 0.86-1.13, P = 0.80). The results were generally comparable, based on age, body mass index (BMI), follow-up period, baseline 25-hydroxyvitamin D (25(OH)D) levels, the designated endpoint, latitude, vitamin D dosage, type of vitamin D administered, and an absence or presence of concurrent calcium supplementation (P > 0.05). Conclusion: Our study revealed that additional vitamin D supplementation did not reduce the risk of stroke. Therefore, additional RCTs of similar design should not be encouraged to assess any association between vitamin D supplementation and reduced stroke risk.

18.
Respirology ; 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36054068

RESUMO

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is the most prevalent chronic respiratory disease. This study investigated the global, regional and country burden of COPD based on gender, age and socio-demographic indices (SDIs) in the last 30-year period from 1990 to 2019. METHODS: The COPD data, including incidence, mortality and disability-adjusted life years (DALYs), were obtained from the 2019 Global Burden of Disease Study. If age-standardized incidence rate (ASIR) or death rate (ASDR) remains almost constant or decreases, the number of cases will still increase as the global population increases substantially. Estimated annual percentage change (EAPC) was calculated to assess incidence, mortality and DALY trends. RESULTS: The incidence of COPD increased by 85.89% from 8,722,966 cases in 1990 to 16,214,828 cases in 2019, and the ASIR decreased from 216.48/100,000 persons in 1990 (95%UI, 204.56-227.33) to 200.49 per 100,000 persons (95%UI, 188.63-212.57) in 2019. The ASIR increased (EAPC = 0.05, 95%CI, 0.01-0.10) in the low SDI region, was stable in the high SDI region, and fell in the other three SDI regions. Men had a higher ASIR than women over the past 30 years, and there were differences in the incidence rates for different age groups. Male mortality and DALYs were higher than female mortality. ASDR decreased by 2.13% (95%CI, -2.23% to -2.02%) per year and the annual age-standardized DALY rate decreased by 1.97% (95%CI, -2.05% to -1.89%). CONCLUSIONS: The ASIR, ASDR and age-standardized DALY rate of COPD declined overall in the last 30 years, and were highest in the low-middle SDI region.

19.
Front Genet ; 13: 995532, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092871

RESUMO

More and more evidences have showed that the unnatural expression of long non-coding RNA (lncRNA) is relevant to varieties of human diseases. Therefore, accurate identification of disease-related lncRNAs can help to understand lncRNA expression at the molecular level and to explore more effective treatments for diseases. Plenty of lncRNA-disease association prediction models have been raised but it is still a challenge to recognize unknown lncRNA-disease associations. In this work, we have proposed a computational model for predicting lncRNA-disease associations based on geometric complement heterogeneous information and random forest. Firstly, geometric complement heterogeneous information was used to integrate lncRNA-miRNA interactions and miRNA-disease associations verified by experiments. Secondly, lncRNA and disease features consisted of their respective similarity coefficients were fused into input feature space. Thirdly, an autoencoder was adopted to project raw high-dimensional features into low-dimension space to learn representation for lncRNAs and diseases. Finally, the low-dimensional lncRNA and disease features were fused into input feature space to train a random forest classifier for lncRNA-disease association prediction. Under five-fold cross-validation, the AUC (area under the receiver operating characteristic curve) is 0.9897 and the AUPR (area under the precision-recall curve) is 0.7040, indicating that the performance of our model is better than several state-of-the-art lncRNA-disease association prediction models. In addition, case studies on colon and stomach cancer indicate that our model has a good ability to predict disease-related lncRNAs.

20.
iScience ; 25(9): 104991, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36093042

RESUMO

Icaritin has shown antitumor activity in a variety of human solid tumors and myeloid leukemia cells. However, the direct target of icaritin and the underlying mechanisms remain unclear. In our study, CDK2 was found to be a direct target of icaritin in tumor cells. On one hand, icaritin interacted with CDK2 and interfered with CDK2/CyclinE complex formation, resulting in downregulation of CDK2 activity as illustrated with attenuated phosphorylation of FOXO1, Rb, and P27, and E2F/Rb dissociation. On the other hand, icaritin reduced the stability and translation efficiency of CDK2-mRNA by modulating microRNA-597 expression. To be of functional importance, icaritin inhibited proliferation and promoted apoptosis of tumor cells in vitro and in vivo, which was consistent with CDK2 inhibitors-k03861. Our data revealed CDK2 as the direct target of icaritin for its antitumor effects, which may suggest new therapeutics of icaritin or combinational therapeutics involving both icaritin and CDK2 inhibitors for cancers.

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