ABSTRACT
OBJECTIVE: The aim of our study was to analyze the factors influencing the occurrence of hyperuricemia and poor cardiac and renal outcomes in chronic kidney disease (CKD). PATIENTS AND METHODS: One hundred and sixteen patients with CKD admitted to our hospital from January 2022 to September 2022 were picked as the subjects. Fasting venous blood of these subjects was collected to value the serum uric acid (SUA) levels on an automatic biochemical analyzer. Patients were then grouped as the CKD-only group (n=80) and hyperuricemia group (n=36), according to the SUA results, or the good prognosis group (n=88) and poor prognosis group (n=28), according to the presence of cardiovascular diseases. The changes in laboratory indexes and clinical data were analyzed and compared. Multivariate logistic regression analysis was used to analyze the risk factors for combined hyperuricemia and the risk factors for poor cardiac and renal outcomes in patients with CKD. The correlation between SUA level and cardiac and renal indexes was analyzed by Pearson analysis. RESULTS: Patients in the CKD hyperuricemia group had markedly higher content of systolic blood pressure (SBP), diastolic blood pressure (DBP), B-type natriuretic peptide (BNP), urinary retinol-binding protein (RBP), urinary N-acetyl-ß-D glucosidase (NAG), much higher proportion of heart failure episodes history, and much lower content of total cholesterol (TC), albumin (Alb), hemoglobin (Hb), urinary α1-microglobulin (α1-MG), and glomerular filtration rate (eGFR) than the CKD-only group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for combined hyperuricemia in CKD patients (p < 0.05). Besides, eGFR, albumin, and hemoglobin were independent protective factors for combined hyperuricemia in CKD patients (p < 0.05). Compared with the good prognosis group, the content of BNP, SBP, DBP, urinary RBP, urinary NAG, and SUA was much higher, the proportion of heart failure episodes history was obviously higher, and the levels of Alb, Hb, TC, eGFR, and urinary α1-MG were sharply lower in the poor prognosis group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for poor cardiac and renal outcomes (p < 0.05), and eGFR was an independent protective factor for poor cardiac and renal outcomes in patients with CKD (p < 0.05). The SUA level in CKD patients was positively correlated with BNP and SBP (r=0.463, 0.215, p < 0.05), but negatively correlated with eGFR (r=0.463, 0.215, p < 0.05). CONCLUSIONS: The serum SUA level was elevated with the aggravation of the CKD stage. High serum SUA level is a risk factor for the development of hyperuricemia and poor cardio-renal outcomes in CKD patients, suggesting that early monitoring of changes in SUA levels may help assess the risk of cardio-renal outcomes in CKD patients.
Subject(s)
Heart Failure , Hyperuricemia , Renal Insufficiency, Chronic , Humans , Hyperuricemia/complications , Uric Acid , Renal Insufficiency, Chronic/complications , Risk Factors , Heart Failure/complications , Glomerular Filtration Rate , Albumins , HemoglobinsABSTRACT
Wastewater-based epidemiology (WBE) is an emerging discipline, which has been applied to drug abuse tracking and infectious disease pathogen surveillance. During the COVID-19 epidemic, WBE has been applied to monitor the epidemic trend and SARS-CoV-2 variants etc. In order to detect hidden COVID-19 cases and prevent transmission in the community, wastewater surveillance system for monitoring SARS-CoV-2 RNA was developed in Shenzhen. The sewage sampling sites were set up in key places such as the port areas, urban villages and residential communities of Futian, Nanshan, Luohu and Yantian districts. From July 26 to November 30, 2022, a total of 369 sewage sampling sites were set up, covering 1.93 million people. Continuous sampling was carried out for 3 hours in the peak period of water use every day. Sewage virus enrichment and SARS-CoV-2 nucleic acid detection were carried out by polyethylene glycol precipitation method and RT-qPCR, and a positive water sample disposal process was molded. This article aims to introduce the case of source tracing of COVID-19 infected patients based on urban sewage in Shenzhen. The sewage monitoring of Honghu water treatment plant in Luohu District played an early warning role, and the source of infection was traced. In the disposal of positive water samples in Futian South Road, Futian District, the important experience of monitoring point layout was obtained. In the sewage monitoring of Nanshan village, Nanshan District, the existence of occult infection was revealed. Sharing the experience of tracing the source of COVID-19 patients to avoid the spread of COVID-19 in the community based on wastewater surveillance of SARS-CoV-2 RNA in Shenzhen, and summarizing the advantages and application prospects of sewage surveillance can provide new ideas for monitoring emerging or re-emerging pathogens that are known to exhibit gastrointestinal excretion in the future.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Wastewater-Based Epidemiological Monitoring , RNA, Viral , Sewage , WastewaterABSTRACT
The study aimed to evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for 28-day mortality in patients treated with extracorporeal membrane oxygenation (ECMO). Patients receiving ECMO treatment were selected from the Department of Intensive Care Medicine of Zhejiang Hospital from January 2019 to February 2022. The moment when patients started receiving ECMO treatment was set as the starting point, and death at 28 days was set as the endpoint. The patients were divided into survivors and deaths. Laboratory tests, such as neutrophil, lymphocyte, and platelet counts, using the peripheral blood of all patients were collected within 24 h after ECMO treatment. NLR and PLR were calculated. The risk factors influencing prognosis were analyzed by logistic regression. The correlation between NLR, PLR, acute physiology, and chronic health score â ¡ (APACHE â ¡) was investigated. Receiver operating characteristic (ROC) curve analysis was used to analyze the value of NLR and PLR in predicting the 28-day mortality of patients treated with ECMO. Kaplan-Meier method was used to analyze the cumulative survival of patients at 28 days. The results showed that of 53 patients, 20 survived, and 33 died. The NLR and PLR of the deceased were higher than those of the survivors (NLR: 30.67±14.48 vs. 17.41±7.06;PLR: 303.34±159.23 vs. 191.54±106.03;P<0.001). NLR and PLR were positively correlated with APACHE â ¡ (r=0.296, r=0.284, P<0.05). ROC curve analysis showed that the area under the curve (AUC) of NLR and PLR to predict the 28 d death of ECMO-treated patients was 0.805 and 0.714, respectively, and the optimal cutoff values of NLR and PLR were 18.93 and 253.0, respectively. The 28-day fatality rate in patients with NLR≥18.93 was higher than that in patients with NLR<18.93 [86.20%(25/29) vs. 33.33%(8/24), χ2=15.625, P<0.01],that in patients with a PLR≥253.0 was higher than that in patients with PLR<253.0 [82.61%(19/23) vs. 46.67%(14/30), χ2=7.158, P<0.01]. Kaplan-Meier survival curve showed that the 28-day cumulative survival rate of NLR≥18.93 was lower than that of NLR<18.93 [9.00 (2.00, 19.50) d vs. 28.00 (10.75, 28.00) d, Z=-3.124, P<0.01], and that of PLR≥253.0 was lower than that of PLR<253.0 [6.00 (2.00, 19.00) d vs. 28.00 (6.25, 28.00) d, Z=-2.673, P<0.01]. Thus, NLR and PLR have good predictive value for 28-day mortality in patients treated with ECMO.
Subject(s)
Extracorporeal Membrane Oxygenation , Neutrophils , Humans , Blood Platelets , Lymphocytes , Platelet Count , Prognosis , Retrospective Studies , ROC CurveABSTRACT
Objective: To observe the dynamic changes of serum RANTES during the treatment with nucleos(t)ide analogues combined with pegylated interferon alpha (peginterferon-α), and further analyze the predictive effect of RANTES on HBsAg clearance in patients with chronic hepatitis B. Methods: 98 cases of chronic hepatitis B with quantitative HBsAg < 3 000 IU/ml and HBV DNA < 20 IU/ml after≥1 year NAs treatment were enrolled. Among them, 26 cases continued to receive NAs monotherapy, 72 cases received NAs combined with pegylated interferon alpha therapy. The changes in RANTES during treatment were observed. The receiver operating characteristic curve was used to analyze the early changes of RANTES to predict the HBsAg clearance during 48 weeks. Results: During 48 weeks, 15 cases (20.83%) had achieved HBsAg clearance in combination group, while no patient had achieved HBsAg clearance in NAs group. The overall serum RANTES level had decreased from baseline in NAs and combination group. At week 48, in the combination group, the serum RANTES level was decreased more significantly in patients with HBsAg clearance than patients without. Further analysis showed that, in combination group, HBsAg clearance rate of patients with serum RANTES decreased at week 12 and 24 was higher than patients with elevated (29.17% vs. 4.17%, P = 0.014; 28.00% vs. 4.55%, P = 0.052), and quantitative HBsAg reduction was larger significantly [(1.49 ± 1.26) log(10)IU/ml vs. (0.73 ± 0.81) log(10)IU/ml, P = 0.017; (1.54 ± 1.27) log(10)IU/ml vs. (0.57 ± 0.56) log(10)IU/ml, P = 0.004]. Receiver operating characteristic curve analysis showed that the baseline quantitative HBsAg and the reduction in quantitative HBsAg and serum RANTES during the early period were predictors of HBsAg clearance after 48-week combination therapy. Furthermore, the combination of baseline quantitative HBsAg and 12 - or 24-week reduction of serum RANTES were better predictors of HBsAg clearance than that of baseline quantitative HBsAg combined with HBsAg decrease at week 12 or 24. The area under the receiver operating characteristic curve of the former was 0.925 and 0.939, while that of the latter was 0.909 and 0.929, respectively. Conclusion: Early reduction of serum RANTES at week 12 and 24 can predict HBsAg loss in CHB patients receiving addition of peginterferon-α to ongoing NAs Therapy, so serum RANTES could be one of the key immunological markers for predicting HBsAg clearance.
Subject(s)
Hepatitis B Surface Antigens , Hepatitis B, Chronic , Antiviral Agents/therapeutic use , Chemokine CCL5/therapeutic use , DNA, Viral , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Treatment OutcomeABSTRACT
Breast cancer (BC) is malignant cancer that threatens the health of millions of females worldwide. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) has been identified as an oncogene in multiple cancers. However, the regulatory role of SNHG12 in BC cell progression is still obscured. The levels of SNHG12, miR-15a-5p, and Sal-like 4 (SALL4) in BC tumor tissues and cells were measured by qRT-PCR. Cell viability, apoptosis, migration, and invasion were examined by CCK8, flow cytometry, and transwell assay, respectively. The interaction between miR-15a-5p and SNHG12 or SALL4 was evaluated by dual-luciferase reporter assay. Protein expression of SALL4 was analyzed by western blot. Xenograft mice were established by subcutaneously injecting BC cells stably transfected with sh-SNHG12 and sh-NC. SNHG12 and SALL4 expressions were upregulated whereas miR-15a-5p was downregulated in BC tumors compared with normal tissues. Besides, miR-15a-5p was correlated with SNHG12 and SALL4 inversely as calculated by Pearson's correlation coefficient. More importantly, SNHG12 knockdown attenuated BC tumor growth in vitro and in vivo. Subsequently, dual-luciferase reporter assay confirmed the interaction between miR-15a-5p and SNHG12 or SALL4. The rescue experiments revealed that miR-15a-5p inhibitor restored SNHG12 silencing induced inhibition on BC cell proliferation, migration, invasion, and promotion of apoptosis. Additionally, SNHG12 was found to accelerate BC cell progression by absorbing miR-15a-5p to enhance SALL4 expression. SNHG12 promotes cell proliferation, migration, and invasion but suppresses apoptosis in BC by upregulating SALL4 expression via sponging miR-15a-5p, representing potential targets for the development of novel diagnosis and treatment methods.
Subject(s)
Breast Neoplasms , MicroRNAs , RNA, Long Noncoding , Transcription Factors , Animals , Apoptosis/genetics , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Humans , Mice , MicroRNAs/genetics , RNA, Long Noncoding/physiology , Transcription Factors/genetics , Transcription Factors/metabolism , Up-RegulationABSTRACT
AIMS: To determine how the microbicide ceragenin-13 (CSA-13) kills Bacillus subtilis spores prepared on growth or sporulation media, and these spores' properties. METHODS AND RESULTS: Spores made on Luria broth (LB) growth or double-strength Schaeffer's-glucose (2xSG) sporulation plates found that spores made on LB plates have coat defects as evidenced by their lower hypochlorite resistance, faster germination with dodecylamine and slower germination with Ca2+ -dipicolinic acid (CaDPA) than 2xSG plate spores. CSA-13 triggered CaDPA release from spores, an early step in germination, but only well at 70°C and better with spores made on LB than on 2xSG plates. Approximately 90% of spores with elevated levels of SpoVA proteins that form a CaDPA release channel, released CaDPA with CSA-13 at 70°C, and faster with spores made on LB than 2xSG plates. Levels of CSA-13 killing of spores made on LB and 2xSG plates were similar to levels of CaDPA release triggered by this agent. CONCLUSIONS: CSA-13 kills bacterial spores, but only at high concentrations and temperatures, and is preceded by CaDPA release. SIGNIFICANCE AND IMPACT OF THE STUDY: CSA-13 is not a direct sporicide as reported previously, but most likely germinates spores via activation of spores' CaDPA channel, albeit inefficiently, and then killing the germinated spores.
Subject(s)
Anti-Infective Agents/pharmacology , Bacillus subtilis/drug effects , Culture Media/chemistry , Culture Media/pharmacology , Spores, Bacterial/drug effects , Spores, Bacterial/growth & development , Steroids/pharmacology , Amines , Picolinic Acids/metabolism , Spores, Bacterial/metabolismABSTRACT
OBJECTIVE: To investigate the regulating roles of miR-199b in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The expression of miR-199b of 45 human HCC tissues and the corresponding para-cancerous tissue samples were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR). Western blot was employed to investigate the level of JAG1. Transwell assay was used to monitor the ability of cell migration and invasion. Cell proliferation was tested by CCK-8 assay and luciferase reporter assay was done to clarify whether JAG1 was a target of mir-199b. RESULTS: miR-199b expression level was decreased in 45 paired tumor tissues in contrast with the corresponding para-carcinoma tissues. The expression level of miR-199b was closely associated with TNM stage, tumor size, and 5-year overall survival. Transwell assay result showed that miR-199b inhibited HCC cell migration and invasion. Cell counting kit-8 (CCK-8) results demonstrated that miR-199b could suppress HCC cell proliferation. Luciferase reporter assay suggested that Jagged1 (JAG1) was a direct target of miR-199b in HCC cells. miR-199b could negatively regulate JAG1 expression by targeting JAG1. CONCLUSIONS: miR-199b exerted tumor suppressive functions in HCC by targeting JAG1, and it may be a potential target treatment for hepatocellular carcinoma.
Subject(s)
Carcinoma, Hepatocellular/genetics , Jagged-1 Protein/metabolism , Liver Neoplasms/genetics , MicroRNAs/genetics , Carcinoma, Hepatocellular/pathology , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Signal Transduction/geneticsABSTRACT
Objective: To explore the gender-specific risk factors of new-onset cerebral hemorrhage. Methods: In this prospective cohort study,a total of 98 961 participants((51.1±12.6)years old), who underwent the 2006 to 2007 physical examination and met the inclusion criteria, were enrolled from the Kailuanstudy cohort. There were 78 908 (79.7%) male,and 20 053 (20.3%) female.The incidence of cerebral hemorrhage was observed once per year until December 31, 2016.The difference on the incidence of cerebral hemorrhage between male and female was compared. Multivariate Cox regression analysis was applied to analyze therisk factors of cerebral hemorrhage events among different genders. Results: The participants were followed up for(10.00±0.73) years,and 860 cerebral hemorrhage events were recorded during follow up. The incidence of cerebral hemorrhage in the population was 86.90/10 million person years (standardized incidence rate of 47.85/10 million person years). The incidence of cerebral hemorrhage was significantly higher in male (49.61/10 million person years) than in female (34.07/10 million person years, P<0.05). Multivariate Cox regression analysis showed that 45-59 years old, ≥ 60 years old, diabetes,and waist-hip ratio were more strongly related to new-onset of cerebral hemorrhage events in female than in male, and the hazard ratios(95%CI) were 2.33 (1.23-4.43) ,2.71 (1.30-5.66) ,2.16 (1.24-3.74) and 8.79 (1.42-54.32) in female versus 1.55 (1.21-1.97) ,2.16 (1.68-2.78) ,1.19 (0.93-1.53) and 3.21 (1.09-9.41) in male, respectively. The risk of male cerebral hemorrhage increased by 29% (HR=1.29, 95%CI 1.19-1.40) in male and 24% (HR=1.24, 95%CI 1.20-1.28) in female,when the systolic blood pressure increased 10 mmHg (1 mmHg=0.133 kPa). Conclusions: The incidence of cerebral hemorrhage is higher in male than in female in this cohort.The association between systolic blood pressure and cerebral hemorrhage is stronger in male than that in female.The associations between age, waist-hip ratio, diabetes and cerebral hemorrhage are stronger in female than in male. Trial Registration: Chinese Clinical Trail Registry, ChiCTR-TNC-11001489.
Subject(s)
Blood Pressure , Cerebral Hemorrhage , Adult , Cerebral Hemorrhage/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Prospective Studies , Risk FactorsABSTRACT
BACKGROUND AND PURPOSE: X-linked Charcot-Marie-Tooth disease type 1 (CMTX1), caused by mutations in gap junction protein beta 1 (GJB1), is characterized by various central nervous system symptoms and gender differences of clinical severity. The aim of this study was to identify the frequency and mutation spectrum of CMTX1 patients in Japan and to demonstrate their phenotypic diversities. METHODS: Using three high-throughput sequencing systems, targeted gene panel sequencing on 1483 unrelated index patients with suspected Charcot-Marie-Tooth (CMT) disease was performed. The peripheral and central nervous system involvements of all patients with GJB1 variants were assessed retrospectively and a detailed gender comparison was conducted with the CMT examination score. RESULTS: Twenty-three novel and 36 described GJB1 variants were identified from 88 pedigrees, in which 34 female and 78 male patients were enrolled. Mean age at onset of the male patients was much younger than the females, 21.56 ± 17.63 years vs. 35.53 ± 23.72 years (P = 0.007). Male patients presented with more severe phenotypes in every examination item, but statistical differences were observed only in motor dysfunctions of the lower extremities and vibration sensation. No significant sensory difference was identified between genders, either clinically or electrophysiologically. Central nervous system dysfunctions were found in 15 patients from 12 pedigrees. Therein, six patients developed stroke-like phenotypes, with dysarthria as the leading symptom. CONCLUSIONS: A relatively lower frequency of CMTX1 (5.9%) was demonstrated and a broad mutation spectrum of GJB1 was described. Detailed clinical differences between genders and various central nervous system symptoms were also illustrated, even in the same pedigree.
Subject(s)
Charcot-Marie-Tooth Disease/diagnosis , Connexins/genetics , Dysarthria/diagnosis , Mutation , Phenotype , Adolescent , Adult , Age of Onset , Charcot-Marie-Tooth Disease/genetics , Child , Child, Preschool , Dysarthria/genetics , Female , Humans , Japan , Male , Middle Aged , Pedigree , Retrospective Studies , Sex Factors , Young Adult , Gap Junction beta-1 ProteinABSTRACT
Objective: To explore the trichloroethylene-induced alteration of methylation on the promoter region of SET and related mechanisms in hepatic L-02 cells. Methods: L-02 cells were treated with different concentrations of TCE(0 mmol/L, 1 mmol/L, 2 mmol/L, 4 mmol/L, 8 mmol/L) for 24 h. The genomic DNA were then extracted and modified by bisulfite sodium. The DNA methylation was then analyzed using bisulfite sequencing PCR (BSP). Results: The overall methylation on promoter region of SET was decreased along with the increased concentrations of TCE in hepatic L-02 cells. Moreover, 73 CpG islands were found abnormally altered, among which 9 were predicted in transcriptional factor binding regions. Conclusion: The decreased levels of CpG islands in the transcriptional factor binding region may contribute to the elevation of SET in TCE-induced hepatotoxicity.
Subject(s)
DNA Methylation/drug effects , Hepatocytes , Promoter Regions, Genetic/genetics , Trichloroethylene/toxicity , Cell Line , CpG IslandsABSTRACT
Objective: To study the oxidative damage of di- (2-ethylhexyl) phthalate (DEHP) on MCF-7 cells, and to investigate the effects of 3ß-hydroxysteroid dehydrogenase (3ß-HSD) gene silence or overexpression on DEHP-induced oxidative damage. Methods: MCF-7 cells, 3ß-HSD gene silencing cells and 3ß-HSD gene overexpression cells were treated with different doses of DEHP (0,0.05,0.1,0.2,0.4,0.8 mmol/L) for 24h, then intracellular oxidative damage index such as MDA, SOD, GSH, GSH-PX were detected, DNA repair gene hOGG1, hMTH1 mRNA expression were tested by Q-PCR, hOGG1, hMTH1 protein expression were detected by western blot. Results: After MCF-7 cells were treated by DEHP, MDA levels increased; SOD activity, GSH content, GSH-PX activity decreased, hOGG1 and hMTH1 mRNA expression levels increased, hOGG1 and hMTH1 protein expression levels increased, the differences were statistically significant when compared with control (P<0.05 or P<0.01) . In 3ß-HSD gene silencing cells which were treated by DEHP, when compared with the same dose group of MCF-7 cells, MDA content increased, SOD activity, GSH content, GSH-PX activity decreased, hOGG1 and hMTH1 mRNA expression levels decreased, hOGG1 and hMTH1 protein expression levels decreased, the difference were statistically significant (P<0.05 or P<0.01) . In 3ß-HSD gene overexpression cells which were treated by DEHP, when compared with the same dose group of MCF-7 cells, MDA content decreased; SOD activity, GSH content, GSH-PX activity increased, of hOGG1 and hMTH1 mRNA expression levels increased, hOGG1 and hMTH1 protein expression levels increased, the difference were statistically significant (P<0.05 or P<0.01) . Conclusion: DEHP could cause oxidative damage in MCF-7 cells, induce the changes of related genes and proteins, 3ß-HSD plays an antioxidant role in the process of DEHP ox-idative damage.
Subject(s)
Diethylhexyl Phthalate/pharmacology , MCF-7 Cells/drug effects , Oxidative Stress/drug effects , HumansABSTRACT
BACKGROUND AND PURPOSE: The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of Charcot-Marie-Tooth disease (CMT) type 2Z in 2016. We aimed to describe the clinical and mutational spectrum of patients with CMT harboring MORC2 mutations in Japan. METHODS: We analyzed samples from 781 unrelated patients clinically diagnosed with CMT using deoxyribonucleic acid microarray or targeted resequencing by next-generation sequencing, and samples from 434 mutation-negative patients were subjected to whole-exome sequencing. We extracted MORC2 variants from these whole-exome sequencing data and classified them according to American College of Medical Genetics standards and guidelines. RESULTS: We identified MORC2 variants in 13 patients. As the second most common causative gene of CMT type 2 after MFN2, MORC2 variants were detected in 2.7% of patients with CMT type 2. The mean age of onset was 10.3 ± 8.7 years, and the inheritance pattern was mostly sporadic (11/13 patients, 84.6%). The clinical phenotype was typically length-dependent polyneuropathy, and electrophysiological studies revealed sensory-dominant axonal neuropathy. Mental retardation was identified in 4/13 patients (30.8%). p.Arg190Trp, as a mutational hotspot, was observed in eight unrelated families. We also identified two novel probably pathogenic variants, p.Cys345Tyr and p.Ala369Val, and one novel uncertain significance variant, p.Tyr332Cys. CONCLUSIONS: Our study is the largest report of patients harboring MORC2 variants. We revealed a clinical and mutational spectrum of Japanese patients with MORC2 variants. More attention should be paid to cognitive impairment, and the responsible mechanism requires further research for elucidation.
Subject(s)
Charcot-Marie-Tooth Disease/genetics , Mutation , Transcription Factors/genetics , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Japan , Male , Middle Aged , Phenotype , Young AdultABSTRACT
The clinical and genetic spectrum of hereditary sensory and autonomic neuropathy (HSAN) is still unknown in Japan. We collected a broad cohort of 33 unrelated patients with predominant sensory and/or autonomic dysfunctions, who were referred to our genetic laboratory. A gene panel sequencing targeting 18 HSAN-related genes was performed using a next-generation sequencing system. A recurrent frame shift mutation in the WNK1/HSN2 gene, c.3237_3238insT (p.Asp1080*), was detected in 5 patients. This mutation was homozygous in 4 cases and of a compound heterozygous genotype in 1 case. Geographic and haplotype analysis of all 5 patients suggested a founder event. In addition, a novel heterozygous nonsense variant, c.2615C>G (p.Ser872*), was identified. All the 5 patients presented with severe sensory and autonomic dysfunctions at birth or during adolescence. In 2 patients, an uncommon phenotype of acute pathological pain presented at ~50 years of age. Here, we present the first founder mutation of WNK1/HSN2, in addition to French Canadian, which accounts for ~15.2% of Japanese patients with HSAN in our cohort. We have also reviewed all previously described mutations in WNK1/HSN2 and reconciled their nomenclature strategy on the basis of the current longest transcript.
Subject(s)
Codon, Nonsense , Founder Effect , Frameshift Mutation , Hereditary Sensory and Autonomic Neuropathies/genetics , WNK Lysine-Deficient Protein Kinase 1/genetics , Adult , Age of Onset , Aged , Asian People , Cohort Studies , Female , Gene Expression , Haplotypes , Hereditary Sensory and Autonomic Neuropathies/diagnosis , Hereditary Sensory and Autonomic Neuropathies/ethnology , Hereditary Sensory and Autonomic Neuropathies/physiopathology , Heterozygote , Homozygote , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Mutations in GDAP1 are responsible for heterogeneous clinical and electrophysiological phenotypes of Charcot-Marie-Tooth disease (CMT), with autosomal dominant or recessive inheritance pattern. The aim of this study is to identify the clinical and mutational spectrum of CMT patients with GDAP1 variants in Japan. MATERIALS AND METHODS: From April 2007 to October 2014, using three state-of-art technologies, we conducted gene panel sequencing in a cohort of 1,030 patients with inherited peripheral neuropathies (IPNs), and 398 mutation-negative cases were further analyzed with whole-exome sequencing. RESULTS: We identified GDAP1 variants from 10 patients clinically diagnosed with CMT. The most frequent recessive variant in our cohort (5/10), c.740C>T (p.A247V), was verified to be associated with a founder event. We also detected three novel likely pathogenic variants: c.928C>T (p.R310W) and c.546delA (p.E183Kfs*23) in Case 2 and c.376G>A (p.E126K) in Case 8. Nerve conduction study or sural nerve biopsy of all 10 patients indicated axonal type peripheral neuropathy. CONCLUSION: We identified GDAP1 variants in approximately 1% of our cohort with IPNs, and established a founder mutation in half of these patients. Our study originally described the mutational spectrum and clinical features of GDAP1-related CMT patients in Japan.
Subject(s)
Charcot-Marie-Tooth Disease/diagnosis , Charcot-Marie-Tooth Disease/genetics , Mutation , Nerve Tissue Proteins/genetics , Phenotype , Adolescent , Adult , Alleles , Child , Child, Preschool , DNA Mutational Analysis , Female , Founder Effect , Genetic Association Studies , Genotype , Haplotypes , Humans , Japan , Male , Middle Aged , Myelin Proteins/genetics , Pedigree , Reproducibility of Results , Exome Sequencing , Young AdultABSTRACT
Objective: To explore the value of 3.0 T MRI using multiple sequences (star VIBE+ BLADE) in evaluating the preoperative T staging for potentially resectable esophageal cancer (EC). Methods: Between April 2015 and March 2016, a total of 66 consecutive patients with endoscopically proven resectable EC underwent 3.0T MRI in the Affiliated Cancer Hospital of Zhengzhou University.Two independent readers were assigned a T staging on MRI according to the 7th edition of UICC-AJCC TNM Classification, the results of preoperative T staging were compared and analyzed with post-operative pathologic confirmation. Results: The MRI T staging of two readers were highly consistent with histopathological findings, and the sensitivity, specificity and accuracy of preoperative T staging MR imaging were also very high. Conclusion: 3.0 T MRI using multiple sequences is with high accuracy for patients of potentially resectable EC in T staging. The staging accuracy of T1, T2 and T3 is better than that of T4a. 3.0T MRI using multiple sequences could be used as a noninvasive imaging method for pre-operative T staging of EC.
Subject(s)
Esophageal Neoplasms , Humans , Magnetic Resonance Imaging , Neoplasm Staging , Organometallic Compounds , Postoperative Period , PyridinesABSTRACT
Objective: To discuss the value of RESOLVE for predicting early therapeutic effect of concourrent radiochemotherapy in advanced stage nasopharngeal carcinoma patients. Methods: Sixty-eight patients with nasopharyngeal carcinoma were confirmed by pathology in Henan Cancer Hospital from June 2014 to January 2016.All patients underwent RESLOVE(b value=800 s/mm(2)) with a 3.0 T MRI scanner.The ADC value and the area of the tumor was measured before treatment and 2 weeks after treatment independently performed by two radiologists with 5 years experiences and the agreement evaluation was performed using ANOVA analysis.The correlation among pretreatment ADC value, pathology type, gender, tumor area and the tumor regression rate were analyzed using Spearman rank correlation test.The difference between pretreatment ADC value was compared in CR group and non-CR group by independent sample t test.ROC curve was drawn and the maximum Youden index value was the cutoff calculating the ADC value and predicting the sensitivity, specificity and area under the curve. Results: (1)The agreement between 2 radiologist was excellent. The ICC values of the ADC and the area of the tumor before treatment and the area of the tumor after treatment were 0.89, 0.92 and 0.95, respectively. (2)The pretreatment ADC values of the CR group and the non-CR group were (0.877±0.103)×10(-3) mm(2)/s and (0.779±0.078)×10(-3) mm(2)/s, respectively. There was statistical difference t value=2.874, P value=0.005.(3)ROC curve showed that the sensitivity and specificity of the pretreatment ADC value in predicting CR was 85.2% and 71.0%, with the cut-off value of 0.792×10(-3) mm(2)/s, and the area under curve was 0.778.(4)There was apparently correlation beween the pretreatment ADC value and the tumor regression rate(r=0.333, P=0.006). There was no correlation among pretreatment ADC value, pathology type, gender and tumor area (P>0.05). Conclusion: There is important value using the pretreatment ADC value measured by RESOLVE for predicting the early effect of concurrent radiochemotherapy in advanced stage nasopharngeal carcinoma patients.
Subject(s)
Chemoradiotherapy , Diffusion Magnetic Resonance Imaging , Carcinoma , Humans , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , ROC CurveABSTRACT
Stretchable electronics offer soft, biocompatible mechanical properties; these same properties make them susceptible to device failure associated with physical impact. This paper studies designs for stretchable electronics that resist failure from impacts due to incorporation of a viscoelastic encapsulation layer. Results indicate that the impact resistance depends on the thickness and viscoelastic properties of the encapsulation layer, as well as the duration of impact. An analytic model for the critical thickness of the encapsulation layer is established. It is shown that a commercially available, low modulus silicone material offers viscous properties that make it a good candidate as the encapsulation layer for stretchable electronics.
ABSTRACT
A mechanics model is developed for the encapsulated piezoelectric thin-film actuators/sensors system imperfectly bonded to the human skin to simultaneously determine the Young's moduli of the epidermis and dermis as well as the thickness of epidermis.
ABSTRACT
OBJECTIVES: To compare the efficacy between unilateral laminectomy approach bilateral decompression and traditional total laminectomy decompression in the treatment of graft bone fusion and internal fixation for degenerative lumbar spinal stenosis with the unilateral symptoms. METHOD: From January 2013 to December 2014, a total of 40 patients with unilateral symptoms of lumbar spinal stenosis were treated in Department of Spinal Surgery Bozhou People's Hospital of Anhui Province. Twenty patients(group A ) were treated by severe symptoms unilateral facetectomy and resection of superior articular and laminectomy and lateral recess decompression, interbody fusion, pedicle screw fixation.Twenty patients(group B ) were treated by total laminectomy interbody fusion and pedicle screw fixation.The time of operation, blood loss of the two groups were recorded.At the same time the visual analog scale (VAS), Oswestry disability index(ODI), Japanese Orthopaedic Association Scores(JOA) before and after operation (3, 6 , 12months) were recorded retrospectively. The effect of surgery were evaluated and compared. RESULT: The VAS, JOA, and ODI of group A preoperation is respectively have no significant differences with the group B (P>0.05). The operation time, blood loss in operation of group A was respectively(133.2±25.3) min, (415.0±42.1) ml, significant differences with the group B[(491.0±46.3)ml; (156.2±28.5) min, P<0.05)]. The VAS, JOA, ODI of group A had no significant differences with the group B (P>0.05) at 3, 6 months after operation.The VAS, JOA, ODI of group A was respectively (3.0±0.6), (25.3±5.1), (16.5±1.5)scores, had significant differences with the group B and preoperation (P<0.05) at 12 months after operation. The radiographic data showed that the interbody fusion rate of group A was 100%, and group B was 95%, had significant differences by statistical analysis (P<0.05) at 12 months afer operation. CONCLUSION: The improved unilateral laminectomy approach and bilateral decompression have less operation time and blood loss, more satisfactory for the lumbar spinal stenosis patients with the unilateral severe symptoms, the other side moderate stenosis and mild symptoms.The efficacy of lumbar stability and bilateral decompression is better by operation of improved unilateral approach.
Subject(s)
Decompression, Surgical/instrumentation , Laminectomy/methods , Pedicle Screws , Spinal Fusion/instrumentation , Spinal Fusion/methods , Spinal Stenosis/surgery , Constriction, Pathologic , Fracture Fixation, Internal , Humans , Lumbar Vertebrae , Pain Measurement , Retrospective Studies , Treatment OutcomeABSTRACT
It has long been known that males are more susceptible than females to hepatocellular carcinoma (HCC), but the reason remains elusive. In this study, we investigated the expression and function of the long noncoding RNA FTX (lnc-FTX), an X-inactive-specific transcript (XIST) regulator transcribed from the X chromosome inactivation center, in both HCC and HCC gender disparity. lnc-FTX is expressed at higher levels in female livers than in male livers and is significantly downregulated in HCC tissues compared with normal liver tissues. Patients with higher lnc-FTX expression exhibited longer survival, suggesting that lnc-FTX is a useful prognostic factor for HCC patients. lnc-FTX inhibits HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, lnc-FTX represses Wnt/ß-catenin signaling activity by competitively sponging miR-374a and inhibits HCC cell epithelial-mesenchymal transition and invasion. In addition, lnc-FTX binds to the DNA replication licensing factor MCM2, thereby impeding DNA replication and inhibiting proliferation in HCC cells. In conclusion, these findings suggest that lnc-FTX may act as a tumor suppressor in HCC through physically binding miR-374a and MCM2. It may also be one of the reasons for HCC gender disparity and may potentially contribute to HCC treatment.