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Objective: This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2 (HER2)-low early breast cancer (BC) and HER2-IHC0 BC. Methods: Patients diagnosed with HER2-negative BC ( N = 999) at our institution between January 2011 and December 2015 formed our study population. Clinicopathological characteristics, association between estrogen receptor (ER) expression and HER2-low, and evolution of HER2 immunohistochemical (IHC) score were assessed. Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes (5-year follow-up) between the HER2-IHC0 and HER2-low groups. Results: HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor (PgR) positivity than HER2-IHC0 BC group ( P < 0.001). The rate of HER2-low status increased with increasing ER expression levels (Mantel-Haenszel χ 2 test, P < 0.001, Pearson's R = 0.159, P < 0.001). Survival analysis revealed a significantly longer overall survival (OS) in HER2-low BC group than in HER2-IHC0 group ( P = 0.007) in the whole cohort and the hormone receptor (HR)-negative group. There were no significant differences between the two groups in terms of disease-free survival (DFS). The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion: HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.
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Neoplasias da Mama , Receptor ErbB-2 , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/genética , Feminino , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Pessoa de Meia-Idade , Prognóstico , Adulto , China/epidemiologia , Idoso , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , População do Leste AsiáticoRESUMO
The microencapsulation of polysaturated fatty acids by spray drying remains a challenge due to their susceptibility to oxidation. In this work, antioxidant Pickering emulsions were attempted as feeds to produce oxidation stable tuna oil microcapsules. The results indicated that the association between chitosan (CS) and ovalbumin (OVA) was a feasible way to fabricate antioxidant and wettable complexes and a high CS percentage favored these properties. The particles could yield tuna oil Pickering emulsions with enhanced oxidation stability through high-pressure homogenization, which were successfully spray dried to produce microcapsules with surface oil content of 8.84 % and microencapsulation efficiency of 76.65 %. The microcapsules exhibited significantly improved oxidation stability and their optimum peroxide values after storage at 50 °C, 85 % relative humidity, or natural light for 15 d were 48.67 %, 60.07 %, and 39.69 % respectively lower than the powder derived from the OVA-stabilized emulsion. Hence, Pickering emulsions stabilized by the CS/OVA polyelectrolyte complexes are potential in the production of oxidation stable polyunsaturated fatty acid microcapsules by spray drying.
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Cápsulas , Quitosana , Emulsões , Ovalbumina , Oxirredução , Secagem por Atomização , Atum , Quitosana/química , Emulsões/química , Ovalbumina/química , Animais , Óleos de Peixe/química , Polieletrólitos/química , Antioxidantes/química , Tamanho da PartículaRESUMO
In the current study, we investigated the effects of acteoside as a phenylpropanoid glycoside on interaction with neurons to assesses locomotor recovery after spinal cord injury (SCI) in rats by focusing on evaluating the factors involved in autophagy, apoptosis, inflammation and oxidative stress processes. 49 Spargue-Dawley rats were prepared and divided into seven healthy and SCI groups receiving different concentrations of acteoside. After 28 days of disease induction and treatment with acteoside, a BBB score test was used to evaluate locomotor activity. Then, by preparing spinal cord cell homogenates, the expression levels of MAP1LC3A, MAP-2, glial fibrillary acidic protein (GFAP), Nrf2, Keap-1, Caspase 3 (Casp3), Bax, Bcl-2, TNF-a, IL-1B, reactive oxygen species (ROS), and malondialdehyde (MDA) were measured. Improvement of locomotor activity in SCI rats receiving acteoside was observed two weeks after the beginning of the experiment and continued until the fourth week. Both MAP1LC3A and MAP-2 were significantly up-regulated in SCI rats treated with acteoside compared to untreated SCI rats, and GFAP levels were significantly decreased in these animals. Pro-apoptotic proteins Bax and Casp3 and anti-apoptotic protein Bcl-2 were down-regulated and up-regulated, respectively, in SCI rats receiving acteoside. In addition, a significant downregulation of iNOS, TNF-α, and IL-1ß and a decrease in contents of both ROS and MDA as well as increases in Nrf2 and Keap-1 were seen in rats receiving acteoside. Furthermore, acteoside strongly interacted with MAP1LC3A, TNF-α, and Casp3 targets with binding affinities of -8.3â¯kcal/mol, -8.3â¯kcal/mol, and -8.5â¯kcal/mol, respectively, determined by molecular docking studies. In general, it can be concluded that acteoside has protective effects in SCI and can be considered as an adjuvant therapy in the treatment of this disease. However, more studies, especially clinical studies, are needed in this field.
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Apoptose , Autofagia , Glucosídeos , Fenóis , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Transdução de Sinais , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Glucosídeos/farmacologia , Ratos , Recuperação de Função Fisiológica/efeitos dos fármacos , Fenóis/farmacologia , Masculino , Locomoção/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Modelos Animais de Doenças , PolifenóisRESUMO
Background: The role of total bilirubin (TBIL) in cardiovascular disease has been increasingly recognized in recent decades. Studies have shown a correlation between total bilirubin levels and the prognosis of patients after heart surgery. This study aimed to investigate the clinical significance of bilirubin elevation in persistent atrial fibrillation (PAF) patients who received radiofrequency catheter ablation (RFCA). Methods and Results: A total of 184 patients with PAF who received RFCA were retrospectively studied. Laboratory examinations and demographic data were analyzed to identify independent predictors of TBIL elevation. The relationship between TBIL and prognosis was further investigated. Our results indicated that TBIL increased significantly after RFCA. Multiple linear regression analysis showed that TBIL elevation owned a negative correlation with the percentile of low voltage areas (LVAs) in left atria (ß=-0.490, P<0.001). In contrast, a positive correlation was observed with the white blood cell (WBC) ratio (ß=0.153, P=0.042) and left atrial diameter (LAD) (ß=0.232, P=0.025). It was found that postoperative TBIL levels increased and then gradually decreased to baseline within 5 days without intervention. The bilirubin ratio <1.211 indicated the possibility of 1-year AF recurrence after ablation with a predictive value of 0.743 (specificity = 75.00%, sensitivity = 66.67%). Conclusion: Bilirubin elevation post PAF RFCA was a common phenomenon and was associated with 1-year recurrence of AF in PAF patients after RFCA.
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Fibrilação Atrial , Bilirrubina , Ablação por Cateter , Recidiva , Humanos , Fibrilação Atrial/cirurgia , Bilirrubina/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Prognóstico , Hospitalização , Modelos Lineares , Fatores de RiscoRESUMO
PURPOSE: This study aimed to establish a nomogram to predict the risk of venous thromboembolism (VTE), identifying potential risk factors, and providing theoretical basis for prevention of VTE after spinal surgery. METHODS: A retrospective analysis was conducted on 2754 patients who underwent spinal surgery. The general characteristics of the training group were initially screened using univariate logistic analysis, and the LASSO method was used for optimal prediction. Subsequently, multivariate logistic regression analysis was performed to identify independent risk factors for postoperative VTE in the training group, and a nomogram for predict risk of VTE was established. The discrimination, calibration, and clinical usefulness of the nomogram were separately evaluated using the C-index, receiver operating characteristic curve, calibration plot and clinical decision curve, and was validated using data from the validation group finally. RESULTS: Multivariate logistic regression analysis identified 10 independent risk factors for VTE after spinal surgery. A nomogram was established based on these independent risk factors. The C-index for the training and validation groups indicating high accuracy and stability of the model. The area under the receiver operating characteristic curve indicating excellent discrimination ability; the calibration curves showed outstanding calibration for both the training and validation groups. Decision curve analysis showed the clinical net benefit of using the nomogram could be maximized in the probability threshold range of 0.01-1. CONCLUSION: Patients undergoing spinal surgery with elevated D-dimer levels, prolonger surgical, and cervical surgery have higher risk of VTE. The nomogram can provide a theoretical basis for clinicians to prevent VTE.
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Nomogramas , Tromboembolia Venosa , Humanos , Estudos Retrospectivos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Procedimentos Neurocirúrgicos , Pescoço , Fatores de RiscoRESUMO
Hepatic ischemia-reperfusion injury (HIRI) is the major complication of liver surgery and liver transplantation, that may increase the postoperative morbidity, mortality, tumor progression, and metastasis. The underlying mechanisms have been extensively investigated in recent years. Among these, oxidative stress, inflammatory responses, immunoreactions, and cell death are the most studied. Non-coding RNAs (ncRNAs) are defined as the RNAs that do not encode proteins, but can regulate gene expressions. In recent years, ncRNAs have emerged as research hotspots for various diseases. During the progression of HIRI, ncRNAs are differentially expressed, while these dysregulations of ncRNAs, in turn, have been verified to be related to the above pathological processes involved in HIRI. ncRNAs mainly contain microRNAs, long ncRNAs, and circular RNAs, some of which have been reported as biomarkers for early diagnosis or assessment of liver damage severity, and as therapeutic targets to attenuate HIRI. Here, we briefly summarize the common pathophysiology of HIRI, describe the current knowledge of ncRNAs involved in HIRI in animal and human studies, and discuss the potential of ncRNA-targeted therapeutic strategies. Given the scarcity of clinical trials, there is still a long way to go from pre-clinical to clinical application, and further studies are needed to uncover their potential as therapeutic targets.
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MicroRNAs , Traumatismo por Reperfusão , Animais , Humanos , RNA não Traduzido/genética , MicroRNAs/genética , Biomarcadores , Traumatismo por Reperfusão/genética , FígadoRESUMO
BACKGROUND: Due to the poor prognosis of gastric cancer (GC), early detection methods are urgently needed. Plasma exosomal circular RNAs (circRNAs) have been suggested as novel biomarkers for GC. AIM: To identify a novel biomarker for early detection of GC. METHODS: Healthy donors (HDs) and GC patients diagnosed by pathology were recruited. Nine GC patients and three HDs were selected for exosomal whole-transcriptome RNA sequencing. The expression profiles of circRNAs were analyzed by bioinformatics methods and validated by droplet digital polymerase chain reaction. The expression levels and area under receiver operating characteristic curve values of plasma exosomal circRNAs and standard serum biomarkers were used to compare their diagnostic efficiency. RESULTS: There were 303 participants, including 240 GC patients and 63 HDs, involved in the study. The expression levels of exosomal hsa_circ_0079439 were significantly higher in GC patients than in HDs (P < 0.0001). However, the levels of standard serum biomarkers were similar between the two groups. The area under the curve value of exosomal hsa_circ_0079439 was higher than those of standard biomarkers, including carcinoembryonic antigen, carbohydrate antigen (CA)19-9, CA72-4, alpha-fetoprotein, and CA125 (0.8595 vs 0.5862, 0.5660, 0.5360, 0.5082, and 0.5018, respectively). The expression levels of exosomal hsa_circ_0079439 were significantly decreased after treatment (P < 0.05). Moreover, the expression levels of exosomal hsa_circ_0079439 were obviously higher in early GC (EGC) patients than in HDs (P < 0.0001). CONCLUSION: Our results suggest that plasma exosomal hsa_circ_0079439 is upregulated in GC patients. Moreover, the levels of exosomal hsa_circ_0079439 could distinguish EGC and advanced GC patients from HDs. Therefore, plasma exosomal hsa_circ_0079439 might be a potential biomarker for the diagnosis of GC during both the early and late stages.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Detecção Precoce de Câncer , RNA Circular , Antígeno CA-19-9 , Biologia ComputacionalRESUMO
OBJECTIVE: Global pincer is a relatively rare form of pincer deformity and is typically associated with technical challenges during surgery. So far, controversy remains whether patients with global pincer have equivalent surgical outcomes compared to patients with focal pincer. This study compares the clinical outcomes of arthroscopic treatment between patients with global pincer femoroacetabular impingement (FAI) and focal pincer FAI in the Chinese population. METHODS: Data were retrospectively collected from patients with global and focal pincer FAI who underwent hip arthroscopy with a minimum two-year follow-up between April 2016 and December 2018. Radiographic measurements, arthroscopic procedures, preoperative and postoperative patient-reported outcomes (PROs) including modified Harris hip score (mHHS), hip outcome score-activities of daily living (HOS-ADL), international hip outcome tool-12 (iHOT-12), and visual analogue scale (VAS) scores, rates of revision surgery and conversion to total hip arthroplasty (THA) were recorded. Achievement of minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) was compared for the VAS, mHHS, HOS-ADL, and iHOT-12 scores between groups. RESULTS: The total of 33 and 167 patients were included in the global and focal group, respectively. There were no intergroup differences in age, gender, body mass index or follow-up times. Lateral center-edge angle (LCEA) was reduced in both groups postoperatively. Both groups demonstrated significant improvements in PROs compared with preoperative levels at the final follow-up. The preoperative scores showed significant differences in terms of mHHS (60.34 vs 62.90, P = 0.031) and HOS-ADL (61.45 vs 64.74, P = 0.022) scores between two groups, and the improvement of HOS-ADL score was significantly higher in global group (P = 0.027). However, the postoperative scores, including VAS, mHHS, HOS-ADL, and iHOT-12 scores, showed no significant differences between two groups. And there were no significant differences in the rate of meeting the PASS and MCID between groups. One (3.0%) in the global group and six (3.6%) patients in the focal group underwent revision arthroscopy respectively, with no significant difference (P = 0.876). There were no conversions to THA in both groups. CONCLUSIONS: Arthroscopic management of global pincer FAI can achieve excellent functional scores at minimum 2-year follow-up. The outcomes were similar to focal pincer FAI patients with a low rate of secondary procedure.
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Impacto Femoroacetabular , Humanos , Impacto Femoroacetabular/cirurgia , Estudos Retrospectivos , Articulação do Quadril/cirurgia , Seguimentos , Artroscopia , Atividades Cotidianas , Resultado do TratamentoRESUMO
AIMS: Experiments confirmed that circular RNAs contributed to the pathogenesis of diabetic foot ulcers (DFUs). CircHIPK3 was upregulated in type 2 diabetes mellitus (T2DM), but its role in DFU remained unknown. Our study aimed to investigate the regulatory functions of exosomal circHIPK3 and its potential mechanisms in DFU. METHODS: Exosomal size and distribution, marker proteins, and circHIPK3 levels were evaluated by transmission electron microscope, ExoView R200, western blot, and qRT-PCR. Flow cytometry, MTT, Wound healing assays, and tube formation assays were used to assess the roles of exosomal circHIPK3 in high glucose (HG)-treated human umbilical vein endothelial cells (HUVECs). The relationships between Nrf2/VEGFA/circHIPK3 and miR-20b-5p, and between Nrf2 and VEGFA were determined by luciferase reporter assay and RNA immunoprecipitation. We used cell and mice models to investigate the mechanisms of exosomal circHIPK3 under diabetic conditions. RESULTS: CircHIPK3 was significantly upregulated in exo-circHIPK3 rather than exo-vector. Exo-circHIPK3 remarkably inhibited cell apoptosis but promoted cell proliferation, migration, and tube formation in HG-treated HUVECs. Luciferase reporter and RIP assays showed that miR-20b-5p targeted and inhibited Nrf2 and VEGFA, and circHIPK3 acted as a ceRNA of miR-20b-5p to inhibit the binding to its downstream genes Nrf2 and VEGFA. Mechanistically, circHIPK3 promoted cell proliferation, migration, and angiogenesis via downregulating miR-20b-5p to upregulate Nrf2 and VEGFA. However, the overexpressed miR-20b-5p could abolish the promoting effects of circHIPK3 overexpression on cell proliferation, migration, and tube formation under HG conditions. CONCLUSION: UCMSCs-derived exosomal circHIPK3 protected HG-treated HUVECs via miR-20b-5p/Nrf2/VEGFA axis. The exosomal circHIPK3 might be a therapeutic candidate to treat DFU.
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Diabetes Mellitus Tipo 2 , MicroRNAs , Humanos , Camundongos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , MicroRNAs/farmacologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Proliferação de Células/genética , Fator A de Crescimento do Endotélio VascularRESUMO
Proline-rich tyrosine kinase-2 (PYK2), also known as calcium dependent tyrosine kinase, regulates different signal transduction cascades that control cell proliferation, migration, and invasion. However, the role of PYK2 in cervical cancer remains to be elucidated. The current study retrospectively included 134 patients with cervical cancer from December 2007 to September 2014. PYK2 expression was detected in tissue microarray and cervical cancer cell lines. Statistical analysis was performed to evaluate its clinicopathological significance. Small interfering RNA (siRNA) was employed to suppress endogenous PYK2 expression in cervical cancer cells to observe the biological function. PYK2 expression was up-regulated in cervical cancer specimens compared with paired adjacent normal cervical tissue samples. Statistical analyses indicated that PYK2 expression might be an independent prognostic indicator for patients with early-stage cervical cancer. A nomogram model was constructed based on PYK2 expression and other clinicopathological risk factors, and it performed well in predicting patients survival. In cellular studies, down-regulation of PYK2 remarkably inhibited cellular proliferation, migration and invasion. PYK2 expression possessed the potential to serve as a novel prognostic marker in cervical cancer patients.
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Quinase 2 de Adesão Focal , Neoplasias do Colo do Útero , Feminino , Humanos , Cálcio , Linhagem Celular Tumoral , Movimento Celular/genética , Quinase 2 de Adesão Focal/genética , Quinase 2 de Adesão Focal/metabolismo , Prognóstico , Prolina , Estudos Retrospectivos , RNA Interferente Pequeno , Neoplasias do Colo do Útero/genéticaRESUMO
A novel and highly efficient dual-targeting PtII system was designed to improve the drug delivery capacity and selectivity in cancer treatment. The dual-targeting monofunctional PtII complexes (1-8) having glycosylated pendants as tridentated ligand were achieved by introducing glycosylation modification in the thioaminocarbazone compounds with potential lysosomal targeting ability. The structures and stability of 1-8 were further established by various techniques. Molecular docking studies showed that 2 was efficiently docked into glucose transporters protein 1 (GLUT1) and P-glycoprotein (Pgp) proteins with the optimal CDocker-interaction-energy of -64.84 and -48.85 kcal mol-1. Complex 2 with higher protein binding capacity demonstrated significant and broad-spectrum antitumor efficacy in vitro, even exhibiting a half maximal inhibitory concentration (IC50) value (â¼10 µM) than cisplatin (â¼17 µM) against human lung adenocarcinoma cells (A549). The inhibitor experiment revealed GLUT-mediated uptake of 2, and the subcellular localization experiment in A549 also proved that 2 could be localized in the lysosome, thereby causing cell apoptosis. Moreover, cellular thermal shift assay (CETSA) confirmed the binding of 2 with the target proteins of GLUT1 and Pgp. The above results indicated that 2 represents a potential anticancer candidate with dual-targeting functions.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Antineoplásicos , Compostos de Platina , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Transportador de Glucose Tipo 1 , Simulação de Acoplamento Molecular , Compostos de Platina/química , Compostos de Platina/farmacologia , Células A549RESUMO
BACKGROUND: Fucosidosis is one of the rare autosomal recessive lysosomal storage diseases (LSDs) attributed to FUCA1 variants causing the deficiency of α-L-fucosidase in vivo. Α-L-fucosidase deficiency will cause excessive accumulation of fucosylated glycoproteins and glycolipids, which eventually leads to dysfunction in all tissue systems and presents with multiple symptoms. Fucosidosis is a rare disease which is approximately 120 cases have been reported worldwide (Wang, L. et al., J Int Med Res 48, 1-6, 2020). The number of reported cases in China is no more than 10 (Zhang, X. et al., J Int Med Res 49:3000605211005975, 2021). CASE PRESENTATION: The patient was an 8-year-old Chinese boy who presented with postnatal motor retardation, intellectual disability, short stature, language development retardation, coarse facial features, hepatomegaly, and diffuse angiokeratoma of both palms. His genetic testing showed the presence of a homozygous pathogenic variant (c.671delC) in the FUCA1 gene. In addition, the enzymatic activity of α-L-fucosidase was low. Ultimately, the patient was diagnosed with fucosidosis. CONCLUSIONS: Fucosidosis is a rare lysosomal storage disease because of FUCA1 variants that cause the deficiency of α-L-fucosidase in vivo. An explicit diagnosis requires a combination of clinical manifestations, imaging examination, genetic testing and enzyme activity analysis. Early diagnosis plays an important role in fucosidosis.
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Fucosidose , Povo Asiático , Criança , Fucosidose/diagnóstico , Fucosidose/genética , Homozigoto , Humanos , Masculino , Mutação , alfa-L-Fucosidase/genéticaRESUMO
Background: Postoperative ileus after colorectal surgery is a frequent problem that significantly delays recovery, increases perioperative costs, and negatively impacts on daily life, physical and psychosocial functioning, and wellbeing. We investigated the effect of acupuncture at different single acupoint combined with standard care on postoperative ileus. Methods: In this single-centre, three-arm, prospective, randomised trial, we enrolled patients with primary colorectal cancer undergoing elective colorectal resection at Cancer Hospital Chinese Academy of Medical Science in Beijing, China. Patients were randomly assigned (1:1:1) to receive either electroacupuncture (EA) at ST36 or ST25 combined with standard care (two EA groups) once daily from post-operative days 1-4, or standard care alone (standard care group). The co-primary outcomes were time to first flatus and time to defecation assessed in the intention-to-treat population. This study is registered with Chictr.org.cn, ChiCTR1900027466. Finding: Between Nov 15, 2019, and Sep 30, 2020, 129 patients were assessed for eligibility, 105 patients (35 patients per group) were enrolled and included in the intention-to-treat analysis. After receiving EA at ST36, the time to first flatus and defecation were shorter (between-group difference -10.98 [97.5% CI -21.41 to -0.56], p = 0·02 for flatus; -25.41 [-47.89 to -2.93], p = 0·02 for defecation). However, we did not observe a significant difference in time to first flatus and defecation between the EA at ST25 group and standard care group (between-group difference -5.54 [97.5% CI -15.78 to 4.70], p = 0·26 for flatus; -17.69 [-40.33 to 4.95], p = 0·08 for defecation). There were no serious adverse events. Interpretation: Compared with standard care alone, standard care combined with EA at ST36, but not ST25, significantly enhances bowel function recovery in a postoperative setting to patients with colorectal cancer with laparoscopic elective colorectal resection. Funding: The National Key R&D Program of China (No: 2019YFC1712100) and the National Science Fund for Distinguished Young Scholars (No:81825024).
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Mycoplasma hyorhinis is a common pathogen of swine and is also associated with various human tumors. It causes systemic inflammation, typically polyserositis and polyarthritis, in some infected pigs. However, the pathogenic mechanism of M. hyorhinis remains unclear. DnaK is a highly conserved protein belonging to the heat-shock protein 70 family of molecular chaperones, which plays important roles as a moonlighting protein in various bacteria. In the present study, we identified the surface exposure of M. hyorhinis DnaK. Two virulent strains expressed more DnaK on their surface than the avirulent strain. Thereafter, the potential moonlighting functions of DnaK were investigated. Recombinant M. hyorhinis DnaK (rMhr-DnaK) was found to be able to adhere to swine PK-15 cells and human NCI-H292 cells. It also bound to four extracellular matrix components-fibronectin, laminin, type IV collagen, and vitronectin-in a dose-dependent manner. ELISA demonstrated an interaction between rMhr-DnaK and plasminogen, which was significantly inhibited by a lysine analog, ε-aminocaproic acid. rMhr-DnaK-bound plasminogen was activated by tissue-type plasminogen activator (tPA), and the addition of rMhr-DnaK significantly enhanced the activation. Finally, a DnaK-specific antibody was detected in the serum of pigs immunized with inactivated vaccines, which indicated good immunogenicity of it. In summary, our findings imply that DnaK is an important multifunctional moonlighting protein in M. hyorhinis and likely participates extensively in the infection and pathogenesis processes of M. hyorhinis.
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This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between ß-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. ß-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that ß-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.
Assuntos
Ganoderma , Medicina Tradicional Chinesa , Neoplasias Gástricas , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genéticaRESUMO
OBJECTIVE: To evaluate the placement feasibility and safety of the newly designed retropharyngeal reduction plate by cadaveric test and to perform morphometric trajectory analysis. METHODS: The five cadaveric specimens with intact atlantoaxial joint were enrolled in this study. They were used for simulating the placement process and evaluating the placement feasibility of the retropharyngeal reduction plate. The atlantoaxial dislocation (AAD) of five cadaveric specimens were obtained by proper external force after dissecting ligaments. The retropharyngeal reduction plate was placed on atlantoaxial joint of cadaveric specimens. The X-ray and three-dimensional (3D) spiral CT were used for evaluating the placement safety of retropharyngeal reduction plate. The DICOM data was obtained after 3D spiral CT scanning for the morphometric trajectory analysis. RESULTS: The reduction plates were successfully placed on the atlantoaxial joint of five cadaveric specimens through the retropharyngeal approach, respectively. The X-ray and 3D spiral CT showed the accurate screw implantation and satisfying plate placement. The length of the left/right atlas screw trajectory (L/RAT) was, respectively, 1.73 ± 0.01 cm (LAT) and 1.71 ± 0.02 cm (RAT). The length of odontoid screw trajectory (OST) was 1.38 ± 0.02 cm. The length of the left/right axis screw trajectory (L/RAXT) was, respectively, 1.67 ± 0.02 cm (LAXT) and 1.67 ± 0.01 cm (RAXT). There was no statistical significance between left side and right side in terms of AT and AXT (P > 0.05). The angles of atlas screw trajectory angle (ASTA), axis screw trajectory angle (AXSTA), and odontoid screw trajectory angle (OSTA) were 38.04° ± 2.03°, 56.92° ± 2.66°, and 34.78° ± 2.87°, respectively. CONCLUSION: The cadaveric test showed that the retropharyngeal reduction plate is feasible to place on the atlantoaxial joint, which is also a safe treatment choice for atlantoaxial dislocation. The meticulous preoperative planning of screw trajectory based on individual differences was also vital to using this technique.
Assuntos
Articulação Atlantoaxial , Luxações Articulares , Fusão Vertebral , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/cirurgia , Placas Ósseas , Parafusos Ósseos , Cadáver , Humanos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Mycoplasma hyorhinis (Mhr) infects pigs, typically causing polyserositis and polyarthritis. It has also been reported in various human tumors. The variable lipoprotein (Vlp) family is a vital surface component mediating the immune evasion of Mhr. We have previously reported its functions in the adherence of Mhr to pig cells. Herein, we further evaluated its role in interacting with host extracellular matrix (ECM) components (fibronectin, collagen type â £ and laminin) and plasminogen. Consequently, the recombinant Vlp proteins of all the seven members (VlpA-VlpG) were able to bind most of the tested host molecules. Further experiment showed that region â ¡ of all Vlp members has a strong binding ability, while the binding ability of region â ¢ of each member varied between different host molecules. Comparing the Vlps containing short (rVlpX3) or long (rVlpX12) region â ¢, we found that the ability of most Vlps binding NCI-H292 cell membrane proteins became weaker as the molecule grows, except VlpG. However, the binding of VlpA, VlpB, VlpC and VlpG to tested ECM components and plasminogen tended to increase as Vlps became longer, and those of VlpE and VlpF decreased, and that of VlpD did not change. Furthermore, the activation of Vlp-bound plasminogen was proved. In summary, the Vlp family participates in the interaction of Mhr with host ECM and plasminogen in addition to cytoadhesion. The size variation of Vlps is likely to further regulate these interactions. The results may help to elucidate the roles of Vlps in the persistent infection of Mhr.
Assuntos
Mycoplasma hyorhinis , Animais , Matriz Extracelular/metabolismo , Lipoproteínas/genética , Mycoplasma hyorhinis/genética , Plasminogênio/metabolismo , Proteínas Recombinantes , SuínosRESUMO
OBJECTIVE: To investigate the efficacy of bevacizumab, paclitaxel and carboplatin in the treatment of ovarian cancer (OC) and the impact on patients' prognosis. METHODS: A total of 90 patients with OC treated at our institution were enrolled in this retrospective analysis. Among them, 30 patients treated with bevacizumab plus paclitaxel and carboplatin regimen were classified as an observation group (OG), and 60 other patients who received paclitaxel and carboplatin were assigned as a control group (CG). The changes of carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA) and carcinoembryonic antigen 242 (CA242) were observed before and after treatment in both groups. The clinical efficacy was observed, and the patients were followed up for 3 years to observe their survival and the adverse effects. Independent factors affecting patient's prognosis were evaluated by Cox regression analysis. RESULTS: After treatment, the objective remission rate and disease control rate were markedly higher in the OG than those in the CG (P<0.05). The serum CA199, CEA and CA242 levels of patients in the OG were dramatically lower than those in the CG after chemotherapy (P<0.05). There was no statistically significant difference in the incidence of leukopenia, hemoglobin reduction, neutropenia, gastrointestinal reactions, abnormal renal function and abnormal liver function between the two groups (P>0.05). Cox regression analysis identified that the degree of differentiation, International Federation of Gynecology and Obstetrics stage, CA199 and treatment regimen were independent factors affecting the prognosis of patients (P<0.05). CONCLUSION: Combined treatment of bevacizumab plus paclitaxel and carboplatin improved the treatment outcome and reduced the levels of CA199, CEA and CA242 in OC without increasing the incidence of adverse events.