MicroRNA(miRNA) affect various biological processes such as cell differentiation, proliferation, and apoptosis by inhibiting the translation of target genes after transcription and are widely involved in the regulation of immune and inflammatory responses in organisms. Autoimmune liver diseases are a group of chronic inflammatory diseases of the hepatobiliary system mediated by abnormal immunity, and abnormal immune inflammatory response of liver tissue with the involvement of miRNA is closely associated with the development and progression of autoimmune liver diseases. This article reviews the current research advances in miRNA in autoimmune liver diseases.

Objective:To analyze the incidence, biochemical and molecular characteristics, and gene mutation spectrum of neonatal methylmalonic acidemia (MMA) in Shaanxi province.Methods:This study involved 146 152 newborns undergoing neonatal screening for methylmalonic acidemia by tandem mass spectrometry in Northwest Women's and Children's Hospital from January 2014 and December 2019. Clinical manifestations and follow-up data of newborns diagnosed with MMA and their acylcarnitine profiles and gene mutations were analyzed. According to whether they had elevated homocysteine or not, these patients were divided into two groups, the complicated group and the isolated MMA group. The control neonates were those excluded from having methylmalonic acid by re-examination. Kruskal-Wallis and Mann-Whitney U test was conducted for statistical analysis. Results:(1) Twenty-one cases of MMA were confirmed with an incidence of 1/6 960, including 11 cases (52.4%) of isolated MMA (isolated MMA group) and 10 (47.6%) complicated by elevated homocysteine (complicated group). Eight patients in the isolated group had symptoms within one month after birth, mainly feeding difficulties, vomiting, drowsiness, poor response and infection, and five died. Patients in the complicated group were all diagnosed before developing typical clinical symptoms, and no developmental abnormalities were reported during follow-up. (2) Blood propionyl carnitine and its ratios to acetylcarnitine and free carnitine in the isolated MMA and complicated groups were higher than those in the control group [ M (min-max), 9.26 (3.70-37.78) μmol/L and 7.27 μmol/L (3.58-13.62 μmol/L) vs 4.51 μmol/L (1.48-8.69 μmol/L), H=23.239; 1.12 (0.32-2.43) and 0.74 (0.36-1.90) vs 0.25 (0.09-0.45), H=47.061; 0.94 (0.12-1.92) and 0.56 (0.18-1.03) vs 0.17 (0.06-0.38), H=36.868; all P<0.001]. The blood methionine level in the complicated group was significantly lower than that in the isolated MMA group [7.64 μmol/L (3.40-19.25 μmol/L) vs 24.22 μmol/L (10.73-56.55 μmol/L), U=3.000, P<0.001]. (3) All 21 patients carried complex heterozygous mutations or homozygous mutations in pathogenic genes, including 15 distinct MMUT mutations and 13 distinct MMACHC mutations. In the isolated MMA group, the most common mutation was c.323G>A (p.Arg108His) in the MMUT gene with a positive rate of 13.6%, and an unreported mutation, c.1676+11A>G, with unidentified clinical significance, was also found. The most common mutations in the complicated group were c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in the MMACHC gene, and the positive rates were both 20.0%. Moreover, two unreported variants, c.430-2A>C and c.648_650delAGA (p.216_217delSEinsS), were detected and suspected to be pathogenic. Conclusions:MMA is not uncommon in Shaanxi province. Children with isolated MMA tend to be more severe clinically. The identification of hotspot mutations, including c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in MMACHC gene and c.323G>A (p.Arg108His) in MMUT gene, provides a foundation for further genetic screening, counseling, and prenatal diagnosis, and is conducive to reduce the mortality and disability rate of neonatal MMA.

Betacoronavirus ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; Single-Cell Analysis

Objective To investigate the clinical effect of angioplasty for symptomatic intracranial atherosclerotic stenosis. Methods Eighty-two patients with symptomatic intracranial atherosclerotic stenosis whom underwent angioplasty after the failure of standard medical therapy were enrolled from Nan-jing Stroke Registry Program from September 2010 to June 2013.Nine of them underwent routine balloon angioplasty alone and 73 underwent intracranial stenting.The median time from onset to surgery was 24.5 days.The occurrence of endpoint events (any stroke ≤30 d after procedure,death and ischemic stroke >30 d in guilty vessels or original stenosis had restenosis and needed to be treated again)was assessed. The incidence of restenosis was followed up with imaging (CTA or DSA). Results (1)In the 82 patients, the success rate of operation was 92.7%(n=72 ),and 78 (95.1%)received follow-up,4 were lost to follow-up.The median follow-up time was 22.5 months (range 9 to 29 months ).Ten patients had an endpoint event,7 of them were ischemic stroke,1 was cerebral hemorrhage,and two were severe asymptomatic restenosis who underwent stenting again.The endpoint events of 3 patients occurred at day 30 after procedure (at ≤24 h after procedure).Kaplan-Meier curves showed that the incidences of cumulative endpoint events at 1,6,12,and 24 months were 3.7%,8.6%,11%,and 13%,respectively.(2)60 patients (73.2%)received imaging examination (11 CTA and 49 DSA ).Restenosis occurred in 17 patients (28.3%),among them the incidence of symptomatic restenosis was 5%(n =3 ),and asymptomatic restenosis was 23.3%(n=14). Conclusion After a comprehensive assessment and a rigorous screening, the safety is high and the mid- and long-term efficacy are satisfactory in patients with symptomatic intracranial arterial stenosis who are treated with angioplasty when their medical treatment is invalid.

Objective To investigate the effects of the intervention,rehabilitation and speech development of children with severe hearing loss in some rural areas.Methods 61 children,including 35 males and 26 females,were diagnosed as severe hearing loss with ABR and 40 Hz-AERP from June 2004 to July 2008.All the children failed hearing screening or visited the hospital as outpatients.The ages ranged from 2 to 72 months with the average age of 17.59 months.During telephone follow-up,the questionnaire was used to gather the data regarding the usage of hearing aids,hearing and speech rehabilitation,speech development,and communication abilities.Results 33 (54.10%) children were fitted with hearing aids,and 2 (3.28%) received cochlear implants,while 26(42.62 %) neither had hearing aids nor cochlear implants.10 cases with hearing aids also had speech training,whereas 23 children with hearing aids did not receive the training.2 cases with cochlear implants and 2 cases with hearing aids were found to have good speech development and communication ability,while 31 cases with hearing aids had delayed speech development.26 cases without any devices had to rely on sign language for their commumication.Conclusion Children in rural area with severe hearing loss experience greater speech and communication difficulties because many of them have no access to intervention and speech training.The results suggest that it would be very important to increase public awareness and educate parents to have their children wear hearing aids and receive speech training.

Objective:To investigate the feasibility of universal newborn hearing screening in countryside in order to provide reliable evidence in launching this program all over the countryside of China. Method:Subjects were 12 638 infants who were born in 9 counties from Jan 2004 to Dec 2005. TEOAE was used for the fast hearing screening. Infants were screened on the 2-7 days after the birth. The re-screening was conducted in 4-6 weeks if failed in the initial screening,and follow-up were provided continually if they also failed in the re-screening. Result; Ten thouand eight hundred and forty-five of 12 638(85. 8%) were screened including 9 963(91. 9%) normal newborns and 882(8. 1%) newborns with high-risk. Seven thouand four hundred and fifty (68. 7%) newborns passed the initial screening, and 3 395 (31. 3%) people failed. One thouand seven hundred and ninty-three (14. 2%) infants were refused to be screened.Only 2 536 (74. 7%) were re-screened on time, and 859(25. 3%) did not receive re-screening. One hundred and twenty were failed in the re-screening or first screening, and 79 (65. 8%)of them received diagnostic assessment. Among the infants received diagnostic assessment, 6(7.6%)ca-ses were found to have profound hearing loss in both ears, 9(11. 4%)cases were found to be severe hearing loss(7 in both ears and 2 in single ear) , 11(13. 9%)cases were found to be moderate hearing loss (5 in both ear and 6 in single ear), 26 (32. 9%) were found to have slight hearing loss (11 in both ear and 15 in single ears), and 27 (34.2%) were normal. Fifty-two infants were diagnosed as hearing loss with a prevalence of congenital hearing loss(in binaural and monaural) of 0. 5%(52/10845)and a prevalence of bilateral hearing loss of 0. 3%(29/10845). A prevalence of congenital hearing loss was 0. 2% (22/9 963) in well infants and 3. 4% (30/882) in high risk infants. Among the 13 cases of children with severe and profound hearing loss in both ears children, 8(61. 5%)cases were fitted with hearing aids and 1 (7. 7%) case was implanted with cochlear implants. Conclusion:It is necessary and feasible to conduct hearing screening program in the rural area. However, the suitable model to perform the program in the countryside needs to be set up as soon as possible in order to get more poor infants to participate into the hearing screening program for free and increase the screening rate.

OBJECTIVE: To investigate the feasibility of universal newborn hearing screening in countryside in order to provide reliable evidence in launching this program all over the countryside of China. METHOD: Subjects were 12,638 infants who were born in 9 counties from Jan 2004 to Dec 2005. TEOAE was used for the fast hearing screening. Infants were screened on the 2-7 days after the birth. The re-screening was conducted in 4-6 weeks if failed in the initial screening, and follow-up were provided continually if they also failed in the re-screening. RESULT: Ten thousand eight hundred and forty-five of 12,638 (85.8%) were screened including 9,963 (91.9%) normal newborns and 882 (8.1%) newborns with high-risk. Seven thousand four hundred and fifty (68.7%) newborns passed the initial screening, and 3,395 (31.3%) people failed. One thousand seven hundred and ninety-three (14.2%) infants were refused to be screened. Only 2,536 (74.7%) were re-screened on time, and 859 (25.3%) did not receive re-screening. One hundred and twenty were failed in the re-screening or first screening, and 79 (65.8%) of them received diagnostic assessment. Among the infants received diagnostic assessment, 6 (7.6%) cases were found to have profound hearing loss in both ears, 9 (11.4%) cases were found to be severe hearing loss (7 in both ears and 2 in single ear), 11 (13.9%) cases were found to be moderate hearing loss (5 in both ear and 6 in single ear), 26 (32.9%) were found to have slight hearing loss (11 in both ear and 15 in single ears), and 27 (34.2%) were normal. Fifty-two infants were diagnosed as hearing loss with a prevalence of congenital hearing loss (in binaural and monaural) of 0.5% (52/10845) and a prevalence of bilateral hearing loss of 0.3% (29/10845). A prevalence of congenital hearing loss was 0.2% (22/9,963) in well infants and 3.4% (30/882) in high risk infants. Among the 13 cases of children with severe and profound hearing loss in both ears children, 8 (61.5%) cases were fitted with hearing aids and 1 (7.7%) case was implanted with cochlear implants. CONCLUSION It is necessary and feasible to conduct hearing screening program in the rural area. However, the suitable model to perform the program in the countryside needs to be set up as soon as possible in order to get more poor infants to participate into the hearing screening program for free and increase the screening rate.
China ; epidemiology ; Feasibility Studies ; Hearing Loss ; diagnosis ; epidemiology ; Hearing Tests ; Humans ; Infant, Newborn ; Neonatal Screening ; Otoacoustic Emissions, Spontaneous ; Prevalence ; Rural Population

Objective To study the correlation between N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac diastolic and systolic function. Methods 60 New Zealand male rabbits were randomly assigned to two groups. The abdominal aorta 1 cm just above right renal artery were constricted in operated group. The clinical manifestation of heart failure was observed, and cardiac structure and function were investigated with echocardiography. Concentration of serum NT-proBNP was determined regularly. Results The concentration of NT-proBNP was correlated with Sm（r=－0.635,P=0.000）, Em（r=－0.693,P=0.000）, E/Em（r=0.688,P=0.000）, E/Vp（r=0.707, P=0.000）, and EF（r=－0.395,P=0.001）. Conclusion Concentration of serum NT-proBNP could prognose the diastolic and long axis systolic function of left ventricle.

Objective To establish an animal model of heart failure with preserved ejection fraction(EF)resulting from hypertension.Methods35 male New-Zealand rabbits were randomly assigned to 2 groups:constriction was performed at the abdominal aorta 1 cm just above right renal artery in operated group(n=25),and the sham-operated animals were taken as control group(n=10).The clinical manifestations of heart failure were followed up carefully.Systolic and diastolic function,and systemic hemodynamics were investigated with echocardiography and left ventricle catheter.ResultsIn operated group,marked ventricular hypertrophy was observed 2 weeks after operation.4 weeks after operation,the clinical manifestations of heart failure presented,and IVRT and LVEDP increased,and-dp/dt max decreased.Tissue doppler image indicated that e/a ratio of annulus of mitral valve decreased(P<0.05).However,EF and +dp/dt max were preserved.ConclusionThe operated animals presented the clinical manifestation of heart failure,and diastolic function of left ventricle injured,however,ejection fraction was preserved,which corresponded with the character of heart failure with preserved ejection fraction resulting from hypertension.

Objective To increase the sensitivity of quantitative PCR using DNA polymerase in combination with aptamer 6-10.Methods The quantitative PCR was performed using DNA polymerase mixed with aptamer 6-10 or specific antibody.The low detection limit of each modified method was compared with that of the conventional method.Results The quantitative PCR using aptamer 6-10(200 nmol/L) or specific antibody increased the low detection limit of human death receptor 5(DR5) plasmid from 105 copies/?l to 103 copies/?l.Melting curves showed that each method had minimal nonspecific amplification when the concentration of DR5 plasmid was 105 copies/?l;however,when the concentration of DR5 plasmid was 103 copies/?l,the conventional method had nonspecific amplification,whereas the method using aptamer 6-10 had minimal nonspecific amplification.Conclusions Aptamer 6-10 of DNA polymerase can increase the sensitivity of quantitative PCR.