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Among minimally invasive surgical procedures, colorectal surgery is associated with a notably higher incidence of incisional hernia (IH), ranging from 1.7% to 24.3%. This complication poses a significant burden on the healthcare system annually, necessitating urgent attention from surgeons. In a study published in the World Journal of Gastrointestinal Surgery, Fan et al compared the incidence of IH among 1614 patients who underwent laparoscopic colorectal surgery with different extraction site locations and evaluated the risk factors associated with its occurrence. This editorial analyzes the current risk factors for IH after laparoscopic colorectal surgery, emphasizing the impact of obesity, surgical site infection, and the choice of incision location on its development. Furthermore, we summarize the currently available preventive measures for IH. Given the low surgical repair rate and high recurrence rate associated with IH, prevention deserves greater research and attention compared to treatment.
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The amyloid-beta peptide (Aß) is the neurotoxic component in senile plaques of Alzheimer's disease (AD) brains. Previously we have reported that Aß toxicity is mediated by the induction of sonic hedgehog (SHH) to trigger cell cycle re-entry (CCR) and apoptosis in post-mitotic neurons. Basella alba is a vegetable whose polysaccharides carry immunomodulatory and anti-cancer actions, but their protective effects against neurodegeneration have never been reported. Herein, we tested whether polysaccharides derived from Basella alba (PPV-6) may inhibit Aß toxicity and explored its underlying mechanisms. In differentiated rat cortical neurons, Aß25-35 reduced cell viability, damaged neuronal structure, and compromised mitochondrial bioenergetic functions, all of which were recovered by PPV-6. Immunocytochemistry and western blotting revealed that Aß25-35-mediated induction of cell cycle markers including cyclin D1, proliferating cell nuclear antigen (PCNA), and histone H3 phosphorylated at Ser-10 (p-Histone H3) in differentiated neurons was all suppressed by PPV-6, along with mitigation of caspase-3 cleavage. Further studies revealed that PPV-6 inhibited Aß25-35 induction of SHH; indeed, PPV-6 was capable of suppressing neuronal CCR and apoptosis triggered by the exogenous N-terminal fragment of sonic hedgehog (SHH-N). Our findings demonstrated that, in the fully differentiated neurons, PPV-6 exerts protective actions against Aß neurotoxicity via the downregulation of SHH to suppress neuronal CCR and apoptosis.
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Peptídeos beta-Amiloides , Apoptose , Ciclo Celular , Proteínas Hedgehog , Neurônios , Polissacarídeos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Proteínas Hedgehog/metabolismo , Animais , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Apoptose/efeitos dos fármacos , Ratos , Polissacarídeos/farmacologia , Polissacarídeos/química , Ciclo Celular/efeitos dos fármacos , Fragmentos de Peptídeos , Sobrevivência Celular/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologiaRESUMO
BACKGROUND: The serratus anterior muscle, located in the lateral aspect of the thorax, plays a crucial role in shoulder movement and stability. Thoracoscopic surgery, while minimally invasive, often results in significant postoperative pain, complicating patient recovery and potentially extending hospital stays. Traditional anesthesia methods may not adequately address this pain, leading to increased complications such as agitation due to inadequate pain management. AIM: To evaluate the application value of ultrasound-guided serratus anterior plane block (SAPB) in patients undergoing thoracoscopic surgery, focusing on its effects on postoperative analgesia and rehabilitation. METHODS: Eighty patients undergoing thoracoscopic surgery between August 2021 and December 2022 were randomly divided into two groups: An observation group receiving ultrasound-guided SAPB and a control group receiving standard care without SAPB. Both groups underwent general anesthesia and were monitored for blood pressure, heart rate (HR), oxygen saturation, and pulse. The primary outcomes measured included mean arterial pressure (MAP), HR, postoperative visual analogue scale (VAS) scores for pain, supplemental analgesic use, and incidence of agitation. RESULTS: The observation group showed significantly lower cortisol and glucose concentrations at various time points post-operation compared to the control group, indicating reduced stress responses. Moreover, MAP and HR levels were lower in the observation group during and after surgery. VAS scores were significantly lower in the observation group at 1 h, 4 h, 6 h, and 12 h post-surgery, and the rates of analgesic supplementation and agitation were significantly reduced compared to the control group. CONCLUSION: Ultrasound-guided SAPB significantly improves postoperative analgesia and reduces agitation in patients undergoing thoracoscopic surgery. This technique stabilizes perioperative vital signs, decreases the need for supplemental analgesics, and minimizes postoperative pain and stress responses, underscoring its high application value in enhancing patient recovery and rehabilitation post-thoracoscopy.
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Behçet's disease (BD) is a chronic inflammatory disorder prone to frequent recurrences, with a high predilection for intestinal involvement. However, the efficacy and long-term effects of surgical treatment for intestinal BD are unknown. In the current issue of World J Gastrointest Surg, Park et al conducted a retrospective analysis of 31 patients with intestinal BD who received surgical treatment. They found that elevated C-reactive protein levels and emergency surgery were poor prognostic factors for postoperative recurrence, emphasizing the adverse impact of severe inflammation on the prognosis of patients with intestinal BD. This work has clinical significance for evaluating the postoperative condition of intestinal BD. The editorial attempts to summarize the clinical diagnosis and treatment of intestinal BD, focusing on the impact of adverse factors on surgical outcomes. We hope this review will facilitate more precise postoperative management of patients with intestinal BD by clinicians.
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Helicobacter pylori (H. pylori) plays an important role in the development of gastric cancer, although its association to colorectal polyp (CP) or colorectal cancer (CRC) is unknown. In this issue of World Journal of Gastrointestinal Surgery, Zhang et al investigated the risk factors for H. pylori infection after colon polyp resection. Importantly, the researchers used R software to create a prediction model for H. pylori infection based on their findings. This editorial gives an overview of the association between H. pylori and CP/CRC, including the clinical significance of H. pylori as an independent risk factor for CP/CRC, the underlying processes of H. pylori-associated carcinogenesis, and the possible risk factors and identification of H. pylori.
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Fibroblast growth factor 21 (FGF21) plays a crucial role in metabolism and brain function. Glucosamine (GLN) has been recognized for its diverse beneficial effects. This study aimed to elucidate the modulation of FGF21 production by GLN and its impact on learning and memory functions. Using both in vivo and in vitro models, we investigated the effects of GLN on mice fed with a normal diet or high-fat diet and on mouse HT22 hippocampal cells, STHdhQ7/Q7 striatal cells, and rat primary cortical neurons challenged with GLN. Our results indicated that GLN promotes learning and memory functions in mice and upregulates FGF21 expression in the hippocampus, cortex, and striatum, as well as in HT22 cells, STHdhQ7/Q7 cells, and cortical neurons. In animals receiving GLN together with an FGF21 receptor FGFR1 inhibitor (PD173074), the GLN-enhanced learning and memory functions and induction of FGF21 production in the hippocampus were significantly attenuated. While exploring the underlying molecular mechanisms, the potential involvement of NF-κB, Akt, p38, JNK, PKA, and PPARα in HT22 and NF-κB, Akt, p38, and PPARα in STHdhQ7/Q7 were noted; GLN was able to mediate the activation of p65, Akt, p38, and CREB in HT22 and p65, Akt, and p38 in STHdhQ7/Q7 cells. Our accumulated findings suggest that GLN may increase learning and memory functions by inducing FGF21 production in the brain. This induction appears to be mediated, at least in part, through GLN's activation of the NF-κB, Akt, p38, and PKA/CREB pathways.
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Fatores de Crescimento de Fibroblastos , Glucosamina , Hipocampo , Aprendizagem , Memória , Animais , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Glucosamina/farmacologia , Camundongos , Memória/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Ratos , Masculino , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Linhagem Celular , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Background Detection of extranodal extension (ENE) at pathology is a poor prognostic indicator for rectal cancer, but whether ENE can be identified at pretreatment MRI is, to the knowledge of the authors, unknown. Purpose To evaluate the performance of pretreatment MRI in detecting ENE using a matched pathologic reference standard and to assess its prognostic value in patients with rectal cancer. Materials and Methods This single-center study included a prospective development data set consisting of participants with rectal adenocarcinoma who underwent pretreatment MRI and radical surgery (December 2021 to January 2023). MRI characteristics were identified by their association with ENE-positive nodes (χ2 test and multivariable logistic regression) and the performance of these MRI features was assessed (area under the receiver operating characteristic curve [AUC]). Interobserver agreement was assessed by Cohen κ coefficient. The prognostic value of ENE detected with MRI for predicting 3-year disease-free survival was assessed by Cox regression analysis in a retrospective independent validation cohort of patients with locally advanced rectal cancer (December 2019 to July 2020). Results The development data set included 147 participants (mean age, 62 years ± 11 [SD]; 87 male participants). The retrospective cohort included 110 patients (mean age, 60 years ± 9; 79 male participants). Presence of vessel interruption and fusion (both P < .001), heterogeneous internal structure, and the broken-ring and tail signs (odds ratio range, 4.10-23.20; P value range, <.001 to .002) were predictors of ENE at MRI, and together achieved an AUC of 0.91 (95% CI: 0.88, 0.93) in detecting ENE. Interobserver agreement was moderate for the presence of vessel interruption and fusion (κ = 0.46 for both) and substantial for others (κ = 0.61-0.67). The presence of ENE at pretreatment MRI was independently associated with worse 3-year disease-free survival (hazard ratio, 3.00; P = .02). Conclusion ENE can be detected at pretreatment MRI, and its presence was associated with worse prognosis for patients with rectal cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Eberhardt in this issue.
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Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Masculino , Pessoa de Meia-Idade , Extensão Extranodal , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Retais/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: Rectal tumor segmentation on post neoadjuvant chemoradiotherapy (nCRT) magnetic resonance imaging (MRI) has great significance for tumor measurement, radiomics analysis, treatment planning, and operative strategy. In this study, we developed and evaluated segmentation potential exclusively on post-chemoradiation T2-weighted MRI using convolutional neural networks, with the aim of reducing the detection workload for radiologists and clinicians. METHODS: A total of 372 consecutive patients with LARC were retrospectively enrolled from October 2015 to December 2017. The standard-of-care neoadjuvant process included 22-fraction intensity-modulated radiation therapy and oral capecitabine. Further, 243 patients (3061 slices) were grouped into training and validation datasets with a random 80:20 split, and 41 patients (408 slices) were used as the test dataset. A symmetric eight-layer deep network was developed using the nnU-Net Framework, which outputs the segmentation result with the same size. The trained deep learning (DL) network was examined using fivefold cross-validation and tumor lesions with different TRGs. RESULTS: At the stage of testing, the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and mean surface distance (MSD) were applied to quantitatively evaluate the performance of generalization. Considering the test dataset (41 patients, 408 slices), the average DSC, HD95, and MSD were 0.700 (95% CI: 0.680-0.720), 17.73 mm (95% CI: 16.08-19.39), and 3.11 mm (95% CI: 2.67-3.56), respectively. Eighty-two percent of the MSD values were less than 5 mm, and fifty-five percent were less than 2 mm (median 1.62 mm, minimum 0.07 mm). CONCLUSIONS: The experimental results indicated that the constructed pipeline could achieve relatively high accuracy. Future work will focus on assessing the performances with multicentre external validation.
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Aprendizado Profundo , Neoplasias Retais , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Terapia Neoadjuvante , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Estudos Retrospectivos , SemânticaRESUMO
OBJECTIVES: By analyzing the distribution of existing and newly proposed staging imaging features in pT1-3 and pT4a tumors, we searched for a salient feature and validated its diagnostic performance. METHODS: Preoperative multiphase contrast-enhanced CT images of the training cohort were retrospectively collected at three centers from January 2016 to December 2017. We used the chi-square test to analyze the distribution of several stage-related imaging features in pT1-3 and pT4a tumors, including small arteriole sign (SAS), outer edge of the intestine, tumor invasion range, and peritumoral adipose tissue. Preoperative multiphase contrast-enhanced CT images of the validation cohort were retrospectively collected at Beijing Cancer Hospital from January 2018 to December 2018. The diagnostic performance of the selected imaging feature, including accuracy, sensitivity, and specificity, was validated and compared with the conventional clinical tumor stage (cT) by the McNemar test. RESULTS: In the training cohort, a total of 268 patients were enrolled, and only SAS was significantly different between pT1-3 and pT4a tumors. The accuracy, sensitivity, and specificity of the SAS and conventional cT in differentiating T1-3 and T4a tumors were 94.4%, 81.6%, and 97.3% and 53.7%, 32.7%, and 58.4%, respectively (all p < 0.001). In the validation cohort, a total of 135 patients were collected. The accuracy, sensitivity, and specificity of the SAS and the conventional cT were 93.3%, 76.2%, and 96.5% and 62.2%, 38.1%, and 66.7%, respectively (p < 0.001, p = 0.021, p < 0.001). CONCLUSION: Small arteriole sign positivity, an indirect imaging feature of serosa invasion, may improve the accuracy of identifying T4a colon cancer. CLINICAL RELEVANCE STATEMENT: Small arteriole sign helps to distinguish T1-3 and T4a colon cancer and further improves the accuracy of preoperative CT staging of colon cancer. KEY POINTS: ⢠The accuracy of preoperative CT staging of colon cancer is not ideal, especially for T4a tumors. ⢠Small arteriole sign (SAS) is a newly defined imaging feature that shows the appearance of tumor-supplying arterioles at the site where they penetrate the intestine wall. ⢠SAS is an indirect imaging marker of tumor invasion into the serosa with a great value in distinguishing between T1-3 and T4a colon cancer.
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Neoplasias do Colo , Humanos , Arteríolas , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To study the corretation between the cross-sectional area of hamstring tenden measured by MRI and gragt in anterior cruciate ligament rexonstruction. METHODS: MRI data of 50 patients who planned to undergo anterior cruciate ligament reconstruction from November 2021 to March 2022 were collected, including 32 males and 18 females, aged from 19 to 48 years old with an average of(31.1±8.7) years. Before the operation, the semitendinosus and gracilis tendons were measured and recorded by MRI, and then the anterior cruciate ligament was reconstructed under arthroscope. During the operation, gracilis and semitendinosus tendons were taken to prepare the final tendon to be transplanted, and the diameter of the prepared final graft was measured during the operation. Finally, the data were analyzed by statistical software. RESULTS: The cross sectional areas of semitendinosus tendon, gracilis tendon, semitendinosus tendon and gracilis tendon measured by MRI were significantly and positively correlated with the diameter of grafts required in anterior cruciate ligament surgery, the r values were 0.858, 0.728, 0.842(P<0.001), respectively. The area under curre (AUC), sensitivity, and specificity of the sum of the cross sectional areas of semitendinosus tendon and gracilis tendon were 0.925, 90.48%, and 85.71%, respectively. CONCLUSION: In patients undergoing anterior cruciate ligament reconstruction, preoperative MRI measurement has a strong statistical correlation with the diameter of hamstring muscle transplantation during operation. The sum of the cross sectional areas of semitendinosus tendon and gracilis tendon has a high predictive value for the diameter of grafts during anterior cruciate ligament reconstruction, and can predict the size of grafts during operation.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Tendões dos Músculos Isquiotibiais , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Tendões dos Músculos Isquiotibiais/cirurgia , Tendões dos Músculos Isquiotibiais/transplante , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgia , Ligamento Cruzado Anterior/diagnóstico por imagem , Ligamento Cruzado Anterior/cirurgia , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: To investigate the association between CT signs and clinicopathological features and disease recurrence in patients with hepatoid adenocarcinoma of stomach (HAS). METHODS: Forty nine HAS patients undergoing radical surgery were retrospectively collected. Association between CT and clinicopathological features and disease recurrence was analyzed. Multivariate logistic model was constructed and evaluated for predicting recurrence by using receiver operating characteristic (ROC) curve. Survival curves between model-defined risk groups was compared using Kaplan-Meier method. RESULTS: 24(49.0%) patients developed disease recurrence. Multivariate logistic analysis results showed elevated serum CEA level, peritumoral fatty space invasion and positive pathological vascular tumor thrombus were independent factors for disease recurrence. Odds ratios were 10.87 (95%CI, 1.14-103.66), 6.83 (95%CI, 1.08-43.08) and 42.67 (95%CI, 3.66-496.85), respectively. The constructed model showed an area under ROC of 0.912 (95%CI,0.825-0.999). The model-defined high-risk group showed poorer overall survival and recurrence-free survival than the low-risk group (both P < 0.001). CONCLUSIONS: Preoperative CT appearance of peritumoral fatty space invasion, elevated serum CEA level, and pathological vascular tumor thrombus indicated poor prognosis of HAS patients.
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Adenocarcinoma , Neoplasias Gástricas , Trombose , Neoplasias Vasculares , Humanos , Estudos Retrospectivos , Prognóstico , Neoplasias Vasculares/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios X , Estadiamento de NeoplasiasRESUMO
Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1ß, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.
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Artrite Reumatoide , Gardenia , Microbioma Gastrointestinal , Ratos , Animais , Cromatografia Líquida , Espectrometria de Massas em Tandem , Ácido alfa-Linolênico , Metabolômica/métodos , Artrite Reumatoide/tratamento farmacológico , Inflamação , GlicerofosfolipídeosRESUMO
This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1ß, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1ß, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.
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Interleucina-18 , NF-kappa B , NF-kappa B/genética , NF-kappa B/metabolismo , Interleucina-18/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , Ciclina D1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Músculo Liso Vascular , Proliferação de Células , Transdução de Sinais , Citocinas/metabolismo , Glucose/toxicidade , Glucose/metabolismoRESUMO
BACKGROUND: Patients undergoing lung tumor surgery may experience various complications after discharge from the hospital. Using patient-reported outcomes (PROs), this study attempted to identify relevant indicators of postdischarge complications after lung tumor surgery and develop a predictive nomogram model to evaluate the risk for individual patients. METHODS: Patients who underwent lung tumor surgery between December 2021 and June 2022 were included in this study. PROs were assessed using the Perioperative Symptom Assessment for Lung Surgery scale and were assessed preoperatively at baseline, on postoperative day 1 (POD1) 1 to POD4, and then weekly until the fourth week. A random forest machine learning prediction model was built to rank the importance of each PRO score of patients on POD1 to POD4. We then selected the top 10 variables in terms of importance for the multivariable logistic regression analysis. Finally, a nomogram was developed. RESULTS: PROs, including coughing (POD3 and POD4), daily activity (POD1), and pain (POD1 and POD2), were associated with postdischarge complications in patients undergoing lung tumor surgery. The predictive model showed good performance in estimating the risk of postdischarge complications, with an area under the curve of 0.833 (95% confidence interval: 0.753-0.912), while maintaining good calibration and clinical value. CONCLUSION: We found that PRO scores on POD1 to POD4 were associated with postdischarge complications after lung tumor surgery, and we developed a helpful nomogram model to predict the risk of postdischarge complications.
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Neoplasias Pulmonares , Alta do Paciente , Humanos , Assistência ao Convalescente , Resultado do Tratamento , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/complicações , Pulmão , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologiaRESUMO
Mismatch repair (MMR) deficiency has been linked to thiopurine resistance and hypermutation in relapsed acute lymphoblastic leukemia (ALL). However, the repair mechanism of thiopurine-induced DNA damage in the absence of MMR remains unclear. Here, we provide evidence that DNA polymerase ß (POLB) of base excision repair (BER) pathway plays a critical role in the survival and thiopurine resistance of MMR-deficient ALL cells. In these aggressive resistant ALL cells, POLB depletion and its inhibitor oleanolic acid (OA) treatment result in synthetic lethality with MMR deficiency through increased cellular apurinic/apyrimidinic (AP) sites, DNA strand breaks and apoptosis. POLB depletion increases thiopurine sensitivities of resistant cells, and OA synergizes with thiopurine to kill these cells in ALL cell lines, patient-derived xenograft (PDX) cells and xenograft mouse models. Our findings suggest BER and POLB's roles in the process of repairing thiopurine-induced DNA damage in MMR-deficient ALL cells, and implicate their potentials as therapeutic targets against aggressive ALL progression.
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DNA Polimerase beta , Leucemia-Linfoma Linfoblástico de Células Precursoras , Animais , Humanos , Camundongos , Dano ao DNA , DNA Polimerase beta/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Mutações Sintéticas Letais , Reparo de Erro de Pareamento de DNA/genéticaRESUMO
Aicardi-Goutières syndrome (AGS) is a rare genetic disorder involving the central nervous system and autoimmune abnormalities, leading to severe intellectual and physical disability with poor prognosis. AGS has a phenotype similar to intrauterine viral infection, which often leads to delays in genetic counseling. In this study, we report a case with a prenatal diagnosis of AGS. The first fetal ultrasound detected bilateral lateral ventricle cystic structures, and fetal MRI was performed to identify other signs. The right parietal lobe signal showed cerebral white matter abnormalities, and fetal brain development level was lower than that of normal fetuses of the same gestational age. Whole-exome sequencing revealed that the fetus carried the TREX1:NM_033629.6:exon2:c.294dup:p. C99Mfs*3 variant, suggesting that the c.294dup mutation of the TREX1 gene was the pathogenic mutation site, and the final comprehensive diagnosis was AGS1. In this article, we also reviewed the previous literature for possible phenotypes in the fetus and found that microcephaly and intrauterine growth retardation may be the first and most important markers of the intrauterine phenotype of AGS.
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Doenças Autoimunes do Sistema Nervoso , Microcefalia , Malformações do Sistema Nervoso , Humanos , Gravidez , Feminino , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/genética , Doenças Autoimunes do Sistema Nervoso/patologia , Fosfoproteínas , MutaçãoRESUMO
Colorectal carcinoma (CRC) is a kind of malignant tumor closely related to ulcerative colitis. Xanthone derivatives are one of the most promising therapeutic drugs which have been used in phase I/II clinical trials for cancer therapy. Our previous study indicated that the aerial parts of Gentianella acuta Michx. Hulten (GA) was rich in xanthones and showed a good therapeutic effect on ulcerative colitis in mice, suggesting that GA xanthones might have some therapeutic or ameliorative effects on CRC. However, no relevant study has been reported. This study aims to find the effective substances of GA inhibiting CRC and clarify their mechanism. Solvent extraction, column chromatographic separation, and LC-MS analysis were used to characterize the 70% EtOH extract of GA and track xanthones abundant fraction XF. MTT assay was carried out to clarify the activity of GA fractions; the result showed XF to be the main active fraction. LC-MS analysis was executed to characterize XF, 38 xanthones were identified. Network pharmacology prediction, in vitro activity screening, and molecular docking assay were combined to predict the potential mechanism; the PI3K/Akt/mTOR signaling pathway was found to be most important. Western blot assay on the main active xanthones 1,3,5-trihydroxyxanthone (16), 1,3,5,8-tetrahydroxyxanthone (17), 1,5,8-trihydroxy-3-methoxyxanthone (18), and 1,7-dihydroxy-3,8-dimethoxyxanthone (19) was used to verify the above prediction; these xanthones were found to inhibit the PI3K/Akt/mTOR signaling pathway, and 17 played a significant role among them through Western blot assay using PI3K/AKT/mTOR agonist IGF-1. In conclusion, this study demonstrated that GA xanthones were effective compounds of GA inhibiting CRC by regulating PI3K/Akt/mTOR signaling pathway transduction, at least. Importantly, 1,3,5,8-tetrahydroxyxanthone (17), the most abundant active xanthone in GA, might be a candidate drug for CRC.
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Colite Ulcerativa , Neoplasias Colorretais , Gentianella , Xantonas , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Gentianella/química , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Xantonas/farmacologia , Xantonas/química , Neoplasias Colorretais/tratamento farmacológico , Proliferação de CélulasRESUMO
BACKGROUND: As a newly discovered muscle factor secreted by skeletal muscle cells, irisin is a polypeptide fragment formed from hydrolysis of fibronectin type â ¢ domain-containing protein 5 (FNDC5). Irisin can promote beigeing of white adipose tissue (WAT) and regulate glucose and lipid metabolisms. However, the functions of irisin in skeletal muscle development remain largely unknown. In order to characterize the expression of irisin, this study investigated the expression of irisin precursor FNDC5 in myoblasts and skeletal muscles during different developmental stages of SPF mice. RESULTS: The Western blot, quantitative real-time PCR (qRT-PCR), and immunofluorescence assay results showed that FNDC5 was expressed in all the developmental stages of myoblasts and gastrocnemius, but its expression differed at different stages. FNDC5 protein exhibited the highest expression in gastrocnemius of sexually mature mice, followed by elderly mice and adolescent mice, and it displayed the lowest expression in pups. Additionally, FNDC5 protein was mainly expressed in cytoplasm, and it had the highest expression in primary myoblasts, followed by the myotubes with the lowest expression in C2C12 myogenic cells. CONCLUSIONS: Overall, FNDC5 was mainly expressed in cytoplasm and extracellular matrix with different expression levels at different developmental stages of skeletal muscle cells and tissues in mice. This study will provide new strategies for promoting skeletal muscle development and treating muscle- and metabolism-related disease by using irisin.
Assuntos
Fibronectinas , Músculo Esquelético , Camundongos , Animais , Fibronectinas/genética , Fibronectinas/metabolismo , Músculo Esquelético/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Background: Pulmonary sarcomatoid carcinoma (PSC) is a kind of rare lung cancer. We aim to analyze the clinical characteristics and prognostic factors of patients with PSC. Methods: From January 1, 2006 to December 31, 2015, 119 patients in the Cancer Hospital Chinese Academy of Medical Sciences were diagnosed with PSC, and they received treatment. We retrospectively collected information on gender, age, body mass index (BMI), symptoms, family history, smoking history, tumor size, tumor location, tumor diameter, tumor-node-metastasis (TNM), pathological type, and other factors to analyze the relationship between these factors and 1-, 3-, 5-year, and overall survival (OS). Results: Male patients who had a smoking history (n=76) comprised the main group of PSC. Median patient age was 60.67±10.50 years (range, 26-89 years). The majority of these patients (n=82) presented with respiratory symptoms. The median survival of patients who died of PSC was 11.87 months (6.38-21.48 months). The 1-, 3-, and 5-year survival rates were 61.3%, 34.5%, and 31.9%, respectively. Patients with a lower T stage and without lymph node metastasis and distant metastasis had a better OS (P<0.05). Other clinical characteristics and the difference in treatments did not influence the prognosis significantly (P>0.05). Conclusions: PSC is a rare malignant neoplasm of the lung with poor prognosis. Surgery is a major therapeutic method for this disease entity. TNM-stage is the main factors affecting prognosis.
RESUMO
This study aimed to use a new special inventory for lung surgery patients to evaluate postoperative symptoms and functional status and to identify factors that may affect these after uniportal video-assisted thoracoscopic surgery (VATS). In this single-center longitudinal cohort observational study, we used a new scale, the perioperative symptom assessment for lung surgery (PSA-Lung), to evaluate the recovery from symptoms and the functional status of patients undergoing uniportal VATS. We divided patients into two groups, according to patients' symptom scores, and compared the clinical characteristics between the two groups under each item. Then, we conducted a qualitative interview regarding coughing in postoperative week 4. Exactly 104 patients were enrolled in this study. The two highest-scoring patient-reported outcome (PRO) items were "shortness of breath" and "coughing" in the fourth week after surgery. Thirty-one patients reported that "coughing" severely influenced their lives in postoperative week 4. Using the PSA-Lung inventory, we found that "shortness of breath" was the worst symptom in postoperative week 4. Although "coughing" was not the most important symptom in the early postoperative period, it affected some patients' lives in postoperative week 4. Therefore, further research is required to determine the optimal cut-off point for coughing.