Objective:To investigate the pathogenic variants and function of a pedigree with syndromic hearing loss using high-throughput sequencing.Methods:Detailed medical history and pedigree history were inquired, and a pedigree chart was drawn. Hearing examinations were performed on this pedigree, and whole-exome sequencing and bioinformatics analysis were performed to screen for suspected pathogenic variants. Then, Sanger sequencing was used to test co-segregation in the family, and transcriptome sequencing was used to investigate the effect of a variant on splicing.Results:The proband has auditory neuropathy combined with symptoms such as development delay, muscle weakness, and seizure. The patient carries two variants in NARS2 (NM_024678.6), namely: c.779A>C (p.Glu260Ala) and c.372+3A>G (intronic variant), of which c.779A>C is inherited from the father and c.372+3A>G from the mother. Both variants have not been reported in the literature or included in any databases. Transcriptome sequencing results indicate that the c.372+3A>G variant leads to the skipping of the third exon during transcription. According to the American College of Medical Genetics and Genomics(ACMG) guidelines, the c.779A>C variant and c.372+3A>G are classified as likely pathogenic. Based on the patient′s phenotype and genetic testing results, the proband has been diagnosed with combined oxidative phosphorylation deficiency 24(COXPD24). Conclusions:The pathogenic variants in the NARS2 gene are the underlying cause of the patient′s disease. The identification of novel variants enriches the mutational spectrum of the NARS2 gene, providing evidence for further clarification of the relationship between NARS2 and COXPD24.

Objective:To investigate the pathogenic variants and function of a pedigree with syndromic hearing loss using high-throughput sequencing.Methods:Detailed medical history and pedigree history were inquired, and a pedigree chart was drawn. Hearing examinations were performed on this pedigree, and whole-exome sequencing and bioinformatics analysis were performed to screen for suspected pathogenic variants. Then, Sanger sequencing was used to test co-segregation in the family, and transcriptome sequencing was used to investigate the effect of a variant on splicing.Results:The proband has auditory neuropathy combined with symptoms such as development delay, muscle weakness, and seizure. The patient carries two variants in NARS2 (NM_024678.6), namely: c.779A>C (p.Glu260Ala) and c.372+3A>G (intronic variant), of which c.779A>C is inherited from the father and c.372+3A>G from the mother. Both variants have not been reported in the literature or included in any databases. Transcriptome sequencing results indicate that the c.372+3A>G variant leads to the skipping of the third exon during transcription. According to the American College of Medical Genetics and Genomics(ACMG) guidelines, the c.779A>C variant and c.372+3A>G are classified as likely pathogenic. Based on the patient′s phenotype and genetic testing results, the proband has been diagnosed with combined oxidative phosphorylation deficiency 24(COXPD24). Conclusions:The pathogenic variants in the NARS2 gene are the underlying cause of the patient′s disease. The identification of novel variants enriches the mutational spectrum of the NARS2 gene, providing evidence for further clarification of the relationship between NARS2 and COXPD24.

Objective: To understand the consciousness of the cancer early treatment and its demographic and socioeconomic factors. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China (CanSPUC) from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The questionnaire collected personal information, the consciousness of the cancer early treatment and relevant factors. The Chi square test was used to compare the difference between the consciousness of the cancer early treatment and relevant factors among the four groups. The logistic regression model was used to analyze the influencing factors related to the consciousness of the cancer early treatment. Results: With the assumption of being diagnosed as precancer or cancer, 89.97% of community residents, 91.84% of cancer risk assessment/screening population, 93.00% of cancer patients and 91.52% of occupational population would accept active treatments (P<0.001). If the immediate family members were diagnosed as precancer or cancer, people who would encourage their family members to receive early treatment in the four groups accounted for 91.96%, 91.94%, 92.44% and 91.55%, respectively (P<0.001). The company employees, annual household income with 40 000 yuan and more and other three groups had a relatively better consciousness of the cancer early treatment (P<0.05). Male, widowed, unemployed and from the central and western regions had a relatively worse consciousness of the cancer early treatment (P<0.05). Conclusion Residents in urban China participants had a good consciousness of the cancer early treatment. The marital status, occupation, annual household income and residential regions were major factors related to the consciousness of the cancer early treatment.

Objective To explore the origin of ovarian high grade serous carcinoma(HGSC) through analysing the expression and significance of PAX8,PAX2,p53 and RAS in the ovary and fallopian tube of different types and grades of serous carcinoma. Methods A total of 44 cases tissue samples of ovarian tumor including 34 malignant ovarian tumor and 10 normal normal tissue (as control group) were collected from the admitted patients in Affiliated Tumor Hospital of Guangxi Medical University from January 2015 to January 2016. Fallopian tube tissues were segmented in accordance with the fimbria, ampulla, isthmus and the corresponding ovarian tissues were by the side. There were 34 cases of patients with ovarian cancer including 29 cases of epithelial ovarian cancer (27 serous carcinoma, 1 mucinous carcinoma,1 endometrioid adenocarcinoma)and 5 non-epithelial ovarian cancer(sex cord-interstitial tumor). Among 27 cases of patients with ovarian serous cancer,there were 23 HGSC and 4 low-grade ovarian serous cancer (LGSC). One hundred fifty-three cases of samples were diagnosed as ovarian serous cancer by Shandong University Affiliated Qilu Hospital from 2005 to 2013 and these samples were made tissue microarray.(1)To analyze the expression and differences of PAX8,PAX2,p53 and RAS in the above tissues and tissue microarray from ovarian and tubal of HGSC and control women by immunohistochemistry methods.(2)To compare the expression levels of PAX8,PAX2,p53 and RAS in ovarian and fallopian tubes of ovarian cancer patients with different pathological types. (3) To analyze the correlations of tubal and ovarian tissue in PAX8,PAX2,p53 and RAS expression of HGSC.(4)To analyze the factors of the prognosis of ovarian serous cancer in tissue microarray by single factor analysis method. Results (1)PAX8,PAX2, p53 and RAS expression was negative in normal ovarian epithelium of control group,but the expression of PAX8, PAX2, p53 and RAS were strongly positive brown in secrete cells of normal fallopian tube epithelium.(2)p53 and RAS expression of fallopian tube epithelium in the epithelial ovarian cancer group were significantly higher than those in the non-epithelial ovarian cancer groups(P<0.05),but the expression of PAX8 and PAX2 in fallopian tube and the expression of PAX8,PAX2,p53 and RAS in ovarian tissue was not statistically significant in the groups(P>0.05).PAX8,PAX2 and p53 expression of the ovarian in HGSC group were significantly higher than those in LGSC group(P<0.05),while the expression of RAS was lower in the ovarian of the high-grade group (P<0.05), while the expression of PAX8, PAX2, p53 and RAS in fallopian tube was not statistically significant in the groups(P>0.05).(3)There was a significantly positive correlation between fallopian tube and the corresponding ovary of HGSC in PAX8 and PAX2 expression(r=0.422, P=0.045; r=0.693, P=0.000), but not correlation in p53 and RAS expression (r=0.058, P=0.793; r=-0.190,P=0.384).(4)Univariate survival analysis showed that the progression free survival time in patients with ovarian serous cancer group was significantly correlated with the protein expression of PAX8, PAX2 and RAS(P<0.05),but there were not correlated with age,surgical staging,cell differentiation,lymph node metastasis and preoperative chemotherapy and p53 protein expression (P>0.05). The total survival time in patients with ovarian serous cancer group was significantly correlated with the protein expression of PAX8 (P<0.05),but there were not correlated with age,surgical staging,cell differentiation,lymph node metastasis and preoperative chemotherapy and the protein expression of PAX2, RAS and p53 (P>0.05). Conclusions PAX8, PAX2, p53, RAS are of great significance for the study of origin of HGSC. HGSC may be derived from fallopian tube, but further investigation would be necessary to confirm this. PAX8, PAX2, p53, RAS could be expected to be used as predictors of survival prognosis in patients with ovarian serous cancer.

Objective: To analyze the efficiency characteristics and trend of tertiary general public hospitals from both static and dynamic perspectives. Methods: After collecting data of personnel, equipment, assets, health services and other inputs-output indicators from 50 tertiary public hospitals from 2006 to 2012 , this paper uses C2 R-DEA and BC2-DEA models, as well as Malmquist Index model to build suitable analysis model. Results:About 10%~12% of the sample hospitals are in a relatively effective operational state, and the mean values of allocation effi-ciency and scale efficiency are 0. 956 and 0. 943, respectively, which are close to the efficient frontier. The mean values of pure technical efficiency, technical efficiency, cost efficiency and overall efficiency are 0. 796, 0. 784, 0. 714 and 0. 714, respectively, which are relatively poor compared with the efficiency frontier. Moreover, the number of hospitals that are in the state of diminishing returns to scale increased from 7 . 69% to 26 . 31%, while the number of hospitals that are in the state of increasing returns to scale decreased from 80. 77% to 58. 34%. The changes in techno-logical progress, Malmquist productivity index, technical efficiency index, pure technical efficiency index and scale effi-ciency index remained a relatively stable consistency, and showed continuous improvement and steady development trend. Conclusion:Tertiary general public hospitals are facing the transformation of driving force for development and incentive mechanisms. This needs not only to change the management concept and development mode of the hospitals, but also to build evaluation standards of optimum efficiency that are relevant to the structure, process and outcome, in order to pro-mote the transformation of hospital governance and development model that includes the functions of government.