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1.
Reprod Biol Endocrinol ; 21(1): 1, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36600238

RESUMO

BACKGROUND: The exact role of sperm reactive oxygen species (ROS) in early embryo development has yet to be fully identified, and most of existing research did not differentiate female infertility factors, ignoring the importance of oocyte quality in embryo development and the large differences in oocyte quality in women with infertility of different etiologies. And there has been no relevant report on whether different types of sperm ROS have distinct effects on embryo development. This study aimed to study the impact of selected sperm ROS, namely, sperm mitochondrial ROS (mROS) and hydrogen peroxide, on human embryo development after conventional in vitro fertilization (IVF) cycles in patients with normo-ovulatory infertility vs. anovulatory infertility. METHODS: This was a prospective investigation including 393 couples underwent IVF cycles, among whom 90 patients had anovulatory infertility and 303 patients had normo-ovulatory infertility in a public university-affiliated in vitro fertilization center. Sperm mROS and hydrogen peroxide testing were performed by flow cytometry and analyzed for their relationship with embryo development indices on days 1-6 after IVF. Multivariate logistic regression analysis was used to control for female potential confounders. The nonlinear effects of sperm ROS on embryo development were analyzed by the Restricted cubic spline (RCS) method. RESULTS: 1. Multivariate linear logistic regression analysis showed that high proportion of mROS positive sperm improved the 2PN rate (OR = 1.325, 95% CI: 1.103-1.595), day 3 embryo utilization rate (OR = 1.362, 95% CI: 1.151-1.614) and good-quality day 3 embryo rate (OR = 1.391, 95% CI: 1.089-1.783) in patients with anovulatory infertility. High percentage of sperm mROS and hydrogen peroxide had adverse effects on cleavage-stage embryo and blastocyst development in patients with normo-ovulatory infertility. 2. For patients with polycystic ovarian syndrome (PCOS) anovulatory infertility, there were significant distinct effects on embryo development indices between sperm mROS and hydrogen peroxide, and the increased rate of sperm mROS improved the good-quality day 3 embryo rate (OR = 1.435, 95% CI: 1.045-1.981); however, high percentage of sperm hydrogen peroxide reduced the blastocyst utilization rate (OR = 0.555, 95% CI: 0.353-0.864) and the good-quality blastocyst rate (OR = 0.461, 95% CI: 0.292-0.718). 3. Multivariate RCS analysis revealed that sperm ROS had a nonlinear (such as a parabolic curve) effect on embryo development in patients with anovulatory infertility (P < 0.05), and either greatly increased or greatly decreased affected cleavage-stage embryo and blastocyst development. The effects of sperm ROS in patients with normo-ovulatory infertility were both linear and nonlinear. CONCLUSIONS: These findings indicate that contrary effects of sperm mROS on embryo development depending on whether patients treated with IVF cycles had normal ovulation. Regardless of whether the patients ovulated normally, increased sperm hydrogen peroxide rate damaged blastocyst development. It is necessary to evaluate male sperm ROS levels and the female ovulatory state to determine an individualized intervention plan before starting cycles, as this may be beneficial for infertile couples.


Assuntos
Peróxido de Hidrogênio , Infertilidade Feminina , Humanos , Masculino , Feminino , Gravidez , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio/farmacologia , Estudos Prospectivos , Sêmen , Fertilização In Vitro/métodos , Desenvolvimento Embrionário , Espermatozoides , Infertilidade Feminina/terapia , Taxa de Gravidez , Estudos Retrospectivos
2.
PLoS One ; 18(1): e0279334, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36652490

RESUMO

Considering the consumer's anticipated regret caused by price discount, the impact of anticipated regret and manufacturers' fairness concerns on pricing and profits is explored, and a revenue-sharing contract to optimize the profits of supply chain is explored. In centralized decision-making model with manufacturer's fairness neutrality and retailer-led decentralized decision-making model with the manufacturer's fairness concerns, numerical simulation and model comparison is used to analyse regret sensitivity coefficient, consumer heterogeneity, the fairness concern coefficient on pricing decisions and profit coordination. Our results reveal that consumer's anticipated regret has a negative impact on product prices, retailer's profit and manufacturer's profit. Manufacturer's fairness concerns also increase product price and reduce profits of all parties. Retailer-led supply chain can share the revenue to achieve Pareto optimization. When formulating promotional strategies, retailers should consider the characteristics of anticipated regrets of consumers.


Assuntos
Comércio , Tomada de Decisões , Comércio/métodos , Custos e Análise de Custo , Contratos , Comportamento do Consumidor
3.
Nat Commun ; 14(1): 296, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36653349

RESUMO

Spatially resolved transcriptomics involves a set of emerging technologies that enable the transcriptomic profiling of tissues with the physical location of expressions. Although a variety of methods have been developed for data integration, most of them are for single-cell RNA-seq datasets without consideration of spatial information. Thus, methods that can integrate spatial transcriptomics data from multiple tissue slides, possibly from multiple individuals, are needed. Here, we present PRECAST, a data integration method for multiple spatial transcriptomics datasets with complex batch effects and/or biological effects between slides. PRECAST unifies spatial factor analysis simultaneously with spatial clustering and embedding alignment, while requiring only partially shared cell/domain clusters across datasets. Using both simulated and four real datasets, we show improved cell/domain detection with outstanding visualization, and the estimated aligned embeddings and cell/domain labels facilitate many downstream analyses. We demonstrate that PRECAST is computationally scalable and applicable to spatial transcriptomics datasets from different platforms.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Humanos , Transcriptoma/genética , Perfilação da Expressão Gênica/métodos , Análise por Conglomerados , Análise Espacial , Análise de Célula Única/métodos
4.
Pathol Res Pract ; 242: 154329, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36680928

RESUMO

Osteosarcoma (OS) is one of the most common primary bone malignancy. Combining chemotherapy and surgical treatment significantly improved clinical outcomes for osteosarcoma patients. Osteosarcoma stem cells (OSCs) are often more malignant than differentiated cancer cells and are a key determinant of responses to chemotherapy and radiation therapy, therefore, the removal of OSCs could be an effective therapeutic strategy. Myxoprotein 1 (MUC1) is aberrantly overexpressed in many human cancers and it promotes cancer stemness through activation of pluripotency networks. In this study, we observed elevated MUC1 in osteosarcoma and a depressed prognosis in patients with high MUC1 expression profiles. Our observations also revealed that MUC1 promoted OS stemness and tumor metastasis both in vivo and in vitro. These data led us to hypothesize that MUC1 may be a therapeutic target for patients with OS.

5.
J Clin Med ; 12(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36675511

RESUMO

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare malignant cutaneous tumour that is commonly located in anogenital regions. The diagnosis of the disease is always delayed, and treatment is usually troublesome. This study aims to summarise the clinicopathological characteristics and the risk factors of prognosis for EMPD in anogenital regions, potentially providing evidence for the diagnosis and treatment of anogenital EMPD. METHODS: 688 patients were sourced from the Surveillance, Epidemiology and End Results (SEER) program between 1992 and 2021. In total, 176 participants from our centre from between 2011 and 2021 were included to investigate the characteristics and prognosis for EMPD in anogenital regions. RESULTS: From the SEER program data, patient age of 65 years or older, metastasis of lymph nodes, Spanish-Hispanic-Latino race, diameter exceeding 10cm and lesions located anally were revealed as independent risk factors for shorter cancer-specific survival (CSS). However, the data from our centre highlighted that metastasis of lymph nodes and tumours extending through the epidermis are independent risk factors of shortened progression-free survival (PFS) and CSS of anogenital EMPD. CONCLUSION: This synthesised study revealed that some characteristics are regarded as risk factors for poor clinical prognosis, which have potential value in formulating more normative and effective strategies for patients with EMPD in anogenital regions.

6.
Heliyon ; 9(1): e12481, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36691533

RESUMO

Background: The growth and aging process of the human population has accelerated the increase in surgical procedures. Yet, the demand for increasing operations can be hardly met since the training of anesthesiologists is usually a long-term process. Closed-loop artificial intelligence (AI) model provides the possibility to solve intelligent decision-making for anesthesia auxiliary control and, as such, has allowed breakthroughs in closed-loop control of clinical practices in intensive care units (ICUs). However, applying an open-loop artificial intelligence algorithm to build up personalized medication for anesthesia still needs to be further explored. Currently, anesthesiologists have selected doses of intravenously pumped anesthetic drugs mainly based on the blood pressure and bispectral index (BIS), which can express the depth of anesthesia. Unfortunately, BIS cannot be monitored at some medical centers or operational procedures and only be regulated by blood pressure. As a result, here we aim to inaugurally explore the feasibility of a basic intelligent control system applied to drug delivery in the maintenance phase of general anesthesia, based on a convolutional neural network model with open-loop design, according to AI learning of existing anesthesia protocols. Methods: A convolutional neural network, combined with both sliding window sampling method and residual learning module, was utilized to establish an "AI anesthesiologist" model for intraoperative dosing of personalized anesthetic drugs (propofol and remifentanil). The fitting degree and difference in pumping dose decision, between the AI anesthesiologist and the clinical anesthesiologist, for these personalized anesthetic drugs were examined during the maintenance phase of anesthesia. Results: The medication level established by the "AI anesthesiologist" was comparable to that obtained by the clinical anesthesiologist during the maintenance phase of anesthesia. Conclusion: The application of an open-loop decision-making plan by convolutional neural network showed that intelligent anesthesia control is consistent with the actual anesthesia control, thus providing possibility for further evolution and optimization of auxiliary intelligent control of depth of anesthesia.

7.
J Clin Med ; 12(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36615184

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) has cystic fluid accumulations in the kidneys, liver, pancreas, arachnoid spaces as well as non-cystic fluid accumulations including pericardial effusions, dural ectasia and free fluid in the male pelvis. Here, we investigate the possible association of ADPKD with pleural effusion. ADPKD subjects (n = 268) and age-gender matched controls without ADPKD (n = 268) undergoing body magnetic resonance imaging from mid-thorax down into the pelvis were independently evaluated for pleural effusion by 3 blinded expert observers. Subjects with conditions associated with pleural effusion were excluded from both populations. Clinical and laboratory data as well as kidney, liver and spleen volume, pleural fluid volume, free pelvic fluid and polycystic kidney disease genotype were evaluated. Pleural effusions were observed in 56 of 268 (21%) ADPKD subjects compared with 21 of 268 (8%) in controls (p < 0.0001). In a subpopulation controlling for renal function by matching estimated glomerular filtration rate (eGFR), 28 of 110 (25%) ADPKD subjects had pleural effusions compared to 5 of 110 (5%) controls (p < 0.001). Pleural effusions in ADPKD subjects were more prevalent in females (37/141; 26%) than males (19/127,15%; p = 0.02) and in males were weakly correlated with the presence of free pelvic fluid (r = 0.24, p = 0.02). ADPKD subjects with pleural effusions were younger (48 ± 14 years old vs. 43 ± 14 years old) and weighed less (77 vs. 70 kg; p ≤ 0.02) than those without pleural effusions. For ADPKD subjects with pleural effusions, the mean volume of fluid layering dependently in the posterior-inferior thorax was 19 mL and was not considered to be clinically significant. Pleural effusion is associated with ADPKD, but its role in the pathogenesis of ADPKD requires further evaluation.

8.
J Phys Chem A ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627248

RESUMO

To investigate the mechanism of this spiro conjugation magnetic behavior, we designed and synthesized three diradicals─22'SBF-NN, 44'SBF-NN, and 27SBF-NN. They are bridged by spirobifluorene and nitronyl nitroxide (NN) diradicals as the spin centers. Notably, by SQUID and electron paramagnetic resonance (EPR) zero-field splitting data analyses, the 22'SBF-NN and 27SBF-NN diradicals exhibit intramolecular, distinctly antiferromagnetic (AF) coupling, with 2J(22'SBF-NN)/kB = -5.86 K and 2J(27SBF-NN)/kB = -24.6 K, respectively. The AF of 22'SBF-NN is opposite to that predicted by the spin density alternation rule based on Hund's rule. Diradical intramolecular conjugation coupling bridged by spiro-carbon conjugation is discussed, in which the 22'SBF-NN is smaller than that of 27SBF-NN, corresponding to the room-temperature EPR characterization. This spiro conjugation is weaker than the traditional planar conjugation and generally leads to a weaker spin-spin coupling in the helical biradical molecule. The EPR spectrum of the 44'SBF-NN diradical shows a deformed nine-line curve, indicating intramolecular exchange coupling. The density functional theory calculation gives a very weak coupling constant of 2Jcalc/kB = 0.06 K, with ferromagnetic (FM) interaction as the proof, which is consistent with the spin-polarized prediction. Further analysis of magnetic susceptibility χm and VT-EPR data shows that there is indeed an extremely weak FM interaction in the 44' position diradical. We find the bridge, which is a 44' substituted SBF structure, blocks the conjugation and contains a larger twist in steric hindrance, which also hampers sufficient spin density delocalization, resulting in a much weaker spin coupling interaction. Combined with the analysis of molecular orbital calculation results, the anomalous intramolecular AF coupling mechanism of 22'SBF-NN is further explained.

9.
Clin Transl Oncol ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36630025

RESUMO

PURPOSE: Breast cancer is one of the leading causes of tumor death worldwide in female, and the five-year overall survival of breast cancer patients remains poor. It is an urgent need to seek novel target for its treatment. Synaptotagmin 13 (SYT13) is a synaptic vesicle transporting protein that regulates the malignant phenotypes of various cancers. However, its role in breast cancer is still unclear. The current study aimed to investigate the effects of SYT13 on the progression of breast cancer. METHODS: Twenty-five pairs of breast cancer tissues and non-tumor tissues were obtained to assess the expression of SYT13. We manually modified the expression of SYT13 in MCF-7 and MDA-MB-231 cells. CCK-8 assay, EdU staining, and cell cycle analysis were carried out to measure the proliferated ability of cells. Annexin V/PI and TUNEL assays were used to detect the apoptotic ability of cells. Wound healing and transwell assays were employed to evaluate the migrated and invasive ability of breast cancer cells. RESULTS: The results revealed that the mRNA and protein levels of SYT13 were higher in breast cancer tissues and cell lines. Knockdown of SYT13 inhibited the cell proliferation and induced cell cycle arrest in G1 phase of MCF-7 cells by downregulating cyclin D1 and CDK4, as well as upregulating p21. The migration and invasion of MCF-7 cells were repressed by the loss of SYT13 via the gain of E-cadherin and the loss of vimentin. Overexpression of SYT13 in MDA-MB-231 cells led to the opposite effects. Silencing of SYT13 induced the apoptosis ability of MCF-7 cells by the upregulation of bax and the downregulation of bcl-2. Moreover, we found that SYT13 depletion suppressed the FAK/AKT signaling pathway. PF573228 (a FAK inhibitor) and MK2206 (an AKT inhibitor) reversed the SYT13 overexpression-induced promotion of proliferation, migration, and invasion of MDA-MB-231 cells. CONCLUSION: The results indicated that SYT13 promoted the malignant phenotypes of breast cancer cells by the activation of FAK/AKT signaling pathway.

10.
Nat Microbiol ; 8(1): 162-173, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36604510

RESUMO

The increasing prevalence and expanding distribution of tick-borne viruses globally have raised health concerns, but the full repertoire of the tick virome has not been assessed. We sequenced the meta-transcriptomes of 31 different tick species in the Ixodidae and Argasidae families from across mainland China, and identified 724 RNA viruses with distinctive virome compositions among genera. A total of 1,801 assembled and complete or nearly complete viral genomes revealed an extensive diversity of genome architectures of tick-associated viruses, highlighting ticks as a reservoir of RNA viruses. We examined the phylogenies of different virus families to investigate virome evolution and found that the most diverse tick-associated viruses are positive-strand RNA virus families that demonstrate more ancient divergence than other arboviruses. Tick-specific viruses are often associated with only a few tick species, whereas virus clades that can infect vertebrates are found in a wider range of tick species. We hypothesize that tick viruses can exhibit both 'specialist' and 'generalist' evolutionary trends. We hope that our virome dataset will enable much-needed research on vertebrate-pathogenic tick-associated viruses.


Assuntos
Vírus de RNA , Carrapatos , Vírus , Animais , Vírus de RNA/genética , Genoma Viral/genética , RNA
11.
Arch Microbiol ; 205(1): 49, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36595076

RESUMO

Campylobacter is regarded as the leading cause of zoonotic diseases and Campylobacter jejuni (C. jejuni) is one of the predominant pathogenic species. To track C. jejuni infections, various genotyping methods have been used. In this study, amplified intergenic locus polymorphism (AILP) was used to type C. jejuni for the first time. To confirm its feasibility, pulsed-field gel electrophoresis (PFGE) was performed as a control, and the results obtained by the AILP and PFGE methods were compared. Fifty-one isolates were resolved into 34 and 29 different genotypes with Simpson's indices of 0.976 and 0.967 using the AILP and PFGE methods, respectively. The adjusted Rand coefficient of the two approaches was as high as 0.845. In summary, the data showed that the two genotyping methods were similar for discriminating isolates and were both appropriate methods to distinguish whether two isolates were indistinguishable, but the AILP was faster and less costly than PFGE. Therefore, the AILP is a reliable, rapid, and highly discriminative method to genotype C. jejuni collected from poultry meat, which is helpful to effectively monitor C. jejuni.


Assuntos
Infecções por Campylobacter , Campylobacter jejuni , Animais , Campylobacter jejuni/genética , Eletroforese em Gel de Campo Pulsado , Tipagem Molecular , Polimorfismo Genético , Genótipo , Galinhas , Técnicas de Tipagem Bacteriana/métodos
12.
Huan Jing Ke Xue ; 44(1): 252-261, 2023 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-36635813

RESUMO

Planktonic and epiphytic bacterial communities play an important role in wetland nitrogen pollutant removal and water purification, yet their community dynamics are far from understood compared with those of the wetland soil bacterial community. Taking the planktonic bacterial community in the Yuguqiao constructed wetland and the epiphytic bacterial community on the leaf surface of the common submerged plant Vallisneria natans as the research objects, the composition, structure, and functional diversity of planktonic and epiphytic bacterial communities were analyzed using high-throughput sequencing. The results showed that the compositions of the planktonic and epiphytic bacterial communities were significantly different, with more heterotrophic and denitrifying bacteria present in the epiphytic bacterial community than in the planktonic bacterial community. The α diversity of the planktonic bacterial community was significantly different among the three sampling sites but not in the epiphytic bacterial community. In general, the OTU index and Shannon index of the epiphytic bacterial community were significantly higher than those of the planktonic bacterial community, and they had obvious spatial heterogeneity. RDA analysis showed that DO, IC, TP, NH+4, and TOC had important effects on the structural changes of both planktonic and epiphytic bacterial communities but had a greater impact on planktonic bacterial communities. Co-occurrence network analysis showed that the epiphytic bacterial community had more niche differentiation, a more stable network, and stronger resistance to external disturbance. The results of FAPROTAX functional prediction analysis showed that the nitrogen cycling, especially denitrification of the epiphytic bacterial community, was significantly greater than that of the planktonic bacterial community. The results of this study revealed the driving mechanism for maintaining the diversity of planktonic and epiphytic bacterial communities, which can provide a scientific basis for excavating and utilizing planktonic and epiphytic bacterial community resources in the construction of constructed wetlands to improve the efficiency of water purification.


Assuntos
Hydrocharitaceae , Plâncton , Áreas Alagadas , Plantas , Bactérias/genética , Nitrogênio
13.
Math Biosci Eng ; 20(1): 572-586, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36650779

RESUMO

The rapid development of modern industrial technology has led to the increase of machinery precision. Laser tracking measurement systems represent a novel type of coordinate measurement method, which was developed on the basis of metrology. In this paper, we aim to define a single-station 3D coordinate rotating laser tracking measurement system based on the principle of the space coordinate method. In view of the current architecture and optical path of the system, we establish the ideal mathematical model of the system and derive the coordinate expression for arbitrary measured points in the measurement space. The output response of the photoelectric position detector to the rotating laser and the linearity of the position signal in the detection circuit have been detected via a concrete experiment. A laser tracking system was used to track the target mirror mounted on the coordinate measuring machine measuring spindle. It is shown that stable tracking is possible during the 3D movement of a cat's eye retroreflector if its velocity is 0.2 m/s and the distance to the moving object is 1-2 m. The corresponding velocity of the object must be 0.4 m/s. Our system provides a feasible implementation method for the tracking of the moving target space position.


Assuntos
Lasers
14.
BMC Bioinformatics ; 24(1): 13, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624376

RESUMO

BACKGROUND: Constructing molecular interaction networks from microarray data and then identifying disease module biomarkers can provide insight into the underlying pathogenic mechanisms of non-small cell lung cancer. A promising approach for identifying disease modules in the network is community detection. RESULTS: In order to identify disease modules from gene co-expression networks, a community detection method is proposed based on multi-objective optimization genetic algorithm with decomposition. The method is named DM-MOGA and possesses two highlights. First, the boundary correction strategy is designed for the modules obtained in the process of local module detection and pre-simplification. Second, during the evolution, we introduce Davies-Bouldin index and clustering coefficient as fitness functions which are improved and migrated to weighted networks. In order to identify modules that are more relevant to diseases, the above strategies are designed to consider the network topology of genes and the strength of connections with other genes at the same time. Experimental results of different gene expression datasets of non-small cell lung cancer demonstrate that the core modules obtained by DM-MOGA are more effective than those obtained by several other advanced module identification methods. CONCLUSIONS: The proposed method identifies disease-relevant modules by optimizing two novel fitness functions to simultaneously consider the local topology of each gene and its connection strength with other genes. The association of the identified core modules with lung cancer has been confirmed by pathway and gene ontology enrichment analysis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Redes Reguladoras de Genes , Análise em Microsséries , Algoritmos , Perfilação da Expressão Gênica/métodos
15.
Int J Epidemiol ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36625552

RESUMO

Prevalence estimates are fundamental to epidemiological studies. Although they are highly vulnerable to misclassification bias, the risk of bias assessment of prevalence estimates is often neglected. Quantitative bias analysis (QBA) can effectively estimate misclassification bias in epidemiological studies; however, relatively few applications are identified. One reason for its low usage is the lack of knowledge and tools for these methods among researchers. To expand existing evaluation methods, based on the QBA principles, three indicators are proposed. One is the relative bias that quantifies the bias direction through its signs and the bias magnitude through its quantity. The second is the critical point of positive test proportion in case of a misclassification bias that is equal to zero. The third is the bound of positive test proportion equal to adjusted prevalence at misclassification bias level α. These indicators express the magnitude, direction and uncertainty of the misclassification bias of prevalence estimates, respectively. Using these indicators, it was found that slight oscillations of the positive test proportion within a certain range can lead to substantial increases in the misclassification bias. Hence, researchers should account for misclassification error analytically when interpreting the significance of adjusted prevalence for epidemiological decision making. This highlights the importance of applying QBA to these analyses. In this article, we have used three real-world cases to illustrate the characteristics and calculation methods of presented indicators. To facilitate application, an Excel-based calculation tool is provided.

16.
Int J Clin Pharm ; 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36680620

RESUMO

BACKGROUND: Ciprofol is a novel 2, 6-disubstituted phenolic derivative anesthetic that binds to the gamma-aminobutyric acid-A receptor. AIM: To determine the equally potent dose of ciprofol compared with propofol as an induction agent for general anesthesia in patients undergoing selective surgery, and to assess its safety. METHOD: A total of 109 patients undergoing selective non-emergency, non-cardiothoracic or non-neurosurgical surgery requiring tracheal intubation for general anesthesia were enrolled. Ten patients per group were assigned to ciprofol-0.3, 0.4 and 0.5 mg/kg, and propofol-2.0 or 2.5 mg/kg groups, respectively to receive an intravenous bolus dose. An additional 20 patients were enrolled in the ciprofol-0.3, 0.5 or propofol-2.0 mg/kg groups. The primary outcome was the success rate of induction defined as a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) ≤ 1 after the initial bolus dose. The secondary outcomes included the time to reach MOAA/S ≤ 1, the time to loss of the eyelash reflex, the incidences and severity of adverse events (AEs). RESULTS: The success rates were 100% for all 5 groups. The mean time to MOAA/S ≤ 1 and the time to loss of the eyelash reflex were not different among the 5 groups, regardless of whether a top-up dose was needed. There were no significant differences in the incidences and severity of AEs in the dose ranges investigated of ciprofol vs. propofol. CONCLUSION: The efficacy and safety of a single bolus dose of ciprofol-0.5 mg/kg for the general anesthesia induction in selective surgery patients was comparable to that of propofol-2.0 mg/kg. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03698617, retrospectively registered.

17.
Cancer Med ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36647765

RESUMO

BACKGROUND: Frontline intensification (including consolidative whole-brain radiotherapy or high-dose chemotherapy with autologous stem-cell transplantation after induction therapy) has been proposed to treat primary central nervous system lymphoma (PCNSL). However, no prospective randomized trials have answered whether frontline intensification can offer a survival benefit to PCNSL patients. We aim to clarify the outcomes and survival influence of frontline intensification on real-world patients with different risk-stratified PCNSLs. METHODS: Between January 2003 and December 2016, 110 PCNSL adults were retrospectively included, and 76 patients achieved at least PR after induction therapy, including 38 patients who received frontline intensification. The median follow-up with the 31 survivors was 7.52 years. RESULTS: Of the 38 induction-completed patients who had not received frontline intensification, 95% achieved post-induction therapy CR/CRu; however, all inevitably recurred. In the 38 who received frontline intensification, CR/CRu improved from 45% (pre-frontline intensification) to 84% (post-frontline intensification), and they achieved significantly better PFS (non-reach vs. 522 days, p < 0.001) and OS (non-reach vs. 899 days, p < 0.001). Additionally, patients had similar PFS and OS rates when receiving HDC-ASCT and/or WBRT as frontline intensification. Frontline intensification significantly improved PFS and OS survival in higher-risk patients (intermediate/high IELSG risk, MSKCC group 2/3, or Nottingham/Barcelona score ≥ 2 points) but did not improve OS in lower-risk patients. Among the 38 patients who received frontline intensification, two had treatment-related mortality; 14 recurred after frontline intensification. MTX-based chemotherapy was the main salvage modality, and the median OS was 295 days after recurrence. Progressive disease and infection (especially pneumonia) are two major causes of mortality in patients who receive frontline intensification. CONCLUSIONS: When achieving CR/CRu/PR after induction chemotherapy, frontline intensification should be adopted to improve PFS and OS in real-world PCNSL patients, especially higher-risk patients.

18.
Nat Commun ; 14(1): 281, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650155

RESUMO

Telomeres are specialized nucleoprotein structures at the ends of linear chromosomes. The progressive shortening of steady-state telomere length in normal human somatic cells is a promising biomarker for age-associated diseases. However, there remain substantial challenges in quantifying telomere length due to the lack of high-throughput method with nucleotide resolution for individual telomere. Here, we describe a workflow to capture telomeres using newly designed telobaits in human culture cell lines as well as clinical patient samples and measure their length accurately at nucleotide resolution using single-molecule real-time (SMRT) sequencing. Our results also reveal the extreme heterogeneity of telomeric variant sequences (TVSs) that are dispersed throughout the telomere repeat region. The presence of TVSs disrupts the continuity of the canonical (5'-TTAGGG-3')n telomere repeats, which affects the binding of shelterin complexes at the chromosomal ends and telomere protection. These findings may have profound implications in human aging and diseases.


Assuntos
Complexo Shelterina , Telômero , Humanos , Telômero/genética , Envelhecimento
19.
Artigo em Inglês | MEDLINE | ID: mdl-36658375

RESUMO

OBJECTIVE: To compare the safety and effectiveness between bronchial artery embolisation (BAE) and conservative treatment for bronchiectasis-related nonmassive haemoptysis patients. MATERIALS AND METHODS: From January 2015 to December 2020, consecutive bronchiectasis-related nonmassive haemoptysis patients who underwent either BAE (n = 98) or conservative treatment (n = 118) were included. Treatment-related complications, length of hospital stays, clinical success rate, patient satisfaction, and recurrence-free survival rates were compared between groups. Prognostic factors related to recurrence were also analysed. RESULTS: During a median follow-up time of 44.8 months (range, 2.4-83.6 months), 34 and 66 patients in the BAE and conservative treatment groups suffered relapse. The 1-year, 2-year, 3-year and 5-year haemoptysis-free survival rates in the BAE and conservative treatment groups were 79.2%, 68.1%, 62.8%, and 57.6% and 64.0%, 52.8%, 44.1%, and 37.0%, respectively (P = 0.007). The minor complication rate after BAE was higher than that after conservative treatment (23/98 vs. 12/118, P = 0.008). BAE was associated with shorter hospital stays (5.0 vs. 7.0 days, P = 0.042) and higher patient satisfaction (88.8% vs. 74.6%, P = 0.008) than those for conservative treatment and with comparable clinical success rates (95.9% vs. 91.5%, P = 0.192). Treatment type, haemoptysis duration, and bronchiectasis severity were independently significant predictors of recurrence for these patients. CONCLUSIONS: BAE could be another option for bronchiectasis-related nonmassive haemoptysis patients. In the patients with longer duration and more severe bronchiectasis, BAE still appeared to have better long-term haemoptysis control than conservative therapy.

20.
Brief Bioinform ; 24(1)2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36611256

RESUMO

Accumulating evidences demonstrate that circular RNA (circRNA) plays an important role in human diseases. Identification of circRNA-disease associations can help for the diagnosis of human diseases, while the traditional method based on biological experiments is time-consuming. In order to address the limitation, a series of computational methods have been proposed in recent years. However, few works have summarized these methods or compared the performance of them. In this paper, we divided the existing methods into three categories: information propagation, traditional machine learning and deep learning. Then, the baseline methods in each category are introduced in detail. Further, 5 different datasets are collected, and 14 representative methods of each category are selected and compared in the 5-fold, 10-fold cross-validation and the de novo experiment. In order to further evaluate the effectiveness of these methods, six common cancers are selected to compare the number of correctly identified circRNA-disease associations in the top-10, top-20, top-50, top-100 and top-200. In addition, according to the results, the observation about the robustness and the character of these methods are concluded. Finally, the future directions and challenges are discussed.


Assuntos
Neoplasias , RNA Circular , Humanos , RNA Circular/genética , Benchmarking , Aprendizado de Máquina , Neoplasias/genética , Biologia Computacional/métodos
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