Zebrafish larvae are useful for identifying chemicals against lateral line (LL) hair cell (HC) damage and this type of chemical screen mainly focuses on searching for protectors against cell death. To expand the candidate pool of HC protectors, a self-built acoustic escape response (AER)-detecting system was developed to apply both low-frequency near-field sound transmission and AER image acquisition/processing modules. The device quickly confirmed the changed LL HC functions caused by most known ototoxins, protectors, and neural transmission modifiers, or knockdown of LL HC-expressing genes. With ten devices wired in tandem, five 'hit' chemicals were identified from 124 cyclin-dependent kinase inhibitors to partially restore cisplatin-damaged AER in less than a day. AS2863619, ribociclib, and SU9516 among the hits, protected the HCs in the mouse cochlea. Therefore, using free-swimming larval zebrafish, the self-made AER-detecting device can efficiently identify compounds that are protective against HC damage, including cell death and loss-of-function.
Animals ; Zebrafish ; Hair Cells, Auditory/physiology* ; Lateral Line System/cytology* ; Escape Reaction/physiology* ; Larva ; Mice ; Cisplatin/toxicity* ; Drug Evaluation, Preclinical/methods*

Alcoholic steatohepatitis (ASH) is a liver disease characterized by steatosis, inflammation, and necrosis of the liver tissue as a result of excessive alcohol consumption. Pregnane X receptor (PXR) is a xenobiotic nuclear receptor best known for its function in the transcriptional regulation of drug metabolism and disposition. Clinical reports suggested that the antibiotic rifampicin, a potent human PXR activator, is a contraindication in alcoholics, but the mechanism was unclear. In this study, we showed that the hepatic expression of fatty acid binding protein 4 (FABP4) was uniquely elevated in ASH patients and a mouse model of ASH. Pharmacological inhibiting FABP4 attenuated ASH in mice. Furthermore, treatment of mice with the mouse PXR agonist pregnenolon-16α-carbonitrile (PCN) induced the hepatic and circulating levels of FABP4 and exacerbated ASH in a PXR-dependent manner. Our mechanism study established FABP4 as a transcriptional target of PXR. Treatment with andrographolide, a natural compound and dual inhibitor of PXR and FABP4, alleviated mice from ASH. In summary, our results showed that the PXR-FABP4 gene regulatory axis plays an important role in the progression of ASH, which may have accounted for the contraindication of rifampicin in patients of alcoholic liver disease. Pharmacological inhibition of PXR and/or FABP4 may have its promise in the clinical management of ASH.

Objective:To investigate the relationships between the expression level of human epidermal growth factor receptor 2 (HER2) in HER2-positive breast cancer and the characteristics of ultrasound imaging and mammography.Methods:The imaging data of 486 patients with HER2-positive breast cancer treated in the Harbin Medical University Cancer Hospital from January 2014 to December 2021 were retrospectively collected. The relationships between the expression level of HER2 and the imaging features of breast ultrasound and mammography were analyzed.Results:49.38% (240/486) of HER2-positive breast cancer patients were HER2 2+, and 50.62% (246/486) of HER2-positive breast cancer patients were HER2 3+. The age of HER2 2+ patients [ (52.88±1.16) years] was older than the age of HER2 3+ patients [ (49.59±1.00) years], and there was a statistically significant difference ( t=18.07, P<0.001) . There was a statistically significant difference of menstrual status between HER2 2+ patients and HER2 3+ patients ( χ2=4.42, P=0.036) . There were statistically significant differences in the ultrasonography showed burr sign ( χ2=8.37, P=0.010) , posterior echo ( χ2=9.68, P=0.017) , axillary lymph node enlargement ( χ2=15.77, P<0.001) between HER2 2+ patients and HER2 3+ patients. There was a statistically significant difference in the mammography showed whether there were lumps between HER2 2+ patients and HER2 3+ patients ( χ2=15.81, P<0.001) . Conclusion:The expression level of HER2 in HER2-positive breast cancer patients is related to burr sign, posterior echo, and axillary lymph node enlargement shown by ultrasound, as well as lumps shown by mammography, which can provide certain information for clinical prediction of malignant degree of breast cancer, prognosis and individualized treatment plan.

Objective:To investigate the clinical characteristics and risk factors of bronchiolitis obliterans (BO) after adenovirus pneumonia.Methods:Clinical data of 266 children with adenovirus pneumonia hospitalized in Children′s Hospital of Soochow University from January 2011 to December 2017 were retrospectively analyzed.Accor-ding to whether they developed BO, children with adenovirus pneumonia were divided into the BO group and the non-BO group.Clinical features of the BO group and the non-BO group were compared by t test, rank sum test or chi square test.Risk factors were analyzed by Logistic regression approach. Results:Among 266 children with adenovirus pneumonia included, 37 patients were developed into BO group, and their age was significantly younger than that of the non-BO group [12.0(8.0, 17.5) months vs.32.0(13.0, 48.0) months, P<0.001]. Compared with the non-BO group, there were more proportion of preterm infants[10.8%(4/37 cases) vs.3.1%(7/229 cases), P=0.028], more instances of comorbidities [21.6%(8/37 cases) vs.4.4%(10/229), P<0.001] and more children with allergic diseas[35.1%(13/37 cases) vs.20.1%(46/229 cases), P=0.041] in the BO group, and the difference was statistically significant.The duration of fever in the BO group was significantly longer than that of the non-BO group [10(4.0, 13.5) d vs.6(4.0, 9.0) d, P=0.011] children with symptoms of wheezing, shortness of breath, and hypoxemia in the BO group were significantly more than the non-BO group[81.1%(30/37 cases) vs.27.9%(64/229 cases), P<0.001; 64.9%(24/37 cases) vs.5.7%(13/229 cases), P<0.001; 59.5%(22/37 cases) vs.6.6%(15/229 cases), P<0.001]. The platelet count, IgG level, and CD3 -CD 19+ lymphocyte percentage were significantly higher in the BO group than the non-BO group [(364±104)×10 9/L vs.(297±105)×10 9/L, P=0.001; 6.74(4.92, 10.16) g/L vs.5.93(1.00, 8.04) g/L, P=0.016; (33.5±15.3)% vs.(26.1±10.2)%, P=0.008]. In contrast, the percentage of CD3 + CD4 + lymphocytes in the BO group was lower than the non-BO group[(29.1±8.0)% vs.(32.5±9.4)%, P=0.044], the difference was statistically significant.The BO group had a higher rate of mixed bacterial infection than the non-BO groups[37.8%(14/37 cases) vs.16.6%(38/229 cases), P=0.003]. An age<26 months, comorbidities, premature birth history, wheezing, shortness of breath, and hypoxemia were independent risk factors for BO after adenovirus pneumonia( OR=4.808, 30.667, 7.558, 3.909, 8.842, 8.607, all P<0.05). Conclusions:An age of less than 26 months, a history of premature delivery comorbidities, wheezing, shortness of breath and hypoxemia, are independent risk factors for BO after adenovirus pneumonia.Children with above manifestations should receive high resolution CT as soon as possible to determine whether it is BO.

Objective To study the epidemiological and clinical features of viral pathogen of acute respiratory tract infection(ARTI)in children in Suzhou. To provide the evidence-based medicine for early warning,diagnosis and treatment of respiratory tract infection in children. Methods The study population comprised of all the children ranging from 28 days to 15 years old with ARTI admitted to Department of Respiration,the Childrenˊs Hospital Affiliated to Soo-chow University,between January 2006 and December 2015. The study cases were divided into 4 age groups based on ages(28 days to <1 year old,1- <3 years old,3- <5 years old and ≥5 years old). The nasopharyngeal aspirates and medical history were obtained by qualified medical personnel. Seven kinds of common respiratory virus were detec-ted by using the direct immunofluorescence. Mycoplasma pneumonia(MP),chlamydia pneumonia(CP)and human bo-cavirus(hBoV)were detected by adopting fluorescence quantitative PCR. Human rhinovirus(HRV)and human metap-neumovirus(hMPV)were detected by means of reverse transcriptionpolymerase chain reaction( RT -PCR). Sputum was cultured for bacteria. Results In 21 624 cases,17 618 cases were detected,and the positive detection rate of virus was 30. 74%(5 416 cases). The highest detection rate of virus was 44. 25%(881/1 991 cases)in 2011 in the 10 years. There were 3 317 cases of single virus pathogen infection,accounting for 18. 83%. Among them,respiratory syn-cytial virus(RSV)was the first with 9. 42%(1 660/17 618 cases),followed by HRV(5. 17%,278/5 372 cases), hBoV(3. 12%,351/11 263 cases),Pinf 3(2. 17%,383/17 618 cases),and the lowest rate was Pinf 2 with 0. 05%(8/17 618 cases). There were 2 099 cases of overlap infection,accounting for 11. 91%. The virus combined with bacte-rial infection accounted for 7. 86%(1 384/17 618 cases),which had the most positive cases. With the increase of age, the single virus pathogen infection rate gradually dropped. The highest detection rate was 22. 82%(1 976/8 656 cases) in the group between 28 days and <1 year old,and the lowest detection rate was 7. 81%(159/2 035 cases)of children over 5 years of age. The virus positive rate of the four seasons was 18. 28%(833/4 556 cases),13. 86%(625/4 508 cases),5. 91%(684/4 298 cases),27. 68%(1 178/4 256 cases),respectively,and detection rate in winter was the highest,and the least in summer. In the single virus infection,bronchiolitis had the highest percentage(36. 32%,25/69 cases),and the least rate was 5. 83%(63/1 080 cases)of lobar pneumonia. Conclusions Monitored for 10 years of the virus respiratory infection in Suzhou area,RSV,HRV and hBoV turned out to play an important role in respiratory tract infection in children. The children less than 3 years old are the most susceptible to virus infection. The epidemic season of each virus is different and characteristic.

Objective To investigate the risk factors of single and multiple bronchoscopic lavage therapy in children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods Retrospective analysis was conducted of the clinical data of 332 RMPP children at Department of Respiratory Disease,Children's Hospital of Soochow University from January 2011 to December 2016.The patients were divided into the single group and the multiple group (≥2 times),and the correlative index were compared between the 2 groups.Logistic regression analysis was performed to analyze the risk factors of multiple bronchoscopic lavage therapy in RMPP patients.Results Among 332 children,223 cases were in the single group and 109 cases in the multiple group.Children undergoing multiple bronchoscopy had the fever duration ≥ 10 days before the bronchoscopy and course of disease ≥ 10 days before the bronchoscopy,more than those in the single group [118 cases (52.9％) vs.71 cases (65.1％),69 cases (29.6％) vs.45 cases(41.3％)],and the differences were statistically significant(all P ＜ 0.05).At the same time,the use of glucocorticoid,macrolide,glucocorticoid combined with macrolide antibiotics in the first week of illness were significantly lower in the multiple groups than those in the single group,and the differences were statistically significant (all P ＜ 0.05).In the multiple group,the percentage of neutrophils (N),C-reactive protein (CRP),CRP ＞ 44 mg/L,lactate dehydrogenase (LDH) and LDH ＞ 480 U/L were higher than those in the single group,and the differences were significant (all P ＜ 0.05).In addition,the mixed infection and pleural effusion of multiple group were higher than those of the single group.The proportion of bronchoscopy in the multiple group was higher than that of the single group.In bronchoscopy,the mucus plug blocking and mucosal erosion were more than those of the single group,and the differences were statistically significant (x2 =5.397,13.31,all P ＜ 0.05).After adjusted by multiple regression analysis,6 factors were independent risk factors for multiple bronchoscopic procedures.They were the fever duration before the bronchoscopy ≥ 10 days[odds ratio (OR) =19.504,95 ％ confidence interval (CI):7.350-51.754,P =0.000],the unuse of macrolide antibiotics in the first week of illness (OR =5.072,95％ CI:2.230-11.537,P =0.000),the unuse of glucocorticoid in the first week of illness (OR =14.051,95 ％ CI:4.755-41.522,P =0.000),CRP ＞ 44 mg/L (OR =2.638,95 ％ CI:1.356-5.133,P =0.004),LDH ＞ 480 U/L(OR =2.326,95％ CI:1.302-4.157,P =0.004) and mucosal erosion (OR =11.15,95％ CI:2.503-49.715,P =0.002).Conclusion Severe inflammatory reaction and whether or not to actively resist infection and inflammation in the early stage,were important risk factors for multiple bronchoscopic procedures.

Objective To analyze the epidemiological characteristics of Streptococcus pneumonia (SP) in children with respiratory tract infection in Suzhou area,and the correlation between the air pollutants and the epidemiological characteristics of SP.Methods The real-time air quality test data of Suzhou in Jiangsu province was recorded from January 2012 to December 2014,and sputum specimens of 6 653 cases of hospitalized children with respiratory tract diseases in the same period were collected.The SP detection content and the correlation between SP and the concentration level of PM2.5,PM 10,nitrogen dioxide (NO2),sulfur dioxide (SO2),carbon monoxide (CO),ozone (O3) in Suzhou were analyzed.Results The SP detection rate was 9.94％ in 6 653 children.The SP detection rates were respoctively 7.69％ (183/2 381 cases),10.87％ (235/2 161 cases),11.51％ (243/2 111 cases) between 2012 and 2014.The SP detection rates of children at the age of ≤ 1 year old,＞ 1-3 years old,＞ 3-＜ 7 years old and ≥ 7 years old more respectively were 7.11％ (227/3 192 cases),13.48％ (244/1 810 cases),13.76％ (168/1 221 cases),5.12％ (22/430 cases).The SP detection rate of children at the age of ＞ 1-3 years old and ＞3-＜7 years old was higher than that of ≤ 1 years old and ≥7 years old,and the difference was significant (x2 =84.980,P ＜ 0.001).The SP detection rates in spring,summer,antumn and winter respectively were 9.79％ (173/1 768 cases),7.66％ (130/ 1 697 cases),11.76％ (187/1 590 cases),10.70％ (171/1 598 cases).The SP detection rate of children in summer was the lowest (x2 =4.897,15.839,9.165,all P ＜ 0.05).The concentrations of PM2.5,PM 10,SO2,NO2,CO and O3 were in a state of fluctuation during the survey period.The SP detection rate had positive correlation with the concentration of PM2.5,PM10,SO2,NO2,CO and O3 (r =0.650,0.586,0.680,0.467,all P ＜ 0.005),and there was no obvious correlation between the SP detection rate and the concentration of CO,O3 (all P ＞ 0.05).Conclusions SP is one of the important pathogens of respiratory tract infection in children in Suzhou area,and the detection rate in infants and preschoolers is higher but the detection rate in summer is lower.The SP detection rate is closely correlated with the concentration of PM2.5,PM10,SO2,NO2.

Objective: To analyze the epidemiological characteristics of influenza virus type A (FluA) in children with respiratory tract infection, and to provide scientific basis for clinical diagnosis and treatment. Methods: Sputum specimens of 35 529 cases of hospitalized children with respiratory tract diseases from January 2006 to December 2015 in Suzhou were collected. FluA was detected by direct immunofluorescence and the FluA detection result was analyzed. Groups were compared with chi-square test. Results: The FluA infection rate was 1.60% in 35 529 children. The FluA infection rate of boys was 1.58%, and the rate of girls was 1.63%. There was no obvious statistically significant difference in sex (χ²=0.139, P=0.709). The FluA infection rates of children at the age of less than 1 year, less than 3 years, less than 7 years and older than 7 years respectively were 1.12%, 2.49%, 1.78%, and 1.24%; there was significant differences among these result (χ²=75.401, P=0.000). The FluA infection rates in spring, summer, autumn and winter respectively were 0.88%, 1.44%, 1.32%, 2.70%. The rates in four seasons had significant difference (χ²=105.432, P=0.000). The FluA infection rate was the highest in winter and the lowest in spring. The FluA infection rate was 6.55% in the autumn of 2008, which was the highest in the recent ten years. Conclusions FluA is one of the important pathogens of respiratory tract infection in children in Suzhou area. The infection rate of infant is higher and the epidemic peak is in winter. The FluA infection has obvious epidemic season and year. The FluA infection rates in Suzhou area are 0.64%-3.49%, and there was no outbreak in the recent ten years.

Objective To analyze the correlation between response to hepatitis B virus (HBV) vaccine and cellular immunity and clinical characteristics in children with respiratory infection.Methods Nine hundred and sixty children in Department of Respiratory in Children's Hospital of of Soochow University,who were over 7 months old and had full course of HBV vaccination between January and December 2015 were enrolled in this study.Peripheral blood (1-2 mL) was collected,and antigen-antibody of HBV was detected by using enzyme-linked immunosorbent assay and PCR included HBV surface antigen,hepatitis B antibody,HBV e antigen,HBV e antibody,HBV core antibody,and HBV nucleic acid.According to the results,these children were divided into 4 groups:non response group,low response group,normal response group and high response group according to their responses to HBV vaccine.Cellular immunity was detected by using flow cytometry and patients' clinical data was collected.Results There was no statistical differences of CD3 + CD4 +,which were (3.43 ± 0.28) ％,(3.42 ± 0.30) ％,(3.43 ± 0.36) ％ and (3.52 ± 0.29) ％,among the four groups (F =0.520,P =0.669).CD3 + CD8 + in non response group was (3.18 ±0.28)％,which was significantly higher than that in low response group,normal response group and high response group [(3.08 ± 0.36)％,(3.05 ±0.34)％,(2.93 ±0.30)％],the differences were significant (all P＜0.05);CD4/CD8 in non response group (0.26 ± 0.43) were significantly lower than that in normal response group (0.40 ± 0.50),the differences were significant (P =0.001).There was no significant difference of CD3 +,CD3 + CD8 + and CD4/CD8 among low response group,normal response group and high response group (all P ＞ 0.05).CD3-CD19 + and CD19 + CD23 + level were lowest in non response group [(3.00 ± 0.57) ％,(2.25 ± 0.67) ％] and highest in high response group [(3.33 ± 0.45) ％,(2.57 ± 0.38) ％],the differences were significant (all P ＜ 0.05).Among the 4 groups,children in normal response group had the shortest average hospitalization days [(1.88 ±-0.31) d],which was significantly shorter than that in non response group,low response group and high response group [(1.96 ± 0.39) d,(1.95 ± 0.38) d,(1.96 ±0.15) d],the differences were significant (all P ＜0.05),there was no significantly difference of average hospitalization days among other 3 groups (all P ＞ 0.05).Proportion of severe pneumonia was significantly higher in non response group [6.1％ (22/363cases)] and high response group [13.3％ (2/15 cases)] compared to those in normal response group [2.6％ (7/274cases)],the differences were statistically significant (x2 =4.417,P =0.036;x2 =5.476,P =0.019).The total white blood cell number was lowest in non response group (F =4.695,P =0.003).Platelet number was increased with higher degree of response to HBV (F =6.598,P ＜ 0.001).Conclusions Cellular immunity is lower in respiratory infection children with non response or low response to HBV vaccine.After they have respiratory infection,children with non response to HBV vaccine may have a longer course of disease and worse condition.

Objective To study the epidemiological and clinical features of human parainfluenza virus (HPIV) infection in children in Suzhou,and to provide the evidence-based foundation for early warning,diagnosis and treatment of respiratory infection in children.Methods The sputum specimens and medical history were obtained from children with acute respiratory tract infection hospitalized at the Childen's Hospital Affiliated to Soochow University from January 2006 to December 2015.Seven kinds of common respiratory viruses including respiratory syncytial virus,influenza virus A,influenza virus B,HPIV Ⅰ,HPIV Ⅱ,HPⅣV Ⅲ and adenovirus were detected by using the direct im-munofluorescence.Mycoplasma pneumoniae(MP),chlamydia pneumoniae,human bocavirns (hBoV) were detected by using fluorescence quantitative PCR.Rhinovirus and human metapneumovirus were detected by using reverse transcription-PCR.Sputum was cultured for bacteria.Results In 21 769 cases,the detection rate of HPIV positive was 3.21％ (829 cases),among which,HPIV Ⅰ,HPIV Ⅱ,HPIV Ⅲ were respectively detected in 113 cases (0.52％),16 cases (0.07 ％) and 700 cases (3.21％),respectively.There were 378 cases of simple infection and 428 cases of mixed infection,and the mixed infection was very common in Streptococcus pneumoniae,Haemophilus influenza,MP and hBoV.There was a difference in HPIV infection among genders,and the detection rate of the boys was higher than that of girls[4.14％ (563/13 591 cases) vs.3.25％ (266/8 178 cases),x2 =11.036,P =0.001].In the 28 d-1 year old and ＞ 1-3 year old group,the detection rate of HPIV was higher[4.71％ (494/10 476 cases) and 4.21％ (244/5 793 cases),respectively].In spring and summer,there was a higher detection rate of HPIV infection.The clinical manifestations with simple infection of HPIV Ⅰ and HPIV Ⅲ were cough,fever and wheezing.The rate of fever and shortness of breath in those of HPIV Ⅰ was 71.74％ (33/46 cases),10.87％ (5/46 cases),and that in HPIV Ⅲ was 40.12％ (134/334 cases),2.10％ (7/334 cases),HPIV Ⅰ infection was more likely to cause fever and shortness of breath than those of HPIV Ⅲ,there were significant differences (x2 =16.410,P ＜ 0.001;x2 =10.177,P =0.001).Pneumonia had the highest detection rate of viral infection.Conclusions HPIV Ⅲ is the leading pathogen among the types of HPIV in the hospitalized children in Suzhou area.Among the subtypes of HPIV,the peak of HPIV infection occurs in spring and summer.The children less than 3 years old are the most susceptible to parainfluenza virus,and the HPIV detection rate is gradually declines with age.