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Circular RNAs (circRNAs) have emerged as essential regulators in cardiovascular disease, including acute myocardial infarction (AMI). This study investigated the role of circRNA Pum1_0014 in myocardial infarction (MI) and its underlying mechanisms using an H9C2 cell model. Through Sanger sequencing, nucleic acid electrophoresis, RNase R, and transcriptional inhibition experiments, Pum1_0014 was identified as a novel circRNA. The cell localization of circRNA Pum1_0014 was detected by qPCR and fluorescence in situ hybridization, and the results revealed that circRNA Pum1_0014 is predominantly located in the cytoplasm. StarBase (URL: http://starbase.sysu.edu.cn/) and TargetScan (URL: https://www.targetscan.org/vert_80/) were used to predict circRNA Pum1_0014 targeting miRNAs and miRNA targeting mRNA, and the results identified miR-146a-5p as a potential target of Pum1_0014, which in turn targets NF2. The plasmid encoding the mutant circRNA Pum1_0014 or the 3'UTR mutant NF2 was constructed, and the interaction between Pum1_0014 and miR-146a-5p or miR-146a-5p and NF2 was detected by luciferase reporter gene assay. The results confirmed the interactions between Pum1_0014, miR-146a-5p, and NF2. In the MI cell model, upregulation of circRNA Pum1_0014 and NF2 and downregulation of miR-146a-5p were observed. Knockdown of circRNA Pum1_0014 inhibited NF2 expression and activated the VEGF/PAK1 pathway, reducing cardiomyocyte apoptosis. Conversely, inhibition of miR-146a-5p and overexpression of NF2 had opposite effects. These findings suggest that circRNA Pum1_0014 acts through the miR-146a-5p/NF2 axis to reduce cardiomyocyte apoptosis in MI via the VEGF/PAK1/NF2 pathway.
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Exosomes of different origins have been found to be protective against ischemic-induced myocardial injury. This study examined the protective effects of circulating exosomes in the mice model of acute myocardial infarction (AMI) and explored the underlying molecular mechanisms. The effects of exosomes on myocardial injury were assessed in the AMI mice model. The in vivo studies showed that circulating exosomes reduced the infarcted size, improved the morphology of heart tissues and also reduced apoptosis of the heart tissues. In addition, the model mice showed an increase in the CD34 + /VEGFR2 + cell population and CD31, CXCR4 and CXCL12 expression after exosomes treatment. MiR-190a-3p was significantly down-regulated in the exosomes derived from the culture medium of hypoxia-treated human cardiomyocytes (HCMs). Further analysis revealed that miR-190a-3p could physically interact with CXCR4/CXCL12 by targeting the respective 3'UTRs. These exosomes could up-regulated CXCR4 and CXCL12 expression in the EPCs; in addition, miR-190a-3p mimics repressed CXCR4/CXCL12 expression in EPCs, while its inhibitor had opposite effects. The in vitro functional assays showed that miR-190a-3p overexpression suppressed the cell viability, proliferation, migration, adhesion and tube formation of EPCs; while miR-190a-3p inhibitor had the opposite effects; exosomes derived from the culture medium of hypoxia-treated HCMs exhibited similar actions of miR-190a-3p inhibitor. Moreover, miR-190a-3p was down-regulated in exosomes from serum in the AMI group when compared to that from sham group. Treatment with exosomes from serum in the AMI group promoted cell proliferation, migration, adhesion and tube formation of EPCs when compared to that in the sham group. More importantly, IT1t attenuated the enhanced effects of miR-190a-3p inhibition on EPC proliferation, migration, adhesion and tube formation. In conclusion, circulating exosomes exerted protective effects on myocardial injury in the AMI mice model, and down-regulation of miR-190a-3p in the circulating exosomes may exert protective effects against myocardial injury. Hypoxia induced the downregulation of miR-190a-3p in the culture medium of HCMs, and the mechanistic investigations indicated that exosomes of hypoxia-conditioned HCM culture medium promoted the cell viability, proliferation, migration, adhesion and tube formation of EPCs via regulating miR-190a-3p/CXCR4/CXCL12 pathway.
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Exossomos , MicroRNAs , Infarto do Miocárdio , Animais , Humanos , Camundongos , Regiões 3' não Traduzidas , Apoptose , Quimiocina CXCL12/metabolismo , Exossomos/metabolismo , Hipóxia/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Receptores CXCR4/metabolismoRESUMO
PURPOSE: To investigate the puncture accuracy and feasibility of contrast-enhanced ultrasound (CEUS) guided percutaneous nephrolithotomy (PCNL) in flank position for patients with no apparent hydronephrosis. METHODS: Between May 2018 and June 2020, 72 kidney stone patients with no or mild hydronephrosis were randomized into two groups: a CEUS-guided PCNL group and a conventional ultrasound (US)-guided group. Patients' demographics and perioperative outcomes were compared, including the success rate of puncture via calyceal fornix, the success rate of a single-needle puncture, puncture time, operative time, postoperative hemoglobin loss, stone-free rate, incidence of complications and postoperative stay. RESULTS: The success rate of puncture via calyceal fornix for CEUS-guided group was significantly higher than that for conventional US-guided group (86.1 vs. 47.2%, p = 0.002). Patients performed with CEUS-guided PCNL required shorter renal puncture time than those guided with conventional US (36.5 s vs. 61.0 s, p < 0.001). The median postoperative hemoglobin loss in the CEUS-guided group was significantly lower than that in conventional US-guided group (2.5 vs. 14.5 g/L, p < 0.01). There was no statistically significant difference in the success rate of a single-needle puncture, operative time, stone-free rate, incidence of complications and postoperative stay between the two groups. CONCLUSION: CEUS guidance facilitates identification of the renal calyx fornix, and benefits more precise renal puncture and less hemoglobin loss in PCNL. CEUS-guided PCNL in flank position is a feasible approach to the treatment of kidney stone patients with no apparent hydronephrosis. TRIAL REGISTRATION NUMBER: ChiCTR1800015417.
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Hidronefrose , Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Estudos de Viabilidade , Humanos , Hidronefrose/diagnóstico por imagem , Hidronefrose/cirurgia , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/cirurgia , Resultado do TratamentoRESUMO
AIMS: Various mycophenolate mofetil (MMF) population pharmacokinetic (popPK) models have been developed to describe its PK characteristics and facilitate its optimal dosing in adult kidney transplant recipients co-administered with tacrolimus. However, the external predictive performance has been unclear. Thus, this study aimed to comprehensively evaluate the external predictability of published MMF popPK models in such populations and investigate the potential influencing factors. METHODS: The external predictability of qualified popPK models was evaluated using an independent dataset. The evaluation included prediction- and simulation-based diagnostics, and Bayesian forecasting. In addition, factors influencing model predictability, especially the impact of structural models, were investigated. RESULTS: Fifty full PK profiles from 45 patients were included in the evaluation dataset and 11 published popPK models were identified and evaluated. In prediction-based diagnostics, the prediction error within ±30% was less than 50% in most published models. The prediction- and variability-corrected visual predictive check and posterior predictive check showed large discrepancies between the observations and simulations in most models. Moreover, the normalized prediction distribution errors of all models did not follow a normal distribution. Bayesian forecasting demonstrated an improvement in the model predictability. Furthermore, the predictive performance of two-compartment (2CMT) models incorporating the enterohepatic circulation (EHC) process was not superior to that of conventional 2CMT models. CONCLUSIONS: The published models showed large variability and unsatisfactory predictive performance, which indicated that therapeutic drug monitoring was necessary for MMF clinical application. Further studies incorporating potential covariates need to be conducted to investigate the key factors influencing model predictability of MMF.
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Rejeição de Enxerto/prevenção & controle , Imunossupressores/farmacocinética , Transplante de Rim/efeitos adversos , Modelos Biológicos , Ácido Micofenólico/farmacocinética , Tacrolimo/farmacocinética , Adulto , Idoso , Área Sob a Curva , Conjuntos de Dados como Assunto , Relação Dose-Resposta a Droga , Interações Medicamentosas , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Tacrolimo/administração & dosagem , Adulto JovemRESUMO
Kangfu Xiaoyan Suppository is widely used in the treatment of gynecological inflammatory diseases. Long-term clinical application and a certain amount of research evidences show that Kangfu Xiaoyan Suppository can alleviate the clinical symptoms of pelvic inflammatory diseases,reduce the recurrence rate,and relieve sequelae,with a better safety and economic characteristics. As a type of nationally protected traditional Chinese medicine and type B medicine included in medical insurance,it has been selected as a Chinese patent medicine for rectal administration. It was included in the Guidelines for diagnosis and treatment of common gynecological diseases of traditional Chinese medicine published by the Chinese Academy of Traditional Chinese Medicine in 2012,the Pelvic inflammatory diseases diagnosis and treatment guidelines issued by the Infectious Diseases Collaborative Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association in 2014,and the group standard of Single use of traditional Chinese medicine/combined antibiot guidelines for clinical practice-pelvic inflammatory diseases of the Chinese Academy of Traditional Chinese Medicine in 2017. To further enhance clinicians' understanding of the drug and better guide its rational clinical use,experts from the field of gynecology of traditional Chinese and Western medicine were invited to develop and compile this expert consensus. This consensus takes full account of clinical evidences and expert clinical experience,and form recommendations for clinical problems based on evidences and consensus recommendations for clinical problems without evidence by nominal grouping method. The expert consensus is mainly formed in the consideration of six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on clinical research evidences and expert experience,this consensus provides a preliminary reference for the clinical use of the drug in a concise and clear format. However,evidence-based support is still required in a large number of high-quality studies,and this consensus will be revised in the future according to new clinical problems and the update of evidence-based evidence in practical application.
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Consenso , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Doença Inflamatória Pélvica/tratamento farmacológico , Feminino , Humanos , Medicamentos sem Prescrição , SupositóriosRESUMO
UNLABELLED: Virus-induced hepatocarcinogenesis involves a series of histological developmental processes with the stepwise acquisition of several genetic changes that are necessary for the malignant transformation of hepatocytes. Although genetic alterations are known to be involved in the pathogenesis of hepatocellular carcinoma (HCC), little is known about the contributions of specific genes to this process. To gain insight into the genetic alterations involved in the neoplastic evolution from chronic hepatitis B virus infection to dysplastic nodules (DN) to HCC, we captured and sequenced the exomes of four DNA samples: one DN sample, two HCC samples, and one control peripheral blood sample from a single HCC patient. Mutations in the UBE3C gene (encoding ubiquitin ligase E3C) were observed in both tumor tissues. Then we resequenced the UBE3C gene in a cohort of 105 HCC patients and identified mutations in 17 out of a total of 106 (16.0%) HCC patients. The subsequent experiments showed that UBE3C promoted HCC progression by regulating HCC cells epithelial-mesenchymal transition. Clinically, a tissue microarray study of a cohort containing 323 HCC patients revealed that the overexpression of UBE3C in primary HCC tissues correlated with decreased survival (hazard ratio [HR] =1.657, 95% confidence interval [CI] =1.220-2.251, P=0.001) and early tumor recurrence (HR=1.653, 95% CI=1.227-2.228, P=0.001) in postoperative HCC patients. CONCLUSION: Our findings indicate that UBE3C is a candidate oncogene involved in tumor development and progression and therefore a potential therapeutic target in applicable HCC patients.
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Carcinoma Hepatocelular/etiologia , Exoma/genética , Hepatite B Crônica/complicações , Neoplasias Hepáticas/etiologia , Ubiquitina-Proteína Ligases/genética , Substituição de Aminoácidos/genética , Carcinogênese/genética , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Hepatite B Crônica/enzimologia , Hepatite B Crônica/patologia , Humanos , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação/genética , Análise de Sequência com Séries de Oligonucleotídeos , Oncogenes/genética , Prognóstico , Análise de Sequência de DNA , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Hepatoma-derived growth factor (HDGF) is an acidic heparin-binding protein involved in tumor progression and poor prognosis of kinds of cancers. Aimed at investigating the functions of HDGF in intrahepatic cholangiocarcinoma (IHCC), we detected the expression of HDGF by immunohistochemistry in 83 patients. Associations of HDGF with clinicopathologic features, microvascular density (MVD), and overall survival rates were further analyzed by Chi-square method, univariate or multivariate analysis. HDGF functions in IHCC proliferation, invasion, and angiogenesis were detected by MTT, transwell, and tube formation assays, respectively. As a result, we found that HDGF-positive expression rate in IHCC was 51.8 % (43/83) in IHCC. HDGF expression was significantly correlated to MVD (P = 0.031), lymphatic invasion (P = 0.030), distant metastasis (P = 0.002), and TNM stage (P = 0.037). HDGF was further identified as an independent prognostic factor in IHCC with Kaplan-Meier method (P = 0.003) and Cox-regression model (P = 0.008). Moreover, both intracellular and extracellular HDGF were proved to promote the proliferation, invasion, and angiogenesis of IHCC cell lines. In conclusion, HDGF was identified as an independent prognostic biomarker in IHCC. HDGF can promote IHCC cells progression, including proliferation, invasion, and angiogenesis, indicating HDGF could become a new promising and potential drug target of IHCC.
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Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Adulto , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Progressão da Doença , Feminino , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Estimativa de Kaplan-Meier , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
OBJECTIVE: The multi-center, randomized, double-blind, double-simulated and positive-control trial was used to verify the contribution degree of Bushen Huoxue for the treatment of ovulatory dysfunction caused infertility, which provided scientific basis for clinical treatment. METHOD: According to diagnostic, inclusion and exclusion criteria, we observed 349 patients which were divided into the treated group (n = 177, treated with Bushen Huoxue ricipe) and control group (n = 172, treated with clomiphene). Ovulation rate, pregnancy rate, clinical effective rate of traditional Chinese medicine, endometrium and diameter of dominant follicle were observed. Serum reproductive endocrine hormones were assayed before and after treatment. RESULT: The treated group showed ovulation rate of 69.34%, with pregnancy rate of 41.35%. The clinical effective rate of treated group and control group were 91.73% and 80.77%. There was remarkable difference in endometrium (P < 0.05) and remarkbale difference in sex hormones PRL and E2in treated group at prior-treatment and post-treatment (P < 0.05). No adverse effects were found in the experiment. Security indicators did not show abnormal change. CONCLUSION: The comparison between the two groups showed that the treated group was significantly different from control group in the pregnancy rate (P < 0.05), without notable difference in ovulation rate. There was significant difference in clinical effective rate between the treated group and control group. Both the two groups could contribute to the mature development and discharge of the follicles. The growth of endometrium and endometrial receptivity in the treated group were higher than control group. The treated group has regulatory effect on PRL and E2.
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Medicamentos de Ervas Chinesas/administração & dosagem , Fármacos para a Fertilidade Feminina/administração & dosagem , Infertilidade Feminina/tratamento farmacológico , Adulto , Método Duplo-Cego , Feminino , Humanos , Infertilidade Feminina/fisiopatologia , Ovário/efeitos dos fármacos , Ovário/fisiopatologia , Ovulação/efeitos dos fármacos , Gravidez , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: From the anal function, inflammatory response and other indicators, acupuncture combined with rehabilitation gymnastics was applied to patients with cancer undergoing low resection, aiming to improve the prognosis of patients. AIM: To explore the effects of acupuncture combined with rehabilitation gymnastics on anal function after lower rectal cancer surgery. METHODS: From January 2020 to December 2022, 128 patients who underwent rectal cancer surgery in the Department of Oncology of Hebei Provincial Hospital of Traditional Chinese Medicine Hospital were selected and divided into two groups using the random number table method, with 64 patients in each group. Patients in the control group were not treated with acupuncture or rehabilitation gymnastics and served as blank controls. Patients in the study group were treated with acupuncture and rehabilitation gymnastics from the 7th postoperative day. The anal incontinence scores, changes in serum interleukin-4, interleukin-6, and interleukin-10 Levels, and serum motilin, 5-hydroxytryptamine, and vasoactive intestinal peptide levels were compared. RESULTS: There were no significant differences in serum interleukin-4, interleukin-6, and interleukin-10 Levels between the groups before treatment (P > 0.05). After treatment, these levels were better than those of the control group (P < 0.05). There was no significant difference in the anal incontinence scores between the groups before and 7 d after surgery (P > 0.05). Anal incontinence scores in the study group were lower than those in the control group at 14 d, 21 d, and 28 d postoperatively (P < 0.05). There were no significant differences in serum motilin, 5-hydroxytryptamine, or vasoactive intestinal peptide levels between the groups before treatment (P > 0.05). After treatment, these levels were higher in the study group than in the control group, and vasoactive intestinal peptide level was lower in the study group than in the control group (P < 0.05). CONCLUSION: Acupuncture combined with rehabilitation gymnastics can promote the recovery of anal function and reduce the inflammatory response in patients with lower rectal cancer after surgery.
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BACKGROUND: According to the indexes of serum and anal function, acupuncture therapy was applied to patients with low rectal cancer in order to avoid the occurrence of anal incontinence and reduce complications. AIM: To explore the clinical application and evaluate the effect of acupuncture therapy for anal function rehabilitation after low-tension rectal cancer surgery. METHODS: From the anorectal surgery cases, we selected 120 patients who underwent colorectal cancer surgery between January 2020 and December 2022 and randomly divided them into a control group (n = 60), observation group (n = 60), and control group after surgery for lifestyle intervention (including smoking cessation and exercise), dietary factor adjustment, anal movement, and oral loperamide treatment. The serum levels of motilin, 5-hydroxytryptamine, and vasoactive intestinal peptide (VIP), Wexner score for anal incontinence, and incidence of complications were compared between groups. RESULTS: After treatment, the VIP and 5-hydroxytryptamine levels in the observation group were lower than those in the control group (P < 0.05). The motilin level was higher than that in the control group (P < 0.05). Postoperative anal incontinence was better in the observation group than in the control group (P < 0.05). The incidence of complications in the observation group was 6.67%, which was significantly lower than that in the control group (21.67%; P < 0.05). CONCLUSION: Acupuncture therapy has a positive effect on the rehabilitation of anal function after low-tension rectal cancer surgery; it can effectively help to improve the serum indices of patients, avoid the occurrence of anal incontinence, and reduce the incidence of complications. Popularizing and applying it will be valuable.
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BACKGROUND: Surgical site infection (SSI) is the prevailing complication that occurs after surgery and significantly escalates healthcare expenses. Published meta-analyses and international standards vary in their recommendations for the most effective preoperative skin antiseptic solution and concentration. OBJECTIVE: The aim of this systematic review and meta-analysis is to assess the effectiveness of Chlorhexidine-alcohol compared to Aqueous/alcoholic iodine solutions in preventing post-operative surgical site infections. METHODS: A systematic search was conducted using four electronic databases (PubMed, EMBASE, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals. The risk ratio (RR) was calculated, along with their 95% confidence intervals. We assessed heterogeneity using Cochrane Q and I2 statistics and the appropriate P-value. The analysis used RevMan 5.4. RESULTS: The current meta-analysis includes 14 Randomized controlled trials (RCTs) comparing either 2-2.5% chlorhexidine alcohol with aqueous/alcoholic iodine. It was demonstrated that the CAG-using group had an overall lower incidence of post-operative surgical site infections compared to the iodine-using group (RR=0.30, 95% CI=0.20 to 0.46, I2=95%, P<0.00001). It exhibits comparable efficacy across various surgical procedures, as evidenced by its RR of 0.25 [95% CI 0.15 to 0.41], I2=51%, and P<0.0001 for general surgery, RR=0.47 [95% CI 0.32 to 0.67], I2=82%, P=0.0002 for caesarean section and RR of 0.47 [95% CI 0.34 to 0.65], I2=76% and P<0.00001 for additional surgical procedures, including neurosurgery, orthopedic surgery etc. CONCLUSION: This meta-analysis suggests using either 2·0-2·5% Chlorhexidine in alcohol instead of aqueous, alcoholic iodine to prevent SSIs in adult patients undergoing surgery. Chlorhexidine in alcohol worked effectively for general surgery, cesarean sections, and other surgeries. Thus, preoperative skin cleansing with Chlorhexidine alcohol minimizes postoperative SSIs and bacterial colonization in diverse procedures.
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BACKGROUND: SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting (SWI/SNF) complexes and plays an essential role in oncogenesis. SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis. There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies. Programmed death 1 (PD-1) antibodies, known as immune checkpoint inhibitor antibodies, potentially play a role in treating gastrointestinal tract malignancies. CASE SUMMARY: We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum. For both patients, SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein, while TP53 gene mutations were observed via next-generation sequencing. Both patients were administered chemotherapy in combination with an anti-PD-1 antibody. The two patients exhibited completely different responses to treatment and had different prognoses. Case 1 experienced rapid progression after PD-1 infusion and chemotherapy, case 2 experienced a remarkable response after treatment, and the progression-free survival was more than 6 months. CONCLUSION: This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum. PD-1 combined with chemotherapy showed a certain efficacy in select patients, providing options for treating these highly malignant tumors. Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.
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BACKGROUND: Diabetic cardiomyopathy (DCM), which is a complication of diabetes, poses a great threat to public health. Recent studies have confirmed the role of NLRP3 (NOD-like receptor protein 3) activation in DCM development through the inflammatory response. Teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes. Teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells. AIM: To examine the therapeutic effects of teneligliptin on DCM in diabetic mice. METHODS: Streptozotocin was administered to induce diabetes in mice, followed by treatment with 30 mg/kg teneligliptin. RESULTS: Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening, ejection fraction, and heart rate; increases in creatine kinase-MB (CK-MB), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels; and upregulated NADPH oxidase 4 were observed in diabetic mice, all of which were significantly reversed by teneligliptin. Moreover, NLRP3 inflammasome activation and increased release of interleukin-1ß in diabetic mice were inhibited by teneligliptin. Primary mouse cardiomyocytes were treated with high glucose (30 mmol/L) with or without teneligliptin (2.5 or 5 µM) for 24 h. NLRP3 inflammasome activation. Increases in CK-MB, AST, and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin, and AMP (p-adenosine 5'-monophosphate)-p-AMPK (activated protein kinase) levels were increased. Furthermore, the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C. CONCLUSION: Overall, teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.
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BACKGROUND: Vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 play important roles in tumor angiogenesis, development, and progression. This study investigates the expression of VEGF combined with MMP-9, their correlation with clinical characteristics, and their effect on the prognosis for patients with pN0 gastric cancer after curative surgery. METHODS: A total of 55 patients were enrolled in the study. They were analyzed by immunohistochemistry, and their correlation with clinical characteristics was then investigated. Their relations and the survival time of patients were retrospectively analyzed. RESULTS: VEGF and MMP-9 were positively expressed in 24 (43.6%) and 16 (29.1%) patients, respectively, and had a positive correlation (r = 0.324, p = 0.016) in the Spearman rank correlation analysis. Univariate analysis showed that VEGF, MMP-9 expression, vascular invasion, T stage, and tumor size were associated with tumor recurrence as well as the disease-specific (DSS) and overall (OS) survival rates. Patients with positive VEGF expression showed significantly higher recurrence and poorer DSS and OS rates compared with those with negative VEGF expression. Multivariate analysis showed that VEGF expression, vascular invasion, T stage (serosal invasion), and tumor size were significant independent prognostic factors for tumor recurrence, DSS, and OS in patients with pN0 gastric cancer with the exception that T stage was not for DSS. CONCLUSIONS: VEGF expression, vascular invasion, T stage (serosal invasion), and tumor size can be used as valuable prognosticators in predicting tumor recurrence and prognosis for patients with pN0 gastric cancer after curative surgery. VEGF may have a synergistic effect with MMP-9 during tumor angiogenesis, development, and progression.
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Biomarcadores Tumorais/metabolismo , Neoplasias Gástricas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Gastrectomia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de SobrevidaRESUMO
Objective: Infection is the most common complication and cause of death after hematopoietic stem cell transplantation (HSCT). Our study aims to investigate the clinical characteristics and risk factors for death of Klebsiella pneumoniae infections in HSCT recipients, so as to provide evidence for guiding antibiotic use and improving prognosis in the future. Methods: The epidemiology, clinical manifestations and drug resistance rate with K. pneumoniae infections among HSCT recipients between January 1, 2012 and September 30, 2021 were retrospectively reviewed. Logistic regression model and Cox regression model were respectively used to determine the risk factors for carbapenem-resistant Klebsiella pneumoniae (CRKP) acquisition and death. Results: Fifty-nine HSCT recipients suffered from K. pneumoniae infections, with a mortality rate of 42.4%. The most common site was lung, followed by blood stream. The resistance rate of K. pneumoniae to various clinically common antibiotics was high, especially CRKP, which was only sensitive to amikacin and tigecycline. Independent risk factor for CPKP acquisition was a previous infection within 3 months before transplantation (OR=10.981, 95% CI 1.474-81.809, P=0.019). Independent risk factors for mortality included interval from diagnosis to transplantation > 180 days (HR=3.963, 95% CI 1.25-12.561, P=0.019), engraftment period > 20 days (HR=8.015, 95% CI 2.355-27.279, P=0.001), non-use of anti-CMV immunoglobulin/rituximab after transplantation (HR=10.720, 95% CI 2.390-48.089, P=0.002), and PCT > 5 µg/L (HR=5.906, 95% CI 1.623-21.500, P=0.007). Conclusion: K. pneumoniae infection has become a serious threat for HSCT recipients, which reminds us to pay enough attention and actively seek new strategies.
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BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is malignancies of the biliary duct system and constitutes approximately 10%-20% of all primary liver cancers. Tumor mutation burden (TMB) is a useful biomarker across many cancer types for the identification of patients who will benefit from immunotherapy. Despite the role of TMB in calculating the effectiveness and prognosis of immune checkpoint inhibitors has been confirmed in multiple human cancer types, the prognostic value of TMB in ICC patients is rare investigated. AIM: To investigate the prognostic value of TMB in patients with ICC. METHODS: Data of 412 patients with ICC were included in the study. TMB was calculated as the total number of somatic non-silent protein-coding mutations divided by the coding region. The Kaplan-Meier method was used to analyze overall survival (OS), and relapse free survival (RFS). The cut-off value of TMB was determined by time-dependent receiver operating characteristic (ROC) curve. Cox regression was performed for multivariable analysis of OS. The nomogram and calibration curve were analyzed to construct and evaluate the prognostic model. RESULTS: In the analysis of the time-dependent ROC curve, we defined 3.1 mut/Mb as the cut-off value of TMB. The Kaplan-Meier plot revealed that patients with high TMB had poor OS (HR = 1.47, P = 0.002) and RFS (HR = 1.42, P = 0.035). Cox regression analysis also demonstrated that TMB was an independent risk predictor for ICC (HR = 1.43, P = 0.0240). Furthermore, independent prognostic factors of ICC included CA19-9 (HR = 1.78, P = 0.0005), chronic viral hepatitis (HR = 1.72, P = 0.0468), tumor resection (HR = 2.58, P < 0.0001) and disease progression (metastatic disease vs. solitary liver tumor; HR = 2.55, P = 0.0002). The nomogram and calibration curve also indicated the effectiveness of the constructed prognostic model. CONCLUSION: TMB was an independent prognostic biomarker in patients with ICC. Moreover, patients with ICC with high TMB had poor OS and RFS as compared to those with low TMB.
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Blood purification therapy is widely used in patients with renal insufficiency and severe infections, where membrane-associated thrombosis is a side effect. How to improve the hemocompatibility of dialysis membranes and reduce thrombosis is a focus of current research, in which platelets play a key role. However, few dialysis membranes that directly inhibit platelets have been developed to date. In this study, a polyethersulfone (PES) membrane was modified with ticagrelor, a platelet P2Y12 receptor inhibitor, and detailed characterization was performed. The ticagrelor modified PES membrane (TMPES) showed good hydrophilicity and anti-protein adsorption and significantly inhibited platelet adhesion, aggregation, and activation, which demonstrated good antithrombotic properties. In addition, the membrane had excellent red blood cell (RBC) compatibility, anticoagulant, and antiinflammatory effects, which demonstrated superior biosafety in cell and animal experiments. Therefore, the TMPES dialysis membrane could have potential in clinical applications.
Assuntos
Membranas Artificiais , Trombose , Animais , Plaquetas/metabolismo , Humanos , Inibidores da Agregação Plaquetária/farmacologia , Polímeros , Diálise Renal , Sulfonas , Trombose/tratamento farmacológico , TicagrelorRESUMO
BACKGROUND: Pylorus and vagus nerve-preserving gastrectomy (PPG) is a function-preserving surgery for early gastric cancer (GC) that has gained considerable interest in the recent years. The operative technique performed using the Da Vinci Xi robot system is considered ideal for open and laparoscopic surgery. AIM: To introduce Da Vinci Xi robot-assisted PPG (RAPPG)-based operative procedure and technical points as well as report the initial experience based on the clinical pathology data of eight cases of early GC. METHODS: Da Vinci Xi robot-assisted pylorus and vagus nerve-preserving gastrectomy (RAPPG) was performed for 11 consecutive patients with middle GC from December 2020 to July 2021. Outcome measures were postoperative morbidity, operative time, blood loss, number of lymph nodes harvested, postoperative hospital stay, time to first flatus, time to diet, and resection margins. RESULTS: Eight of the 11 patients who were pathologically diagnosed with early GC were enrolled in a retrospective study to assess the feasibility and safety of RAPPG. The mean operative time, mean blood loss, mean number of lymph nodes harvested, length of preserved pylorus canal, distal margin, and proximal margin were 330.63 ± 47.24 min, 57.50 ± 37.70 mL, 18.63 ± 10.57, 3.63 ± 0.88 cm, 3.50 ± 1.31 cm, and 3.63 ± 1.19 cm, respectively. None of the cases required conversion to laparotomy. Postoperative complications occurred in two (25.0%) patients. Postoperative complications were hyperamylasemia and gastric stasis in one case and incision infection in the other. Time to first flatus was 3.75 ± 2.49 d after the operation, and postoperative hospital stay was 10.13 ± 4.55 d. CONCLUSION: The core technique in the Da Vinci Xi RAPPG is lymph node dissection and the anatomic method of the nerve. Robotic surgical procedures are feasible and safe. With the progress of surgical technology, optimization of medical insurance structure, and emergence of evidence-based medicine, automated surgery systems will have a broad application in clinical treatment.
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BRCA1-Associated Protein 1 (BAP1) is a deubiquitylase that is found associated with multiprotein complexes that regulate key cellular pathways, and subsequent researches have revealed that BAP1 acts independently as a tumor suppressor. Somatic BAP1 mutations occur in various malignancies, but malignancies arising from mutation of tumor suppressors have unexplained tissue proclivity. Whether somatic mutation or expression alteration of BAP1 in hepatocellular carcinoma (HCC) influence carcinogenesis or immunogenicity is still unknown. In this study, we analyzed RNA expression, immune infiltration, survival and mutation data of HCC from The Cancer Genome Atlas databases. The association between BAP1 and clinicopathological features was further investigated by immunohistochemistry on tissue microarray. We found that the prognosis of patients with high BAP1 expression was significantly worse than that of patients with low BAP1 expression, and multivariate analyses revealed that BAP1 expression was an independent prognostic factor for poor prognosis. HCC with high BAP1 expression was associated with low ESTIMATE Score, recruitment of more tumor-infiltrating macrophage, and elevated levels of tumor mutation burden, microsatellite instability, neoantigen count, as well as programmed death-ligand1 in HCC. In addition, BAP1 mutated HCC showed reduced ability to promote ferroptosis and high BAP1 expression was correlated with ferroptosis. In conclusion, high BAP1 expression reflects immunosuppression and ferroptosis in HCC. BAP1 is a promising prognostic marker for survival of HCC and may act as a complementary indicator for patients to receive ferroptosis-promoting therapy or immunotherapy.
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Growing evidence suggests that the bidirectional interactions between cancer cells and their surrounding environment, namely the tumor microenvironment (TME), contribute to cancer progression, metastasis, and resistance to treatment. Intense investigation of the Hippo pathway, which controls multiple central cellular functions in tumorigenesis, was focused on cancer cells. However, the role of the Hippo pathway in modulating tumor-stromal interactions in triple-negative breast cancer remains largely unknown. Therefore, this study focused on revealing the effects of Hippo-YAP/TAZ signaling on the immune microenvironment. Our findings reveal that the activity of the Hippo pathway is associated with worse disease outcomes in TNBC and could increase TAM infiltration through the TAZ/IL-34 axis, leading to an immunosuppressive microenvironment and impairing the treatment efficacy of anti-PD-L1. Thus, the TAZ/IL-34 axis may serve as a novel target for TNBC patients.