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Objective:To explore the application of microfluidic chip in detection of hereditary deafness-associated hotspot mutations.Methods:The dedicatedly designed and fabricated microfluidic chip was integrated with kompetitive allele-specific polymerase chain reaction amplification system, scanned via laser-excited confocal fluorescence scanner, and finally analyzed programmatically to acquire the typing results of the 23 mutation sites of the four common genes associated with hereditary hearing loss. Dried blood spots were collected from 276 neonates containing the 131 cases with hearing loss who were born in 2019 in Chengdu (deafness group) and the 145 cases with normal hearing who were born in 2020 in Chengdu (control group), and analyzed by the microfluidic chip to evaluate its clinical performance.Results:By cluster analysis, the microfluidic chip correctly analyzed the 23 positive reference samples and acquired the same typing results as their actual results, with a limit of detection of 1 mg/L. For the 276 newborn blood spots, the detection results of the microfluidic chips were confirmed to be correct by the contrasting methods. Among Deafness Group, 66 (50.4%) tested positive for the selected 23 mutation hotspots; among Control Group, 40(27.6%) were positive. Among these mutations, c.109G>A of the GJB2 gene was the most prevalent one, whose carrier rate in deafness group and control group were 46.6%(61/131) and 23.4% (34/145), respectively.Conclusions:The micro-fluidic chip system was succeeded in fulfilling the hereditary deafness-related mutation detection, and offered many advantages including high specificity, avoiding the amplicon carryover contamination, simplifying the entire experimental operation process and short detection time, so as to better meet the detection requirement of genetic testing for deafness in newborn screening and other fields.
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Objective To observe the efficacy of transcatheter arterial chemoembolization (TACE) combined with microwave ablation,125I radioactive seed implantation and Apatinib targeted therapy for large hepatocellular carcinoma.Methods 120 patients with large hepatocellular carcinoma admitted to our hospital from May 2015 to May 2017 were selected as the subjects and randomly divided into four groups.30 patients in the control group were treated with TACE,30 patients in the combined treatment group 1 were treated with TACE combined with microwave ablation,30 patients in the combined treatment group 2 were treated with TACE combined with 125I radioactive seeds implantation,and 3 patients in the combined treatment group 3 were treated with TACE combined with Apatinib.The clinical efficacy,changes of alpha-fetoprotein (AFP),survival rate,levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) and adverse reactions were compared among the four groups.Results The disease control rate of the combined treatment group was significantly higher than that of the control group (P ＜0.05).The reduction rate of AFP in the combined treatment group was significantly higher than that in the control group (P ＜ 0.05).There was no significant difference in survival rate between the combined treatment group 2,combined treatment group 3 and the control group at 6 months and 1 year later (P ＞ 0.05),while the survival rate of the combined treatment group 1 was significantly higher than that of the control group (P ＜0.05).After treatment,the levels of VEGF and MMP-9 in the four groups were significantly lower than those before treatment (P ＜ 0.05),and the combined treatment group was significantly lower than the control group (P ＜ 0.05).The incidence rates of adverse reactions such as elevated blood pressure,nausea and vomiting,skin itching,proteinuria and bone marrow suppression in the combined treatment group 1 were significantly lower than those in the control group (P ＜ 0.05),and the incidences of skin itching in the combined treatment group 2 and the combined treatment group 3 were significantly lower than those in the control group (P ＜ 0.05).Conclusions TACE combined with microwave ablation,125I radioactive seed implantation and Apatinib targeting therapy for large hepatocellular carcinoma are more effective than TACE alone,and TACE combined with microwave ablation can significantly prolong the survival time of patients.
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OBJECTIVE:To investigate related factors for valproic acid-induced fibrinogenopenia in epilepsy patients. METHODS:A retrospective survey was conducted to collect the epilepsy patients treated with routine dose of valproic acid regularly more than one week in Epilepsy Diagnosis and Treatment Center of Xuanwu Hospital,Capital Medical University during Jan. 1st,2017 to Mar. 1st,2017. The general situation,drug use (dosage of valproic acid,dosage form of valproic acid,drug combination),liver function,blood routine indexes and coagulation indexes,etc. were collected. Univariate and binary Logistic regression analysis were used to analyze the relationship of above factors with fibrinogenopenia. ROC curve was used to screen and predict the cut-off points when sensitivity and specificity of fibrinogenopenia were good. RESULTS:A total of 59 valid cases were collected,including 40 male(67.8％)and 19 female(32.2％);35 patients(59.3％)were under 14 years of age,and 24 patients (40.7％)over 14 years of age,with average age of(17.2±15.7). Of these,24 had fibrinogenopenia(40.7％). Univariate analysis showed that fibrinogenopenia was negatively correlated with age(P=0.042),but was positively correlated with dosage of valproic acid(P=0.003);fibrinogenopenia was not correlated with gender(P=0.679),dosage form of valproic acid(P=0.790)or drug combination (P=0.502). Binary Logistic regression analysis showed that dosage of valproic acid and neutrophil percentage, erythrocyte count and platelet count of patients were related risk factors of fibrinogenopenia;odds ratios of related risk factors were 1.101,0.925,0.132,0.976. ROC curve showed that the area under the ROC curve which was correlated with dosage of valproic acid was 0.766,sensitivity and specificity were 98.5％ and 54.3％;the cut-off dosage was 13.3117 mg/kg. CONCLUSIONS:The greater the dosage of valproic acid and the younger the age,the greater the possibility of the fibrinogenopenia. For patients with long-term use of valproic acid,even if the normal dosage are used,it is necessary to monitor fibrinogen changes regularly,for whom the dosage are greater than 13.3117 mg/kg,the frequency of fibrinogen monitoring should be increased.