Aim To investigate the mechanism through which liraglutide (LRG) inhibited high glucose (HG)-induced cardiomyocyte hypertrophy. Methods Cultured H9c2 were divided into control (CON) group, HG group, low-, middle- and high-dose LRG (LRG-L, LRG-M and LRG-H) groups, LRG-H + autophagy inhibitor trimethyladenine (3-MA) group. The relative cell surface change was assessed phalloidin staining. Membrane bound Na, K

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

To investigate the efficacy and value of optical genome mapping (OGM) in detecting chromosomal structural variations. In a clinical study about high-precision analysis of genomic structural variation for complex genetic diseases, a retrospective study was performed on the cases with karyotyping at the department of Obstetrics and Gynecology, and Endocrinology of Peking Union Medical College Hospital from January to December 2021. Ten cases with abnormal karyotype was detected by OGM. Partial cases were verified by fluorescence in situ hybridization (FISH), SNP array or CNV-seq. Results of ten cases, nine were detected with abnormality by OGM, including unbalanced chromosomal rearrangements (n=3), translocation (n=5) and paracentric inversion (n=1), and the results were in concordance with other standard assays. However, one case with breakpoint and reconnected at centromere has not been detected. In conclusion, ten samples were comprehensively analyzed by karyotyping, FISH, SNP array or CNV-seq, and OGM, and results demonstrated that optical genome mapping as a new technology can not only detect unbalanced rearrangements such as copy number variants as well as balanced translocations and inversions, but more importantly, it can refine breakpoints and orientation of duplicated segments or insertions. So it can contribute to the diagnosis of genetic diseases and prevent birth defect. However, the current technology is not yet capable of detecting breakpoints of balanced structural variations lying within unmapped regions.
Chromosome Mapping ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Pregnancy ; Retrospective Studies ; Translocation, Genetic

OBJECTIVE: We wanted to investigate the radial peripapillary capillary (RPC) network in patients with Bietti crystalline dystrophy (BCD). METHODS: We compared RPC densities in the disk and different peripapillary regions, obtained using optical coherence tomography angiography in 22 patients with BCD (37 eyes) and 22 healthy subjects (37 eyes). The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging, comparing the RPC densities of the two. RESULTS: The disk area RPC density was 38.8% ± 6.3% in the BCD group and 49.2% ± 6.1% in the control group ( P < 0.001), and peripapillary region RPC density was significantly lower in the BCD group than in the control group (49.1% ± 4.7% and 54.1% ± 3.0%, respectively, P < 0.001). There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups; the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD. CONCLUSION The BCD group RPC density was significantly lower than the control group. The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD. In contrast, the reduction of RPC density in superior, inferior, and nasal quadrants occurred mainly in Stage 2.
Adult ; Aged ; Angiography ; Corneal Dystrophies, Hereditary/physiopathology* ; Female ; Humans ; Male ; Microvascular Density ; Microvessels/physiopathology* ; Middle Aged ; Retinal Diseases/physiopathology* ; Retinal Vessels/physiopathology* ; Tomography, Optical Coherence

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Humans ; Mississippi/epidemiology* ; Influenza, Human/epidemiology* ; Meteorological Concepts ; Virus Diseases

Aim To investigate the effeets of liraglutide ( LRG) on myocardial injury in type 2 diabetes melli- tus (T2DM) rats and its mechanisms.Methods For¬ty male SD rats were alloeated into eontrol group, T2DM group, LRG group, and LRG + AMPK inhibitor Compound C group (LRG + CC ).Four weeks later blood glucose and blood lipids of T2DM rats were measured.The eardiae function was measured by echo¬cardiography.The activities of superoxide dismutase (SOD ) , glutathione ( GSH ) and the malondialdehyde (MDA) eontent were assessed with corresponding rea¬gent kits.Cardiomyoeyte apoptosis was analyzed by TXJNEL staining.The expressions of inflammation, oxi-dative stress, apoptosis, autophagy, and AMPK/ mTOR signaling related proteins were deteeted by Western blot.Results Treatment with LRG alleviated hyperglycemia and hyperlipidemia, and improved heart function markers in T2DM rats.LRG inhibited inflam¬mation, oxidative stress and apoptosis and restored au- tophagy in T2DM rats by decreasing the expression of IL-6, TNF-a, IL-lp, N0X2, N0X4, cleaved caspase-3, Bax, p-mTOR/mTOR and the MDA con¬tent , and increasing the expression of Bcl-2, Atg5, Beclin-1 , LC3-II/LC3-I, p-AMPK/AMPK and the ac¬tivities of SOD and GSH.However, these effects were largely abolished by the AMPK inhibitor Compound C.Conclusions LRG exerts a protective role against dia¬betes-induced myocardial injury by ameliorating in-flammation, oxidative stress and apoptosis via the AMPK/mTOR autophagy signaling.

Objective    To analyze the correlation between the gray value of epicardial fat and the prognosis of patients with atrial fibrillation (AF) treated by thoracoscopic radiofrequency ablation. Methods    The clinical data of 97 patients, including 75 males and 22 females with an average age of 57.8±9.4 years, who underwent thoracoscopic radiofrequency ablation in Fuwai Hospital from 2017 to 2018 were analyzed retrospectively. The left atrial fat volume and average gray scale were calculated by left atrial enhanced CT. According to the average gray scale of left atrial fat tissue, the patients were divided into three groups: a high gray scale group, a medium gray scale group and a low gray scale group. The patients were followed up at 3, 6 and 12 months after operation. The end point of follow-up was the recovery rate of sinus rhythm. Survival analysis was used to analyze the correlation between CT features of epicardial fat enhancement and prognosis. Results    After adjustment of body mass index, body surface area, gender and left atrial end diastolic diameter, regression analysis showed that the fat gray of left atrial enhanced CT was correlated with the type of AF (OR=0.30, 95%CI 0.12-0.79, P=0.014). Cox regression analysis showed that the fat gray value of left atrial CT predicted the recurrence of AF after thoracoscopic radiofrequency ablation (OR=0.92, 95%CI 0.85-0.99). The Kaplan-Meier curve showed significant difference in the long-term recurrence rate of AF among the three groups (P=0.011). The lower left atrial fat enhanced CT gray scale was, the higher long-term recurrence rate of AF was. Conclusion    The gray value of left atrial fat enhanced CT can effectively predict the recurrence of AF after radiofrequency ablation in thoracoscopic surgery.

Objective To study the severe fever with thrombocytopenia syndrome bunyavirus (SFTSV)-related vector biological monitoring in Daishan County, Zhoushan Island of Zhejiang Province, and to explore the prevention and control strategies. Methods The monitoring was conducted as follows:squirrel-cage method was used for rodents from 2012 to 2014;the Buqi method for free tick density in villages and towns with confirmed cases in Daishan County from 2015 to 2018;and body surface comb method for parasitic ticks.RT-PCR method was used to detect SFTSV in ticks and rat specimens.Epidemiological survey followed by extensive health education was conducted from 2011 to 2015.Comprehensive health prevention and control measures, such as precision health education and chemical elimination of vectors were taken from 2016 to 2018. Results A total of 327 rodents were captured, including 172 stinking shrews, accounting for 52.60%, and 92 yellow mice, accounting for 28.13%.The main species of ticks was Haematopsus longicortus, accounting for 94.20%.Among them, there were 135 parasitic ticks in three species:Haematopsus longicorum, S.scallopus, and T.nigra. There were 382 free ticks in 6 species, including Haematopsichum longicorum, Sickle fan tick, Hemophilus fannicus, Ixodes ovaliformis, Ixodes granulata, and Ixodes sinensis.From May to October in 2015, the density of field ticks was ≥50 per cloth flag.From May 2016 to 2018, after the elimination application of chemical agents for elimination, the density of ticks was ≤50 per cloth flag.All ticks and rodent specimens tested by RT-PCR were negative for SFTSV.Since precision education in 2016, the awareness rate of SFTS in rural areas has increased from 32.05% to 83.33%.Approximately 70 early warning notices for the epidemic situation were issued in advance.Since 2017, the number of SFTS has been declining year by year, and only 8 cases occurred in 2018. Conclusion In the field environment, chlorothalonil is the dominant mouse species and long horn blood ticks are the dominant ticks.The government leadership, cooperation among departments, technical service provided by professional organization, health education, reduction of tick density in residential environment, timely risk early warning notice, and other comprehensive prevention and control hand strategy all contribute to the achieved result of prevention and control.

Objective:To investigate clinicopathological characteristics of misdiagnosed pediatric extraskeletal Ewing′s sarcoma in children, its diagnosis and differential diagnosis, and the reasons of misdiagnosis by pathologists.Methods:The clinical data of 34 cases of pediatric extraskeletal Ewing′s sarcoma diagnosed by the Department of Pathology, Xi′an Children′ Hospital and Xijing Hospital Fourth Military Medical University from January 2011 to July 2019 were retrospectively analyzed.Hematoxylin-eosin staining, immunohistochemical staining and EWSR1 fusion gene detection by fluorescence in situ hybridization (FISH) were performed on 6 primarily misdiagnosed cases.The clinical features, histological morphology, immunophenotype and molecular genetics of these 6 patients were studied. Results:The median age of 6 cases was 7 years old.There were 5 cases with slowly-growing, painless and localized masses.Four masses were located in the superficial subcutaneous fascia, and 1 was a rapidly growing soft tissue mass.Tumor cells were lobular and nest-like under low power microscopy.At high power microscopy, 2 cases were composed of small blue round cells, and 4 cases had morphological changes, including an increase in cell volume and enriched cytoplasm.Among the 4 cases with tumor morphological changes, tumor cells of 1 case had fine and smooth chromatin, tumor cells of 1 case had clear nuclei and prominent nucleoli, tumor cells of 1 case were composed of epithelioid cells, and tumor cells of 1 case were mixed spindle and epithelioid cells in large round and oval cells.The positive rates of CD 99, friend leukaemia integration-1(FLI1) and ERG were 5/6 cases, 5/6 cases and 2/6 cases, respectively.Rearrangements of EWSR1 gene were detected in all 6 cases. Conclusions:Biological characteristics including young onset age, superficial position and primary benign tumor, histological diversity and atypical immunohistochemical markers are 3 important factors contributing the misdiagnosis of extraskeletal Ewing′s sarcoma in children.The diagnosis should be made by combining the clinical features, morphology, immunohistochemical staining and EWSR1 gene detection.