Objective To analyze and determine the genetic characteristics of a large Chinese family with autosomal dominant nonsyndromic deafness(named pedigree Z029).Methods A hereditary deafness family was found from the profuse genetic resource established in the Otolaryngology Institute of PLA General Hospital.A sequence of bilateral sensorineural hearing impairment transmitted through five generations was found by investigating 47 individuals in the pedigree.The genetic forms of hearing loss in 18 members of the Z029 pedigree were diagnosed by otologic,audiologic,and physical examination,as well as by the study on their family history.Pedigree map was drawn by using Cyrillic2.1 software.Results The phynotype of Z029 family showed that most affected individuals had sensorineural hearing impairment with subsequent gradual progression covering all frequencies.The phynotype was transmitted from 1 to 5 generations.One of the parents of every patient was definitely a patient of the same disease.The affected ratio was same in both sexes,and the incidence of deafness declined through the first to fifth generation.Conclusion The phenotype characteristics of Z029 family were of autosomal dominant nonsyndromic hereditary deafness.In this pedigree,hearing impairment occurred in the majority of affected individuals after their twentieth year of age,and the penetrance of the impairment appeared to be age-correlated.No obvious vestibular dysfunction and other associated abnormalities were found.It may provide a foundation for the study of gene mapping and gene cloning of the pathogenic gene to analyze and determine the phenotype characteristics of this pedigree.This pedigree also provided an excellent model for the further study on the pathological and molecular mechanisms of hereditary hearing impairment related to age.

BACKGROUND: Angiostatin(AS) can effectively inhibit proliferation and migration of vascular endothelial cells and also inhibit tumor angiogenesis.OBJECTIVE: To observe the inhibitory action of angiostatin, 131I and 131 I labeled angiostatin(131I-AS) on proliferation of human umbilical vein endothelial cell ECV304 and on mass and volume of Lewis lung carcinoma (LLC) in mice.DESIGN: A randomized controlled trial with human umbilical vein endothelial cell ECV304 and Lewis lung carcinoma tumors growing in C57BL/6 mice as subjects of research.SETTING: A radiological lab and a nuclear medicine department in a military university.MATERIALS: Totally 28 LLC carrying male C57BL/6 mice, weighing(20± 2) g, 5 - 7 weeks old.METHODS: 131I-AS solutions of four concentrations were made: solution A(131I 0. 74 GBq/L, AS 0. 5 mg/L); solution B(131I 0.74 GBq/L, AS 16 mg/L); solution C(131I 1.48 GBq/L, AS 0.5 mg/L); solution D(131I 1.48 GBq/L, AS 16 mg/L). The effect of 131I-AS, AS alone and 131I alone on proliferation of human umbilical vein endothelial cell ECV304 was observed with MTT method. The 28 tumor carrying mice were randomly assigned into 4 groups, in each of which was injected 0.3 mL of 131I AS(131I 11.1 MBq and AS 2.5 mg/kg), AS(2.5 mg/kg), 131I(11.1MBq) and saline respectively for twice with 7 days interval. Then the change in tumor mass and volume was observed.MAIN OUTCOME MEASURES: ① The inhibition rate on cell proliferation with MTT method; ② Change in tumor mass and volume.RESULTS: ① The inhibition rate of AS alone(0. 5 -64 mg/L) on ECV304 was (7.3 ± 3.5) % - (41.9 ± 4. 3 )% ( P = 0. 003 vs AS of 0). The inhibition rate of the 4 concentrations of 131I-AS on ECV304 was(23.9±2.8)% ,(58.2±3.9)%, (39. 1 ±4. 1)% and(78.4 ±5.4)%, which were much higher than AS alone or 131I alone( P =0. 000 3) . ② The mean volume of LLC in the four groups were (3 943 ± 236), (5 219 ± 351 ), ( 1 963 ± 126),(7 353 ±350) mm3 respectively. Compared with saline group, the tumor inhibiton rate in the other 3 groups were 46.4% , 29.0% , 73.3% respectively( P =0. 000 1 ).CONCLUSION: 131I-AS inhibits proliferation of endothelial cells in vitro and inhibits LLC growth in vivo and it outdoes AS or 131I alone.

Objective:To observe the effect of tuina manipulations on blood pressure and its variability in hypertension patients. Methods:Forty hypertension patients were randomized into an observation group and a medication group, 20 cases in each group. The observation group was intervened by tuina manipulations of kidney-tonifying blood-circulating and collaterals- unblocking in addition to regular medication, while the medication group was by the same medication. The 24-hour blood pressure monitoring was performed before intervention and after 3-month intervention. The blood pressure and its variability were observed and compared. Results:There were no significant differences in comparing the blood pressure and blood pressure variability between the two groups before intervention (P>0.05); after 3-month intervention, the blood pressure and its variability were significantly improved in both groups (P<0.05); the improvements in the observation group were more significant than those in the control group (P<0.05). Conclusion:Tuina manipulations of kidney-tonifying blood-circulating and collaterals-unblocking plus medication can produce a better effect than regular medication in promoting blood pressure and its variability, and this method is worth applying in clinic as it’s easy-to-operate and has no adverse effect.

Knee osteoarthritis (KOA ) is a common chronic degenerative disease in the elderly population .It is character-ized by knee-joint pain ,swelling ,morning stiffness and seriously affects the patients′motor function and physical health .So far ,there is no early diagnosis and effective treatment for it .This paper outlined the recent researches on knee osteoarthritis and inflammatory cytokines to discuss the relationship between knee osteoarthritis and inflammatory factors such as IL-1β,IL-6 ,TNF-α,TGF-β,IL-10 ,IL-17 and IL-37 ,and provide the theoretical basis for the diagnosis and treatment of knee osteoar-thritis .

OBJECTIVE This study aimed at identifying inner ear malformation underlying molecular determinant(s) using a large five-generation Chinese family with multiple familial cases. METHODS Model-based genetic linkage analyses were performed with the use of microsatellite polymorphisms to determine the disease locus. Mutation screening was performed with the family and unrelated population-based controls to establish molecular evidence that caused the specific X-linked inheritance pattern in the family. RESULTS Clinical investigations of the pedigree demonstrated the extremely high penetrance in the male members, but no penetrance in the female members. Linkage analyses mapped the disease to the chromosomal region Xq13.1-Xq23 (maximum X-linkage LOD score = 3.27). Mutation screening of the candidate genes in the linkage region by direct sequencing revealed a de novo missense substitution (925T→C) in the well-known deaf gene POU3F4. Direct sequencing on 110 unrelated controls did not detect any mutation. CONCLUSION a novel mutation of POU3F4 gene was identified to be the causative reason for the hearing loss in family with inner ear malformation.

OBJECTIVE To investigate whether the KCNN4 gene and KPTN gene contribute to a Chinese non-syndromic hearing loss pedigree linked to DFNA4 with positional candidate approach. METHODS The complete coding region of the two genes were amplified with polymerase chain reaction (PCR), and bidirectional sequencing of the PCR products was subsequently applied in the 36 family members to identify the possible mutations or polymorphisms in the candidate genes. RESULTS Sequence analysis of coding regions and splice sites of the two candidate genes in 36 members including 12 hearing-impaired individuals in family Z002 failed to demonstrate any deafness-causing mutations of KCNN4 gene. There was one heterozygous mutation identified in exon10 coding sequence (942C/T) of KPTN gene, which did not result in amino acid change (P302P) as a repoerted synonymous SNP site (rs2293424). This SNP site did not cosegregate with the phenotype of family Z002. CONCLUSION Our study excluded the two candidates, KCNN4 and KPTN , as the causative genes involved in this Chinese DFNA4 pedigree.

OBJECTIVE To investigate the contribution of the GJB6 gene [encoding connexin 30 (C?30)] mutations in Chinese population with sporadic non-syndromic hearing impairment. METHODS PCR reactions were performed with two pair of primers for the coding sequence of GJB6 gene and for the deletion of GJB6. PCR products bidirectional sequencing was subsequently applied in 214 patients with hearing loss and 86 normal controls. RESULTS A novel heterozygous mutation-233(C→A) was found, which results in amino acid change, A78D. This mutation wasn't detected in the control subjects. The altered valine residue lies within the second conserved transmembrane domain. The large deletion△(GJB6/ D13S1830)] of GJB6 was not found in this group. CONCLUSION The large deletion of GJB6 was not found in the Chinese deafness population. A novel heterozygous mutation of GJB6 was found. These results indicated GJB6 mutations are not a major cause of hearing loss in the Chinese population.

OBJECTIVE To investigate the incidence of the mitochondrial DNA 12SrRNA A1555G and connexin 26 gene (GJB2) in Chinese northwest population with nonsyndromic sensorineural hearing loss,and to explore the relationship between mitochondrial DNA A1555G and mutation of GJB2 gene. METHODS Blood samples were obtained from 221 patients with nonsyndromic sensorineural hearing loss in Northwest of China; Genomic DNA was extracted from the isolated leukocytes ; Screening the mitochondrial A1555G mutation by PCR-Alw26l digestion and sequence analysis, PCR and direct sequencing were used to analyze the coding region of GJB2 gene. RESULTS The homoplasmic A1555G mutation was found in 21 individuals of 221 patients,17 of these 21 patients had been treated with aminoglycosides. Eleven different variants of GJB2 were found in all patients ,the disease-causing mutations of GJB2 were 44 individuals in these patients(44/221), The mutation 235delC is found in 54.54 % of all disease-causing mutations ; Among 21 patients with the A1555G mutation, 11 cases were found polymorphic change in GJB2 gene ,only 1 case had V37I heterozygous mutations ,other 9 cases were not found any nucleotide changes of GJB2 gene. CONCLUSION The mtDNA 12SrRNA A1555G mutation has a high incidence in Chinese northwest population with non-syndromic sensorineural hearing loss.The 235delC mutation in the GJB2 gene is most frequent mutations responsible for non-syndromic hearing impairment in this region .It is unlikely that the GJB2 gene is a major modulatory factor for hearing loss due to the A1555G mutation in Chinese population.

Objective: To analyze the clinical characteristics of hepatic flare and evaluate efficacy of antiviral treatment in pregnant women with chronic HBV infection. Methods: A single-center, open-label, prospective study was conducted, and pregnant women with chronic HBV infection were enrolled. Liver function, HBV serum markers and HBV DNA of pregnant women with chronic HBV infection were reviewed during every 4 to 12 weeks of gestation period. The proportion and clinical characteristics of hepatitis flare during pregnancy were observed. Logistic regression analysis was used to predict hepatic flare in pregnant women with chronic HBV infection. Antiviral therapy with telbivudine (LdT) or tenofovir dipivoxil (TDF) was used to treat hepatic flare during pregnancy. Sequential entecavir (ETV) or TDF was applied after the delivery. Treatment course and drug withdrawal in pregnant women with hepatic flare was the same as those of the general patients with chronic hepatitis B. Liver function, HBV serum markers and HBV DNA were measured in pregnant women with hepatic flare at different time points (4, 12, 24 and 52 weeks). A t-test was used to compare the hepatic flare in pregnant women with and without hepatitis group. HBsAg and HBeAg were used to quantify the receiver operating characteristic (ROC) curve of pregnant women with hepatic flare during pregnancy. Area under the ROC curve was used to calculate the optimal cut-off value corresponding to the maximum sensitivity and specificity of the ROC curve. Results: Of the 220 pregnant women with chronic HBV infection, 55 (25%) had hepatitis flare during pregnancy and received antiviral treatment. Among the 55 women with hepatic flare during gestation, 47 (85.46%) had hepatic flare in the mid-second trimester (12-24 weeks); average peak value of alanine aminotransferase (ALT) was 220.62 U/L, and the average peak value of ALT in 32 cases (58.18%) of pregnant women with hepatic flare was between 2–5 × ULN. HBsAg and HBeAg quantification were significantly lower in pregnant women with hepatic flare during pregnancy than with non-hepatitis (t = -3.745, P < 0.001; t = -2.186, P = 0.030). Multivariate logistic regression analysis showed that pregnant women with HBeAg < 3.065 log10 s/co were 7.576 times more likely to have hepatic flare during pregnancy (95% confidence interval: 3.779-15.190). ALT normalization, undetectable HBV DNA levels, HBeAg loss and HBeAg seroconversion in 55 pregnant women with hepatic flare at 52-week treatment was 100% (55/55), 74.55% (41/55), 47.27% (26/55) and 41.82% (23/55), respectively. HBsAg quantification at 52 weeks was significantly lower than baseline HBsAg quantification (3.32 + 0.37) log₁₀ IU/ml and (3.95 + 0.40) log₁₀ IU/ml; t = 8.465, P < 0.001). Conclusion Hepatic flare often occurs in the second trimester of pregnancy in pregnant women with chronic HBV infection and baseline HBeAg quantification is an independent predictor of hepatic flare. HBeAg seroconversion rate increased at 52 weeks after antiviral therapy.

Objective:To explore the experience of self-management dilemma ofadults with emerging ankylosing spondylitis, and to provide reference for the construction of self-management intervention strategies for emerging adults with ankylosing spondylitis.Methods:Descriptive phenomenology was used to conduct in-depth interviews with 14 adults with emerging ankylosing spondylitis in the Rheumatology and Immunology Department of Drum Tower Hospital Affiliated to Medical College of Nanjing University from August 2022 to March 2023. The interview data were analyzed by Colaizzi′s seven-step analysis method.Results:A total of 14 patients completed the interview,10 males, 4 females, aged 21-30 years. In adults with emerging ankylosing spondylitis, there were dilemmas of role maladjustment and disease management disorder, including role maladjustment of disease management and social role maladjustment. Barriers to disease management included weak self-management awareness, insufficient support for self-management information, inadequate self-management skills, and poor compliance with self-management behaviors.Conclusions:The role adaptation and self-management ability of adults with emerging ankylosing spondylitis are seriously inadequate. It is urgent to construct health management strategies for adults with emerging ankylosing spondylitis to help them improve the level of role adaptation and disease management.