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Objective: To assess the prevalence, risk factors and treatment of anemia in patients with chronic kidney disease (CKD). Methods: A descriptive method was used to analyze the prevalence and treatment of anemia in CKD patients based on regional health data in Yinzhou District of Ningbo during 2012-2018. The multivariate logistic regression analysis was used to identify independent influence factors of anemia in the CKD patients. Results: In 52 619 CKD patients, 15 639 suffered from by anemia (29.72%), in whom 5 461 were men (26.41%) and 10 178 were women (31.87%), and anemia prevalence was higher in women than in men, the difference was significant (P<0.001). The prevalence of anemia increased with stage of CKD (24.77% in stage 1 vs. 69.42% in stage 5, trend χ2 test P<0.001). Multivariate logistic regression analysis revealed that being women (aOR=1.57, 95%CI: 1.50-1.63), CKD stage (stage 2: aOR=1.10, 95%CI: 1.04-1.16;stage 3: aOR=2.28,95%CI: 2.12-2.44;stage 4: aOR=4.49,95%CI :3.79-5.32;stage 5: aOR=6.31,95%CI: 4.74-8.39), age (18-30 years old: aOR=2.40,95%CI: 2.24-2.57, 61-75 years old: aOR=1.35,95%CI:1.28-1.42, ≥76 years old: aOR=2.37,95%CI:2.20-2.55), BMI (<18.5 kg/m2:aOR=1.29,95%CI: 1.18-1.41;23.0-24.9 kg/m2:aOR=0.79,95%CI: 0.75-0.83;≥25.0 kg/m2:aOR=0.70,95%CI: 0.66-0.74), abdominal obesity (aOR=0.91, 95%CI: 0.86-0.96), chronic obstructive pulmonary disease (aOR=1.15, 95%CI: 1.09-1.22), cancer (aOR=3.03, 95%CI: 2.84-3.23), heart failure (aOR=1.44, 95%CI: 1.35-1.54) and myocardial infarction (aOR=1.54, 95%CI:1.16-2.04) were independent risk factors of anemia in CKD patients. Among stage 3-5 CKD patients with anemia, 12.03% received iron therapy, and 4.78% received treatment with erythropoiesis-stimulating agent (ESA) within 12 months after anemia was diagnosed. Conclusions: The prevalence of anemia in CKD patients was high in Yinzhou. However, the treatment rate of iron therapy and ESA were low. More attention should be paid to the anemia management and treatment in CKD patients.
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Objective To investigate the role of glutathione transferase in nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet using the RNA-Seq technique in combination with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes. Methods A total of 14 male C57BL/6J mice were divided into control group with 6 mice and model group with 8 mice by random sampling. The mice in the control group were fed with normal diet, and those in the model group were fed with high-fat diet for 7 consecutive weeks to establish a model of NAFLD. Kits were used to measure the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the level of triglyceride (TG), and HE staining and oil red staining were used to observe liver pathology and deposition of lipid droplets. Liver tissue RNA was extracted for RNA-Seq, and genes with a fold change of ≥2.0 and a P value of 0.05). Compared with the control group, the model group had a significantly higher serum level of TG (2.02±0.50 mmol/L vs 1.00±0.29 mmol/L, t =-4.45, P =0.001). HE staining showed diffuse steatosis and ballooning degeneration in the model group, and oil red staining showed that the model group had a significant increase in orange-red lipid droplets in the cytoplasm of hepatocytes and a significantly higher grade of hepatocyte steatosis than the control group (1.88±0.64 vs 1.00±0.00, t =-3.86, P =0.006). RNA-seq results showed a total of 1367 differentially expressed genes between the two groups, among which there were 608 upregulated genes and 759 downregulated genes, and there were 17 differentially expressed GST genes between the two groups. The top 10 GST genes in terms of fold change were validated, and compared with the control group, the model group had downregulated expression of GSTa2, GSTa3, GSTa4, GSTm1, GSTm2, GSTm3, GSTm4, GSTp1, and GSTo1 and upregulated expression of GSTk1. The results of qRT-PCR were consistent with the results of sequencing. Conclusion GST affects lipid metabolism by participating in various biological processes such as steroid metabolism, fatty acid metabolism, and cholesterol metabolism and is closely associated with the pathogenesis of NAFLD.
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Objectives: To analyze the reasons of missed diagnosis or misdiagnosis on anomalous origin of left coronary artery from pulmonary artery (ALCAPA) by echocardiography. Methods: This is a retrospective study. Patients with ALCAPA who underwent surgical treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from August 2008 to December 2021 were included. According to the results of preoperative echocardiography and surgical diagnosis, the patients were divided into confirmed group or missed diagnosis/misdiagnosis group. The results of preoperative echocardiography were collected, and the specific echocardiographic signs were analyzed. According to the experience of the doctors, the echocardiographic signs were divided into four types, namely clear displayed, vague/doubtful displayed, no display and no notice, and the display rate of each sign was calculated (display rate=number of clearly displayed cases/total number of cases×100%). By referring the surgical data, we analyzed and recorded the pathological anatomy and pathophysiological characteristics of the patients, and the rate of missed diagnosis/misdiagnosis of echocardiography in patients with different characteristics was compared. Results: A total of 21 patients were enrolled, including 11 males, aged 1.8 (0.8, 12.3) years (range 1 month to 47 years). Except for one patient with anomalous origin of left anterior descending artery, the others were all originated from the main left coronary artery (LCA). There were 13 cases of ALCAPA in infant and children, and 8 cases of adult ALCAPA. There were 15 cases in the confirmed group (diagnostic accuracy was 71.4% (15/21)), and 6 cases in the missed diagnosis/misdiagnosis group (three cases were misdiagnosed as primary endocardial fibroelastosis, two cases were misdiagnosed as coronary-pulmonary artery fistula; and one case was missed diagnosis). The working years of the physicians in the confirmed group were longer than those in the missed diagnosis/misdiagnosed group ((12.8±5.6) years vs. (8.3±4.7) years, P=0.045). In infants with ALCAPA, the detection rate of LCA-pulmonary shunt (8/10 vs. 0, P=0.035) and coronary collateral circulation (7/10 vs. 0, P=0.042) in confirmed group was higher than that in missed diagnosis/misdiagnosed group. In adult ALCAPA patients, the detection rate of LCA-pulmonary artery shunt was higher in confirmed group than that in missed diagnosis/misdiagnosed group (4/5 vs. 0, P=0.021). The missed diagnosis/misdiagnosis rate of adult type was higher than that of infant type (3/8 vs. 3/13, P=0.410). The rate of missed diagnosis/misdiagnosis was higher in patients with abnormal origin of branches than that of abnormal origin of main trunk (1/1 vs. 5/21, P=0.028). The rate of missed diagnosis/misdiagnosis in patients with LCA running between the main and pulmonary arteries was higher than that distant from the main pulmonary artery septum (4/7 vs. 2/14, P=0.064). The rate of missed diagnosis/misdiagnosis in patients with severe pulmonary hypertension was higher than that in patients without severe pulmonary hypertension (2/3 vs. 4/18, P=0.184). The reasons with an echocardiography missed diagnosis/misdiagnosis rate of≥50% included that (1) the proximal segment of LCA ran between the main and pulmonary arteries; (2) abnormal opening of LCA at the right posterior part of the pulmonary artery; (3) abnormal origin of LCA branches; (4) complicated with severe pulmonary hypertension. Conclusions: Echocardiography physicians' knowledge of ALCAPA and diagnostic vigilance are critical to the accuracy of diagnosis. Attention should be paid to the pediatric cases with no obvious precipitating factors of left ventricular enlargement, regardless of whether the left ventricular function is normal or not, the origin of coronary artery should be routinely explored.
Subject(s)
Male , Adult , Infant , Child , Humans , Bland White Garland Syndrome/diagnostic imaging , Pulmonary Artery/diagnostic imaging , Retrospective Studies , Missed Diagnosis , Hypertension, Pulmonary , Echocardiography , Coronary Vessel Anomalies/diagnostic imagingABSTRACT
Purpose@#Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis. @*Materials and Methods@#We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity. @*Results@#We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. @*Conclusion@#Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.
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A quantitative analysis of multi-components by single marker method (QAMS) was established for simultaneous determination of gallic acid, protocatechuic acid, catechin, epicatechin, p-coumaric acid, ferulic acid and phloridzin in Cynomorium songaricum Rupr. The analysis was performed on a ChromCore Polae C18 column (250 mm×4.6 mm, 5 μm) , with a mobile phase consisting of acetonitrile-0.3% phosphoric acid aqueous solution for gradient elution. The volume flow rate, column temperature and sample injection volume were set at 1.0 mL·min-1, 25 ℃, and 40 µL, respectively. The relative correction factors of gallic acid and protocatechuic acid, catechin, epicatechin, p-coumaric acid, ferulic acid and phloridzin were calculated and the durability was also investigated. The contents of these seven compounds in fourteen batches of Cynomorium songaricum Rupr. from different producing areas or batches were determined by external standard method (ESM) and quantitative analysis of multi-components with a single-marker method (QAMS), respectively. SPSS and Origin Pro software were employed for principal components assay, similarity evaluation and cluster analysis. The specificity, precision, repeatability, stability and linear range (R2 > 0.999 0) of the seven components were all good. The average recovery was 96.89%-103.16% and RSD was 0.55%-2.76%. Then gallic acid was chosen as internal reference for calculation the correction factors for the other six components, the average relative correction factors of protocatechuic acid, catechin, epicatechin, p-coumaric acid, ferulic acid and phloridzin were 1.141 5, 0.200 5, 0.208 0, 2.361 9, 1.867 7, 0.204 6, respectively. Student's test results showed that there was no significant difference between the data analyzed by ESM and the data obtained from QAMS method. Through data visualization analysis, the contents of gallic acid, protocatechuic acid, catechin and epicatechin in different samples were significantly different, indicating that these four components might be the main quality markers of Cynomorium songaricum Rupr. for gaving more contributes to the principal components. The cluster analysis showed that samples from Xinjiang and samples from Inner Mongolia were clustered in significantly different categories, meaning that the quality of Cynomorium songaricum Rupr. had great relation with producing areas. The method of QAMS established in this study is a simple, economical and practical method with scientific and applicable charactistics for evaluating the quality of Cynomorium songaricum Rupr. efficiently and scientifically.
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Objective:To create radiomics models based on abbreviated multimodal magnetic resonance imaging (MRI) for the diagnosis of breast cancer.Methods:All breast MR imaging data between Jun 2014 and Mar 2019 were retrospectively collected. Patients with pathological results of puncture or surgical resection were involved in this study. One thousand three hundred and six patients (416 benign and 890 breast cancer) were divided into training cohort ( n=702), internal validation cohort ( n=302), and external validation cohort ( n=302). All images were reduced to: the joint model group [including T2 weighted imaging (T2WI), DWI (diffusion-weighted imaging) and first contrast-enhanced sequences], non-enhanced group (T2WI and DWI) and single-phase enhanced group (first contrast-enhanced sequences). Analysis of variance (ANOVA) and least absolute shrinkage and selection operator (LASSO) were used to reduce the dimension of texture features. Three supervised machine learning algorithms (Bagging decision tree, Gaussian process, support vector machine) were used to predict benign and malignant breast lesions, and the best classifier was selected to construct breast cancer diagnosis model. Models were validated by internal and external validation cohorts. Results:The Gaussian process algorithm was chosen. The area under the curve (AUC) of the joint model and the non-enhanced model for predicting breast cancer were 0.903 and 0.893 for the training cohort, 0.893 and 0.863 for the internal validation cohort, and 0.878 and 0.864 for the external validation cohort.Conclusions:The radiomics model based on abbreviated multimodal MRI can accurately diagnose breast cancer. And the non-enhanced model can accurately diagnose breast cancer without contrast enhancement, which provides feasibility for simplifying the diagnosis process.
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Background/Aims@#Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. @*Methods@#We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. @*Results@#The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). @*Conclusions@#SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.
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OBJECTIVE@#To explore the genetic basis for a fetus with cerebellar dysplasia and widened lateral ventricles.@*METHODS@#The couple have elected induced abortion after careful counseling. Skin tissue sample from the abortus and peripheral venous blood samples from both parents were collected for the extraction of genomic DNA, which was then subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing.@*RESULTS@#Prenatal ultrasonography showed increased nuchal translucency (0.4 cm) and widened lateral ventricles. Magnetic resonance imaging revealed infratentorial brain dysplasia. By DNA sequencing, the fetus was found to carry compound heterozygous variants c.1A>G and c.1564G>A of the RARS2 gene, which were inherited from its father and mother, respectively. Among these, c.1A>G was known to be pathogenic, but the pathogenicity of c.1564G>A was unreported previously. Based on the American College of Medical Genetics and Genomics guidelines, the c.1564G>A variant of RARS2 gene was predicted to be likely pathogenic(PM2+PM3+PP3+PP4).@*CONCLUSION@#The compound heterozygous variants c.1A>G and c.1564G>A of RARS2 gene contributed to the fetus suffering from pontocerebellar hypoplasia type 6, which expanded variant spectrum of RARS2 gene.
Subject(s)
Female , Humans , Pregnancy , Fetus , Genomics , Mutation , Olivopontocerebellar Atrophies , Exome SequencingABSTRACT
OBJECTIVE@#To investigate the effect of Kangquan Recipe (, KQR) on bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) expression and its mechanism in rats with benign prostatic hyperplasia (BPH).@*METHODS@#Forty-eight male Sprague-Dawley rats were divided into 6 groups using a random number table, with 8 in each group: the normal group (normal saline 10 mL/kg), the model group (normal saline 10 mL/kg), the finasteride group (0.5 mg/kg), the low-dose KQR group (3.5 g/kg), the middle-dose KQR group (7 g/kg), and the high-dose KQR group (14 g/kg). The 40 rats were subcutaneously injected with testosterone propionate after castration for 30 days to establish the BPH rat model except for those in the normal group. At the same time, the corresponding drugs were administered by gavage for 30 consecutive days. The effects of different doses of KQR on the protate wet weight, prostate volume and prostate index (PI) were observed. The changes in histopathology were monitored with hematoxylin-eosin staining. BAMBI protein and mRNA expression contents were determined by Western blot and quantitative real-time polymerase chain reaction, respectively.@*RESULTS@#All doses of KQR could decrease prostatic epithelial tissue proliferation. Compared to the model group, the high and middle-dose KQR significantly reduced prostate wet weight, prostate volume and PI; increased BAMBI protein expression in the hypothalamus, pituitary and prostate tissue; all doses of KQR up-regulated BAMBI mRNA expression in serum, prostatic fluid and prostate tissue (P<0.05 or P<0.01).@*CONCLUSIONS@#KQR could inhibit the proliferation of rat prostatic tissue, promote BAMBI protein expression in the hypothalamic-pituitary-prostate of rats with BPH; and increase BAMBI mRNA expression in the blood, prostatic fluid and prostate tissue of rats with BPH, showing a dose-effect relationship. KQR can be used as a potential drug for the treatment of BPH.
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Objective To investigate the molecular mechanism of aristolochic acid Ⅰ (AAⅠ) inducing acute hepatotoxicity in mice. Methods A total of 15 male C57BL/6 mice were randomly divided into normal group with 6 mice and treatment group with 9 mice. The mice in the treatment group were given intraperitoneal injection of AAⅠ at a dose of 20 mg/kg for 5 consecutive days and were sacrificed to collect samples on day 6. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and HE staining was used to observe liver histological changes; three liver tissue samples were randomly selected from each group, and RNA was extracted for high-throughput transcriptome sequencing. Bioinformatics analysis and functional prediction were used to screen out differentially expressed genes, and quantitative real-time PCR (qRT-PCR) was used for validation. The t -test was used for comparison of continuous data between two groups. Results Compared with the normal group, the treatment group had significant increases in the activities of ALT and AST ( t =4.331 and 4.947, both P 2 and P < 0.05, among which there were 703 upregulated genes and 649 downregulated genes. The GO and KEGG enrichment analyses of these differentially expressed genes showed significant enrichment in GO terms (such as small molecular catabolism, immune response involving neutrophils, cytoplasmic vesicle lumen in secretory granules, cytoplasmic vesicle lumen, extracellular structural organization, and extracellular matrix) and KEGG pathways (such as chemical carcinogenesis, retinol metabolism, arachidonic acid metabolism, steroid hormone biosynthesis, transcriptional dysregulation in cancer, protein digestion and absorption, regulation of TRP channel by inflammatory mediators, drug metabolism, complement and coagulation cascade, glutathione metabolism, and the PPAR signaling pathway). A cluster analysis ( P < 0.05) showed that significantly downregulated genes included Srd5a1, Lipc, Aqp8, Hba-a1, Slco1a1, and Pklr, which were validated by qRT-PCR (all P < 0.05). Conclusion AA Ⅰ can lead to significant acute hepatotoxicity, which mainly involves the processes such as chemical carcinogenesis, retinol metabolism, arachidonic acid metabolism, steroid hormone biosynthesis, and transcriptional dysregulation in cancer.
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Objective To investigate the mechanism of Fuzheng Huayu(FZHY) decoction in the treatment of liver cancer based on network pharmacology. Methods TCMSP, BATMAN, and Drugbank databases were searched for the main chemical components and corresponding targets of FZHY, and STRING database was used to perform a PPI network analysis. Cytoscape software was used to establish a drug-disease network model and perform a network analysis, and R language was used to perform GO and KEGG enrichment analysis of targets. Results A total of 192 intersection genes between FZHY and liver cancer and 95 potential compounds were screened out, among which quercetin and luteolin were the active components with an important regulatory role. INS, IL-6, and EGFR were the key targets for the potential effect of FZHY. The GO enrichment analysis showed the involvement in various biological processes such as response to drug and response to oxygen level, and the KEGG enrichment analysis showed the involvement in the signaling pathways including apoptosis and tumor necrosis factor signaling pathways. Conclusion Based on the method of network pharmacology, this study reveals the mechanism of action of multiple targets and targets of FZHY in the treatment of liver cancer, which provides a theoretical basis for clinical and basic scientific research.
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Objective To investigate the molecular mechanism of aristolochic acid Ⅰ (AAⅠ) inducing acute hepatotoxicity in mice. Methods A total of 15 male C57BL/6 mice were randomly divided into normal group with 6 mice and treatment group with 9 mice. The mice in the treatment group were given intraperitoneal injection of AAⅠ at a dose of 20 mg/kg for 5 consecutive days and were sacrificed to collect samples on day 6. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and HE staining was used to observe liver histological changes; three liver tissue samples were randomly selected from each group, and RNA was extracted for high-throughput transcriptome sequencing. Bioinformatics analysis and functional prediction were used to screen out differentially expressed genes, and quantitative real-time PCR (qRT-PCR) was used for validation. The t -test was used for comparison of continuous data between two groups. Results Compared with the normal group, the treatment group had significant increases in the activities of ALT and AST ( t =4.331 and 4.947, both P 2 and P < 0.05, among which there were 703 upregulated genes and 649 downregulated genes. The GO and KEGG enrichment analyses of these differentially expressed genes showed significant enrichment in GO terms (such as small molecular catabolism, immune response involving neutrophils, cytoplasmic vesicle lumen in secretory granules, cytoplasmic vesicle lumen, extracellular structural organization, and extracellular matrix) and KEGG pathways (such as chemical carcinogenesis, retinol metabolism, arachidonic acid metabolism, steroid hormone biosynthesis, transcriptional dysregulation in cancer, protein digestion and absorption, regulation of TRP channel by inflammatory mediators, drug metabolism, complement and coagulation cascade, glutathione metabolism, and the PPAR signaling pathway). A cluster analysis ( P < 0.05) showed that significantly downregulated genes included Srd5a1, Lipc, Aqp8, Hba-a1, Slco1a1, and Pklr, which were validated by qRT-PCR (all P < 0.05). Conclusion AA Ⅰ can lead to significant acute hepatotoxicity, which mainly involves the processes such as chemical carcinogenesis, retinol metabolism, arachidonic acid metabolism, steroid hormone biosynthesis, and transcriptional dysregulation in cancer.
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Objective To investigate the mechanism of Fuzheng Huayu(FZHY) decoction in the treatment of liver cancer based on network pharmacology. Methods TCMSP, BATMAN, and Drugbank databases were searched for the main chemical components and corresponding targets of FZHY, and STRING database was used to perform a PPI network analysis. Cytoscape software was used to establish a drug-disease network model and perform a network analysis, and R language was used to perform GO and KEGG enrichment analysis of targets. Results A total of 192 intersection genes between FZHY and liver cancer and 95 potential compounds were screened out, among which quercetin and luteolin were the active components with an important regulatory role. INS, IL-6, and EGFR were the key targets for the potential effect of FZHY. The GO enrichment analysis showed the involvement in various biological processes such as response to drug and response to oxygen level, and the KEGG enrichment analysis showed the involvement in the signaling pathways including apoptosis and tumor necrosis factor signaling pathways. Conclusion Based on the method of network pharmacology, this study reveals the mechanism of action of multiple targets and targets of FZHY in the treatment of liver cancer, which provides a theoretical basis for clinical and basic scientific research.
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Background/Aims@#Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. @*Methods@#We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. @*Results@#The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). @*Conclusions@#SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.
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SUMMARY OBJECTIVE Long noncoding RNA neuroblastoma-associated transcript 1 (NBAT1) has been reported to be involved in cancer progression. However, the clinical significance of NBAT1 in non-small cell lung cancer (NSCLC) is still unclear. Our present research aimed to explore whether NBAT1 serves as a biomarker for NSCLC prognosis. METHODS The expression of NBAT1 was examined by RT-PCR in tissue samples of 162 NSCLC patients and was compared with the adjacent non-tumor lung specimens. Then the association between NBAT1 expression and clinical-pathological parameters was further evaluated. Survival analysis was performed using the Kaplan-Meier method. The prognostic significance of NBAT1 expression in NSCLC patients was explored by the use of univariate and multivariate analyses. RESULTS NBAT1 expression was prominently decreased in NSCLC tissues compared with matched normal lung specimens (p < 0.01). Moreover, survival analyses indicated that patients with low expression displayed dramatically decreased 5-year overall survival (p = 0.008). CONCLUSIONS NBAT1 expression might contribute to tumor progression and poor prognosis of NSCLC and might be a new therapeutic target in NSCLC.
RESUMO OBJETIVO Há relatos de que o NBAT1 está associado à progressão do câncer. Contudo, o significado clínico do NBAT1 no câncer de pulmão de células não pequenas (NSCLC) ainda não está claro. O objetivo da nossa pesquisa foi explorar se NBAT1 serve como biomarcador para o prognóstico de NSCLC. MÉTODOS A expressão de NBAT1 foi examinada por RT-PCR em amostras de tecido de 162 pacientes com NSCLC e comparada a amostras adjacentes não tumorais de pulmão. Em seguida, a associação entre a expressão do NBAT1 e os parâmetros clínico-patológicos foi avaliada. A análise de sobrevivência foi realizada utilizando o método Kaplan-Meier. A significância prognóstica da expressão do NBAT1 em pacientes com NSCLC foi explorada através de análises univariadas e multivariadas. RESULTADOS A expressão do NBAT1 foi claramente diminuída nos tecidos de NSCLC em comparação aos espécimes normais dos pulmões (p<0,01). Além disso, as análises de sobrevivência indicaram que pacientes com baixa expressão apresentavam uma diminuição drástica da sobrevivência global em cinco anos (p=0,008). CONCLUSÃO A expressão do NBAT1 pode contribuir para a progressão tumoral e um prognóstico negativo do NSCLC e pode ser um novo alvo de terapia no NSCLC.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , RNA, Long Noncoding/metabolism , Lung Neoplasms/genetics , Neuroblastoma , Prognosis , Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Kaplan-Meier EstimateABSTRACT
OBJECTIVE@#To analyze FOXC2 gene variant in a family affected with lymphodema-distichiasis syndrome (LDS).@*METHODS@#Peripheral blood samples were collected for the extraction of DNA and protein. Whole-exome sequencing was carried out to detect variants in the proband. Suspected variant was validated by Sanger sequencing. Western blotting was used to detect changes in protein expression.@*RESULTS@#The proband and his mother were both found to carry a heterozygous nonsense variant c.177C>G (p.Tyr59X) of the FOXC2 gene, which was previously unreported. Down-regulated expression of FOXC2 was detected by Western blotting. Prenatal ultrasonography of the fetus indicated increased nuchal thickness. Amniocentesis was performed at 21+1 weeks of pregnancy, genetic testing suggested that the fetus also carried the c.177C>G variant.@*CONCLUSION@#The patients' condition may be attributed to the heterozygous nonsense variant c.177C>G of the FOXC2 gene, which resulted in a significant decrease in FOXC2 expression. Increased nuchal thickness may also be related with decreased FOXC2 expression. Above finding has expanded the variant spectrum of the FOXC2 gene.
Subject(s)
Female , Humans , Pregnancy , Codon, Nonsense , Eyelashes , Congenital Abnormalities , Forkhead Transcription Factors , Genetics , Metabolism , Gene Expression , Genetic Testing , Genetic Variation , Lymphedema , Genetics , Pedigree , Prenatal DiagnosisABSTRACT
OBJECTIVE@#To explore the relationship between obesity and lumbar disc herniation in adolescents.@*METHODS@#From January 2018 to July 2019, 581 patients (337 males, 244 females) with lumbar disc herniation were included in the surgical treatment. According to the age classification standard of the World Health Organization, they were divided into two groups:the adolescent group, 235 cases (145 males, 90 females), age 14 to 44 years old with an average of (32.2±7.3) years. The middle-aged and elderly group, 346 cases (192 males, 154 females), age 45 to 85 years old with an average age of (58.7± 9.8) years. At the time of admission, the same trained investigator measured height, waist circumference and hip circumference with tape measure and weight with electronic scale. All the data were measured twice and the average value was taken and recorded. The body mass index and the waist-hip ratio were calculated. According to each parameter standard, the patients were divided into normal, overweight and obese. The proportion of obese people in different age groups was calculated and analyzed statistically.@*RESULTS@#The normal of the BMI, waist circumference and waist-hip ratio of the young patients were 78(33.2%), 91 (38.7%) and 85(36.2%) respectively;104(44.3%), 95(40.4%), 99(42.1%) were overweight, 53(22.5%), 49(20.9%), 51 (21.7%) were obese. The normal of the BMI, waist circumference and waist-hip ratio of the middle-aged and old patients were 145 (41.9%), 138 (39.9%) and 147 ( 42.5%) respectively;153 (44.2%), 162 (46.8%), 155 (44.8%) were overweight, 48 (13.9%), 46 (13.3%), 44 (12.7%) were obese. Among the three parameters, the proportion of obese people in the adolescent group was higher than that in the middle-aged group, and the difference was significant (χ was 8.836, 6.228 7, 8.536 3 respectively, <0.05).@*CONCLUSION@#For adolescent patients, obesity may increase the load of lumbar disc, affect its metabolism and accelerate its degeneration. For adolescent, obesity is a more significant risk factor of lumbar disc herniation, so it is more important to control weight and prevent obesity in adolescent to reduce the incidence of lumbar disc herniation.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Body Mass Index , Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Lumbar Vertebrae , Obesity , Risk FactorsABSTRACT
Objective:To explore the effect of the interaction between estimated glomerular filtration rate (eGFR) and serum uric acid (SUA) on all-cause and cardiovascular mortality in patients on peritoneal dialysis (PD).Methods:Patients who performed PD catheterization at the PD center of the First Affiliated Hospital of Sun Yat-sen University and had initiated PD therapy for over 3 months from January 2006 to December 2016 were enrolled and followed up until December 2018. Demographic data, baseline clinical and laboratory examination results of the patients were collected. Kaplan-Meier survival curve and Cox regression analysis were used to explore the correlation between SUA and all-cause mortality, cardiovascular mortality in different eGFR groups of PD patients.Results:A total of 2 124 PD patients were enrolled with age of (47.0±15.2) years, among whom 1 269 patients were male and 536 patients had diabetes. The SUA level was (429±96) μmol/L and the median level of eGFR was 6.69(5.17, 8.61) ml·min -1·(1.73 m 2) -1. After a median follow-up time of 42 months, 554 patients died, among whom 275 patients were cardiovascular death. The Cox regression analysis revealed that there was a significant interaction between eGFR and SUA on all-cause mortality ( P=0.043). The Kaplan-Meier curve showed that the tertile 1 (SUA<384 μmol/L) and tertile 3 (SUA>460 μmol/L) group had significantly higher all-cause mortality ( P=0.009) than the reference group of tertile 2 (SUA 384-460 μmol/L) in the higher eGFR group [eGFR>6.69 ml·min -1·(1.73 m 2) -1]but not in the lower eGFR. After adjusting for relevant demographic data, complications, biochemical results and other variables, in patients with higher eGFR, the risk of all-cause mortality increased by 0.2% ( HR=1.002, 95% CI 1.000-1.003, P=0.019) for every 1 μmol/L increase in SUA. In addition, compared with the tertile 2 reference group, the tertile 3 group was independently correlated with higher risk of all-cause mortality ( HR=1.670, 95% CI 1.242-2.245, P=0.001). Conclusions:The eGFR and SUA level significantly interacts with all-cause mortality, and the higher SUA level in higher eGFR group is an independent risk factor for all-cause mortality in PD patients.
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Objectives: To determine the clinical characteristics and risk factors of Deep Venous Thrombosis [DVT] in patients with gynecological malignant tumor, facilitating gynecologists better prevent the fatal complication
Methods: The patients with gynecological malignant tumor treated in department of gynecology of our hospital between May 2013 and May 2018 were reviewed retrospectively. The clinical data of patients including gender, age, tumor staging, adenocarcinoma, surgery, operation time, hypertension, hyperlipemia, diabetes, coronary heart disease, radiotherapy, chemotherapy, hospital stay, and postoperative rehabilitation exercise were collected to analyze the clinical characteristics of patients and determine the risk factors of DVT
Results: In the current study, 67 patients were included in DVT group, and 554 patients were included in Non-DVT group. There were significant differences in age, hypertension, hyperlipemia, operation time, adenocarcinoma, tumor staging, radiotherapy and postoperative rehabilitation exercises between DVT and non-DVT groups [p<0.05]. However, there was no significant differences in gender, coronary heart disease, diabetes, surgical treatment and hospital stay [p>0.05]. In multivariate analysis, the factors including age, hypertension, adenocarcinoma, radiotherapy, and hyperlipemia were independent risk factors, while rehabilitation exercise was protective factor for DVT
Conclusion: In cases of gynecological malignant tumor, DVT screening should be given due importance, especially for those patients with old age, hypertension, hyperlipemia, adenocarcinoma, or history of radiotherapy. Rehabilitation exercise should be encouraged in these patients
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Objective: Adiponectin (APN) is an endogenous cytokine that mediates the development and progression of various tumors through its receptors (AdipoRs). The present study aimed to detect the expression and distribution of APN and its receptors (AdipoR1 and AdipoR2) in tongue squamous cell carcinoma (TSCC). Moreover, we explored whether the locoregional expression of APN was reg-ulated by HIF-1α in the hypoxic microenvironment. Methods: The expression and distribution of APN and its receptors in TSCC tissues were analyzed by immunohistochemical. Lentiviral expression vector for HIF-1α shRNA was constructed and stably transfected in TSCC cells to knock down HIF-1α expression. The mRNA and protein expression levels of APN and its receptors were detected using RT-PCR and Western blot, respectively, after hypoxic treatment. Results: The locoregional expression of APN and AdipoR1, but not AdipoR2, was upregulated at the early stages of T1, T2, and/or N0 stage, respectively, in tumor tissues compared to that in control paracancer-ous tissues (P<0.05 or P<0.01). The expression of APN and AdipoR1, but not AdipoR2, in TSCC cells was up-regulated on hypoxic treat-ment. Moreover, the expression of APN and AdipoR1 was down-regulated after shRNA knockdown of HIF-1α under hypoxia. Conclu-sions: The APN-AdipoR1 signaling pathway was activated and regulated by HIF-1α in the hypoxic environment of TSCC tissues.