Mitochondrial DNA mutations are one of the most important causes of sensorineural hearing loss. A1555G and C1494T mutations of mitochondrial 12S rRNA gene are the molecular basis for aminoglycoside hyper- sensitivity and can lead to aminoglycoside-induced hearing loss. Primary mutations in tRNA such as tRNA(Ser(UCN))7472insC are associated with syndromic hearing loss. While other mutations such as tRNA"(Se(UCN) )G7444A were considered synergy with the primary RNA mutations, modulating the phenotypic manifestation. This review de- scribes a detailed summary of hearing loss associated with mtDNA mutations and/or aminoglycoside antibiotics, and provides the possible molecular mechanisms in deafness expression.
Aminoglycosides ; adverse effects ; Anti-Bacterial Agents ; adverse effects ; DNA, Mitochondrial ; genetics ; Hearing Loss, Sensorineural ; chemically induced ; genetics ; Humans ; Mutation ; RNA, Ribosomal ; genetics

Objective To investigate introvoxel incoherent motion (IVIM) sequence features of cervical cancer and to analyze the difference between cervical cancer and normal cervix by using biexponential model parameters of IVIM sequence.Methods MR imaging data of 26 patients with cervical cancer confirmed by surgical pathology and 26 patients of normal cervical confirmed by clinical or MR examination were analyzed retrospectively.All patients underwent routine pelvic MRI sequences,including T1WI,T2WI,DWI (b =800 s/mm2) and IVIM sequence.The IVIM sequence was applied using a biexponential model with factors from 0 to 1200 s/mm2.The standard ADC,slow ADC,fast ADC and fraction of fast ADC values of cervical cancer and normal cervix groups were measured and analyzed by using t test.Diagnostic efficacy of these parameters in cervical cancer group was evaluated by using area under the curve.Results The standard ADC,slow ADC,fast ADC and fraction of fast ADC of cervical cancer group were (0.47 ± 0.09) × 10-3 mm2/s,(0.45 ± 0.09) × 10-3 mm2/s,(5.00 ± 1.68) × 10-3 mm2/s,0.30 ±0.06 and those of normal cervical group were (0.77 ± 0.15) × 10-3 mm2/s (0.61 ± 0.06) × 10-3 mm2/s,(4.29 ±0.57) × 10-3 mm2/s and 0.44 ± 0.04,respectively.The differences of standard ADC,slow ADC value and fraction of fast ADC value between two groups were statistically significant (t =8.841,7.540,10.591,P ＜0.01,respectively).There was no difference of fast ADC between the two groups (t =0.120,P ＞ 0.05).The area under the curve of fraction of fast ADC was the maximum,and it may be the most valuable parameter for the diagnosis of cervical cancer.Conclusions Cervical cancer group has characters on IVIM with lower standard ADC,slow ADC and fraction of fast ADC compared with the normal cervix group.IVIM sequence can reflect diffusion and perfusion of cervical cancer quantitatively.It may play a complementary role in the diagnosis and has some application prospects.

ObjectiveTo study the role and mechanism of low-dose aspirin with IFN-α in inhibiting growth and metastasis of hepatocellular carcinoma (HCC).MethodsMHCC97L cells were cultured and a metastatic model of human HCC was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude (nu/nu) mice.After administration of different doses of Aspirin and IFN-α for 40 days,the mice bearing xenografts in liver were killed,and the tumor volume and lung metastasis were evaluated.Cell proliferation and MMP-2 activity were measured by MTT and gelatin zymography,respectively.The expressions of VEGF and MMP-2 were measured by western blot and ELISA.ResultsCompared to the control group,there were no significant differences in the high-dose Aspirin [45 mg/(kg · d)] treated group regarding tumor volume [(1.89 ±0.88) cm3 vs (3.12±0.85) cm3,P＞0.05] and incidence of lung metastases (58.3％ vs 66.7％,P＞0.05),but the tumor volume and incidence of lung metastasis were significantly inhibited in the highdose IFN-α group [1.5 × 107/(kg · d)],the high-dose IFN-α combined with high-dose Aspirin group,and the low-dose IFN-α [7.5 × 106 / (kg · d) ] combined with low-dose Aspirin [15 mg/(kg · d] group (P＜0.05).2 mmol/L Aspirin did not inhibit the proliferation of MHCC97 cells (P＞0.05),but inhibited the activities and expressions of MMP-2 and VEGF.Low-dose IFN-α combined with low-dose Aspirin significantly decreased the expressions of MMP-2 and VEGF in nude mice (P＜0.05).ConclusionLow-dose Aspirin combined with low-dose IFN-α significantly inhibited the growth and metastasis of HCC through suppressing the expressions of MMP-2 and VEGF.

Objective To assess the diagnostic value of MR imaging in follow-up evaluation of patients with hepatocellular carcinomas ( HCC ) treated with radiofrequency ablation ( RFA ) and to compare it with that of multi-slice CT.Methods From December 2009 to September 2011,there were 48 patients (56 HCCs) treated with RFA after transcatheter arterial chemoembolization (TACE). MR imaging and multi-slice CT were performed for follow-up.Two radiologists independently reviewed these images,detection of residual or recurrent tumor were assessed on a five-point scale and compared with Kappa test and with the method of receiver operating characteristic (ROC) curve analysis.Sensitivity,specificity and accuracy were evaluated.Results The observer agreement rate for MR imaging was higher ( 0.925 ) than for multi-slice CT (0.701,P ＜ 0.05).The area under the ROC curve (AUC)of MR imaging( 0.987 and 0.971 by two radiologists respectively) was significantly higher than that of CT( 0.674 and 0.598 by two radiologists respectively),P ＜0.05. The sensitivity, specificity and accuracy of detection rate for MRI [100％(22/22),95.5％ (86/90) and 95.5％ ( 107/112),respectively] were significantly different with that for multi-slice CT [40.9％ ( 9/22 ),57.8％ ( 52/90 ) and 60.7％ ( 68/112 ),respectively]. Conclusion Diagnostic accuracy and detection rate of residual or recurrent tumor were found to be superior with MR imaging than with multi-slice CT.

Objective To evaluate diagnostic value of the novel virtual touch tissue imaging quantification (VTIQ) technique of acoustic radiation force impulse (ARFI) shear wave elastography in the differential diagnosis between benign and malignant thyroid lesions. Methods From June to July 2014, the imaging data of 82 thyroid lesions in 75 patients proven by fine needle aspiration cytology (FNAC) biopsy on conventional ultrasound and VTIQ were retrospectively analyzed. The thyroid nodules were examined by conventional ultrasound firstly and then the lesions were classified by thyroid imaging report and data system (TI-RADS). The maximum, minimum, median and average of shear wave velocity (SWV) values were obtained from multiple SWV measurement under the VTIQ speed mode. The region of interest (ROI) was determined according to the VTIQ quality mode after the patients holding the breath. According to the FNAC cytology results, ROC curve were plotted to determine the most accurate SWV value and the cut-off value for differential diagnosis. Results According to the FNAC results, grading≥5 level was set as the positive results and FNAC<5 level as the negative results. There were 28 positive nodules and 54 negative nodules in 82 thyroid nodules. The positive rates of TI-RADS classification were consistent with the theoretical results. The SWVmax, SWVmin, SWVmedian, and SWVmean on VTIQ of negative and positive thyroid nodules were (3.2±0.6), (2.2±0.4), (2.7±0.4), (2.6±0.4) m/s, and (4.6±1.7), (3.1±0.8), (3.5±1.0), (3.6±1.1) m/s. There were significant differences between positive and negative thyroid nodules in SWVmax, SWVmin, SWVmedian, and SWVmean on VTIQ (t=3.53, 3.68, 3.32, 3.81, all P<0.01). Based on the area under curve of ROC, the SWVmean value in the nodule was the best value in comparison with other SWV values. The cut-off value of VTIQ mean was 2.9 m/s. According to ROC curve analysis, the sensitivity, specificity and Youden index for VTIQ were 70.6%, 88.5%, 0.59, respectively. Conclusion The study proved that VTIQ elastography technique plays an important role in differential diagnosis of thyroid nodules and the VTIQ SWVmean is the best parameter for differential diagnosis.

Objective To investigate the role of the hypothalamus, medullary visceral zone (MVZ)and vagus in cerebral hemorrhage (CH) in multiple organ dysfunction syndrome (MODS) rat model.To reveal the possible regulatory mechanism of the hypothalamus-MVZ-vagus pathway in CMODS.Methods 80 Wistar rats were randomly divided into sham-operative group (n = 10), subdiaphragmatic vagotomy group (SDV, n = 10), CH group (n = 20), CH + SDV group (n = 20) and CH + vagus stimulation group (CH +SIV, n = 20).Rat CH model was made by stereotaxis injection of collagenase in caudate nucleus.Its endotoxin in serum was evaluated with a test kit.The expression of FOS in the hypothalamus and CHAT in the MVZ in the rats were examined using immunohistochemistry methods.Results Abnormality of hepatic and renal function, myocardium enzyme in CH + SDV group, CH + SIV group and CH group were more severe than those in sham-operative group and SDV group; CH + SDV group more severe than CH group.CH +SIV group were much milder than CH group.The serum endotoxin level (EU/ml) in CH group,compared with the sham-operated group, were significantly different (1.03 ± 0.25 and 0.18 ± 0.03respectively, t = 10.61, P <0.01).The expression of FOS in hypothalamus of CH + SDV group (9.3 ±2.6) were significantly higher than those in sham-operative group (2.5 ± 0.4, t = 8.17, P < 0.01) and SDV group (2.9 ±0.5, t =7.64, P <0.01), but significantly lower than those in CH group (48.6 ± 18.1,t =6.80, P<0.01); was higher in CH +SIV group than those in CH group (74.3 ±6.3 and 48.6 ± 18.1,t=4.23, P <0.01).The expression of CHAT in MVZ in CH + SDV group (138.5 ± 11.8) was significantly higher than those in sham-operative group (108.2 ±9.5, t =5.39, P <0.01) and SDV group (110.7 ±9.9, t =4.83, P <0.01), but significantly lower than those in CH group (164.4 ± 12.4, t =3.53, P <0.01); was higher in CH + SIV group than in CH group (189.4 ± 15.0 and 164.4 ± 12.4, t =3.14, P < 0.05).Conclusion Hypothalamus may be related to the nerve immunity adjustment in MODS after cerebral hemorrhage.The hypothalamus-MVZ-vagus pathway may be distinctive in CMODS.Vagus nerve may be a Bi-directional Channel of the rats following cerebral hemorrhage and MODS.

Objective To investigate the clinical value of 18F-FDG PET/CT in diagnosing G3 NEN and compare it with 68Ga-DOTA-NOC PET/CT.Methods Twenty-three patients (12 males,11 females;average age (63± 12) years) diagnosed of NEN between January 2006 and November 2016 were retrospectively recruited in this study:11 patients with gastroenteropancreatic NEN (GEP-NEN),10 with G3 NEN in lungs,1 with malignant pheochromocytoma and 1 with G3 NEN of unknown primary site.All patients underwent 18F-FDG PET/CT for staging and evaluation of biological behavior,and 9 of them also underwent 68Ga-DOTA-NOC PET/CT within 1 week.Image interpretation was analyzed by visual and semi-quantitative analysis,and SUVmax was calculated.Results All 23 cases showed positive results on 18F-FDG PET/CT (100％,23/23),with primary tumor SUVmax 10.56±3.94.Compared with 18F-FDG PET/CT,the positive detection rate of 68Ga-DOTA-NOC PET/CT was lower (6/9 vs 9/9),with primary tumor SUVmax 14.24± 10.00.There were 22 patients with distant metastasis.The most frequent metastatic sites associated with G3 NEN in lungs were lymph nodes and bones,while those with GEP-NEN were lymph nodes and the liver.In one patient with non-functional NEN,some metastatic lesions showed negative results on 18F-FDG PET/CT but positive results on 68 Ga-DOTA-NOC PET/CT.Conclusions 18 F-FDG PET/CT has higher diagnostic ability for G3 NEN and may serve as a useful tool for evaluating biological behavior of G3 NEN.68Ga-DOTA-NOC PET/CT is valuable as a complementary diagnostic tool in a small proportion of high differentiated G3 NEN.

OBJECTIVETo investigate whether gene expression profiles can be used to determine risk genes and predict HBV-related cirrhosis progression to liver carcinoma using Significance Analysis of Microarray (SAM) and Prediction Analysis of Microarray (PAM) methods.

METHODSThe Affymetrix GeneChip was used to establish the gene expression profiles of liver tissues from 15 patients with chronic hepatitis B and cirrhosis or hepatocellular carcinoma (HCC). Differentially expressed genes (fold-change more than 2; P value less than 0.01) were selected by GeneSpring GX software. Risk genes related to cirrhosis and liver carcinoma were generated by SAM and PAM methods. Real-time PCR was used to verify the expression of risk genes in the liver tissues.

RESULTSSamples were clustered into the cirrhosis subgroup (n =15) or the HCC subgroup (n =15). A total of 497 differentially expressed genes were identified, SAM identified 162 significant genes, including 18 up-regulated genes and 144 down-regulated genes (fold-change:-1.46 to 1.28). PAM identified 22 genes with a "poor risk signature" (defined with a threshold of 5.5), which were associated with classifying cirrhosis and liver carcinoma; of these risk genes, 4 were down-regulated and 18 were up-regulated in the HCC group compared to the cirrhosis group (fold-change: 2.038 to 7.897, P value less than 0.01). The correction of classification was more than 80% . FOXP1, SPINK1 and KCNJ16 were verified by real-time PCR as differently expressed in the two subgroups (P value =0.011, 0.002 and 0.004, respectively).

CONCLUSIONThe altered gene profiles of carcinogenesis in HBV-related cirrhosis involves hundreds of genes. The combination of three "poor risk genes" may represent potential targets for diagnosis and prediction of liver carcinoma progression.

Adult ; Carcinoma, Hepatocellular ; genetics ; pathology ; Female ; Gene Expression Profiling ; Hepatitis B, Chronic ; complications ; genetics ; pathology ; Humans ; Liver Cirrhosis ; genetics ; pathology ; virology ; Liver Neoplasms ; genetics ; pathology ; Male ; Microarray Analysis ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Transcriptome

BACKGROUNDConstructing replication defective recombinant adenovirus vector expressing the group specific antigen VP6 of human rotavirus and studying the immune responses induced in vivo.

METHODSThe cDNA of full length VP6 was inserted into the adenovirus vector pShuttle-CMV, and recombinant adenovirus genome DNA was obtained through homological recombination in E.coli,then the recombinant adenovirus was gained after transfecting 293 cell line with the genome DNA. Gene integration of VP6 in resultant adenovirus was confirmed by PCR and Southern blot, respectively gene expression was confirmed in 293 cells by Western blot. BALB/c mice were immunized intranasally(inl)and orally(ora), respectively, to test the immunization effects of the adenovirus.

RESULTSRecombinant adenovirus named rvAd-VP6 was obtained. The cDNA of VP6 was integrated in the adenovirus and was able to be expressed in 293 cells stably. The systemic immune responses to rotavirus VP6 could be induced effectively in both oral and intranasal group, the titer of serum IgG antibody in the two group of mice were 1?1 000 and 1?10 000-1?100 000, respectively. In addition to IgG, the serum IgA specific to VP6 could also be detected at a titer of 1?10-1?100. Secretory IgA(sIgA) was detected in both lung lavage fluid and intestinal homogenate when administered intranasally to BALB/c mice, whereas only found in intestinal homogenate in the oral group. The results indicated that the immunization efficacy of intranasal inoculation was superior to that of oral inoculation.

CONCLUSIONSThe recombinant adenovirus vector expressing human rotavirus VP6 was successfully constructed, its ability to induce immune responses has laid a solid foundation for the development of rotavirus genetically engineering vaccine against rotavirus infection.

Adenoviridae ; genetics ; Animals ; Antibodies, Viral ; blood ; Antigens, Viral ; Capsid Proteins ; biosynthesis ; immunology ; Genetic Vectors ; Mice ; Mice, Inbred BALB C ; Recombination, Genetic ; Rotavirus ; immunology

Objective:To describe the epidemiological characteristics of mental disorders in community resi-dents aged 18 years and over in the Chifeng City of Inner Mongolia Autonomous Region.Methods:Six thousand three hundred and seventy six individuals aged 18 years and over were sampled using stratified Probability-Propor-tional-to-Size Sampling in Chifeng City in 2010.All respondents were investigated by face-to-face interview.The Composite International Diagnostic Interview-3.0 Computer Assisted Personal Interview (CIDI-3.0-CAPI)was used to make diagnoses based on the definition and criteria of the Diagnostic and Statistical Manual of Mental Dis-orders,Fourth Edition (DMS-IV).Results:A total of 4528 subjects completed the CIDI-3.0-CAPI.Regarding anxi-ety disorder,mood disorder,substance use disorder,and impulse control disorder,the 30-day adjusted prevalence rates (95%CI)were 2.5%(2.08% -2.99%,0.9%(0.67% -1.23%),0.5%(0.34% -0.76%),and 0.6%(0.41% -0.86%)respectively,and the 12 -month prevalence rates were 4.5% (3.93% -5.15%),2.4%(2.0% -2.90%),1.1% (0.84% -1.45%),and 1.0% (0.74% -1.32%)respectively.The lifetime adjusted prevalence rates were 6.6% (5.92% -7.36%),6.5% (5.81% -7.24%),2.7% (2.26% -3.21%),and 1.4%(1.23% -1.95%)respectively.Conclusion:According to morbidity,anxiety disorders,mood disorder,substance use disorders and impulse control disorders are common in Chifeng City of Inner Mongolia Autonomous Region se-quencely,being a prominent public health problem.