AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

Diurnal variation of serum hypoxia inducible factor-1 α in obese patients with obstructive sleep apnea / 国际外科学杂志

Objective:To observe the diurnal changes of serum hypoxia inducible factor-1α (HIF-1α) and its relationship with polysomnography (PSG) parameters in obese patients with obstructive sleep apnea (OSA).Methods:In this study, 64 obese subjects with OSA (experimental group) and 24 normal subjects (control group) were included. PSG monitoring was performed in all subjects, and peripheral blood samples were collected at night and next early morning to detect the expression level of HIF-1 α mRNA and protein concentration in serum. The data were analyzed by SPSS25.0 software. The counting data was represented by n(%), and t-tests were used for inter group comparisons. The measurement data of normal distribution adopted mean ± standard deviation ( ± s), and the inter group comparison adopted Chi-square. Serum HIF-1α mRNA levels and protein concentrations in the two groups were compared and analyzed by Two-way ANOVA, and Spearman rank correlation was used to analyze the correlation. Results:The ratio of male to female in the control group was 15: 9 and the average age was (39.25 ±10.58) years old, while that in the experimental group was 41∶24 with an average age of (41.31 ±15.20) years. The body mass index (BMI) of experimental group was higher, while all the relevant parameters recorded by PSG were significantly different between two groups ( P<0.001). The results showed that there was no significant difference in the expression of HIF-1α mRNA between the control group and the experimental group ( P=0.914), or between night and morning ( P=0.167). The concentration of HIF-1α protein in the control group was significantly lower than that in the experimental group ( P<0.001), but there was no significant difference in the concentration of HIF-1α protein in the same group at night and in the morning ( P=0.798). The results of correlation analysis showed that there was a significant correlation between PSG related indexes(AHI, minimum blood oxygen, mean blood oxygen and SIT90), night and morning mRNA expression and protein concentration ( P<0.05). Conclusions:Compared with normal people, the concentration of serum HIF-1 α protein in obese patients with OSA is higher, but there is no difference between night and morning. The process of HIF-1 α induced by CIH may be involved in post-translational regulation rather than transcription, and other compensatory mechanisms may also be involved.

Comparative metabolomics provides novel insights into the basis of petiole color differences in celery (Apiumgraveolens L.) / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Plant metabolites are important for plant development and human health. Plants of celery (Apiumgraveolens L.) with different-colored petioles have been formed in the course of long-term evolution. However, the composition, content distribution, and mechanisms of accumulation of metabolites in different-colored petioles remain elusive. Using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), 1159 metabolites, including 100 lipids, 72 organic acids and derivatives, 83 phenylpropanoids and polyketides, and several alkaloids and terpenoids, were quantified in four celery cultivars, each with a different petiole color. There were significant differences in the types and contents of metabolites in celery with different-colored petioles, with the most striking difference between green celery and purple celery, followed by white celery and green celery. Annotated analysis of metabolic pathways showed that the metabolites of the different-colored petioles were significantly enriched in biosynthetic pathways such as anthocyanin, flavonoid, and chlorophyll pathways, suggesting that these metabolic pathways may play a key role in determining petiole color in celery. The content of chlorophyll in green celery was significantly higher than that in other celery cultivars, yellow celery was rich in carotenoids, and the content of anthocyanin in purple celery was significantly higher than that in the other celery cultivars. The color of the celery petioles was significantly correlated with the content of related metabolites. Among the four celery cultivars, the metabolites of the anthocyanin biosynthesis pathway were enriched in purple celery. The results of quantitative real-time polymerase chain reaction (qRT-PCR) suggested that the differential expression of the chalcone synthase (CHS) gene in the anthocyanin biosynthesis pathway might affect the biosynthesis of anthocyanin in celery. In addition, HPLC analysis revealed that cyanidin is the main pigment in purple celery. This study explored the differences in the types and contents of metabolites in celery cultivars with different-colored petioles and identified key substances for color formation. The results provide a theoretical basis and technical support for genetic improvement of celery petiole color.

Analysis of perioperative risk factors for seizures in children with congenital heart disease following cardiopulmonary bypass / 中华实用儿科临床杂志

Objective:To examine the occurrence of seizures and perioperative risk factors in children after obtaining cardiopulmonary bypass (CPB).Methods:Electroencephalograph (EEG) and cerebral oxygen saturation (ScO 2) were monitored in 87 patients (aged 3 days-110 months, with the median at 4.4 months) and they were admitted to the Cardiac Intensive Care Unit (CICU) from May 2018 to April 2019, with 77 patients for 72 h after CPB and 10 cases with clinical seizures after CICU discharge for 8-180 h. Clinical data were recorded every 4 hours, including blood pressure, central venous pressure (CVP), temperature, arterial blood gases, lactate, doses of Dopamine, Milrinone, and Adrenalin, and daily C-reaction protein (CRP) and N-terminal pro-brain natriuretic peptide(NT-proBNP). Demographic data, the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery(STAT) mortality classification and clinical outcomes (duration of mechanical ventilation, CICU and hospital stay, and death) were recorded. Results:Seizures occurred in 24 patients (27.6%) within 48 h after CPB.EEG seizures appeared in 7 patients, both EEG and clinical seizures in 7 patients, and clinical seizures in 10 patients.Three patients developed epilepsy.There were 2 hospital deaths and both had EEG seizures.Patients with seizures had higher STAT categories, longer operative time and worse clinical outcomes (all P<0.05). Univariate regression revealed that the occurrence of seizures was positively related to adrenalin, temperature, lactate level (all P<0.01), blood pressure, CVP (all P<0.05) and CRP ( P<0.1), and negatively correlated with arterial carbon dioxide tension[ pa(CO 2)], ScO 2 and dose of Milrinone (all P<0.05). In multivariate regression, only dose of Adrenalin ( P<0.001) and lactate level ( P<0.01) remained significant. Conclusions:The incidence of seizures was high in children after CPB.Numerous perioperative factors that were related to seizures were identified.The most significant risk factors were higher dose of adrenaline and lactate level.Studies on neurological injury after CPB are urgently needed in China in order to reduce brain injury and improve neurodevelopmental outcomes.

Effect of HLA-G expressed in platelets on Tax protein of human T lymphocyte leukemia type 1 virus / 中国输血杂志

【Objective】 To investigate the effect of HLA-G expressed in platelets on Tax protein of human T cell leukemia type 1 virus (HTLV-1). 【Methods】 Platelets were isolated from anticoagulant whole blood, and HLA-G molecule on platelet membrane was detected by flow cytometry. The content of secretory HLA-G before and after platelet lysis was detected by ELISA, HTLV-1 human lymphoma cells MT2 were cultured with platelet lysate (PL). The effect of HLA-G in platelets on the expression of HTLV-1 protein Tax was evaluated by Western blot (WB). 【Results】 Membrane type mHLA-G was highly expressed on the surface of platelet membrane. The expression of secretory sHLA-G (ng/mL) increased after platelet lysis (15.73±1.01) vs (6.65±0.47), the expression of sHLA-G increased with the increase of platelet concentration in a dose-dependent manner. Compared with fetal bovine serum, PL significantly promoted the high expression of HLA-G protein and HTLV-1 virus tax protein in MT2 cells, and the addition of anti-HLA-G antibody to PL could effectively inhibit the expression of Tax and HLA-G protein. 【Conclusion】 High expression of immune tolerance molecule HLA-G on platelets can induce high expression of HTLV-1 protein Tax in human lymphoma cell MT2, which contributes to viral infection.

Prevalence of iron deficiency anemia and the association with dietary nutrition factors of preschool children in rural Anhui Province / 中国学校卫生

Objective@#To evaluate the dietary quality for preschool children by diet balance index(DBI_C), and to provide an empirical reference for scientific guidance for a reasonable diet and controlling and preventing iron deficiency anemia(IDA).@*Methods@#During September to December of 2018, 306 left behind children and 598 non left behind children aged 3-6 years old of Anhui Province were selected. Four scoring methods (TS Total Score, LBS Low Bound Score, HBS High Bound Score, DQD Diet Quality Distance) were used to evaluate the dietary quality by DBI_C, and multivariate Logistic regression was used to assess the relationship between DBI_C and IDA.@*Results@#The anemia prevalence (AP) was 13.3% among the 3-6 year old children in Anhui rural area, whereas the left behind children (LBC) was 16.7% and the non left behind children was 10.9%, and there was statistical significance of the differences ( χ 2=8.8, P <0.05). There were significant differences of TS[-18.3(25.2，-12.7)，-15.2(-19.8，-8.6)], LBS[25.4(18.3，32.5)，22.7(16.5，30.6)] and DQD[36.8(23.9，43.4)，34.1(27.5，41.0)] in DBI_C scores between anemia group and nonanemia group ( P <0.05). There were significant differences of milk and beans [-5.9(-10.7，-0.4)，-5.0(-8.7，0.2)], animal food [-2.4(-5.6，0.8)，-0.6(3.5，1.9)], food species [-7.5(-9.1，-4.8)，-6.3(-8.0，-2.9)] in food intake scores between anemia group and non anemia group ( P <0.05). Left behind children ( OR =1.27, 95% CI =1.15-1.49) had higher proportions of getting anemia. Meat consumption >3 times per week ( OR =0.81, 95% CI =0.68-0.94) and ≥two types of fresh vegetable consumption every day ( OR =0.84, 95% CI =0.73-0.95) were associated with lower rate of anemia( P <0.05).@*Conclusion@#The AP was relatively high in 3-6 year old children in Anhui rural area, especially in those LBC. Anemia should be reduced by improving the caregivers dietary literacy, increasing intakes of animal foods and fresh vegetables.

Research progress on macrophage in radiation induced lung injury / 浙江大学学报·医学版

Radiation-induced lung injury (RILI), including acute radiation pneumonitis and chronic radiation-induced pulmonary fibrosis (RIPF), is a side effect of radiotherapy for lung cancer and esophageal cancer. Pulmonary macrophages, as a kind of natural immune cells maintaining lung homeostasis, play a key role in the whole pathological process of RILI. In the early stage of RILI, classically activated M1 macrophages secrete proinflammatory cytokines to induce inflammation and produce massive reactive oxygen species (ROS) through ROS-induced cascade to further impair lung tissue. In the later stage of RILI, alternatively activated M2 macrophages secrete profibrotic cytokines to promote the development of RIPF. The roles of macrophage in the pathogenesis of RILI and the related potential clinical applications are summarized in this review.

Developing the Symptoms and Functional Impairment Rating Scale: A Multi-Dimensional ADHD Scale

OBJECTIVE: This research developed a practical, multi-dimensional attention deficit hyperactivity disorder (ADHD) rating scale (i.e., the Symptoms and Functional Impairment Rating Scale, SFIRS) for Chinese children, aged 6–12 years, with ADHD. METHODS: The structural validity, criterion validity, internal consistency, and test-retest reliability of the scale were evaluated. Item screening was conducted with 412 ADHD patients and 322 developmentally typical controls. RESULTS: The scale includes 44 items, divided among Hyperactivity-Impulsivity, Self-Control, Inattention, Self-Management, Academic Performance, and Social Interaction. The six-factor model showed good data fit, with each factor significantly correlated with its corresponding criterion (r=0.690–0.841). The Cronbach's α of the full scale was 0.976. Total score test-retest reliability was r=0.816 (p < 0.01). CONCLUSION: The SFIRS thus demonstrated good reliability and validity and may be used to assess ADHD among children aged 6–12 years in China.

Occupational mental health and job satisfaction in university teachers in Shenyang, China / 中华劳动卫生职业病杂志

Objective@#To investigate the current status of occupational mental health and job satisfaction in university teachers in Shenyang, China and related influencing factors.@*Methods@#A total of 1500 teachers from 6 universities in Shenyang were randomly selected as study subjects from November 2013 to January 2014. Self-administered questionnaires were used to investigate mental health, including effort-reward imbalance questionnaire, Minnesota Satisfaction Questionnaire, Center for Epidemiological Survey-Depression Scale, and Psychological Capital Questionnaire.@*Results@#Of all teachers, 58.9% had depressive symptoms. Depressive symptoms in university teachers were negatively correlated with the scores of psychological capital, supervisory commitment, and perceived organizational support (r=-0.461, -0.306, and -0.366, all P<0.01) and were positively correlated with the score of occupational stress (r=0.414, P<0.01) . Job satisfaction was positively correlated with psychological capital, perceived organizational support, and supervisory commitment (r=0.650, 0.715, and 0.636, all P<0.01) and negatively correlated with occupational stress (r=-0.475, P<0.01) . The direct effects of occupational stress, perceived organizational support, and supervisory commitment on job satisfaction were -0.30, 0.26, and 0.14, respectively, and their indirect effects were -0.0176, 0.0656, and 0.0368, respectively. The direct effects of occupational stress, perceived organizational support, and supervisory commitment on depressive symptoms were 0.20, -0.08, and -0.05, respectively, and their indirect effects was 0.033, -0.123, and -0.069, respectively.@*Conclusion@#Occupational mental health is closely associated with job satisfaction in university teachers in Shenyang, and psychological capital has a mediating effect on perceived organizational support, supervisory commitment, occupational stress, job satisfaction, and depressive symptoms.

Resveratrol alleviates ISO-induced cardiomyocyte hypertrophy in rat / 基础医学与临床

Objective To explore the role of resveratrol (RES) on cardiomyocyte hypertrophy of rat induced by isoproternol (ISO) and the effect of Res on the expression of GRP78 and GRP94 in endoplasmic reticulum stress of cardiomyocyte hypertrophy.Methods Hypertrophic model of cardiomyocytes was induced by ISO.Cardiomyocytes was divided into four group: control group, the model group, RES+ISO group and RES group.Hypertrophy status of cardiomyocytes was determined by Leica 2Q500 image analysis system measuring the cell surface area and the gene expression of ANP.The content of LDH and MDA was measured in different groups, and the protein expressions of GRP78 and GRP94 were detected by Western blot.Results Compared with control group, ISO induced cardiomyocytes hypertrophy, endoplasmic reticulum stress related factors GRP78 and GRP94 protein expression were increased, compared with ISO group, RES intervention effectively suppressed the cardiomyocytes hyper-trophy induced by ISO, reduced the protein expression of GRP78 and GRP94, at the same time, reduced lactate dehydrogenase (LDH) and malondialdehyde (MDA) release in cell medium.Conclusions Treatment of RES may protect cardiomyocytes hypertrophy, which is partially mediated by inhibiting the expression of ERS factors GRP78 and GRP94.

Relationship between parental personality,mood disorders and family functions of the children with autism spectrum disorder / 中华实用儿科临床杂志

Objective The number of children diagnosed with autism spectrum disorder (ASD)has increased dramatically in the past years.Parents of children with ASD usually experience a variety of chronic and acute stressors that may decrease marital satisfaction and family functioning.The aim was to explore the characteristics of parental per-sonality,mood disorders and family functions of the Children with ASD and to explore the relevance factors in order to draw out methods to improve parental family functions.Methods A cross -sectional survey was conducted and 593 outpatients with ASD diagnosed in Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine form January 201 0 to January 201 4 were straight into the group,their parents were tested by Family Assessment Device (FAD),Zung Self -Rating Depression Scale(SDS),Zung Self -Rating Anxiety Scale(SAS)and Eysenck Personality Questionnaire(EPQ).SPSS 1 7.0 software was adopted to establish the database and statistical analysis.Results Ac-cording to FAD,parents of children with ASD had lower scores in problem solving[(2.1 0 ±0.37)scores]and roles [(2.09 ±0.27)scores](t =-6.669,P =0.000;t =-1 8.707,P =0.000)than the standard scores,while other di-mensions score were significantly higher than the standard scores in communicdtion[(2.25 ±0.35)scores],emotional reaction[(2.38 ±0.40)scores],emotional involvement[(2.36 ±0.37)scores],behavioral control[(2.31 ±0.27) scores]and general function[(2.1 2 ±0.38)scores],there were significant differences(t =3.1 35,1 1 .1 1 5,1 6.997, 37.1 1 6,8.064;P =0.002,0.000,0.000,0.000,0.000).For EPQ of parents,mother had obviously higher scores than father in psychoticism scale[(53.68 ±1 .36)scores vs (52.65 ±1 .1 7)scores,t =-1 3.841 ,P =0.000],and signifi-cantly lower scores in Lie scale[(52.27 ±0.79)scores vs (52.1 7 ±0.75)scores,t =2.449,P =0.01 4].Compared to fathers,mothers were coded as higher depression and anxiety scores(t =-6.276,-6.440,all P =0.000)and higher prevalence rate(χ2 =1 5.893,27.592,all P =0.000),which were statistically significant.According to the asso-ciation study of FAD and the others(especially in mood of parents),it was found that several dimensions showed obvious correlation.Conclusions Parents of children with ASD have family function damaged badly,except for prob-lem solving and roles.The parents showed different personality traits and mood disorders,particularly mothers′mood disorder problem was prominent.Parental family functioning were closely related to their personality traits and emotional disorders in various dimensionalities,which was worthy of attention.

Clinical application of standardized rating scales for attention deficit hyperactivity disorder in school-age children / 中华实用儿科临床杂志

Attention deficit hyperactivity disorder(ADHD) is one of the most common psychiatric disorders among school-age children.The diagnosis and treatment of ADHD rely on a comprehensive evaluation of symptom,functional impairment and comorbidity.Therefore the standardized rating scales is widely used clinically.The standardized rating scales can be categorized into: Broad-band scales,evaluating the general misbehavior and sociopsychological functions andNarrow-band scales,evaluating ADHD specific symptoms,and also functional impairment rating scales.Useful comorbidity and functional impairment rating scales are in need domestically.This paper reviewed the published literature about the clinical application and progression of frequently-used rating scales for school-age ADHD evaluation,at home and abroad.

Comparation between Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation (review) / 中国康复理论与实践

@#Difference between transcranial magnetic stimulation and transcranial direct current stimulation in theory, safety, detection of brain function and clinic treatment were reviewed in order to help reasonably select and effectively apply them in clinic.