RESUMO
Dynamic optical coherence tomography (dOCT) utilizes time-dependent signal intensity fluctuations to enhance contrast in OCT images and indirectly probe physiological processes in cells. Majority of the dOCT studies published so far are based on acquisition of 2D images (B-scans or C-scans) by utilizing point-scanning Fourier domain (spectral or swept-source) OCT or full-field OCT respectively, primarily due to limitations in the image acquisition rate. Here we introduce a novel, high-speed spectral domain line-field dOCT (SD-LF-dOCT) system and image acquisition protocols designed for fast, volumetric dOCT imaging of biological tissues. The imaging probe is based on an exchangeable afocal lens pair that enables selection of combinations of transverse resolution (from 1.1 µm to 6.4 µm) and FOV (from 250 × 250 µm2 to 1.4 × 1.4 mm2), suitable for different biomedical applications. The system offers axial resolution of â¼ 1.9 µm in biological tissue, assuming an average refractive index of 1.38. Maximum sensitivity of 90.5â dB is achieved for 3.5â mW optical imaging power at the tissue surface and maximum camera acquisition rate of 2,000 fps. Volumetric dOCT images acquired with the SD-LF-dOCT system from plant tissue (cucumber), animal tissue (mouse liver) and human prostate carcinoma spheroids allow for volumetric visualization of the tissues' cellular and sub-cellular structures and assessment of cellular motility.
RESUMO
Gemcitabine serves as a first-line chemotherapeutic treatment for pancreatic cancer (PC), but it is prone to rapid drug resistance. Increasing the sensitivity of PC to gemcitabine has long been a focus of research. Fasting interventions may augment the effects of chemotherapy and present new options. SIRT7 is known to link metabolism with various cellular processes through post-translational modifications. We found upregulation of SIRT7 in PC cells is associated with poor prognosis and gemcitabine resistance. Cross-analysis of RNA-seq and ATAC-seq data suggested that GLUT3 might be a downstream target gene of SIRT7. Subsequent investigations demonstrated that SIRT7 directly interacts with the enhancer region of GLUT3 to desuccinylate H3K122. Our group's another study revealed that GLUT3 can transport gemcitabine in breast cancer cells. Here, we found GLUT3 KD reduces the sensitivity of PC cells to gemcitabine, and SIRT7 KD-associated gemcitabine-sensitizing could be reversed by GLUT3 KD. While fasting mimicking induced upregulation of SIRT7 expression in PC cells, knocking down SIRT7 enhanced sensitivity to gemcitabine through upregulating GLUT3 expression. We further confirmed the effect of SIRT7 deficiency on the sensitivity of gemcitabine under fasting conditions using a mouse xenograft model. In summary, our study demonstrates that SIRT7 can regulate GLUT3 expression by binding to its enhancer and altering H3K122 succinylation levels, thus affecting gemcitabine sensitivity in PC cells. Additionally, combining SIRT7 knockdown with fasting may improve the efficacy of gemcitabine. This unveils a novel mechanism by which SIRT7 influences gemcitabine sensitivity in PC and offer innovative strategies for clinical combination therapy with gemcitabine.
Assuntos
Desoxicitidina , Resistencia a Medicamentos Antineoplásicos , Gencitabina , Regulação Neoplásica da Expressão Gênica , Transportador de Glucose Tipo 3 , Neoplasias Pancreáticas , Sirtuínas , Regulação para Cima , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Humanos , Sirtuínas/genética , Sirtuínas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Animais , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Camundongos , Transportador de Glucose Tipo 3/genética , Transportador de Glucose Tipo 3/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Antimetabólitos Antineoplásicos/farmacologia , Técnicas de Silenciamento de Genes , Camundongos Nus , FemininoRESUMO
BACKGROUND: Pituitary gland metastasis is an unusual event, and pituitary metastasis from lung adenocarcinoma is extremely rare and associated with poor prognosis. To date, approximately 15 cases have been reported. CASE SUMMARY: Here, we present the case of a 64-year-old woman with pituitary metastasis derived from lung adenocarcinoma, which was difficult to distinguish from other sellar tumors. The patient presented to the neurosurgery clinic with blurred vision and intermittent headache. During hospitalization, brain computed tomography (CT) and magnetic resonance imaging revealed a pituitary macroadenoma. Chest CT revealed irregular nodules in the basal segment of the lower lobe of the left lung, which were likely lung cancer. Positron emission tomography-CT revealed a carbohydrate metabolism tumor in the lungs and sellar region, which was considered malignant. Postoperative pathological examination of the sellar tumor revealed lung adenocarcinoma. CONCLUSION: Excision of pituitary metastases combined with radiotherapy and chemotherapy should be a priority treatment for patients with pituitary metastasis.
RESUMO
OBJECTIVE: To study the efficacy of ultrasound-guided parasternal block (US-PSI) in pediatric patients undergoing auricular reconstruction surgery. METHODS: For this study, the authors recruited 60 children between the ages of 5 and 12 years who underwent auricular reconstruction with autologous costal cartilage (ACC) to correct microtia. They were randomized to receive either ultrasound-guided modified parasternal block or periprostatic local infiltration anesthesia (PLIA), with 30 cases in each group. Ultrasound-guided parasternal block was administered following anesthesia induction, whereas PLIA was administered after ACC harvest. Lastly, following surgery, all children were provided with patient-controlled intravenous analgesia with sufentanil, and the numeric pain rating scale (NRS) was used to assess the intensity of pain. Our primary outcomes were the resting NRS pain scores and the NRS scores upon coughing at 1, 6, 12, 24, and 48 hours postsurgery. Sufentanil consumption within the first 24 hours of surgery, the mean duration to first ambulation, and the usage of rescue analgesics were our secondary outcomes. The authors also recorded the occurrence of undesirable side effects as well as more serious side effects like pneumothorax. RESULTS: Pediatric patients who were administered US-PSI showed significantly reduced NRS chest pain scores at 6 and 12 hours postsurgery compared to those who received PLIA (P<0.05). In addition, sufentanil consumption within the first 24 hours postsurgery, duration to first ambulation, and use of rescue analgesics were significantly lower among patients in the US-PSI group when compared to those in the PLIA group (P<0.05). CONCLUSIONS: This study found that US-PSI was a highly efficacious and safe technique for postsurgical analgesia following auricular reconstruction with ACC in pediatric patients. LEVEL OF EVIDENCE: Level II, therapeutic study.
RESUMO
Two-dimensional (2D) mesoporous transition metal oxides are highly desired in various applications, but their fast and low-cost synthesis remains a great challenge. Herein, a Maillard reaction inspired microexplosion approach is applied to rapidly synthesize ultrathin 2D mesoporous tin oxide (mSnO2). During the microexplosion between granular ammonia nitrate with melanoidin at high temperature, the organic species can be carbonized and expanded rapidly due to the instantaneous release of gases, thus producing ultrathin carbonaceous templates with rich functional groups to effectively anchor SnO2 nanoparticles on the surface. The subsequent removal of carbonaceous templates via calcination in air results in the formation of 2D mSnO2 due to the confinement effect of the templates. Pd nanoparticles are controllably deposited on the surface of 2D mSnO2 via in situ reduction, forming ultrathin 2D Pd/mSnO2 nanocomposites with thicknesses of 6-8 nm. Owing to the unique 2D mesoporous structure with rich oxygen defects and highly exposed metal-metal oxide interfaces, 2D Pd/mSnO2 exhibits excellent sensing performance toward acetone with high sensitivity, a short response time, and good selectivity under low working temperature (100 °C). This fast and convenient microexplosion synthesis strategy opens up the possibility of constructing 2D porous functional materials for various applications including high-performance gas sensors.
RESUMO
PURPOSE: Pain following costal cartilage harvest surgery is the most common complaint of auricular reconstruction (AR). Anesthesiologists are continuously searching for an effective postoperative pain control method. METHODS: This study was conducted from 10 April 2022 to 10 June 2022. Sixty children undergoing AR using costal cartilage were randomly assigned to either a serratus anterior plane block performed before costal cartilage harvest (SAPB-pre-cohort; n = 30) or the SAPB-post-cohort (Post-costal cartilage Harvest Cohort: n = 30). The primary endpoint measures were the Numerical Rating Scale (NRS) scores of the chest and ear pain degrees recorded at 1-, 6-, 12-, 24-, and 48-h after surgery. Intraoperative anesthetic and analgesic dosages, sufentanil consumption and rescue analgesia consumption during the first 24 h post-operation, cough score during extubation, extubation agitation score, length of stay, the extubation time, first ambulatory time, analgesia duration, and opioid-related adverse effects and SAPB-related adverse effects were the secondary endpoints. RESULTS: The rest and coughing NRS scores were significantly reduced in the SAPB-pre-cohort 6 and 12 h post-operation in comparison with the SAPB-post-cohort (rest 6 h p = 0.002, others p < 0.001). No significant difference in the NRS ear scores existed between the two cohorts (p > 0.05). The use of propofol and remifentanil for general anesthesia during the SAPB-pre-procedure was significantly reduced compared to the SAPB-post-group, with statistical significance (p < 0.001). Sufentanil consumption and rescue analgesia consumption were significantly reduced in the SAPB-pre-cohort (p = 0.001, p = 0.033). The extubation time and first ambulatory time were markedly shorter in the SAPB-pre-cohort (all p < 0.001). Analgesia duration was markedly longer in the SAPB-pre-cohort (p < 0.001). No significant differences were noted in the cough score during extubation, extubation agitation score, length of stay between the two cohorts (all p > 0.05). Opioid-related adverse effects occurred more in the SAPB-post-cohort, while there was no statistical significance (16.7 vs. 36.7%; p = 0.082). There were no blockade-related complications observed in either cohort. CONCLUSION: The analgesic effect of the SAPB-pre-cohort was better than the SAPB-post-cohort suggesting both efficacy and feasibility of preemptive analgesia. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Assuntos
Microtia Congênita , Cartilagem Costal , Bloqueio Nervoso , Dor Pós-Operatória , Procedimentos de Cirurgia Plástica , Ultrassonografia de Intervenção , Humanos , Masculino , Feminino , Criança , Dor Pós-Operatória/prevenção & controle , Microtia Congênita/cirurgia , Bloqueio Nervoso/métodos , Procedimentos de Cirurgia Plástica/métodos , Cartilagem Costal/transplante , Medição da Dor , Adolescente , Estudos de CoortesRESUMO
This study aimed to evaluate the effects of natural extracts from nine medicinal herbs (SMA) on the growth performance, immunity, and intestinal integrity of broilers experimentally infected with Eimeria tenella. A total of 252 one-day-old broiler chicks were divided into 7 groups with 3 replicates per group and 12 broilers per cage. The groups were uninfected-untreated blank control group (BC), infected-untreated negative control group (NC), SMA treatment groups, Chinese medicine positive control group (CM), and chemical drug positive control group (CD). The SMA groups were infected and fed a basal diet supplemented with 0.6 (SMA-L), 0.8 (SMA-M), and 1.0 (SMA-H) g/kg SMA. The CM and CD groups were infected and fed a basal diet supplemented with 15 g/kg Jiqiuchong San and 0.2 g/kg Diclazuril, respectively. Results showed that feeding SMA could significantly reduce the number of oocysts in infected chickens, especially 1.0 g/kg SMA, which exhibited moderate anticoccidial efficacy. When infected with E. tenella, the supplementation of 1.0 g/kg SMA increased the renal index; restored the hepatic, splenic, and bursal indexes to BC levels; increased the levels of immunoglobulin A (IgA), IgM, and IgY; and reduced the contents of tumor necrosis factor (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), and IL-10 of the infected chickens. Moreover, treatment with 1.0 g/kg SMA alleviated the pathological changes in cecal tissue and increased the contents of zonula occludens-1 (ZO-1), occludin, claudin-1, and mucoprotein 2 (mucin-2) in cecal tissues of E. tenella-infected chickens. We found that 1.0 g/kg SMA reduced the number of oocysts, improved immunity, and alleviated intestinal barrier damage, which could improve the growth performance of infected chickens. Thus, SMA proved to be an effective natural extract against E. tenella and has the potential to be used as an efficient anticoccidial drug or additive.
Assuntos
Coccidiose , Coccidiostáticos , Eimeria tenella , Plantas Medicinais , Doenças das Aves Domésticas , Animais , Galinhas , Coccidiostáticos/farmacologia , Coccidiostáticos/uso terapêutico , Coccidiose/tratamento farmacológico , Coccidiose/veterinária , Coccidiose/patologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Fator de Necrose Tumoral alfa , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/patologiaRESUMO
Characterizing the tumor microenvironment at the molecular level is essential for understanding the mechanisms of tumorigenesis and evolution. However, the specificity of the blood proteome in localized region of the tumor and its linkages with other systems is difficult to investigate. Here, we propose a spatially multidimensional comparative proteomics strategy using glioma as an example. The blood proteome signature of tumor microenvironment was specifically identified by in situ collection of arterial and venous blood from the glioma region of the brain for comparison with peripheral blood. Also, by integrating with different dimensions of tissue and peripheral blood proteomics, the information on the genesis, migration, and exchange of glioma-associated proteins was revealed, which provided a powerful method for tumor mechanism research and biomarker discovery. The study recruited multidimensional clinical cohorts, allowing the proteomic results to corroborate each other, reliably revealing biological processes specific to gliomas, and identifying highly accurate biomarkers.
Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Proteômica/métodos , Neoplasias Encefálicas/patologia , Proteoma/metabolismo , Glioma/patologia , Biomarcadores , Microambiente TumoralRESUMO
BACKGROUND: The course of disease after microvascular decompression (MVD) in patients with hemifacial spasm (HFS) is variable. The purpose of this study was to develop and validate a nomogram to predict the probability of delayed cure after microvascular decompression in patients with hemifacial spasms based on clinical multivariate factors. METHODS: A retrospective data collection was performed on 290 patients with HFS undergoing MVD at our center from January 2017 to January 2022. The patients were randomly assigned to the training cohort (n = 232) and validation cohort (n = 58) at a ratio of 8:2. Retrospective analysis was performed of information on clinical, radiological, and intraoperative findings and clinical outcomes. Univariate and multivariate analyses were performed in the training cohort, and a nomogram was constructed using a stepwise logistic regression approach. The receiver operating characteristic (ROC) was calculated to evaluate the reliability of the nomogram model. Decision curve analysis (DCA) was used to assess the clinical application value of the nomogram model. RESULTS: In the training cohorts, 73 patients (73/232) had a delayed cure. In the validation cohorts, 18 patients (18/58) had a delayed cure. We developed a novel nomogram model to predict the risk of delayed cure after MVD in HFS patients based on the presence of vertebral artery compression, venous compression, absence of LSR, degree of facial nerve indentation, degree of neurovascular compression, and internal auditory canal vascular looThe area under the curve (AUC) of the nomogram model was 0.9483 in the training cohort and 0.9382 in the validation cohort. The calibration curve showed good correspondence between the predicted and actual probabilities in the training and validation groups. The decision curve showed that the nomogram model had good performance in clinical applications. CONCLUSIONS: We developed and validated a preoperative and intraoperative multivariate factors nomogram to predict the possibility of delayed cure after MVD in HFS patients, which may help clinicians in the comprehensive management of HFS.
Assuntos
Espasmo Hemifacial , Cirurgia de Descompressão Microvascular , Humanos , Espasmo Hemifacial/cirurgia , Resultado do Tratamento , Nomogramas , Estudos Retrospectivos , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To explore changes in the symptom clusters of perioperatively elderly patients with lung cancer at different time points (i.e., the day of admission [T0]), 2-4 days after surgery [T1], 1 month after discharge [T2] and 3 months after discharge [T3]) and to analyze correlations between cluster severity, frailty and quality of life (QOL). METHODS: A longitudinal study was conducted from August 2020 to June 2021 among elderly lung cancer patients undergoing surgery at hospitals in Jiangsu Province. Data were collected using the Chinese Tilburg Frailty Indicator, the MD Anderson Symptom Inventory and the Quality of Life-Core scale. RESULTS: According to exploratory factor analysis, a total of 5 symptom clusters were found and three of them (the global mental function symptom cluster, the special mental function symptom cluster and the respiratory function symptom cluster) were persistent. The incidence of the top four symptoms varied at different time points. The severity of symptom clusters at different time points was positively correlated with frailty and negatively correlated with QOL. CONCLUSIONS: The findings may serve as a reference for medical staff to implement symptom management in elderly lung cancer patients after surgery. Frailty may be an important variable affecting the severity of symptom clusters and the QOL of patients.
Assuntos
Fragilidade , Neoplasias Pulmonares , Humanos , Idoso , Neoplasias Pulmonares/cirurgia , Qualidade de Vida , Síndrome , Estudos Longitudinais , Fragilidade/diagnóstico , Fragilidade/epidemiologiaRESUMO
Purpose: Dexmedetomidine exerts a sedative effect by promoting the sleep pathway endogenously and producing a state similar to N2 sleep. This study aimed to study the efficacy and safety of dexmedetomidine nasal spray in the treatment of postoperative sleep disturbance. Methods: This study enrolled 120 participants [men and women; age, 18-40 years; American Society of Anesthesiologists grade, I or II] who underwent maxillofacial surgery under general anesthesia through nasotracheal intubation. The participants were randomly divided into three groups: blank control group (BC group), 1.0 µg/kg dexmedetomidine group (1.0 Dex group), and 1.5 µg/kg dexmedetomidine group (1.5 Dex group), with 40 patients allocated to each group. At 21:30 on the night after the operation, the intervention groups were administered their corresponding doses of dexmedetomidine nasal spray. The Pittsburgh Sleep Quality Index (PSQI) scale was used to evaluate the baseline sleep status of participants 1 month preoperatively and on the night after the operation. Polysomnography (PSG) was used to record the sleep status on the night after the operation. We recorded the rescue times of sedative and analgesic drugs on the first night after surgery, adverse reactions, total hospital stay duration, and total costs. Results: Compared with patients in the BC group, those in 1.0 Dex and 1.5 Dex groups had longer N2 sleep duration, were awake for a shorter time after dose administration, woke up less often, and had significantly improved sleep efficiency (p < 0.05). Compared with the BC group, the PSQI scores of 1.0 Dex and 1.5 Dex groups were significantly lower on the night after operation, and the proportion of PSQI > 5 was significantly lower (p < 0.05). Compared with patients in the BC group and the 1.0 Dex group, those in the 1.5 Dex group had significantly prolonged N3 sleep, reduced frequency of requiring sufentanil rescue, lower incidence of sore throat after surgery, and shorter average length of hospital stay (all, p < 0.05). Conclusion: The sleep quality of participants on the night after having undergone maxillofacial surgery was safely and effectively improved by 1.0-1.5 µg/kg dexmedetomidine atomized nasal sprays. Notably, only the latter could prolong N3 sleep. Level of Evidence II: Evidence was obtained from at least one properly designed randomized controlled trial.
Assuntos
Dexmedetomidina , Transtornos do Sono-Vigília , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Dexmedetomidina/uso terapêutico , Dexmedetomidina/efeitos adversos , Sprays Nasais , Hipnóticos e Sedativos/uso terapêutico , Analgésicos , Transtornos do Sono-Vigília/tratamento farmacológico , Método Duplo-CegoRESUMO
Purpose: To examine whether intraoperative dexmedetomidine reduces postoperative delirium (POD) in elderly patients who underwent a laryngectomy. Methods: Patients were randomly assigned to receive dexmedetomidine or a saline placebo infused during surgery. The study period was July 2020 to January 2022. Participants were elderly individuals (≥65 years) who underwent a laryngectomy. Immediately after induction of anesthesia, a 0.5 µg.kg-1 bolus of study solution was administered for 10 min, followed by a maintenance infusion of 0.2 µg.kg-1.hr-1 until the end of surgery. Patients were assessed daily for POD (primary outcome). Plasma inflammatory factors were measured at baseline, on the first postoperative day, and on the third postoperative day. Results: In total, 304 male patients were randomized; 299 patients [median (interquartile range) age, 69.0 (67.0-73.0) years] completed in-hospital delirium assessments. There was no difference in the incidence of POD between the dexmedetomidine and control groups (21.3% [32 of 150] vs 24.2% [36 of 149], P=0.560). However, dexmedetomidine reduced POD in patients with laryngeal cancer and a higher tumor stage (21.6% vs 38.5%; OR, 0.441; 95% CI, 0.209-0.979; P=0.039). Dexmedetomidine reduced levels of C-reactive protein (CRP) (P=0.0056) and interleukin 6 (IL-6) (P<0.001) on the first and third postoperative days, respectively. More patients had intraoperative hypotension in the dexmedetomidine group (29.3% [44 of 150] vs 17.4% [26 of 149], P=0.015). Conclusion: Intraoperative dexmedetomidine administration did not prevent POD in patients with laryngeal cancer. Dexmedetomidine reduced serum CRP and IL-6 levels postoperatively but caused a higher occurrence of intraoperative hypotension in elderly patients after a laryngectomy.
RESUMO
In 2021, breast cancer accounted for a substantial proportion of cancer cases and represented the second leading cause of cancer deaths among women worldwide. Although tumor cells originate from normal cells in the human body, they possess distinct biological characteristics resulting from changes in gene structure and function of cancer cells in contrast with normal cells. These distinguishing features, known as hallmarks of cancer cells, differ from those of normal cells. The hallmarks primarily include high metabolic activity, mitochondrial dysfunction, and resistance to cell death. Current evidence suggests that the fundamental hallmarks of tumor cells affect the tissue structure, function, and metabolism of tumor cells and their internal and external environment. Therefore, these fundamental hallmarks of tumor cells enable tumor cells to proliferate, invade and avoid apoptosis. Modifying these hallmarks of tumor cells represents a new and potentially promising approach to tumor treatment. The key to breast cancer treatment lies in identifying the optimal therapeutic agent with minimal toxicity to normal cells, considering the specific types of tumor cells in patients. Some herbal medicines contain active ingredients which can precisely achieve this purpose. In this review, we introduce Ginsenoside's mechanism and research significance in achieving the therapeutic effect of breast cancer by changing the functional hallmarks of tumor cells, providing a new perspective for the potential application of Ginsenoside as a therapeutic drug for breast cancer.
RESUMO
Electrocatalytic reduction of CO2 (CO2RR) to value-added fuels and chemicals can potentially serve as a promising strategy to curb CO2 accumulation and carbon neutral cycle, but is still plagued by sluggish kinetics, poor selectivity and weak durability. Herein, we developed highly-dispersed nickel species on the nitrogen-doped carbon materials (Ni/NC) via the double solvent method (DSM), followed by the pyrolysis. The as-prepared Ni/NC possesses high CO2-to-CO selectivity of 93.2%â¼98.6% at broad potential range (0.57 â¼ 0.97 VRHE), decent jCO of 57.9 mAcm-2 at -1.07 VRHE, and significant robustness (retaining 96.3% of the initial faradaic efficiency for CO formation after 50 h electrolysis). As manifested by the rotating ring-disk electrode (RRDE) tests, the DSM-based Ni/NC possesses more significant pH-buffering capacity than Ni nanoparticles, thus promotes the CO2-to-CO. DFT calculations unveil that Ni/NC exhibits relatively lower d-band center, hence resulting in favorable desorption of CO from the catalyst surface that intrinsically boost the CO2-to-CO compared with the nanoparticle catalyst. These results suggest that the DSM-derived Ni/NC catalysts is a promising candidate towards large-scale application of CO2-to-CO.
RESUMO
OBJECTIVES: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). METHODS: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. RESULTS: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). CONCLUSIONS: The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
Assuntos
Hepatite B Crônica , Humanos , Hepatite B Crônica/complicações , Antígenos E da Hepatite B/uso terapêutico , Fosfatase Alcalina , DNA Viral , Estudos Retrospectivos , Fibrose , Vírus da Hepatite B/genética , Cirrose Hepática/etiologia , Inflamação/tratamento farmacológico , Antivirais/uso terapêutico , Alanina TransaminaseRESUMO
BACKGROUND: Tranexamic acid (TXA) has been widely used in orthopedic surgery, but its efficacy in adolescent scoliosis (AS) surgery remains unclear in the literature. The purpose of this systematic review and meta-analysis is to evaluate the safety and efficacy of TXA compared to placebo treatment during or after AS surgery, by gathering data from randomized both controlled trials (RCTs) and non-RCTs. METHODS: English and Chinese electronic databases including PubMed, Web of Science, Embase, Cochrane, CNKI, and Wan Fang database were searched to identify the relevant literature up until August 2022. The primary outcomes were intraoperative blood loss and total blood loss. The secondary outcomes included the need for transfusion, postoperative hemoglobin (Hb) level, and change in Hb level. Stata 17 was used for data analysis and the risk of bias was assessed. We followed the PRISMA checklist to ensure the quality of this article. RESULTS: Twelve studies (795 participants) were included in the meta-analysis for intraoperative blood loss during surgery. The results suggest that TXA can reduce the intraoperative blood loss of the patients (MD = -306.40ml, 95%CI = -404.04ml to -208.77ml, p < 0.001). Six studies (2027 patients) were included in the meta-analysis for total blood loss. The pooled result shows that the total blood loss of the TXA group was significantly lower than that of the control group (MD = -779.24ml, 95% CI = -1157.10ml to -410.39ml, p < 0.001). Five studies (419 patients) were included in the meta-analysis for postoperative Hb level and shows a non-significant outcome (MD = 5.09 g/l, 95%CI = 2.92 g/l to 7.25 g/l, p = 0.611). Three studies (268 patients) were included in the meta-analysis for the postoperative Hb level. There is a non-significant decrease in the TXA group (MD = -0.23 g/l, 95%CI = -0.48 g/l to 0.01 g/l, p = 0.319). Eight studies (670 patients) reported data on the need for transfusion after surgery. The overall relative risks (RR) showed a significant difference between the TXA and control group, with a lower risk of transfusion in the TXA group (RR = 0.547, 95%CI = 0.308 to 0.972, p = 0.04). CONCLUSIONS: The meta-analysis of the data reveals that TXA usage is associated with a significant reduction in intraoperative and total blood loss, a lower risk of transfusion, and a non-significant change in postoperative Hb levels in AS surgery However, it should be noted that the surgical operation situations varied across different studies. Therefore, further research is required to investigate the effects of TXA on specific subgroups of gender, operation time, and blood transfusion indicators. Overall, our study provides valuable evidence for the clinical management of AS surgery and may inform the development of practice guidelines and protocols for the use of TXA in this setting.
Assuntos
Procedimentos Ortopédicos , Escoliose , Ácido Tranexâmico , Adolescente , Humanos , Perda Sanguínea Cirúrgica/prevenção & controle , Ácido Tranexâmico/efeitos adversos , Escoliose/cirurgia , Exsanguinação , Procedimentos Ortopédicos/efeitos adversosRESUMO
The areca nut is often consumed as a chewing food in the Asian region. Our previous study revealed that the areca nut is rich in polyphenols with high antioxidant activity. In this study, we further assessed the effects and molecular mechanisms of the areca nut and its major ingredients on a Western diet-induced mice dyslipidemia model. Male C57BL/6N mice were divided into five groups and fed with a normal diet (ND), Western diet (WD), WD with areca nut extracts (ANE), areca nut polyphenols (ANP), and arecoline (ARE) for 12 weeks. The results revealed that ANP significantly reduced WD-induced body weight, liver weight, epididymal fat, and liver total lipid. Serum biomarkers showed that ANP ameliorated WD-enhanced total cholesterol and non-high-density lipoprotein (non-HDL). Moreover, analysis of cellular signaling pathways revealed that sterol regulatory element-binding protein 2 (SREBP2) and enzyme 3-hydroxy-3-methylglutaryld coenzyme A reductase (HMGCR) were significantly downregulated by ANP. The results of gut microbiota analysis revealed that ANP increased the abundance of beneficial bacterium Akkermansias and decreased the abundance of the pathogenic bacterium Ruminococcus while ARE shown the opposite result to ANP. In summary, our data indicated that areca nut polyphenol ameliorated WD-induced dyslipidemia by increasing the abundance of beneficial bacteria in the gut microbiota and reducing the expressions of SREBP2 and HMGCR while areca nut ARE inhibited this improvement potential.
Assuntos
Areca , Hepatopatia Gordurosa não Alcoólica , Masculino , Camundongos , Animais , Areca/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Nozes , Dieta Ocidental/efeitos adversos , Camundongos Endogâmicos C57BL , Arecolina/farmacologia , Extratos Vegetais/farmacologiaRESUMO
Recent studies have demonstrated that the combination of Cyclin-Dependent Kinase 4/6 Inhibitor (CDK4/6i) and endocrine therapy (ET) is more effective than ET alone and significantly improves progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2-) breast cancer (BC). Palbociclib is the first CDK4/6i approved for use, and its clinical advantages have been shown. However, 30% of patients will continue to develop secondary drug resistance. Therefore, exploring the parameters that can predict the efficacy of Palbociclib and developing a clinical prediction model is essential for evaluating the prognosis of patients.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Prognóstico , Modelos Estatísticos , Quinase 4 Dependente de Ciclina/metabolismo , Receptor ErbB-2/metabolismo , Quinase 6 Dependente de Ciclina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
Objectives: Approximately 240 million individuals are infected with chronic hepatitis B virus (HBV) worldwide. HBV infection can develop into liver fibrosis. The mechanism of HBV-related liver fibrosis has not been fully understood, and there are few effective treatment options. The goal of this study was to use transcriptomics in conjunction with experimental validation to identify new targets to treat HBV-related liver fibrosis. Methods: To identify differentially expressed genes (DEGs), five liver tissues were collected from both healthy individuals and patients with chronic hepatitis B. NovoMagic and Java GSEA were used to screen DEGs and key genes, respectively. Immunocell infiltration analysis of RNA-seq data was, and the results were confirmed by Western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry. Results: We evaluated 1,105 genes with differential expression, and 462 and 643 genes showed down- and upregulation, respectively. The essential genes, such as tumor necrosis factor (TNF) receptor-associated factor-2 (TRAF2), were screened out of DEGs. TRAF2 expression was abnormally high in hepatic fibrosis in patients with hepatitis B compared with healthy controls. The degree of hepatic fibrosis and serum levels of glutamate transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were positively linked with TRAF2 expression. TRAF2 may be crucial in controlling T lymphocyte-mediated liver fibrosis. Conclusion: Our findings imply that TRAF2 is essential for HBV-induced liver fibrosis progression, and it may potentially be a promising target for the treatment of hepatic fibrosis in hepatitis B.
RESUMO
PURPOSE: Phyllodes tumors (PTs) are rare neoplasms with a certain risk of recurrence and/or metastasis. In clinical practice, there is a lack of high-quality clinical studies and unified guidelines to guide the treatment. MATERIALS AND METHODS: All malignant and recurrence/metastasis PTs were retrospectively collected, which were diagnosed from 2008 to 2022. RESULTS: A total of 82 patients were enrolled, including 69 malignant and 13 borderline tumors. 96.3% (79/82) received surgical treatment. During a median follow-up of 55.5 months, 20 patients (20/82, 24.4%) had distant metastasis (DM), while 32 (32/82, 39.0%) had local recurrence (LR). Univariate analysis showed the survival of PTs was associated with surgical methods (p < 0.001), tumor size (p = 0.026), and biological behavior (p = 0.017), but not age at diagnosis. In relapsed borderline PTs, we did not find deaths due to disease progression. Patients with DM were all malignant PTs, with disease-progression occurring within 3 years in more than 80% of patients. Among salvage treatments, the combination of antiangiogenic drugs improved the prognosis to some extent, with a significant increase in mPFS (2.77 vs. 1.53 months), but no significant statistical results were obtained (p = 0.168). Lactate dehydrogenase (LDH) was an independent predictor of the prognosis for malignant PTs (p = 0.001, HR = 1.203, 95%CI, 1.082-1.336). CONCLUSION: Borderline PTs rarely metastasize, and even if LR occurs, surgical resection can lead to long-term survival. In metastatic phyllodes tumors (MPT), systemic therapy is not effective, but antiangiogenic drugs may prolong survival. LDH is an independent prognostic factor for malignant PTs to identify high-risk tumors.