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1.
Biology (Basel) ; 13(6)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38927254

RESUMO

The endothelial barrier plays a critical role in immune defense against bacterial infection. Efficient interactions between neutrophils and endothelial cells facilitate the activation of both cell types. However, neutrophil activation can have dual effects, promoting bacterial clearance on one hand while triggering inflammation on the other. In this review, we provide a detailed overview of the cellular defense progression when neutrophils encounter bacteria, focusing specifically on neutrophil-endothelial interactions and endothelial activation or dysfunction. By elucidating the underlying mechanisms of inflammatory pathways, potential therapeutic targets for inflammation caused by endothelial dysfunction may be identified. Overall, our comprehensive understanding of neutrophil-endothelial interactions in modulating innate immunity provides deeper insights into therapeutic strategies for infectious diseases and further promotes the development of antibacterial and anti-inflammatory drugs.

2.
Nat Nanotechnol ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783058

RESUMO

Therapeutic genome editing of haematopoietic stem cells (HSCs) would provide long-lasting treatments for multiple diseases. However, the in vivo delivery of genetic medicines to HSCs remains challenging, especially in diseased and malignant settings. Here we report on a series of bone-marrow-homing lipid nanoparticles that deliver mRNA to a broad group of at least 14 unique cell types in the bone marrow, including healthy and diseased HSCs, leukaemic stem cells, B cells, T cells, macrophages and leukaemia cells. CRISPR/Cas and base editing is achieved in a mouse model expressing human sickle cell disease phenotypes for potential foetal haemoglobin reactivation and conversion from sickle to non-sickle alleles. Bone-marrow-homing lipid nanoparticles were also able to achieve Cre-recombinase-mediated genetic deletion in bone-marrow-engrafted leukaemic stem cells and leukaemia cells. We show evidence that diverse cell types in the bone marrow niche can be edited using bone-marrow-homing lipid nanoparticles.

3.
PLoS One ; 19(4): e0297337, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564647

RESUMO

OBJECTIVE: With the improvement of medical level, the number of elderly patients is increasing, and the postoperative outcome of the patients cannot be ignored. However, there have been no studies on the relationship between preoperative heart rate variability (HRV) and Perioperative Neurocognitive Disorders (PND). The purpose of this study was to explore the correlation between (HRV) and (PND), postoperative intensive care unit (ICU), and hospital stay in patients undergoing non-cardiac surgery. METHOD: This retrospective analysis included 687 inpatients who underwent 24-hour dynamic electrocardiogram examination in our six departments from January 2021 to January 2022. Patients were divided into two groups based on heart rate variability (HRV): high and low. Possible risk factors of perioperative outcomes were screened using univariate analysis, and risk factors were included in multivariate logistic regression to screen for independent risk factors. The subgroup analysis was carried out to evaluate the robustness of the results. The nomogram of PND multi-factor logistic prediction model was constructed. The receiver operating characteristic (ROC) curve was drawn, and the calibration curve was drawn by bootstrap resampling 1000 times for internal verification to evaluate the prediction ability of nomogram. RESULT: A total of 687 eligible patients were included. The incidence of low HRV was 36.7% and the incidence of PND was 7.6%. The incidence of PND in the low HRV group was higher than that in the high HRV group (11.8% vs 5.2%), the postoperative ICU transfer rate was higher (15.9% than 9.3%P = 0.009), and the hospital stay was longer [15 (11, 19) vs (13), 0.015]. The multivariable logistic regression analysis showed that after adjusting for other factors, decreased low HRV was identified as an independent risk factor for the occurrence of PND (Adjusted Odds Ratio = 2.095; 95% Confidence Interval: 1.160-3.784; P = 0.014) and postoperative ICU admission (Adjusted Odds Ratio = 1.925; 95% Confidence Interval: 1.128-3.286; P = 0.016). This study drew a nomogram column chart for a multivariate logistic regression model, incorporating age and HRV. The calibration curve shows that the predicted value of the model for the occurrence of cardio-cerebrovascular events is in good agreement with the actual observed value, with C-index of 0.696 (95% CI: 0.626 ~ 0.766). Subgroup analysis showed that low HRV was an independent risk factor for PND in patients with gastrointestinal surgery and ASA Ⅲ, aged ≥ 65 years. CONCLUSION: In patients undergoing non-cardiac surgery, the low HRV was an independent risk factor for PND and postoperative transfer to the ICU, and the hospitalization time of patients with low HRV was prolonged. Through establishing a risk prediction model for the occurrence of PND, high-risk patients can be identified during the perioperative period for early intervention.


Assuntos
Transtornos Neurocognitivos , Nomogramas , Idoso , Humanos , Estudos Retrospectivos , Frequência Cardíaca , Fatores de Risco
4.
Medicine (Baltimore) ; 103(9): e37289, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428860

RESUMO

Adenocarcinoma of the esophagogastric junction (AEG) has a high incidence, and the extent of lymph node dissection (LND) and its impact on prognosis remain controversial. This study aimed to explore the risk factors for lymph node metastasis (LNM) and prognosis in Siewert II/III AEG patients. A retrospective review of 239 Siewert II/III AEG patients surgically treated at Beijing Friendship Hospital from July 2013 to December 2022 was conducted. Preoperative staging was conducted via endoscopy, ultrasound gastroscopy, CT, and biopsy. Depending on the stage, patients received radical gastrectomy with LND and chemotherapy. Clinicopathological data were collected, and survival was monitored semiannually until November 2023. Utilizing logistic regression for data analysis and Cox regression for survival studies, multivariate analysis identified infiltration depth (OR = 0.038, 95% CI: 0.011-0.139, P < .001), tumor deposit (OR = 0.101, 95% CI: 0.011-0.904, P = .040), and intravascular cancer embolus (OR = 0.234, 95% CI: 0.108-0.507, P < .001) as independent predictors of LNM. Lymph nodes No. 1, 2, 3, 4, 7, 10, and 11 were more prone to metastasis in the abdominal cavity. Notably, Siewert III AEG patients showed a higher metastatic rate in nodes No. 5 and No. 6 compared to Siewert II. Mediastinal LNM was predominantly found in nodes No. 110 and No. 111 for Siewert II AEG, with rates of 5.45% and 3.64%, respectively. A 3-year survival analysis underscored LNM as a significant prognostic factor (P = .001). Siewert II AEG patients should undergo removal of both celiac and mediastinal lymph nodes, specifically nodes No. 1, 2, 3, 4, 7, 10, 11, 110, and 111. Dissection of nodes No. 5 and No. 6 is not indicated for these patients. In contrast, Siewert III AEG patients do not require mediastinal LND, but pyloric lymphadenectomy for nodes No. 5 and No. 6 is essential. The presence of LNM is associated with poorer long-term prognosis. Perioperative chemotherapy may offer a survival advantage for AEG patients.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Metástase Linfática/patologia , Neoplasias Gástricas/patologia , Neoplasias Esofágicas/patologia , Prognóstico , Excisão de Linfonodo , Adenocarcinoma/patologia , Junção Esofagogástrica/patologia , Fatores de Risco
5.
Artigo em Inglês | MEDLINE | ID: mdl-38518150

RESUMO

Objective: Investigating the application effectiveness of using loop-mediated isothermal amplification (LAMP) on a microfluidic chip to detect the pathogens associated with ventilator-associated pneumonia (VAP). Methods: Eighty samples of bronchoalveolar lavage fluid from patients with ventilator-associated pneumonia (VAP) were collected at The First Hospital of Hebei Medical University from July 2022 to July 2023. The bacterial culture technique and the LAMP method were used to detect the nucleic acid of the pathogens in the patient samples. The positivity rates of bacterial culture and LAMP method in detecting VAP pathogens were analyzed. Results: A total of 80 specimens were examined, with 73 positive specimens detected using the LAMP method (positivity rate of 91.25%) and 60 positive specimens detected using bacterial culture (positivity rate of 75.00%). The LAMP method exhibited a higher number of positive detections compared to bacterial culture. Both methods showed a high level of concordance and were virtually identical in detecting methicillin-resistant Staphylococcus aureus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterobacter aerogenes, Haemophilus influenzae, and Streptococcus pneumoniae. Conclusion: The LAMP method demonstrates significantly improved performance in the detection of pathogens for VAP, with a higher pathogen positivity rate compared to bacterial culture. This method holds promising prospects for clinical application.

6.
Int J Comput Assist Radiol Surg ; 19(2): 345-353, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37914911

RESUMO

PURPOSE: This study aimed to classify laparoscopic gastric cancer phases. We also aimed to develop a transformer-based artificial intelligence (AI) model for automatic surgical phase recognition and to evaluate the model's performance using laparoscopic gastric cancer surgical videos. METHODS: One hundred patients who underwent laparoscopic surgery for gastric cancer were included in this study. All surgical videos were labeled and classified into eight phases (P0. Preparation. P1. Separate the greater gastric curvature. P2. Separate the distal stomach. P3. Separate lesser gastric curvature. P4. Dissect the superior margin of the pancreas. P5. Separation of the proximal stomach. P6. Digestive tract reconstruction. P7. End of operation). This study proposed an AI phase recognition model consisting of a convolutional neural network-based visual feature extractor and temporal relational transformer. RESULTS: A visual and temporal relationship network was proposed to automatically perform accurate surgical phase prediction. The average time for all surgical videos in the video set was 9114 ± 2571 s. The longest phase was at P1 (3388 s). The final research accuracy, F1, recall, and precision were 90.128, 87.04, 87.04, and 87.32%, respectively. The phase with the highest recognition accuracy was P1, and that with the lowest accuracy was P2. CONCLUSION: An AI model based on neural and transformer networks was developed in this study. This model can identify the phases of laparoscopic surgery for gastric cancer accurately. AI can be used as an analytical tool for gastric cancer surgical videos.


Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Inteligência Artificial , Gastrectomia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgia
7.
Cancer Sci ; 115(2): 589-599, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38146096

RESUMO

Although intravenous bevacizumab (IVBEV) is the most promising treatment for cerebral radiation necrosis (CRN), there is no conclusion on the optimal dosage. Our retrospective study aimed to compare the efficacy and safety of high-dose with low-dose IVBEV in treating CRN associated with radiotherapy for brain metastases (BMs). This paper describes 75 patients who were diagnosed with CRN secondary to radiotherapy for BMs, treated with low-dose or high-dose IVBEV and followed up for a minimum of 6 months. The clinical data collected for this study include changes in brain MRI, clinical symptoms, and corticosteroid usage before, during, and after IVBEV treatment. At the 3-month mark following administration of IVBEV, a comparison of two groups revealed that the median percentage decreases in CRN volume on T2-weighted fluid-attenuated inversion recovery and T1-weighted gadolinium contrast-enhanced image (T1CE), as well as the signal ratio reduction on T1CE, were 65.8% versus 64.8% (p = 0.860), 41.2% versus 51.9% (p = 0.396), and 37.4% versus 35.1% (p = 0.271), respectively. Similarly, at 6 months post-IVBEV, the median percentage reductions of the aforementioned parameters were 59.5% versus 62.0% (p = 0.757), 39.1% versus 31.3% (p = 0.851), and 35.4% versus 28.2% (p = 0.083), respectively. Notably, the incidence of grade ≥3 adverse events was higher in the high-dose group (n = 4, 9.8%) than in the low-dose group (n = 0). Among patients with CRN secondary to radiotherapy for BMs, the administration of high-dose IVBEV did not demonstrate superiority over low-dose IVBEV. Moreover, the use of high-dose IVBEV was associated with a higher incidence of grade ≥3 adverse events compared with low-dose IVBEV.


Assuntos
Neoplasias Encefálicas , Humanos , Bevacizumab/efeitos adversos , Estudos Retrospectivos , Necrose/etiologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia
8.
Cancer Immunol Res ; 12(3): 350-362, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38113030

RESUMO

The existing T cell-centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSC), that inhibit antitumor immunity and support multiple steps of tumor development are recognized as one of the major obstacles in cancer treatment. Leukocyte Ig-like receptor subfamily B3 (LILRB3), an immune inhibitory receptor containing tyrosine-based inhibitory motifs (ITIM), is expressed solely on myeloid cells. However, it is unknown whether LILRB3 is a critical checkpoint receptor in regulating the activity of immunosuppressive myeloid cells, and whether LILRB3 signaling can be blocked to activate the immune system to treat solid tumors. Here, we report that galectin-4 and galectin-7 induce activation of LILRB3 and that LILRB3 is functionally expressed on immunosuppressive myeloid cells. In some samples from patients with solid cancers, blockade of LILRB3 signaling by an antagonistic antibody inhibited the activity of immunosuppressive myeloid cells. Anti-LILRB3 also impeded tumor development in myeloid-specific LILRB3 transgenic mice through a T cell-dependent manner. LILRB3 blockade may prove to be a novel approach for immunotherapy of solid cancers.


Assuntos
Células Supressoras Mieloides , Neoplasias , Camundongos , Animais , Humanos , Células Mieloides , Neoplasias/terapia , Linfócitos T , Receptores Imunológicos , Microambiente Tumoral , Antígenos CD
9.
Nat Commun ; 14(1): 8165, 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38071397

RESUMO

Cells living in geometrically confined microenvironments are ubiquitous in various physiological processes, e.g., wound closure. However, it remains unclear whether and how spatially geometric constraints on host cells regulate bacteria-host interactions. Here, we reveal that interactions between bacteria and spatially constrained cell monolayers exhibit strong spatial heterogeneity, and that bacteria tend to adhere to these cells near the outer edges of confined monolayers. The bacterial adhesion force near the edges of the micropatterned monolayers is up to 75 nN, which is ~3 times higher than that at the centers, depending on the underlying substrate rigidities. Single-cell RNA sequencing experiments indicate that spatially heterogeneous expression of collagen IV with significant edge effects is responsible for the location-dependent bacterial adhesion. Finally, we show that collagen IV inhibitors can potentially be utilized as adjuvants to reduce bacterial adhesion and thus markedly enhance the efficacy of antibiotics, as demonstrated in animal experiments.


Assuntos
Aderência Bacteriana , Colágeno , Animais , Aderência Bacteriana/fisiologia , Colágeno/metabolismo , Fenômenos Mecânicos , Bactérias/metabolismo , Adesão Celular
10.
Front Med (Lausanne) ; 10: 1260139, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38111698

RESUMO

Background: The treatment of condyloma acuminatum (CA), especially the very persistent and recurrent CA, is currently the focus of our research. Immunotherapies have recently been shown to be well-tolerated and effective in treating warts, particularly refractory warts. However, there is still a lack of corresponding evidence-based medical evidence on the effectiveness of different immunotherapies in treating warts. The difference between network meta-analysis and meta-analysis is that network meta-analysis can be used to compare multiple treatments by combining direct and indirect evidence to assess the interrelationship between all treatments. We intend to compare the efficacy of different treatments for CA using a network meta-analysis. Methods: PubMed, Cochrane Library and Embase from inception to June 1st, 2023 were searched using a computer. All articles on immunotherapies for CA were included. Stata MP17.0 software was used for data analyses. Results: A total of 8 randomly-controlled trials involving 493 patients were included. Result showed that all treatment measures had a significant efficacy compared with the regular saline group (BCG (bacillus Calmette-Guérin vaccine) OR = 96.00, 95%CI: 10.35-890.58; MMR (measle, mumps and rubella vaccine) OR = 29.69, 95%CI: 7.47-118.04; Candida antigens OR = 27.34, 95%CI: 8.64-86.52; PPDs (purified protein derivatives) OR = 23.33, 95%CI: 6.75-80.60; VD3 OR = 21.36, 95%CI: 4.34-105.16 and purified protein derivatives (general) OR = 13.14, 95%CI: 3.38-51.12). The area under the curve (SUCRA) ranking results showed that the bacillus Calmette-Guérin vaccine had the highest total efficiency, which was 88.2%, with the rest in the order of measle, mumps and rubella vaccine, which was 68.9%, Candida antigens, which was 63.6%, purified protein derivatives, which was 52.9%, vitamin D3, which was 49.0%, purified protein derivatives (general), which was 27.4%, and saline, which was 0%. Conclusion: In summary, we found that the bacillus Calmette-Guérin vaccine was superior to other treatments in terms of efficacy according to the SUCRA value.

12.
Front Nutr ; 10: 1288837, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841409

RESUMO

[This corrects the article DOI: 10.3389/fnut.2022.915865.].

13.
BMJ Open ; 13(9): e070735, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37770279

RESUMO

INTRODUCTION: Benign gastric outlet obstruction (BGOO) severely impacts the quality of life of patients. The main treatment methods for BGOO include surgery and endoscopy, but both have significant drawbacks. Therefore, this study aims to explore the safety and efficacy of a new technique, to develop a new option for treating BGOO. METHODS AND ANALYSIS: This is an ongoing prospective, single-centre, single-blind randomised controlled trial. The study will be conducted from January 2022 to December 2025, and 50 patients will be enrolled. The participants will be randomly assigned in a 1:1 ratio to either the experimental (stomach-partitioning gastrojejunostomy with distal selective vagotomy) or control groups (conventional gastrojejunostomy with highly selective vagotomy). We will collect baseline characteristics, laboratory tests, auxiliary examinations, operation, postoperative conditions and follow-up data. Follow-up will last for 3 years. The main outcome is the incidence of delayed gastric emptying within 30 days after surgery. Secondary outcomes include the efficacy indicator (consisting of serum gastrin level, pepsinogen level, 13C breath test, gastrointestinal quality of life index, operation time, blood loss and postoperative recovery), a safety evaluation index (consisting of complications and mortality within 30 days after surgery) and follow-up data (consisting of the incidence of primary ulcer progression in 3 years after surgery, and the gastroscopy results in 1 and 3 years after surgery). ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Beijing Friendship Hospital, Capital Medical University (no. 2021-P2-274-02). The study conformed to the provisions of the Declaration of Helsinki (as revised in 2013). Written informed consent will be obtained prior to study enrolment. The results of this study will be published in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2100052197.


Assuntos
Derivação Gástrica , Obstrução da Saída Gástrica , Humanos , Vagotomia Gástrica Proximal , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Estudos Prospectivos , Qualidade de Vida , Método Simples-Cego , Vagotomia/efeitos adversos , Obstrução da Saída Gástrica/etiologia , Obstrução da Saída Gástrica/cirurgia , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
J Agric Food Chem ; 71(28): 10729-10741, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37421368

RESUMO

Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) is increasingly used as a co-fermentation culture in fermented milk production. Recently, a capsular polysaccharide (CPS)- and exopolysaccharide (EPS)-producing mutant of Probio-M9, HG-R7970-3, was generated by space mutagenesis. This study compared the performance of cow and goat milk fermentation between the non-CPS/-EPS-producing parental strain (Probio-M9) and the CPS/EPS producer (HG-R7970-3), and the stability of products fermented by the two bacteria. Our results showed that using HG-R7970-3 as the fermentative culture could improve the probiotic viable counts, physico-chemical, texture, and rheological properties in both cow and goat milk fermentation. Substantial differences were also observed in the metabolomics profiles between fermented cow and goat milks produced by the two bacteria. Comparing with Probio-M9-fermented cow and goat milks, those fermented by HG-R7970-3 were enriched in a number of flavor compounds and potential functional components, particularly acids, esters, peptides, and intermediate metabolites. Moreover, HG-R7970-3 could improve the post-fermentation flavor retention capacity. These new and added features are of potential to improve the techno-functional qualities of conventional fermented milks produced by Probio-M9, and these differences are likely imparted by the acquired CPS-/EPS-producing ability of the mutant. It merits further investigation into the sensory quality and in vivo function of HG-R7970-3-fermented milks.


Assuntos
Produtos Fermentados do Leite , Lacticaseibacillus rhamnosus , Probióticos , Animais , Feminino , Bovinos , Leite/química , Lacticaseibacillus rhamnosus/genética , Lacticaseibacillus , Probióticos/química , Fermentação , Bactérias , Cabras , Produtos Fermentados do Leite/microbiologia
15.
J Cancer Res Clin Oncol ; 149(13): 12103-12113, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37422882

RESUMO

PURPOSE: The purpose of this meta-analysis is to systematically review the diagnostic performance of radiomic techniques in predicting peritoneal metastasis in patients with gastric cancer, and to evaluate the quality of current research. METHODS: We searched PubMed, Web of Science, EBSCO, Embase, and Cochrane databases for relevant studies up to April 3, 2023. Data extraction and quality evaluation were performed by two independent reviewers. Then we performed statistical analysis, including plotting the forest plot and summary receiver operating characteristic (SROC) curve, and source of heterogeneity analysis, through the MIDAS module in Stata 15. We performed meta-regression and subgroup analyses to analyze the sources of heterogeneity. Using the QUADAS-2 scale and the RQS scale to assess the quality of retrieved studies. RESULTS: Ten studies with 6199 patients were finally included in our meta-analysis. Pooled sensitivity and specificity were 0.77 (95% confidence interval [CI]: 0.66, 0.86), and 0.88 (95% CI 0.80, 0.93), respectively. The overall AUC was 0.89 (95% CI 0.86, 0.92). The heterogeneity of this meta-analysis was high, with I2 = 88% (95% CI 75,100). The result of meta-regression showed that QUADAS-2 results, RQS results and machine learning method led to heterogeneity in sensitivity and specificity (P < 0.05). Furthermore, the image segmentation area and the presence or absence of combined clinical factors were associated with sensitivity heterogeneity and specificity heterogeneity, respectively. CONCLUSION: Undoubtedly, radiomics has potential value in diagnosing peritoneal metastasis of gastric cancer, but the quality of current research is inconsistent, and more standardized and high-quality research is still needed in the future to achieve the transformation of radiomics results into clinical applications.


Assuntos
Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Peritoneais/diagnóstico por imagem , Sensibilidade e Especificidade , Curva ROC
16.
Langenbecks Arch Surg ; 408(1): 260, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37392263

RESUMO

PURPOSE: This study aimed to evaluate the safety and efficacy of augmented-rectangle technique (ART) versus delta-shaped anastomosis (DA) for treating gastric cancer in total laparoscopic distal gastrectomy. METHODS: In total, 99 patients with distal gastric cancer who underwent ART (n = 60) or DA (n = 39) were considered. Operative data, postoperative recovery, complications, quality of life, and endoscopic findings of both groups were compared. RESULTS: The ART group had faster postoperative recovery than the DA group, and was better than DA regarding complications. The mode of reconstruction remained an independent predictor of complications, but not postoperative recovery. Dumping syndrome occurred in 3 (5.0%) and 2 patients (5.1%) of ART and DA groups within 30 days after surgery, and 3 (5.0%) and 2 patients (5.1%) 1 year after surgery. Regarding global health status on the EORTC-QLQ-C30 scale, the ART group had better outcomes than the DA group. Gastritis occurred in 38 (63.3%) and 27 (69.3%) patients of ART and DA groups, respectively. Residual food occurred in 8 (13.3%) and 11 (28.2%) patients of ART and DA groups. Reflux esophagitis occurred in 5 (8.3%) and 4 (10.3%) patients of ART and DA groups. Further, bile reflux occurred in 8 (13.3%) and 4 (10.3%) patients of ART and DA groups. CONCLUSIONS: ART has similar advantages to DA for total laparoscopic reconstruction and is superior to DA regarding the incidence of complications, complication grade, and global health status. Furthermore, ART may have potential advantages in postoperative recovery and anastomotic stenosis.


Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Qualidade de Vida , Anastomose Cirúrgica/efeitos adversos , Gastrectomia/efeitos adversos , Laparoscopia/efeitos adversos
17.
Nucleic Acids Res ; 51(14): 7451-7464, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37334828

RESUMO

5-Methylated cytosine is a frequent modification in eukaryotic RNA and DNA influencing mRNA stability and gene expression. Here we show that free 5-methylcytidine (5mC) and 5-methyl-2'-deoxycytidine are generated from nucleic acid turnover in Arabidopsis thaliana, and elucidate how these cytidines are degraded, which is unclear in eukaryotes. First CYTIDINE DEAMINASE produces 5-methyluridine (5mU) and thymidine which are subsequently hydrolyzed by NUCLEOSIDE HYDROLASE 1 (NSH1) to thymine and ribose or deoxyribose. Interestingly, far more thymine is generated from RNA than from DNA turnover, and most 5mU is directly released from RNA without a 5mC intermediate, since 5-methylated uridine (m5U) is an abundant RNA modification (m5U/U ∼1%) in Arabidopsis. We show that m5U is introduced mainly by tRNA-SPECIFIC METHYLTRANSFERASE 2A and 2B. Genetic disruption of 5mU degradation in the NSH1 mutant causes m5U to occur in mRNA and results in reduced seedling growth, which is aggravated by external 5mU supplementation, also leading to more m5U in all RNA species. Given the similarities between pyrimidine catabolism in plants, mammals and other eukaryotes, we hypothesize that the removal of 5mU is an important function of pyrimidine degradation in many organisms, which in plants serves to protect RNA from stochastic m5U modification.


Assuntos
Arabidopsis , RNA , Animais , Timina , Uridina/metabolismo , Pirimidinas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , DNA , Mamíferos/genética
18.
Plant Cell ; 35(10): 3739-3756, 2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37367221

RESUMO

The biological function of RNA can be modulated by base modifications. Here, we unveiled the occurrence of N4-acetylation of cytidine in plant RNA, including mRNA, by employing LC-MS/MS and acRIP-seq. We identified 325 acetylated transcripts from the leaves of 4-week-old Arabidopsis (Arabidopsis thaliana) plants and determined that 2 partially redundant N-ACETYLTRANSFERASEs FOR CYTIDINE IN RNA (ACYR1 and ACYR2), which are homologous to mammalian NAT10, are required for acetylating RNA in vivo. A double-null mutant was embryo lethal, while eliminating 3 of the 4 ACYR alleles led to defects in leaf development. These phenotypes could be traced back to the reduced acetylation and concomitant destabilization of the transcript of TOUGH, which is required for miRNA processing. These findings indicate that N4-acetylation of cytidine is a modulator of RNA function with a critical role in plant development and likely many other processes.


Assuntos
Arabidopsis , Citidina , Animais , RNA Mensageiro/genética , Acetilação , Citidina/genética , Citidina/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , RNA de Plantas , Arabidopsis/genética , Arabidopsis/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
19.
Front Bioeng Biotechnol ; 11: 1109295, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873355

RESUMO

Purpose: This study evaluated the gastric emptying performance of stomach-partitioning gastrojejunostomy (SPGJ) versus conventional gastrojejunostomy (CGJ) for treating gastric outlet obstruction (GOO). Methods: First, 73 patients who underwent SPGJ (n = 48) or CGJ (n = 25) were involved. Surgical outcomes, postoperative recovery of gastrointestinal function, delayed gastric emptying, and nutritional status of both groups were compared. Second, a three-dimensional stomach model was constructed based on the gastric filling CT images from a GOO patient with a standard stature. The present study evaluated SPGJ numerically by comparing it with CGJ in terms of local flow parameters such as flow velocity, pressure, particle retention time, and particle retention velocity. Results: Clinical data found that SPGJ had significant advantages over CGJ in terms of time to pass gas (3 versus 4 days, p < 0.001), time to oral intake (3 versus 4 days, p = 0.001), postoperative hospitalization (7 versus 9 days, p < 0.001), the incidence of delay gastric emptying (DGE) (2.1% versus 36%, p < 0.001), DGE grading (p < 0.001), and complications (p < 0.001) for GOO patients. Moreover, numerical simulation revealed that the SPGJ model would induce contents in stomach discharge to the anastomosis at a higher speed, and only 5% of that flowed to the pylorus. SPGJ model also had a low-pressure drop as the flow from the lower esophagus to the jejunum, reducing the resistance to food discharge. Besides, the average retention time of particles in the CGJ model is 1.5 times longer than that in the SPGJ models, and the average instantaneous velocity in CGJ and SPGJ models are 22 mm/s and 29 mm/s, respectively. Conclusion: Compared with CGJ, patients after SPGJ had better gastric emptying performance and better postoperative clinical efficacy. Therefore, we think that SPGJ may be a better option for treating GOO.

20.
Langenbecks Arch Surg ; 408(1): 69, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36715889

RESUMO

PURPOSE: Side overlap with fundoplication by Yamashita (SOFY) is an anti-reflux form of esophagogastrostomy. We compared the safety and efficacy of laparoscopic proximal gastrectomy (PG) with SOFY to that of laparoscopic total gastrectomy (TG) with Roux-en-Y for treating cT1-2 Siewert II/III adenocarcinoma of the esophagogastric junction. METHODS: Fifty-two patients who underwent PG (n = 28) or TG (n = 24), without conversion to laparotomy, were included. Surgical outcomes, complications, reflux symptoms, quality of life, and nutritional status of both groups were compared. RESULTS: Significant differences between PG and TG groups regarding operative time (245.7 versus 294.6 min, P = 0.005), reconstruction time (22.1 versus 28.5 min, P < 0.001), time to pass gas (3 versus 4 days, P = 0.021), time to oral intake (4.5 versus 5 days, P = 0.043), and gastroesophageal reflux (60.7% versus 4.2%, P < 0.001) were observed. Reflux esophagitis for the PG group was 42.9% (12/28). The incidence of Los Angeles grade B and above was 10.7%. Between-group differences in terms of global health status, diarrhea, reflux, and eating were observed. Body weight maintenance was better in the PG group than in the TG group 6 months and 1 year postoperatively. CONCLUSION: SOFY is simple and more advantageous than TG in terms of postoperative recovery, body weight, eating, and diarrhea. However, the occurrence of postoperative reflux after SOFY was high. The limitations of this study are the significant differences in pathological T stage of patients in the two groups and the small sample size.


Assuntos
Adenocarcinoma , Refluxo Gastroesofágico , Laparoscopia , Neoplasias Gástricas , Humanos , Fundoplicatura , Qualidade de Vida , Estudos Prospectivos , Neoplasias Gástricas/patologia , Junção Esofagogástrica/cirurgia , Junção Esofagogástrica/patologia , Gastrectomia/efeitos adversos , Refluxo Gastroesofágico/cirurgia , Refluxo Gastroesofágico/etiologia , Laparoscopia/efeitos adversos , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Estudos Retrospectivos , Resultado do Tratamento , Complicações Pós-Operatórias/cirurgia
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