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The removal of surface-attached particles with cavitation bubbles is usually attributed to the jetting or shear stresses when bubbles collapse. In this Letter, we report an unexpected phenomenon that millimeter-sized spherical particles made of heavy metals (e.g., stainless steel), when initially resting on a fixed rigid substrate, are suddenly accelerated like projectiles through the production of nearby laser-induced cavitation bubbles of similar sizes. We show experimentally and theoretically that the motion of a particle with radius R_{p} is determined by the maximum bubble radius R_{b,max}, the initial distance from the laser focus to the center of the particle L_{0}, and the initial azimuth angle φ_{0}. We identify two dominant regimes for the particle's sudden acceleration, namely, the unsteady liquid inertia dominated regime and the bubble contact dominated regime, determined by R_{b,max}R_{p}/L_{0}^{2}. We find the nondimensional maximum vertical displacement of the particle follows the fourth power and the square power scaling laws for respective regimes, which is consistent with the experimental results. Our findings can be applied to nonintrusive particle manipulation from solid substrates in a liquid.
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BACKGROUND: Breast cancer is an aggressive tumor, which poses a heavy burden to human health. Circular RNAs have been involved in the pathogenesis of breast cancer. This study aims to investigate whether circ_0008673 mediates breast cancer malignant progression by microRNA-153-3p (miR-153-3p)/cofilin 2 (CFL2) pathway. METHODS: The RNA levels of circ_0008673, miR-153-3p and CFL2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of CFL2, E-cadherin and N-cadherin was determined by western blot analysis. Cell proliferation was demonstrated through cell counting kit-8 and cell colony-formation assays. Cell apoptosis was detected by flow cytometry analysis. Cell migratory and invasive capacities were determined by transwell assay. The associated relationship between miR-153-3p and circ_0008673 or CFL2 was predicted by online databases, and testified by dual-luciferase reporter and RNA immunoprecipitation assays. In vivo assay was employed to demonstrate the effects of circ_0008673 silencing on tumor formation in vivo. RESULTS: Circ_0008673 and CFL2 expressions were upregulated, while miR-153-3p expression was downregulated in breast cancer tissues and cells compared with adjacent normal breast tissues and cells, respectively. Circ_0008673 overexpression promoted cell proliferation, migration and invasion, and repressed cell apoptosis, while circ_0008673 silencing had opposite effects. Additionally, circ_0008673 served as a sponge of miR-153-3p. And circ_0008673 was proved to regulate breast cancer cell malignancy by sponging miR-153-3p. MiR-153-3p was found to modulate breast cancer cell carcinogenesis via targeting CFL2. Furthermore, circ_0008673 silencing repressed tumor growth in vivo. CONCLUSION: Circ_0008673 promoted breast cancer progression by upregulating CFL2 expression through sponging miR-153-3p. This study provides a theoretical basis for researching circRNA-directed treatment of breast cancer.
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Neoplasias da Mama , MicroRNAs , Fatores de Despolimerização de Actina , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Cofilina 2 , Feminino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genéticaRESUMO
Background and objectives: Combined peripheral neutrophil−platelet indexes reflecting the systemic inflammatory status have been reported to predict the clinical outcome in patients with various types of cancer. However, the prognostic value of combined neutrophil−platelet indexes in operable esophageal squamous cell carcinoma (ESCC) remains unclear. The study introduced a novel combined neutrophil−meanplateletvolume−platelet ratio (NMPR) index and investigated its clinical and prognostic value in patients with operable ESCC receiving curative surgery. Materials and Methods: A retrospective analysis of the clinicopathologic data of 277 consecutive ESCC patients who received curative resection at Zhejiang Cancer Hospital in China between January 2007 and December 2010 was conducted (the training cohort). In addition, the clinicopathologic data of 101 resectable ESCC patients at Renmin Hospital of Hubei University of Medicine between December 2018 and June 2021 were collected (the external validation cohort). The optimal cutoff value of NMPR concerning overall survival (OS) in the training cohort was determined by X-tile software. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of NMPR along with other variables in the training cohort, which was further validated with the same cutoff value in the external validation cohort. Significant predictors of OS were used to construct the nomogram, of which the discrimination and calibration was evaluated by concordance index (C-index) and calibration plots. Results: With a cutoff value of 16.62, the results from both the training and external validation cohorts supported the association of high NMPR (>16.62) with increased tumor length and advanced T stage but not with other variables. In the training cohort, a significant association between shorter OS and high NMPR (p = 0.04) as well as high CRP (p < 0.001), poor tumor differentiation (p = 0.008), advanced T stage (p = 0.006), advanced N stage (p < 0.001) and high CEA (p = 0.007) was revealed. Additionally, the high NMPR was verified to independently predict unfavorable OS (p = 0.049) in the external validation cohort. The C-index of the OS nomogram cooperating significant predictors in the training cohort was 0.71 and the calibration plots of the OS nomogram fitted well. Conclusions: The present study demonstrates that high NMPR is an independent predictor of unfavorable OS in resectable ESCC patients without neoadjuvant therapy.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/cirurgia , Estudos Retrospectivos , Plaquetas , PrognósticoRESUMO
BACKGROUND Impaired heart function induced by myocardial infarction is a leading cause of chronic heart failure (HF). This study aimed to investigate the effects and mechanism of noninvasive positive-pressure ventilation (NIPPV) in a rat model of HF due to myocardial infarction. MATERIAL AND METHODS To explore the therapeutic effect and mechanism of NIPPV on acute myocardial infarction-induced HF, we established a rat model of HF by ligating the anterior descending branch of the left coronary artery and confirmed by ultrasonic cardiography and brain natriuretic peptide 45 detection. RESULTS The levels of heat-shock protein (HSP)-70 increased and matrix metalloproteinase (MMP)-2, MMP-9, and tumor necrosis factor (TNF)-alpha decreased in the group that received NIPPV treatment compared with the control group. In addition, the histopathologic results showed less severe inflammatory infiltration and a smaller area of myocardial fibrosis in the NIPPV treatment group. CONCLUSIONS In a rat model of HF due to myocardial infarction, NIPPV resulted in increased levels of HSP70 and reduced expression of MMP2, MMP9, and TNF-alpha and reduced myocardial neutrophil infiltration and fibrosis. Taken together, we showed that NIPPV is an effective treatment for HF induced by myocardial infarction by inhibiting the release of inflammatory factors and preventing microvascular embolism.
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Insuficiência Cardíaca/terapia , Infarto do Miocárdio/terapia , Respiração com Pressão Positiva/métodos , Animais , Cardiomiopatias/patologia , Modelos Animais de Doenças , Ecocardiografia/métodos , Fibrose/patologia , Proteínas de Choque Térmico HSP70/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Miocárdio/patologia , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo , Remodelação Ventricular/efeitos dos fármacosRESUMO
Clinical manifestations of deletion 18p syndrome vary a lot, which makes it easily overlooked in the clinical practice. Familial transmission of deletion 18p syndrome is rare. We report a Chinese familial deletion 18p syndrome, which was diagnosed by anatomizing the underlying reason for the discrepancy between noninvasive prenatal testing (NIPT) and prenatal diagnosis. A 35-year-old pregnant woman was recruited to our center owing to the abnormal NIPT result with a high risk of chromosome 18 monosomy. However, the karyotype of the fetus was normal after amniocentesis. Further analysis indicated that the pregnant woman herself had an abnormal karyotype of 46,XX,del(18)(p11.2), (arr18p11.32p11.21[136,227-15,099,116]×1) and her first 12-year-old son had got the same deletion of 18p as her. A distinct phenotype variability was noted although they share identical deletion. We consider that adequate clinical genetic counseling is vital for women with adverse pregnancy history before getting pregnant. Maternal CNVs may be one of the main causes of the false-positive result on NIPT. NIPT, especially extended NIPT may provide extra valuable evidence when used as routine prenatal screening method.
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Transtornos Cromossômicos , Teste Pré-Natal não Invasivo , Adulto , Criança , China , Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 18 , Feminino , Humanos , Gravidez , Diagnóstico Pré-NatalRESUMO
The authors wish to make the following correction to this paper [...].
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Mitochondria has been identified as a promising target in several cancers. However, little is known on the effects of targeting mitochondria in retinoblastoma. In this work, we show that anti-malarial atovaquone, at clinically achievable concentration, demonstrates inhibitory effects to retinoblastoma cells, to a more extent than in normal retinal cells. Atovaquone also significantly increases chemosensitivity in retinoblastoma. Importantly, we show that retinoblastoma cells have higher level of mitochondrial respiration, membrane potential, mass and ATP compared to normal retinal cells. Although atovaquone significantly inhibits mitochondrial respiration and decrease ATP level in both malignant and normal retinal cells in a similar manner, atovaquone induces much more oxidative stress and damage in retinoblastoma than normal retinal cells. These suggest that normal retinal cells are more tolerable to mitochondrial dysfunctions than retinoblastoma cells. We further demonstrate that atovaquone targets Akt/AMPK/mTOR signaling via inducing mitochondrial dysfunction. Our pre-clinical work demonstrates the translational potential of atovaquone as an addition to the treatment armamentarium for retinoblastoma. Our work also demonstrates the differences of mitochondrial biogenesis and function in malignant versus normal retinal cells which are important for the targeted therapy in retinoblastoma.
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Antineoplásicos/farmacologia , Atovaquona/farmacologia , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Retinoblastoma/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Antimaláricos/farmacologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Dano ao DNA , Glicólise , Humanos , Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Retina/metabolismo , Retinoblastoma/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
PURPOSE: The present study was to evaluate the prognostic value of protein expression of Pofut1 and Notch1 signaling in breast cancer. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded 314 breast specimens including 174 infiltrating ductal carcinoma(IDC), 50 ductal carcinoma in situ(DCIS) and 90 adjacent normal tissue(ANT) were immunohistochemically examined to evaluate the protein expression of Pofut1, activated Notch1(N1IC) and Slug on specimens. Survival analysis was performed by Kaplan-Meier method and Cox's proportional-hazards model. A online database was computationally used to further explore the prognostic role of Pofut1 and Notch1 mRNA expression by Kaplan-Meier Plotter. RESULTS: Pofut1, Slug and N1IC expression were significantly increased in IDC compared to ANT(all p < 0.05). High expression of Pofut1, Slug and N1IC were associated with tumor aggressiveness including lymph node metastasis (LNM: p = 0.005 for Pofut1, p < 0.001 for N1IC, p = 0.017 for Slug), advanced stage(p = 0.039 for Pofut1, p = 0.025 for N1IC) and higher histological grade(p = 0.001 for N1IC). Additionally, high expression of Pofut1 was found to be significantly associated with high expressions of N1IC and Slug in IDC(r = 0.244, p = 0.001; r = 0.374, p < 0.001, respectively), similar correlation was also observed between high N1IC and Slug expression(r = 0.496, p < 0.001). Moreover, Kaplan-Meier and Cox's regression analysis indicated the significant prognostic value of elevated Pofut1, N1IC, Slug expressions, positive LNM and advanced tumor stage for the prediction of a shorter disease-free survival (DFS) and overall survival(OS). The web-based analysis also suggested a significant association of high Pofut1 and Notch1 mRNA expression with worse survival outcome. CONCLUSION: Our findings suggested that overexpression of Pofut1 and activated Notch1 signaling may be associated with a poor prognosis in breast cancer.
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Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Fucosiltransferases/metabolismo , Receptor Notch1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Taxa de Sobrevida , Regulação para CimaRESUMO
We document experimentally four different interactions of a laser-induced bubble and a free-settling particle, with different combinations of the geometric and physical parameters of the system. Our force balance model shows that four nondimensional factors involving the particle radius a, the maximum bubble radius R_{max}, the initial separation distance l_{0} between the particle center and the bubble center, the fluid viscosity µ_{f}, and the particle and fluid densities ρ_{p} and ρ_{f}, respectively, in detail l_{0}/R_{max}, a/R_{max}, ρ_{p}/ρ_{f}, and µ^{*}=µ_{f}T_{c}/ρ_{f}R_{max}^{2}, where T_{c}=0.915R_{max}sqrt[ρ_{f}/(p_{∞}-p_{v})], influence the particle-bubble dynamics, and reasonably predict the maximum particle velocity and the limiting condition when the particle starts to "bounce off" the bubble during bubble growth. In particular, we also discover the high-speed ejection of the particle, and a cavity behind the particle, in cases when initially the particle is in very close proximity to the bubble. These observations offer new insights into the causal mechanism for the enhanced cavitation erosion in silt-laden water.
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OBJECTIVE: To observe the effect of Xuebijing injection on sepsis combined with acute gastrointestinal injury (AGI), and analyze the risk factors of sepsis combined with AGI. METHODS: A retrospective cohort study was conducted. Patients with non-gastrointestinal origin admitted to the department of intensive care medicine of the First Hospital of Qinhuangdao from May 1, 2021 to October 30, 2023 were enrolled. The baseline data, source of sepsis infection, vital signs, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), laboratory tests, comorbidities, interventions during treatment, and the 28-day prognosis were collected. The patients were divided into Xuebijing group and non-Xuebijing group according to whether Xuebijing injection was used or not. According to whether AGI was merged or not, patients were divided into merged AGI group and non-merged AGI group. The main observational indexes were the difference in the incidence of AGI between the Xuebijing group and non-Xuebijing group and the difference in the magnitude of the decline in procalcitonin (PCT), C-reactive protein (CRP), and white blood cell count (WBC) at 7 days after admission, and the difference in the 28-day morbidity and mortality. Risk factors for AGI in septic patients were explored by univariate analysis, and statistically significant indicators were screened and included in binary Logistic regression analysis to determine independent risk factors. RESULTS: A total of 129 patients with sepsis of non-gastrointestinal origin were enrolled, including 57 patients in the Xuebijing group and 72 patients in the non-Xuebijing group. Among 129 patients, 80 patients in the merged AGI group and 49 patients in the non-merged AGI group. There were no statistically significant differences between Xuebijing group and non-Xuebijing group in gender, age, body mass index (BMI), underlying disease, source of infection, vital sign, APACHE II score, SOFA score, and clinical intervention, and there were no statistically significant differences in laboratory tests except for aspartate aminotransferase (AST) and blood urea nitrogen (BUN). The incidence of AGI was significantly lower in the Xuebijing group than that in the non-Xuebijing group [50.87% (29/57) vs. 70.83% (51/72), P < 0.05], and the 28-day mortality was slightly lower than that in the non-Xuebijing group [24.56% (14/57) vs. 30.56% (22/72), P > 0.05]. In the Xuebijing group, the decreases in CRP, PCT and WBC at 7 days after admission were greater than those in the non-Xuebijing group, with statistically significant differences in the decreases of CRP and PCT [CRP (mg/L): 47.12±67.34 vs. 7.76±111.03, PCT (µg/L): 14.08 (-1.22, 50.40) vs. 2.94 (-1.27, 14.80), all P < 0.05]. Univariate analysis showed that the use of acid suppressants, the use of analgesic sedation, the non-use of Xuebijing injections, pulmonary infections, and urinary tract infections were the risk factors for the development of AGI in patients with sepsis. Binary Logistic regression analysis further showed that the use of acid suppressants [odds ratio (OR) = 2.450, 95% confidence interval (95%CI) was 1.021-5.883, P = 0.045], use of analgesic sedatives (OR = 2.521, 95%CI was 1.074-5.918, P = 0.034), and urinary tract infection (OR = 4.011, 95%CI was 1.085-14.831, P = 0.037) were independent risk factors for sepsis combined with AGI, in which the use of Xuebijing injection was a protective factor (OR = 0.315, 95%CI was 0.137-0.726, P = 0.007). CONCLUSIONS: Xuebijing injection reduced the incidence of AGI in patients with non-gastrointestinal sepsis. PCT and CRP decreased more markedly than in patients who did not use Xuebijing injection. The use of acid-suppressing agents, analgesic and sedative agents, and urinary tract infections were independent risk factors for sepsis in combination with AGI, while the use of Xuebijing injection is a protective factor.
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Medicamentos de Ervas Chinesas , Sepse , Humanos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Estudos Retrospectivos , Sepse/complicações , Sepse/tratamento farmacológico , Proteína C-Reativa , Pró-Calcitonina/sangue , Fatores de Risco , APACHE , Prognóstico , Gastroenteropatias/epidemiologia , Masculino , Feminino , Estudos de Coortes , Pessoa de Meia-IdadeRESUMO
We experimentally, numerically, and theoretically investigate the dynamics of cavitation bubbles in viscous liquids in a tube during a transient process. In experiments, cavitation bubbles are generated by a modified tube-arrest setup, and the bubble evolution is captured with high-speed imaging. Numerical simulations using OpenFOAM are employed to validate our quasi-one-dimensional theoretical model, which effectively characterizes the bubble dynamics. We find that cavitation onset is minimally affected by the liquid viscosity. However, once cavitation occurs, various aspects of bubble dynamics, such as the maximum bubble length, bubble lifetime, collapse time, and collapse speed, are closely related to the liquid viscosity. We further establish that normalized bubble dynamics are solely determined by the combination of the Reynolds number and the Euler number. Moreover, we also propose a new dimensionless number, Ca2, to predict the maximum bubble length, a critical factor in determining the occurrence of liquid column separation.
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Surface-attached micro- and nanobubbles are known for their resistance to external forces. This study experimentally and theoretically investigates their response to strong ultrasonic fields. Surface-attached micro- and nanobubbles with contact radii from 2 µm to 20 µm are generated in a microchannel and exposed to ultrasound through a vibrating glass substrate. At a driving frequency over 200 kHz up to 2 MHz tested, no significant response from the micro- and nanobubbles is observed. By contrast, at 100 kHz-200 kHz, ultrasonic cavitation bubbles appear in the microchannel and migrate toward the surface micro- and nanobubbles. Then the surface micro- and nanobubbles merge with the ultrasonic cavitation bubbles, detach from the substrate, and become free gaseous nuclei susceptible to further cavitation. Notably, the removal process leaves no observable residue. Theoretical analysis suggests that the directional migration of cavitation bubbles is driven by mutual acoustic radiation forces. This work demonstrates that ultrasonic fields can effectively remove surface micro- and nanobubbles, transforming them into free gaseous cavitation nuclei.
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Cementogenesis is of great importance for normal teeth root development and is involved in the repair process of root resorption caused by orthodontic treatment. As highly differentiated mesenchymal cells, cementoblasts are responsible for this process under the regulation of many endogenous agents. Among these molecules, sclerostin has been much investigated recently for its distinct antagonism effect on bone metabolism. Encoded by the sost gene, sclerostin is expressed in osteocytes and cementocytes of cellular cementum. it is still unclear. In the current study, we investigated the effects of sclerostin on the processes of proliferation and differentiation; a series of experiments including MTT, apoptosis examination, alkaline phosphatase (ALP) activity, gene analysis, and alizarin red staining were carried out to evaluate the proliferation and differentiation of cementoblasts. Protein expression including osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) were also checked to analyze changes in osteoclastogenesis. Results show that sclerostin inhibits cementoblasts proliferation and differentiation, and promotes osteoclastogenesis. Interestingly, the monoclonal antibody for sclerostin has shown positive effects on osteoporosis, indicating that it may facilitate cementogenesis and benefit the treatment of cementum related diseases.
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Diferenciação Celular/fisiologia , Cementogênese/fisiologia , Cemento Dentário/metabolismo , Cemento Dentário/fisiologia , Glicoproteínas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Fosfatase Alcalina/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular , Proliferação de Células , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Osteoprotegerina/metabolismo , Ligante RANK/metabolismoRESUMO
Background: Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection, which can cause acute gastrointestinal injury (AGI). The gut microbiota is dynamic and plays a role in the immune and metabolic. The aim of this study was to investigate the composition and function of gut microbiota in patients with sepsis, as well as the gut microbiome that may be involved in the occurrence of AGI. Methods: A total of 23 stool samples from healthy control individuals and 41 stool samples from sepsis patients were collected. Patients with sepsis were followed up for one week to observe whether AGI has occurred. Finally, 41 patients included 21 sepsis complicated with AGI (referred to as Com-AGI) and 20 sepsis without complicated with AGI (referred to as No-AGI). The gut microbiota was analyzed by 16S rRNA gene sequencing, followed by composition analysis, difference analysis, correlation analysis, functional prediction analysis. Results: The diversity and evenness of gut microbiota were decreased in patients with sepsis. Compared with No-AGI, the gut microbiota of Com-AGI has higher community diversity, richness, and phylogenetic diversity. Escherichia-Shigella, Blautia and Enterococcus may be important indicators of sepsis. The correlation analysis showed that aspartate aminotransferase (AST) and Barnesiella have the most significant positive correlation. Moreover, Clostridium_innocuum_group, Christensenellaceae_R-7_group and Eubacterium were all significantly correlated with LAC and DAO. Clostridium_innocuum_group, Barnesiella, Christensenellaceae_R-7_group and Eubacterium may play important roles in the occurrence of AGI in sepsis. PICRUSt analysis revealed multiple functional pathways involved in the relationship between gut microbiota and sepsis, including starch degradation V, glycogen degradation I (bacterial), Lipoic acid metabolism and Valine, leucine and isoleucine biosynthesis. BugBase analysis showed that the gut microbiota with Aerobic phenotype may play an important role in sepsis. Conclusion: Dysfunction of gut microbiota was associated with sepsis and AGI in patients with sepsis.
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BACKGROUND AND PURPOSE: Immunotherapy has revolutionized the treatment of advanced and metastatic esophageal squamous cell carcinoma (ESCC), but most patients eventually developed disease progression. Immuno-resistance is becoming an unavoidable clinical problem. Oligometastasis is a limited-metastatic state, and patients at this stage should be evaluated for the addition of metastasis-directed local intervention, which may be associated with improved prognosis. As an immunomodulator, radiotherapy may exhibit synergistic effect when added to immunotherapy. This study assessed the efficacy and safety of low-dose radiotherapy plus immunotherapy and second-line chemotherapy in oligometastatic ESCC. MATERIALS AND METHODS: In this phase II trial (ChiCTR2000040533), oligometastatic ESCC patients after first-line immunotherapy plus chemotherapy failure were treated with low dose radiotherapy plus camrelizumab and second-line irinotecan chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and safety. Abscopal response rate (ARR) and abscopal control rate (ACR) were also been explored. RESULTS: Between November 19, 2018 and March 17, 2021, 49 patients were enrolled. With a median follow-up of 12.8 months, median PFS and OS were 6.9 months (95%CI, 4.6-9.3) and 12.8 months (95%CI, 10.1-15.5), respectively. ORR was 40.8% (95%CI, 27.3-55.7). DCR was 75.5% (95%CI, 60.8-86.2). ARR was 34.7% (95%CI, 22.1-49.7). ACR was 69.4% (95%CI, 54.4-81.3). The most common adverse effects of any grade were myelosuppression, weight loss and fatigue. Grade 3 or 4 treatment-related adverse events occurred in 31 (63.3%) patients, with the most common being leukopenia (30.6%). No treatment-related deaths occurred. CONCLUSION: Low dose radiotherapy plus camrelizumab and irinotecan exhibited survival benefit with manageable safety for oligometastatic ESCC patients after first-line immunotherapy plus chemotherapy failure. It deserves to be validated in a larger trial.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Irinotecano/efeitos adversos , Carcinoma de Células Escamosas do Esôfago/terapia , Neoplasias Esofágicas/tratamento farmacológico , Imunoterapia/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
This study aims to evaluate the effect of dexmedetomidine (DEX)-on esophageal cancer (EC) via regulating long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). The effect of DEX on MALAT1 expression and EC cell viability was detected. EC cells were divided into Blank, DEX, scrambled/MALAT1 siRNA, and DEX + control/MALAT1 groups, followed by a series of experiments including quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blotting, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), Annexin V-FITC/PI staining, wound healing, and Transwell assays. Additionally, mice were subjected to the subcutaneous injection of Eca109 cells transfected by control/MALAT1 activation lentiviral vector to construct EC models with the DEX treatment, and then the tumor volume and the expression of Ki-67 and active caspase-3 were determined. DEX reduced the expression of MALAT1 in EC cells in a dose-dependent manner. DEX inhibited the viability of EC cells, but increased the cell apoptosis, which, however, was reversed by MALAT1 overexpression. Moreover, MALAT1 overexpression abolished the inhibitory effect of DEX on the epithelial-mesenchymal transition (EMT) of EC cells, with enhanced migration and invasion. Furthermore, DEX succeeded in decreasing the tumor volume with the down-regulation of MALAT1. In comparison with the DEX group, mice in the DEX + MALAT1 group had larger tumors, with the up-regulation of Ki-67 and the down-regulation of active caspase-3. DEX can reduce the expression of MALAT1 in EC cells, thereby inhibiting the proliferation, invasion and migration, as well as EMT, and promoting the apoptosis of EC cells.
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Adenocarcinoma , Dexmedetomidina , Neoplasias Esofágicas , MicroRNAs , RNA Longo não Codificante , Animais , Apoptose/genética , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Dexmedetomidina/farmacologia , Regulação para Baixo/genética , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Antígeno Ki-67/metabolismo , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Gastric, liver, and colorectal cancers belong to gastrointestinal (GI) cancers, one of the most threatening diseases in the world. The tonics class in Chinese medicines plays a critical role in antigastrointestinal cancer as adjuvants. However, it is a challenge to study the effects and underlying mechanisms of tonics due to their multiple components and multiple targets; OMICs were introduced to facilitate the investigation of the complex mixture of tonics. In this review, the online databases PubMed, ProQuest, Web of Knowledge, China National Knowledge Infrastructure (CNKI), Chongqing VIP, and Wanfang were retrieved from 1 January 2011 to 31 May 2022, in an aim to summarize and discuss the research progress of the effects and, especially, the underlying mechanisms of tonics for antigastrointestinal cancers via OMICs. The results showed that through the combination of OMICs and other technologies, tonics have been used for gastrointestinal cancer by targeting cancer hallmarks, enhancing body resistance to carcinogenesis, enhancing therapeutic effects, and/or decreasing side effects. In conclusion, tonics may play a promising role in gastric, liver, and colorectal cancers as adjuvants and can be well investigated via the combination of OMICs and other technologies, which deserves further study.
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OBJECTIVE: To determine the risk factors of extubation failure and its effect on the prognosis of patients who had successfully passed a spontaneous breathing trial (SBT). METHODS: The clinical data of patients with mechanical ventilation more than 24 hours who passed SBT admitted to department of intensive care unit (ICU) of First Hospital of Qinhuangdao from November 2018 to November 2019 were retrospectively analyzed. According to the outcome of weaning within 48 hours after weaning, patients were divided into weaning success group and weaning failure group. The baseline data, the presence of basic cardiopulmonary diseases, B-type natriuretic peptide (BNP), fluid balance, albumin and hemoglobin within 24 hours before weaning, the time of mechanical ventilation before weaning, rapid shallow breathing index (RSBI) during SBT, oxygenation index, cough peak flow at the end of SBT, and prognostic indicators were collected. The outcome of weaning was taken as the dependent variable, and the observation factors were taken as the independent variable for univariate analysis. The factors with statistical significance in univariate analysis were analyzed by binary Logistic regression to determine the influencing factors of weaning failure. RESULTS: Of the 204 patients, 167 (81.9%) were successfully weaned, and 37 (18.1%) failed. Compared with the weaning success group, the total duration of mechanical ventilation and the length of ICU stay in the weaning failure group were significantly longer [days: 13.0 (7.5, 23.5) vs. 5.0 (3.0, 8.0), 17.0 (12.5, 31.0) vs. 10.0 (6.0, 15.0), both P < 0.01], and the tracheotomy rate and mortality were significantly higher (32.4% vs. 0%, 51.4% vs. 0%, both P < 0.01). Univariate analysis showed that there were significant differences in age, proportion of patients with cardiopulmonary diseases, BNP and cough peak flow between weaning failure group and weaning success group [age (years old): 70.65±15.78 vs. 62.69±15.82, cardiopulmonary diseases: 62.2% vs. 24.6%, BNP (ng/L): 416.87 (32.70, 1 225.80) vs. 45.36 (10.00, 273.60), cough peak flow (L/min): 59.89±9.06 vs. 83.84±16.52, all P < 0.01]. However, there were no significant differences in gender, acute physiology and chronic health evaluation II (APACHE II) at admission, mechanical ventilation time before weaning, albumin, hemoglobin, oxygenation index, RSBI and fluid balance 24 hours before weaning between weaning failure group and weaning success group [male: 51.4% vs. 68.3%, APACHE II: 16.70±6.65 vs. 15.67±6.28, mechanical ventilation time before weaning (days): 6.0 (2.5, 11.0) vs. 5.0 (3.0, 8.0), albumin (g/L): 27.78±4.15 vs. 27.76±4.46, hemoglobin (g/L): 102.43±15.80 vs. 100.61±17.19, oxygenation index (mmHg, 1 mmHg = 0.133 kPa): 359.33±79.83 vs. 365.75±78.23, RSBI (times×L-1×min-1): 50.73±24.97 vs. 46.76±15.53, positive fluid balance: 70.3% vs. 69.5%, all P > 0.05]. The results of binary Logistic regression analysis showed that age ≥ 75 years old [odds ratio (OR) = 3.099, 95% confidence interval (95%CI) was 1.003-9.574, P = 0.049], presence of cardiopulmonary diseases (OR = 3.599, 95%CI was 1.126-11.498, P = 0.031), BNP within 24 hours before weaning (OR = 1.002, 95%CI was 1.000-1.003, P = 0.005) were the risk factors of extubation failure, while cough peak flow at the end of SBT was the protective factor (OR = 0.869, 95%CI was 0.823-0.917, P = 0.000). CONCLUSIONS: For patients who had successfully passed SBT, age ≥ 75 years old, the presence of cardiopulmonary diseases and an increased level of BNP within 24 hours were the risk factors of extubation failure. In addition, the higher the cough peak flow at the end of SBT, the lower the risk of weaning failure will be.
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Extubação , Desmame do Respirador , Humanos , Unidades de Terapia Intensiva , Masculino , Respiração Artificial , Estudos RetrospectivosRESUMO
BACKGROUND: During the coronavirus disease 2019 (COVID-19) epidemic, tumor patients and their families might suffer from greater psychological stress as a result of anxiety or other psychological disorders. We conducted an online study during the epidemic to explore the mental state of tumor patients and their families during this extraordinary time. METHODS: A cross-sectional survey was carried out. Questionnaires were distributed through the WeChat "Questionnaire Star" network. The snowball sampling technique was adopted and further promoted by subjects who had completed the questionnaire. RESULTS: A total of 1,030 valid questionnaires were collected. There were 609 (59.13%) tumor patients and 421 (40.87%) family members. One hundred and fifty-six (15.15%) subjects had anxiety, among which 65 (6.31%) had moderate to severe anxiety. Single-factor analysis indicated that age (>60 years old), the farmer occupation, and a high sleep disorder assessment score were risk factors for anxiety, while the latter two might also be independent risk factors, as suggested by multi-factor analysis. Infrequent contact with doctors was an independent risk factor for cancer patients, while uninterrupted anti-tumor therapy was an independent protective factor. 40.19% of the subjects expressed a need for psychosocial support during the COVID-19 period. CONCLUSIONS: The COVID-19 outbreak resulted in tumor patients and their relatives experiencing greater psychological pressure than usual, and patients were more worried about anti-tumor treatment and disease progression impacted by the epidemic. Both groups had a significant need for psychosocial help.
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COVID-19 , Neoplasias , Ansiedade/epidemiologia , China/epidemiologia , Estudos Transversais , Depressão , Humanos , Saúde Mental , Pessoa de Meia-Idade , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
Monitoring of early-stage breast cancer is critical in promptly addressing disease relapse. Circulating cell-free DNA provides a minimally invasive and sensitive means to probing the disease. In a longitudinal analysis of 250 patients with early breast cancer, we compared the circulating cell-free DNA recovered from both plasma and urine specimens. For comparison, 50 healthy controls were also recruited. Specific mutations associated with the disease were profiled to determine the clinical sensitivity and specificity. Correlations of recovered concentrations of cell-free DNA with outcomes were examined to address early prognostication. PIK3CA mutation profiling in both plasma and urinary cell-free DNA showed an agreement of 97.2% compared with the results obtained for tumor tissues. The analysis of healthy controls revealed that cell-free DNA measurements were stable and consistent over time. Over the short 6-month period of monitoring, our analyses showed declines in recovered cell-free DNA; these findings may aid physicians in stratifying patients at higher risk for relapse. Similar results were observed in both plasma and urine specimens (hazard ratios: 2.16 and 2.48, respectively). Cell-free DNA presents a novel and sensitive method for the monitoring of early-stage breast cancer. In the present study, serial measurements of both plasma and urine specimens were useful in probing the disease.