Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 340
Filtrar
1.
Nucleic Acids Res ; 51(20): 10909-10923, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37819036

RESUMO

Phylogenetic tree inference is a classic fundamental task in evolutionary biology that entails inferring the evolutionary relationship of targets based on multiple sequence alignment (MSA). Maximum likelihood (ML) and Bayesian inference (BI) methods have dominated phylogenetic tree inference for many years, but BI is too slow to handle a large number of sequences. Recently, deep learning (DL) has been successfully applied to quartet phylogenetic tree inference and tentatively extended into more sequences with the quartet puzzling algorithm. However, no DL-based tools are immediately available for practical real-world applications. In this paper, we propose Fusang (http://fusang.cibr.ac.cn), a DL-based framework that achieves comparable performance to that of ML-based tools with both simulated and real datasets. More importantly, with continuous optimization, e.g. through the use of customized training datasets for real-world scenarios, Fusang has great potential to outperform ML-based tools.


Assuntos
Aprendizado Profundo , Filogenia , Algoritmos , Teorema de Bayes , Alinhamento de Sequência , Funções Verossimilhança
2.
Am J Respir Cell Mol Biol ; 71(1): 30-42, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38579159

RESUMO

Alveoli are complex microenvironments composed of various cell types, including epithelial, fibroblast, endothelial, and immune cells, which work together to maintain a delicate balance in the lung environment, ensuring proper growth, development, and an effective response to lung injuries. However, prolonged inflammation or aging can disrupt normal interactions among these cells, leading to impaired repair processes and a substantial decline in lung function. Therefore, it is essential to understand the key mechanisms underlying the interactions among the major cell types within the alveolar microenvironment. We explored the key mechanisms underlying the interactions among the major cell types within the alveolar microenvironment. These interactions occur through the secretion of signaling factors and play crucial roles in the response to injury, repair mechanisms, and the development of fibrosis in the lungs. Specifically, we focused on the regulation of alveolar type 2 cells by fibroblasts, endothelial cells, and macrophages. In addition, we explored the diverse phenotypes of fibroblasts at different stages of life and in response to lung injury, highlighting their impact on matrix production and immune functions. Furthermore, we summarize the various phenotypes of macrophages in lung injury and fibrosis as well as their intricate interplay with other cell types. This interplay can either contribute to the restoration of immune homeostasis in the alveoli or impede the repair process. Through a comprehensive exploration of these cell interactions, we aim to reveal new insights into the molecular mechanisms that drive lung injury toward fibrosis and identify potential targets for therapeutic intervention.


Assuntos
Comunicação Celular , Microambiente Celular , Fibroblastos , Lesão Pulmonar , Alvéolos Pulmonares , Humanos , Animais , Lesão Pulmonar/patologia , Lesão Pulmonar/metabolismo , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose Pulmonar/patologia , Fibrose Pulmonar/metabolismo , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Fibrose , Macrófagos/metabolismo , Macrófagos/patologia
3.
J Cell Mol Med ; 28(10): e18398, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38785203

RESUMO

Behçet's disease (BD) is a complex autoimmune disorder impacting several organ systems. Although the involvement of abdominal aortic aneurysm (AAA) in BD is rare, it can be associated with severe consequences. In the present study, we identified diagnostic biomarkers in patients with BD having AAA. Mendelian randomization (MR) analysis was initially used to explore the potential causal association between BD and AAA. The Limma package, WGCNA, PPI and machine learning algorithms were employed to identify potential diagnostic genes. A receiver operating characteristic curve (ROC) for the nomogram was constructed to ascertain the diagnostic value of AAA in patients with BD. Finally, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were conducted. The MR analysis indicated a suggestive association between BD and the risk of AAA (odds ratio [OR]: 1.0384, 95% confidence interval [CI]: 1.0081-1.0696, p = 0.0126). Three hub genes (CD247, CD2 and CCR7) were identified using the integrated bioinformatics analyses, which were subsequently utilised to construct a nomogram (area under the curve [AUC]: 0.982, 95% CI: 0.944-1.000). Finally, the immune cell infiltration assay revealed that dysregulation immune cells were positively correlated with the three hub genes. Our MR analyses revealed a higher susceptibility of patients with BD to AAA. We used a systematic approach to identify three potential hub genes (CD247, CD2 and CCR7) and developed a nomogram to assist in the diagnosis of AAA among patients with BD. In addition, immune cell infiltration analysis indicated the dysregulation in immune cell proportions.


Assuntos
Aneurisma da Aorta Abdominal , Síndrome de Behçet , Biomarcadores , Biologia Computacional , Análise da Randomização Mendeliana , Humanos , Síndrome de Behçet/genética , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/complicações , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/diagnóstico , Biologia Computacional/métodos , Curva ROC , Redes Reguladoras de Genes , Predisposição Genética para Doença , Mapas de Interação de Proteínas/genética , Nomogramas , Receptores CCR7
4.
Mol Cancer ; 23(1): 124, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849840

RESUMO

BACKGROUND: Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression. METHODS: In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM. RESULTS: Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3ß and resulted in increased ß-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells. CONCLUSIONS: OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.


Assuntos
Progressão da Doença , Glicogênio Sintase Quinase 3 beta , Metaplasia , Cadeias Pesadas de Miosina , beta Catenina , Humanos , Metaplasia/metabolismo , Metaplasia/patologia , Metaplasia/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Animais , beta Catenina/metabolismo , beta Catenina/genética , Camundongos , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Feminino , Via de Sinalização Wnt , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Modelos Animais de Doenças , Masculino , Organoides/metabolismo , Organoides/patologia
5.
Genome Res ; 31(4): 622-634, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33722936

RESUMO

Heterosis or hybrid vigor is a common phenomenon in plants and animals; however, the molecular mechanisms underlying heterosis remain elusive, despite extensive studies on the phenomenon for more than a century. Here we constructed a large collection of F1 hybrids of Saccharomyces cerevisiae by spore-to-spore mating between homozygous wild strains of the species with different genetic distances and compared growth performance of the F1 hybrids with their parents. We found that heterosis was prevalent in the F1 hybrids at 40°C. A hump-shaped relationship between heterosis and parental genetic distance was observed. We then analyzed transcriptomes of selected heterotic and depressed F1 hybrids and their parents growing at 40°C and found that genes associated with one-carbon metabolism and related pathways were generally up-regulated in the heterotic F1 hybrids, leading to improved cellular redox homeostasis at high temperature. Consistently, genes related with DNA repair, stress responses, and ion homeostasis were generally down-regulated in the heterotic F1 hybrids. Furthermore, genes associated with protein quality control systems were also generally down-regulated in the heterotic F1 hybrids, suggesting a lower level of protein turnover and thus higher energy use efficiency in these strains. In contrast, the depressed F1 hybrids, which were limited in number and mostly shared a common aneuploid parental strain, showed a largely opposite gene expression pattern to the heterotic F1 hybrids. We provide new insights into molecular mechanisms underlying heterosis and thermotolerance of yeast and new clues for a better understanding of the molecular basis of heterosis in plants and animals.


Assuntos
Carbono/metabolismo , Homeostase , Temperatura Alta , Vigor Híbrido , Saccharomyces cerevisiae , Homeostase/genética , Vigor Híbrido/genética , Hibridização Genética , Oxirredução , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Regulação para Cima
6.
Opt Express ; 32(5): 7513-7519, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38439429

RESUMO

Tm,Ho:CaYLuAlO4 (Tm,Ho:CALYLO) crystal has wide emission spectra both for π-polarization and σ-polarization, showing significant potential for the generation of ultrashort pulses. Here, a widely tunable and passively mode-locked laser operation based on Tm,Ho:CALYLO crystal under two polarizations was demonstrated for what we believe to be the first time ever. For π-polarization, a maximum output power of 1.52 W and a tuning range of 255.3 nm were achieved in the continuous wave (CW) regime. In the mode-locked regime, a pulse duration of 68 fs and an average output power of 228 mW were achieved upon GaSb-based semiconductor saturable absorber mirror (SESAM). As for σ-polarization, a broader tuning range of 267.1 nm was realized, leading to the shorter pulse duration of 58 fs at 79.7 MHz repetition rate.

7.
J Org Chem ; 89(7): 5019-5028, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38502934

RESUMO

In this paper, we reported the palladium-catalyzed formal [5 + 4] cycloaddition reactions between 4-vinyl-4-butyrolactones (VBLs) and azadienes. Under mild reaction conditions, a wide range of benzofuran-fused 9-membered heterocyclic compounds had been provided in moderate to excellent yields with exclusive regioselectivities and excellent diastereoselectivities. The practical applicability of the synthesis was demonstrated through scale-up reaction and further transformation.

8.
Med Sci Monit ; 30: e943233, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38279530

RESUMO

BACKGROUND The degree of postoperative symptom improvement in patients with lumbar spinal stenosis (LSS) is crucial to their postoperative rehabilitation process and functional exercise. Corticosteroids have certain anti-inflammatory effects. This study aimed to explore whether small doses of corticosteroids would improve postoperative neurological symptoms in patients with lumbar spinal stenosis. MATERIAL AND METHODS Patients with lumbar spinal stenosis who underwent open surgery were divided into a corticosteroid therapy group (CTG) and a non-corticosteroid therapy group (NCTG). They were followed up for 24 months after surgery. The numeric rating scale (NRS) for leg pain (NRS-LP) and leg numbness (NRS-LN), Oswestry Disability Index (ODI) scores, and Short Form Health Survey (SF-36) scores of the 2 groups were compared at different time points to evaluate the therapeutic effect. RESULTS Of the 232 eligible patients enrolled, 128 received corticosteroids and 104 did not. At the 1-month postoperative follow-up, patients in the CTG had significantly lower NRS-LP and NRS-LN scores than those in the NCTG (P=0.017; P=0.043). At the 3-month follow-up, the NRS-LP and ODI scores of patients in the CTG were significantly lower than those of the NCTG (P=0.015; P=0.027), and SF-36 scores were significantly higher than that of the NCTG (P=0.012). At the 6-month follow-up, the SF-36 scores of patients in the CTG was significantly higher than that of the NCTG (P=0.008). CONCLUSIONS Small doses of corticosteroid therapy for postoperative lumbar spinal stenosis reduced symptoms and improved quality of life scores after surgery. However, it had little long-term impact on final patient outcomes.


Assuntos
Estenose Espinal , Humanos , Estenose Espinal/tratamento farmacológico , Estenose Espinal/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Qualidade de Vida , Vértebras Lombares/cirurgia , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Descompressão Cirúrgica
9.
Proc Natl Acad Sci U S A ; 118(5)2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33495330

RESUMO

Multiplex assays, involving the simultaneous use of multiple circulating tumor DNA (ctDNA) markers, can improve the performance of liquid biopsies so that they are highly predictive of cancer recurrence. We have developed a single-tube methylation-specific quantitative PCR assay (mqMSP) that uses 10 different methylation markers and is capable of quantitative analysis of plasma samples with as little as 0.05% tumor DNA. In a cohort of 179 plasma samples from colorectal cancer (CRC) patients, adenoma patients, and healthy controls, the sensitivity and specificity of the mqMSP assay were 84.9% and 83.3%, respectively. In a head-to-head comparative study, the mqMSP assay also performed better for detecting early-stage (stage I and II) and premalignant polyps than a published SEPT9 assay. In an independent longitudinal cohort of 182 plasma samples (preoperative, postoperative, and follow-up) from 82 CRC patients, the mqMSP assay detected ctDNA in 73 (89.0%) of the preoperative plasma samples. Postoperative detection of ctDNA (within 2 wk of surgery) identified 11 of the 20 recurrence patients and was associated with poorer recurrence-free survival (hazard ratio, 4.20; P = 0.0005). With subsequent longitudinal monitoring, 14 patients (70%) had detectable ctDNA before recurrence, with a median lead time of 8.0 mo earlier than seen with radiologic imaging. The mqMSP assay is cost-effective and easily implementable for routine clinical monitoring of CRC recurrence, which can lead to better patient management after surgery.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Neoplasias do Colo/cirurgia , Metilação de DNA/genética , Biópsia Líquida , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/metabolismo , DNA Tumoral Circulante/sangue , Estudos de Coortes , Neoplasias do Colo/sangue , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mutação/genética , Cuidados Pós-Operatórios , Reprodutibilidade dos Testes , Septinas/genética
10.
Environ Toxicol ; 39(7): 4058-4065, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38661261

RESUMO

Platinum-based antineoplastic drugs, including cisplatin, carboplatin, and oxaliplatin, are widely used in the treatment of various cancers. Ototoxicity is a common adverse effect of platinum-based drugs. Ototoxicity leads to irreversible hearing impairment. We hypothesize that different platinum-based drugs exhibit varying ototoxic concentrations, time effects, and ototoxic mechanisms. We tested this hypothesis by using a zebrafish model (pvalb3b: TagGFP) to assess the viability of hair cells collected from zebrafish larvae. Cisplatin, carboplatin, and oxaliplatin were administered at dosages of 100, 200, or 400 µM, and the ototoxic effects of these drugs were assessed 1, 2, or 3 h after administration. Fm4-64 and a TUNEL assay were used to label the membranes of living hair cells and to detect cell apoptosis, respectively. We observed that >50% of hair cells were damaged at 1 h after cisplatin (100 µM) exposure, and this ototoxic effect increased at higher dosages and over time. Owing to the smaller ototoxic effects of carboplatin and oxaliplatin, we conducted higher-strength and longer-duration experiments with these drugs. Neither carboplatin nor oxaliplatin was obviously ototoxic, even at 1600 µM and after 6 h. Moreover, only cisplatin damaged the membranes of the hair cells. Cell apoptosis and significantly increased antioxidant gene expression were observed in only the cisplatin group. In conclusion, cisplatin significantly damages sensory hair cells and has notable dosage and time effects. Carboplatin and oxaliplatin are less ototoxic than cisplatin, likely due to having different ototoxic mechanisms than cisplatin.


Assuntos
Antineoplásicos , Apoptose , Carboplatina , Cisplatino , Ototoxicidade , Oxaliplatina , Peixe-Zebra , Animais , Cisplatino/toxicidade , Oxaliplatina/toxicidade , Carboplatina/toxicidade , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Células Ciliadas Auditivas/efeitos dos fármacos , Larva/efeitos dos fármacos
11.
Mol Cancer ; 22(1): 95, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37316830

RESUMO

Clinical hyperthermic intraperitoneal chemotherapy (HIPEC) is regarded as a potential treatment that can prolong survival of patients with peritoneal metastases after cytoreductive surgery. However, treated tumor cells are prone to becoming heat resistant to HIPEC therapy through high expression of heat shock proteins (HSPs). Here, a carrier-free bifunctional nanoinhibitor was developed for HIPEC therapy in the management of peritoneal metastases. Self-assembly of the nanoinhibitor was formed by mixing Mn ion and epigallocatechin gallate (EGCG) in a controllable manner. Such nanoinhibitor directly inhibited HSP90 and impaired the HSP90 chaperone cycle by reduced intracellular ATP level. Additionally, heat and Mn ion synergistically induced oxidative stress and expression of caspase 1, which activated GSDMD by proteolysis and caused pyroptosis in tumor cells, triggering immunogenic inflammatory cell death and induced maturation of dendritic cells through the release of tumor antigens. This strategy to inhibit heat resistance in HIPEC presented an unprecedented paradigm for converting "cold" tumors into "hot" ones, thus significantly eradicating disseminated tumors located deep in the abdominal cavity and stimulating immune response in peritoneal metastases of a mouse model. Collectively, the nanoinhibitor effectively induced pyroptosis of colon tumor cells under heat conditions by inhibiting heat stress resistance and increasing oxidative stress, which may provide a new strategy for treatment of colorectal peritoneal metastases.


Assuntos
Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais , Animais , Camundongos , Neoplasias Peritoneais/tratamento farmacológico , Proteínas de Choque Térmico HSP90 , Proteólise , Colo
12.
Anal Chem ; 95(35): 13289-13296, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37615071

RESUMO

Metallacycles are a novel class of supramolecular materials with circular structures, internal cavities, and abundant host-guest chemical properties that have exhibited good application prospects in many fields. However, to the best of our knowledge, no research on the use of metallacycles as stationary phases for gas chromatographic (GC) separations has been published yet. In this work, we report for the first time the use of a homochiral metallacycle, [ZnCl2L]2, as a stationary phase for GC separations. [ZnCl2L]2 was synthesized by reaction of (S)-(1-isonicotinoylpyrrolidin-2-yl)methyl-isonicotinate (L) with ZnCl2 via coordination-driven self-assembly. The [ZnCl2L]2-coated column displayed an excellent separation performance not only of organic isomers but also of racemic compounds. Sixteen racemates (including alcohols, esters, amino acid derivatives, ethers, organic acids, and epoxides) and 21 isomeric compounds (including positional, structural, and cis/trans-isomers) were well separated on the [ZnCl2L]2-coated column. Impressively, some racemates were resolved with high resolution values (Rs), including 1,2-butanediol diacetate (Rs = 25.86), ethyl 3-hydroxybutyrate (Rs = 20.97), 1,3-butanediol diacetate (Rs = 18.09), and threonine derivative (Rs = 18.61). Compared with the commercial ß-DEX 120 column for separation of the tested racemates, the [ZnCl2L]2-coated column exhibited good enantioseparation complementarity, enabling separation of some racemates that could not be separated, or were not well resolved, by the ß-DEX 120 column. In addition, many organic mixtures, such as n-alkanes, alkylbenzenes, n-alcohols, and a Grob test mixture, were also well separated on the [ZnCl2L]2-coated column. The column also has good reproducibility and thermal stability on separation. This work not only reveals the great potential of metallacycles for GC separations but also opens up a new application of metallacycles in separation science.

13.
Plant Cell ; 32(4): 888-903, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32075864

RESUMO

R-loops are a common chromatin feature with essential functions in multiple cellular processes and diseases. However, little is known about the dynamic patterns of R-loops in a given organism. Here, using our recently developed genome-wide R-loop profiling method, we generated a comprehensive atlas quantifying the R-loop patterns of Arabidopsis (Arabidopsis thaliana) in 53 samples during development and during responses to environmental stimuli. The R-loop patterns were fairly stable in plants at the vegetative stage and in response to different light spectra and other environmental stimuli. Notably, the R-loops showed turnover during the plant life cycle, with patterns switching between generations. Importantly, R-loop dynamics was not strongly associated with RNA abundance, indicating that the mechanisms regulating R-loop formation and RNA accumulation are independent. We also observed enrichment of R-loops in transcription factor binding regions, suggesting that R-loops could function as potential cis-transcriptional regulators. This study provides an overview of R-loop dynamics in Arabidopsis during development and stress responses, highlights the unique dynamics of R-loops in the flowering plant Arabidopsis, and lays the groundwork for elucidating the functions of R-loops.


Assuntos
Arabidopsis/genética , Arabidopsis/fisiologia , Meio Ambiente , Estruturas R-Loop/genética , Sequência Conservada , Lógica Fuzzy , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Loci Gênicos , Genoma de Planta , RNA Polimerase III/metabolismo , RNA de Plantas/genética , Sítio de Iniciação de Transcrição , Transcrição Gênica
14.
Opt Lett ; 48(17): 4544-4547, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656549

RESUMO

We report on the spectral properties and laser performances of a novel, to the best of our knowledge, Tm,Ho:CaY0.9Lu0.1AlO4 (Tm,Ho:CYLA) crystal. The polarized absorption spectra, luminescence spectra, and fluorescence lifetime are systematically investigated, presenting a broad and smooth luminescence band. Furthermore, a maximum continuous wave (CW) laser output power of 0.51 W at 2092 nm is obtained under an absorbed pump power of 2.89 W, corresponding to a slope efficiency of 20.4%. The beam quality factors (M2) are measured to be 1.04 in both the x and y axes. A tuning range of 123.4 nm, from 2017.8 nm to 2141.2 nm, is achieved in the CW regime by using a birefringent filter (BF). A stable passively Q switched Tm,Ho:CYLA laser employing Cr2+:ZnSe as a saturable absorber (SA) is realized for the first time, delivering the shortest pulse width of 560 ns with a transmittance of 1%. The results indicate that the Tm,Ho:CYLA crystal is an excellent laser medium for generating high-efficiency laser at ∼2 µm and has a potential in ultrafast laser generation.

15.
BMC Gastroenterol ; 23(1): 231, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37420205

RESUMO

BACKGROUND: Helicobacter pylori infection and associated diseases are a growing global public health issue. H. pylori infection is the major cause of gastric cancer, over 90% of duodenal ulcers, and over 70% of gastric ulcers. The infection rate of H. pylori is approximately 50%, and approximately 50% of new cases of gastric cancer worldwide occur in China. Bismuth (BI)-based quadruple therapy is recommended as the first-line treatment for H. pylori in China. Vonoprazan (VPZ), a new potassium-competitive acid blocker that can inhibit gastric acid secretion more effectively than proton pump inhibitors (PPIs), has been combined with antibiotics to effectively eradicate H. pylori. In this study, we compared the efficacy and safety of two VPZ-based therapies with that of BI-based therapy for H. pylori treatment. METHODS: A three-armed randomised controlled trial (RCT) is being conducted in Shenzhen, with 327 participants recruited from the Gastroenterology Clinic of the University of Hong Kong-Shenzhen Hospital. Patients were diagnosed with H. pylori infection based on a positive 13C-urea breath test (UBT). Patients are kept naïve to their treatment and are randomly assigned in a 1:1:1 ratio to either VPZ-based triple, VPZ-based dual, or BI-based quadruple therapy for 14 days. All groups are subjected to follow-up evaluations of safety, adverse drug reactions, and clinical variables in the first, second, and fourth weeks after treatment. Successful eradication is confirmed by a negative 13C-UBT six weeks after treatment. If initial treatment fails, (1) those patients are turned to another regimen, or (2) a drug resistance test is conducted, after which an individualised treatment regimen shall be prescribed according to antimicrobial susceptibility testing. The resulting data will be evaluated using intention-treat and a per-protocol analysis. DISCUSSION: This study is the a RCT aims to evaluate the efficacy and safety of 14-day VPZ-based triple and dual therapies in comparison with BI-based quadruple therapy. The outcomes of this study may allow treatment recommendations and update drug instructions in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=141314.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Bismuto/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/diagnóstico , Antibacterianos/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Amoxicilina/efeitos adversos , Resultado do Tratamento , Claritromicina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Int J Geriatr Psychiatry ; 38(10): e6013, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37817385

RESUMO

OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in patients with Alzheimer's disease (AD), causing burdens on caregivers. Behavioral and psychological symptoms of dementia and subclinical epileptiform discharge (SED) increased with the disease course of AD. However, the interaction between them was still unknown. The present study aimed to evaluate the associations between SED and BPSD. METHODS/DESIGN: Patients with AD from Kaohsiung Municipal Ta-tung Hospital were included in this study. International 10-20 system scalp electroencephalography (EEG) for 13 min was performed to detect SED. Behavioral and psychological symptoms of dementia was assessed by neuropsychiatric inventory (NPI) questionnaires. The occurrence of BPSD subsyndromes was compared between patients with and without SED. RESULTS: Two hundred sixty-three adult patients qualified for the inclusion criteria and were enrolled in this study. The mean age of patients was 80.2 years, and approximately 62% were women. 17.1% of patients showed SED on EEG. Apathy was the most commonly reported BPSD subsyndrome in this cohort. There was no significant difference in the prevalence of BPSD between patients with and without SED. (75.6% vs. 67.4%, p = 0.2806). However, the NPI score of irritability subsyndrome was significantly higher in the SED (+) group (2.6 ± 3.7 vs. 1.2 ± 2.7, p = 0.0028). In addition, subclinical epileptiform discharge in the frontal lobe was associated with a considerably higher occurrence of hyperactivity subsyndrome, including irritability. CONCLUSIONS: SED may not be a direct cause of BPSD, but the presence of SED may affect the manifestation of BPSD.


Assuntos
Doença de Alzheimer , Apatia , Demência , Humanos , Feminino , Idoso de 80 Anos ou mais , Masculino , Doença de Alzheimer/psicologia , Demência/psicologia , Cuidadores/psicologia , Sintomas Comportamentais/psicologia , Testes Neuropsicológicos
17.
Anesth Analg ; 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37478025

RESUMO

BACKGROUND: Emergence agitation (EA) is an adverse complication during early recovery from sevoflurane anesthesia. Continuous intravenous infusion of dexmedetomidine (DEX) is commonly used for EA prevention. However, a wide dose range is used for preventing EA, and the optimal dose remains unknown. This study was aimed at determining the optimal dose (the 90% effective dose [ED90]) of DEX for continuous intraoperative infusion for EA prevention in children. METHODS: We enrolled children aged 3 to 7 years who underwent dental treatment under sevoflurane anesthesia. DEX was continuously infused from the time of the establishment of the intravenous access until 5 minutes before the end of surgery. The initial DEX dose was 0.5 µg/kg/h, and subsequent dose adjustments were determined based on the response of the previous patient by using an up-down sequential allocation with a biased-coin design. The primary outcome was the ED90 for continuous DEX infusion based on the success or failure of the EA-preventing dose. RESULTS: Forty-five patients were enrolled in the study. The DEX dose ranged from 0.50 to 0.90 µg/kg/h. The estimated ED90 (95% confidence interval [CI]) for preventing EA was 0.74 µg/kg/h (0.67-1.05 µg/kg/h). The duration of surgery (mean ± standard deviation [SD]) was 113 ± 30 minutes. The times (mean ± SD) for extubation, time to emergence, and recovery time were 5 ± 2 minutes, 27 ± 9 minutes, and 39 ± 7 minutes, respectively. CONCLUSIONS: The ED90 for continuous intraoperative DEX infusion for EA prevention in pediatric patients receiving dental treatment under sevoflurane anesthesia was 0.74 µg/kg/h (95% CI, 0.67-1.05 µg/kg/h).

18.
Med Sci Monit ; 29: e938837, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36843310

RESUMO

BACKGROUND The efficacy of lumbar fusion surgery in patients age 80 years and older with lumbar spinal stenosis (LSS) is still controversial. This retrospective study aimed to evaluate the surgical outcomes of LSS patients ³80 vs 65-79 years. MATERIAL AND METHODS The study included 66 patients diagnosed with LSS from 2014 to 2020; 33 patients were ³80 years and 33 patients were 65-79 years. The 2 groups were matched for sex and surgical segment. All patients underwent posterior lumbar decompression, fixation, and fusion surgery. The Numerical Rating Scale (NRS) of leg and back pain, Oswestry Disability Index (ODI), Short-Form Health Survey (SF-36), and radiographic data were collected before surgery and at 3, 6, and 12 months postoperatively. RESULTS NRS (back) in the ≥80 years group was significantly higher than in the 65-79 years group at 3 months [2 (0-3) vs 1 (0-3), P=0.001]. Improvement of SF-36 (3 months: 15.7±4.9 vs 27.6±5.4, P<0.001; 6 months: 27.3±6.8 vs 31.5±5.6, P=0.011) and Physical Component Score (PCS) (3 months: 6.5±2.5 vs 17.0±3.6, P<0.001; 6 months: 15.9±3.4 vs 20.1±3.1, P<0.001) at 3 and 6 months in the ≥80 years group were significantly smaller than in 65-79 years group. There was a difference of Pfirrmann index of adjacent segment disc between the 2 groups at 12 months [≥80 vs 65-79 years group: 5.5 (4-8) vs 5 (3-8), P=0.003]. CONCLUSIONS Lumbar fusion surgery in patients ≥80 years with LSS can provide comparable improvements in clinical and radiographic outcomes compared with younger patients. Postoperative physiological function recovery was slower in patients ≥80 years.


Assuntos
Fusão Vertebral , Estenose Espinal , Humanos , Idoso de 80 Anos ou mais , Idoso , Estenose Espinal/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Descompressão Cirúrgica/métodos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos
19.
Nucleic Acids Res ; 49(12): 6771-6787, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34133716

RESUMO

Proper repair of damaged DNA is crucial for genetic integrity and organismal survival. As semi-autonomous organelles, plastids have their own genomes whose integrity must be preserved. Several factors have been shown to participate in plastid DNA damage repair; however, the underlying mechanism remains unclear. Here, we elucidate a mechanism of homologous recombination (HR) repair in chloroplasts that involves R-loops. We find that the recombinase RecA1 forms filaments in chloroplasts during HR repair, but aggregates as puncta when RNA:DNA hybrids accumulate. ssDNA-binding proteins WHY1/3 and chloroplast RNase H1 AtRNH1C are recruited to the same genomic sites to promote HR repair. Depletion of AtRNH1C or WHY1/3 significantly suppresses the binding of RNA polymerase to the damaged DNA, thus reducing HR repair and modulating microhomology-mediated double-strand break repair. Furthermore, we show that DNA polymerase IB works with AtRNH1C genetically to complete the DNA damage repair process. This study reveals the positive role of R-loops in facilitating the activities of WHY1/3 and RecA1, which in turn secures HR repair and organellar development.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Cloroplastos/genética , Proteínas de Ligação a DNA/metabolismo , Recombinases Rec A/metabolismo , Reparo de DNA por Recombinação , Arabidopsis/enzimologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Cloroplastos/enzimologia , Cloroplastos/metabolismo , Dano ao DNA , DNA de Plantas/metabolismo , Proteínas de Ligação a DNA/genética , DNA Polimerase Dirigida por DNA/genética , Instabilidade Genômica , Mutação , RNA de Plantas/metabolismo
20.
Chem Biodivers ; 20(6): e202201126, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37062706

RESUMO

As a dietary supplement, the efficacy of prebiotics has become a hot issue in recent years. Inulin is one of internationally recognized prebiotics and belongs to a group of non-digestible and fermentable carbohydrates. Currently, the food industry is increasingly using prebiotic inulin as a health-promoting substrate, not just as food supplement. In addition, inulin has also shown great promise in the treatment of various diseases. This article reviews the application of inulin in the food industry and summarizes physiological function of inulin. Through the review and prospect of the research on obesity, diabetes and mental illness, it provides the theoretical basis for the joint development of inulin in food industry and medical application.


Assuntos
Frutanos , Inulina , Frutanos/farmacologia , Prebióticos , Suplementos Nutricionais , Indústria Alimentícia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA