Clinical diagnosis and treatment of hereditary thrombocytopenia and purpura: a report of five cases and literature review / 中华血液学杂志

Objective: To report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods: Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results: The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions: The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.

Physical fitness among children at ages of 3 to 6 years in Chaoyang District / 预防医学

Objective@#To investigate the status of physical fitness among children at ages of 3 to 6 years in Chaoyang District, Beijing Municipality, so as to provide insights into improvements in children's physical fitness. @*Methods@#Physical fitness test data were collected from children at ages of 3 to 6 years in Chaoyang District based on the Fifth National Physical Fitness Monitoring Program, including basic characteristics, body shape, physical function and quality. The physical fitness test results were compared among children with different genders and ages, and factors affecting the physical fitness were identified among children at ages of 3 to 6 years using a multiple linear regression model.@*Results@#Totally 988 children at ages of 3 to 6 years were enrolled, including 490 boys (49.60%) and 498 girls (50.40%), and 300 children at an age of 3 years (30.36%), 329 children at an age of 4 years (33.30%), 297 children at an age of 5 years (30.06%) and 62 children at an age of 6 years (6.28%). The participants had a mean height of (109.46±7.31) cm, body weight (18.98±3.82) kg, sitting height of (61.99±3.39) cm, chest circumference of (52.87±4.04) cm, static heart rate of (98.04±9.61) beats per minute, grip strength of (4.78±2.22) kg, standing long jump of (75.01±21.89) cm, seated forward bend of (10.07±4.51)cm, double-foot continuous jump of (7.54±3.84) s, 15-meter obstacle run of (8.73±1.66) s and balance beam walking of (8.54±4.72) s. Boys had greater sitting height, chest circumference and grip strength and lower 15-meter obstacle run and static heart rate than girls (P<0.05), while girls had higher seated forward bend than boys (P<0.05). There were significant differences in all test items among children at different ages (P<0.05). Multiple linear regression analysis identified non-only child (β'=0.064), non-overweight/obesity (β'=0.192), 2 hours and longer daily indoor physical activity (β'=0.156), exercise intensitby (adequate, β'=0.218; generally, β'=0.151), father's height of 170 cm and shorter (β'=-0.075), mother's height of 160 cm and shorter (β'=-0.081), and parents' educational level (undergraduate, β'=0.017; postgraduate, β'=0.084) as factors affecting physical fitness among children at ages of 3 to 6 years in Chaoyang District. @*Conclusions@#The body shape development is relatively good among children at ages of 3 to 6 years in Chaoyang District; however, the physical quality remains to be improved. The only child, overweight/obesity, duration of indoor physical activity, exercise intensity, parental height and parental educational level are factors affecting physical fitness among children.

Overweight and obesity among children and adolescents in Jinan City in 2021 and comparison with Chinese and international standards / 中国学校卫生

Objective@#To describe the prevalence of overweight and obesity among children and adolescents in Jinan City according the national and international criteria, as well as to compare the Chinese and international standards, so as to provide basic data for relevant intervention strategies.@*Methods@#From September to December 2021, using the height and weight data obtained from the health checkup reports of 746 985 primary and secondary school students in Jinan City in 2021, body mass index(BMI) was calculated to evaluate the current status of the prevalence of overweight and obesity among this sample of children and adolescents aged 6- 18 years old. The consistency of the Chinese standard, U.S. Centers for Disease Control and Prevention (CDC) standard, International Obesity Task Force (IOTF) standard, and World Health Organization (WHO) standard was compared by calculating the weighted Kappa value.@*Results@#Based on the Chinese, U.S. CDC, IOTF and WHO standards, the overweight rates of children and adolescents aged 6-18 years in Jinan were 17.3%, 16.5%, 21.1% and 13.6%, respectively, and the obesity rates were 23.1%, 19.5%, 13.5% and 6.6%, respectively. The overweight and obesity rates of boys were higher than those of girls under the four criteria (China: χ 2=1 418.48, 9 868.51, U.S. CDC: χ 2=145.78, 23 211.41, IOTF: χ 2=1 326.94, 13 615.62, WHO: χ 2=873.13, 46.41, P <0.01).The overweight rate of adolescents in the 13-18 year-old age group was higher than that of children aged 6-12 years (China: χ 2=29.13, U.S. CDC: χ 2=6.43, IOTF: χ 2=15.87, WHO: χ 2=19.48, P <0.01) and the obesity rate of the group aged 6-10 years was significantly higher than that of the group aged 11-18 years (China: χ 2=217.02, U.S. CDC: χ 2=227.54, IOTF: χ 2=171.91, WHO: χ 2=165.91, P <0.01). The rates of overweight and obesity in urban children and adolescents were slightly higher than those in rural children and adolescents (China: χ 2=25.06, 245.12, U.S. CDC: χ 2=56.13, 205.93, IOTF: χ 2= 182.34 , 22.04, WHO: χ 2=200.88, 21.61, P <0.01). The Chinese standard showed good agreement with the IOTF standard and U.S. CDC standard, with weighted Kappa values of 0.72 and 0.83, but poor agreement with the WHO standard, with a weighted Kappa value of 0.33.@*Conclusion@#The current prevalence of overweight and obesity among children and adolescents in Jinan is serious. The Chinese standard has good consistency with IOTF standard and American CDC standard, and poor consistency with WHO standard.

Quality assessment of screening for neonatal inherited metabolic disease in Chaoyang District from 2012 to 2021 / 预防医学

Objective @#To evaluate the quality of neonatal inherited metabolic diseases screening in Chaoyang District, Beijing Municipality from 2012 to 2021, so as to provide insights into improvements in the screening quality and efficiency of neonatal inherited metabolic diseases. @*Methods@#Data pertaining to screening of neonatal inherited metabolic disease in Chaoyang District from 2012 to 2021 were captured from Beijing Center for Neonatal Disease Screening. The percentage of screening, eligible rate of blood smears collection, re-examination rate of suspected cases, and definitive diagnosis of congenital hypothyroidism (CH), phenylketonuria (PKU) and congenital adrenal hyperplasia (CAH) were analyzed to evaluate the quality of neonatal inherited metabolic diseases screening in Chaoyang District.@*Results@#There were 484 002 live neonates in Chaoyang District from 2012 to 2021, and 481 395 neonates were screened for inherited metabolic diseases, with a screening rate of 99.46% and 99.71% eligible rate of blood smears collection. A total of 4 305 suspected positive cases were screened, including 4 148 cases recalled for re-examinations, with a 96.35% re-examination rate of suspected cases, and the re-examination rates of CH, PKU and CAH were 96.37%, 96.79% and 95.65%, respectively. Totally 482 neonates were definitively diagnosed with inherited metabolic diseases, with an overall incidence rate of 1/999, and the incidence rates of CH (307 cases), hyperthyrotropinemia (103 cases), PKU (66 cases) and CAH (6 cases) were 1/1 568, 1/4 674, 1/7 294 and 1/20 233, respectively.@*Conclusions@#The screening rate and re-examination rate of neonatal inherited metabolic diseases was both more than 95% in Chaoyang District from 2012 to 2021. Improving the management of neonatal inherited metabolic diseases screening and the recall of suspected cases is required.

Mechanistic study of endothelium independent vasodilation effects of wogonin

Scutellaria baicalensis Georgi, locally known as HuangQin, and commonly as Baikal or Chinese skullcap, is an important herb in Chinese traditional medicine. The flavonoids from this plant are main active substances responsible for its medicinal applications. Wogonin is one such active ingredient derived from this plant. Here, we investigated the mechanism of the vasodilation effect of wogonin on isolated rat thoracic aortas. For this study, endothelium intact and endothelium removed thoracic aortic rings were prepared from rats. Using a tension transducer, the tension of the rat thoracic aortic rings was recorded. Results showed that wogonin is able to relax the endothelium-intact aortic rings, but L-NAME, indomethacin (Indo), and methylene blue (MB) could not reduce the tension in these rings. Wogonin was also able to relax endotheliumremoved rings. However, treatment with tetraethylammonium (TEA), BaCl2, glibenclamide (Gly), 4-aminopyridine (4-AP), and verapamil (Ver) had no effect on vasodilation induced by wogonin. Using wogonin to pre-treat endothelium-removed aortic rings reduced the contraction induced by K+. Pre-treatment of endothelium-removed aortic rings with wogonin markedly reduced the contraction induced by 10-6 M PE in Ca2+-free solution. It could be concluded that L-type calcium channels and intracellular Ca2+ release is inhibited by wogonin.

Effects of the ITGA2B Nonsense Mutation (c.2659C > T, p.Q887X) on Platelet Function in a Mouse Model of Glanzmann's Thrombasthenia Generated with CRISPR/Cas9 Technology / 中国实验血液学杂志

OBJECTIVE@#To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbβ3 on the surface of platelet membrane.@*METHODS@#The donor oligonucleotide and gRNA vector were designed and synthesized according to the ITGA2B gene sequence. The gRNA and Cas9 mRNA were injected into fertilized eggs with donor oligonucleotide and then sent back to the oviduct of surrogate mouse. Positive F0 mice were confirmed by PCR genotyping and sequence analysis after birth. The F1 generation of heterozygous GT mice were obtained by PCR and sequencing from F0 bred with WT mice, and then homozygous GT mice and WT mice were obtained by mating with each other. The phenotype of the model was then further verified by detecting tail hemorrhage time, saphenous vein bleeding time, platelet aggregation, expression and function of αIIbβ3 on the surface of platelet.@*RESULTS@#The bleeding time of GT mice was significantly longer than that of WT mice (P<0.01). Induced by collagen, thrombin, and adenosine diphosphate (ADP), platelet aggregation in GT mice was significantly inhibited (P<0.01, P<0.01, P<0.05). Flow cytometry analysis showed that the expression of αIIbβ3 on the platelet surface of GT mice decreased significantly compared with WT mice (P<0.01), and binding amounts of activated platelets to fibrinogen were significantly reduced after thrombin stimulation (P<0.01). The spreading area of platelet on fibrinogen in GT mice was significantly smaller than that in WT mice (P<0.05).@*CONCLUSION@#A GT mouse model with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation has been established successfully by CRISPR/Cas9 technology. The aggregation function of platelet in this model is defective, which is consistent with GT performance.

Research on the health system of community sports framework based on function orientation / Pesquisa sobre a estrutura do sistema de saúde esportiva comunitária com base na orientação funcional / Investigación sobre el marco del sistema de salud del deporte comunitario basado en la orientación funcional

ABSTRACT Introduction: Community sports activities are performed by people in the community environment, using beneficial factors such as sports equipment, facilities, and natural resources in the community to improve their body structure and functions, and their activity participation levels. Objective: The thesis studies how to use the framework and theory of "International Classification of Functions, Disability and Health" and World Health Organization "Community Rehabilitation Guidelines" to construct a sports service system to promote community health. Methods: The thesis uses the theory and methods related to function, disability, and health of the International Classification of Functions, Disability, and Health, and the matrix of the World Health Organization's Community Rehabilitation Guidelines as the framework for community sports activities and integrated development. Results: The development of community sports activity services can improve the physical function and athletic ability of different participants, promote healthy behaviors, improve mental health, and improve happiness. Community sports activities can promote the community's health, rehabilitation, education, career development, and empowerment. The integrated development of community sports activities and community health and rehabilitation activities will build a modern health service system. Conclusions: Use "International Classification of Function, Disability, and Health" to construct a community sports activity framework based on function orientation and overall health. Use the matrix and methods of the World Health Organization's "Community Rehabilitation Guidelines" to promote the integration of sports activities with activities such as health, rehabilitation, education, professional development, and empowerment to achieve inclusive community development and overall community health. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: As atividades esportivas comunitárias são realizadas por pessoas do meio comunitário, utilizando fatores benéficos como equipes esportivas, instalações e recursos naturais da comunidade para melhorar sua estrutura e funções corporais e seus níveis de participação na atividade. Objetivo: A tese estuda como usar a estrutura e a teoria da "Classificação Internacional de Funções, Incapacidade e Saúde" e as "Diretrizes de Reabilitação Comunitária" da Organização Mundial de Saúde para construir um sistema de serviços esportivos para promover a saúde da comunidade. Métodos: A tese usa a teoria e métodos relacionados à função, deficiência e saúde da Classificação Internacional de Funções, Incapacidade e Saúde, e a matriz das Diretrizes de Reabilitação Comunitária da Organização Mundial de Saúde como uma estrutura para atividades esportivas comunitárias e desenvolvimento integrado. Resultados: O desenvolvimento de serviços de atividades esportivas comunitárias pode melhorar a função física e a capacidade atlética dos diferentes participantes, promover comportamentos saudáveis, melhorar a saúde mental e melhorar a felicidade. As atividades esportivas da comunidade podem promover saúde, reabilitação, educação, desenvolvimento profissional e empoderamento da comunidade. O desenvolvimento integrado de atividades esportivas comunitárias e atividades de saúde e reabilitação comunitárias criará um sistema moderno de serviços de saúde. Conclusões: Use a "Classificação Internacional de Função, Incapacidade e Saúde" para construir uma estrutura de atividade esportiva comunitária baseada na orientação funcional e saúde geral. Use a matriz e os métodos das "Diretrizes de Reabilitação da Comunidade" da Organização Mundial da Saúde para promover a integração das atividades esportivas com atividades como saúde, reabilitação, educação, desenvolvimento profissional e capacitação para alcançar o desenvolvimento comunitário inclusivo e saúde da comunidade em geral. Nível de evidência II; Estudos terapêuticos: investigação dos resultados do tratamento.

RESUMEN Introducción: Las actividades deportivas comunitarias son realizadas por personas del entorno comunitario, utilizando factores beneficiosos como equipos deportivos, instalaciones y recursos naturales de la comunidad para mejorar su estructura y funciones corporales, y sus niveles de participación en la actividad. Objetivo: La tesis estudia cómo utilizar el marco y la teoría de la "Clasificación internacional de funciones, discapacidad y salud" y las "Pautas de rehabilitación comunitaria" de la Organización Mundial de la Salud para construir un sistema de servicios deportivos para promover la salud comunitaria. Métodos: La tesis utiliza la teoría y los métodos relacionados con la función, la discapacidad y la salud de la Clasificación Internacional de Funciones, Discapacidad y Salud, y la matriz de las Pautas de rehabilitación comunitaria de la Organización Mundial de la Salud como marco para las actividades deportivas comunitarias y el desarrollo integrado. Resultados: El desarrollo de servicios comunitarios de actividades deportivas puede mejorar la función física y la capacidad atlética de los diferentes participantes, promover comportamientos saludables, mejorar la salud mental y mejorar la felicidad. Las actividades deportivas comunitarias pueden promover la salud, la rehabilitación, la educación, el desarrollo profesional y el empoderamiento de la comunidad. El desarrollo integrado de las actividades deportivas comunitarias y las actividades comunitarias de salud y rehabilitación construirá un moderno sistema de servicios de salud. Conclusiones: Utilice la "Clasificación internacional de función, discapacidad y salud" para construir un marco de actividad deportiva comunitaria basado en la orientación funcional y la salud en general. Utilice la matriz y los métodos de las "Pautas de rehabilitación comunitaria" de la Organización Mundial de la Salud para promover la integración de actividades deportivas con actividades como salud, rehabilitación, educación, desarrollo profesional y empoderamiento para lograr el desarrollo comunitario inclusivo y la salud comunitaria en general. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

miR-199a-5p regulates DDR1 to inhibit proliferation and migration of human glioma cells / 中国药理学通报

Aim To investigate the effect of miR-199a-5p on the proliferation and migration of human glioma cells. Methods U251 cells were selected as experimental subjects to construct a U251 cell line overexpressing miR-199a-5p. The experiment was divided into; control group (U251 cells without transfection, Control), negative control group (transfected with empty vector plasmid U251 cells, NC) and experimental group (transfected with miR-199a-5p mature mimics, mimics). Real-time fluorescent quantitative PCR was used to detect the expression of miR-199a-5p in each group; CCK-8 was used to detect the proliferation of cells transfected with miR-199a-5p; the cell scratch test and Transwell migration test were used to detect the migration of U251 in each group; Western blot was applied to detect DDR1 expression; a U251 cell line overexpressing DDR1 was constructed to detect the effect of overexpression of DDR1 on the proliferation and migration of U251 cells transfected with miR-199a-5p. Results The level of miR-199a-5p in mimics group was significantly higher than that in control group (P < 0.01), the cell viability was reduced (P < 0.01), and the proliferation ability was weakened (P <0. 01). The expression of DDR1 in miR-199a-5p group cells was significantly reduced (P < 0. 01). Compared with mimincs group, the pcDNA3. 1-DDR1 transfected group could up-regulate DDR1 (P < 0. 01), increase cell viability, and promote cell proliferation (P < 0. 05 or P < 0. 01). Conclusions miR-199a-5p can down-regulate the expression of DDR1 and inhibit the proliferation and migration of human glioma cells.

Predictive value of vascular structure and hemodynamic characteristics for clinical ischemic symptoms in patients with severe carotid atherosclerotic stenosis / 中国脑血管病杂志

Objective To investigate the predictive value of carotid remodeling index (CRI), plaque characteristics, and hemodynamic changes in patients with severe carotid atherosclerotic stenosis. Methods A total of 185 continuous patients with unilateral severe carotid artery atherosclerotic stenosis who underwent surgical treatment were enrolled retrospectively in the Department of Neurosurgery and Vascular Surgery of Xuanwu Hospital, Capital Medical University from January 2016 to January 2019. According to the clinical symptoms, patients were divided into the symptom group ( 104cases) and the asymptomatic group (81 cases). The general clinical data, CRI, echo characteristics of plaque, and hemodynamic parameters were compared between the two groups. Multivariate logistic regression analysis was performed after excluding the collinearity of parameters. The value of CRI for predicting clinical ischemic events was analyzed through the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results (1) There were no significant differences in age and risk factors of cerebrovascular disease between the two groups (all P >0. 05). However, the rate of male patients was significantly higher in the symptom group compared with the asymptomatic group (92. 3% [96/104] vs. 80. 2% [65/81) , P < 0.05). (2)There were lower in the peak systolic velocity( PSV) of the distal internal carotid artery (50.0[28.3, 62.8] cm/s vs. 60. 0[44.5, 74.5] cm/s, P<0.01), the end-diastolic velocity (EDV) of the distal internal carotid artery(23.0[14.0, 30.0] cm/s vs. 29. 0[21. 5 , 33. 5 ] cm/s, P<0.01), the PSV of the ipsilateral middle cerebral artery ( [74 ±21 ] cm/s vs. [ 85±21]cm/s, P<0.01) , and the EDV of the ipsilateral middle cerebral artery([39 ±11] cm/s vs. [42 ± 10] cm/s, P <0.05) in the symptom group compared with the asymptomatic group. There were higher in the ratio of PSV at the stenosis lesion of the internal carotid artery to the distal internal carotid artery( PSVprox/PSVdist, 10. 3[6.1, 16.6]ta.7.2[5.0, 11.8]), CRI ( 1. 82 [ 1. 65, 2. 08] is. 1. 64 [ 1. 51, 1.80]), hypoechoic plaques (83.7% [ 87/104 ] vs. 37. 0% [ 30/81 ]) , and ulcerative plaques (27. 9% [ 29/104 ] vs. 7. 4% [6/81]) in the symptom group compared with the asymptomatic group (all P <0. 05). (3) Multivariate logistic regression analysis showed that CRI ( OR = 12. 43, 95% CI 2. 85 -54. 25 , P < 0. 01) , ulcerative plaque (Oft =4. 04, 95% CI 1.40-11.62, P<0.05), and hypoechoic plaque( OR =5. 54, 95% C/2.65-11.58, P<0.01) were independent risk factors for ischemic clinical events. (4)The best cutoff value of CRI was 1.74 for predicting ischemic clinical events in severe carotid artery atherosclerotic stenosis ( AUC = 0.714,95% C/0.64-0.79, P<0.05), with the specificity of 69. 1% , and sensitivity of 65. 4% . Conclusions CRI, ulcerative plaques, and hypoechoic plaques can increase the risk of clinical ischemic events in patients with severe carotid atherosclerotic stenosis. CRI can be used to predict clinical ischemic events in patients with severe carotid stenosis.

Impact of thoracic duct ligation on substance metabolism and surgical complications in patients with type-2 diabetes mellitus during esophagectomy / 中国胸心血管外科临床杂志

@#Objective    To investigate the impact of thoracic duct ligation (TDL) on metabolism and postoperative complications during esophagectomy in patients with type-2 diabetes mellitus (T2DM). Methods    We conducted a retrospective clinical data analysis of 230 esophageal carcinoma patients with T2DM who underwent esophagectomy in our hospital from January 2003 to December 2018. Patients were divided into a TDL+ group (n=112), including 78 males and 34 females aged 63.47±7.23 years, and a TDL– group (n=118), including 84 males and 34 females aged 64.38±7.57 years. We compared the blood glucose, liver function parameters and lipid metabolic parameters at different time points before and after surgery. In addition, we compared the postoperative major complications between the two groups. Propensity score-matched (PSM) was used to control the observed confounders. Results    Compared with the TDL–group, patients in TDL+ group had higher blood glucose level (P<0.05, except the fourth postoperative day). The total protein and albumin levels on the first and fourth postoperative days in the TDL+ group were lower than those in the TDL– group (P<0.05). The alanine transaminase (P=0.027) and aspartate transaminase (P=0.007) levels on the fourth postoperative day in the TDL+ group were higher than those in the TDL– group. More pulmonary complications (P=0.014) and anastomotic leaks (P=0.047) were found in the TDL+ group. Conclusion    Given that TDL may aggravate metabolic disorders, increase anastomotic leaks and the pulmonary complications, it is cautious to perform TDL, and prophylactic TDL should not be performed routinely for patients with T2DM.

Quality control on clinical research in the thoracic oncology / 中国胸心血管外科临床杂志

@#This article reviewed other literatures in the quality management of clinical trials and summarized author’s experience in quality control of clinical trials which the author conducted as principle investigator over the past years. It provides a reference for fresh investigators before they conduct their own clinical trials.

Clinical observation of desmopressin in the treatment of 15 patients with DDAVP / 中华血液学杂志

Objective: To assess the significance of DDAVP use in the diagnosis and treatment of VWD. Methods: An analysis of 15 VWD cases who referred to Hematology Division of First affiliated Hospital of Soochow University and treated with DDAVP from March 2016 to August 2018 was conducted. Efficacy and treatment response of DDAVP were monitored by observations of changes in factor Ⅷ procoagulant (FⅧ∶C) and von Willebrand Factor (VWF) related indicators before and 2 h after DDAVP injection. Results: Of 15 cases with VWD, 7 males and 8 females with a median age of 23 (6-46) years, 7 of 9 type I VWD patients achieved complete response (CR) , 1 type 2A VWD case CR, 5 type 3 VWD ones no response (NR) . The VWF multimer analysis in 5 patients combined with other plasma VWF values were in accordance with the known diagnosis. Conclusions: DDAVP was effective in most type 1 patients, and ineffective in some type 2 and almost all type 3 cases. It was helpful for diagnosis and subsequent treatment planning.

Application of Next Generation Sequencing in Genetic Diagnosis of Hereditary Platelet Disorders - Review / 中国实验血液学杂志

Hereditary platelet disorders are a heterogeneous group of disorders characterized by abnormal number or function of platelets, sometimes even involving other systems apart from blood abnormalities. The great clinical and genetic heterogeneity makes the diagnosis and treatment of hereditary platelet disorders as a huge challenge for clinicians. At present, only a small number of patients have received a clear molecular diagnosis of hereditary platelet diseases, and a lot of pathogenic genetic variations still remain unknown. The popularity of next generation sequencing (NGS) promotes the development of individualized gene sequencing. Researchers have made great progress in the field of hemostasis and thrombosis using whole genome sequencing (WGS), whole exone sequencing (WES) and target gene sequencing (TGS). The development of NGS has not only promoted the individualized molecular diagnosis of hereditary platelet diseases, but also laid a solid foundation for gene therapy in the future. In this review, the new progress of the diagnosis of platelet-related diseases by using next generation sequencing techniques, is summarized.

The diagnostic value of PLASMIC score in the discrimination between thrombotic thrombocytopenic purpura and disseminated intravascular coagulation / 中华血液学杂志

Objective: PLASMIC score was evaluated its value in differential diagnosis between the patients with thrombotic thrombocytopenic purpura (TTP) and those with disseminated intravascular coagulation (DIC) . Method: Twenty-four patients with TTP and 41 cases with DIC were retrospectively analyzed in this study. The platelet count, average red blood cell volume, indirect bilirubin, creatinine and prothrombin time international normalised ratio were collected, and then PLASMIC scores were calculated. Results: According to the risk classification of PLASMIC score, three (12.5%) TTP patients had moderate risk, and the rest 21 (87.5%) cases had high risk. In DIC patients, 92.7% cases were in low risk group, 4.9% at moderate risk, and only one case had high risk. Of these 65 patients, the sensitivity and the specificity to TTP of the high risk of the scoring system were 87.5% and 97.6%, respectively. Conclusion: The patients with high risk of PLASMIC score correlated well with clinical TTP diagnosis. The scoring system showed to be an excellent diagnostic model to distinguish TTP patients from those with DIC.

A new napthalenone from roots of Rumex nepalensis / 中国中药杂志

A new napthalenone, rumexone A (1), was isolated from the roots of Rumex nepalensis. The structure of 1 was elucidated by extensive spectroscopic analyses, including 1D and 2D NMR spectra and MS data. Its cytotoxic effect was evaluated using four clinically relevant human cancer cell lines, gastric carcinoma SGC7901, breast carcinoma MDA-MB-231, lung carcinoma A549, and hepatocellular carcinoma HepG2.

Independent Relationship between Body Mass Index and LH Peak Value of GnRH Stimulation Test in ICPP Girls: A Cross-sectional Study / 华中科技大学学报（医学）（英德文版）

The effect of obesity on idiopathic central precocious puberty (ICPP) girls is still under discussion.The relationship between body mass index (BMI) and sexual hormone levels of gonadotropin-releasing hormone (GnRH) stimulation test in ICPP girls is controversial and the underlying mechanism is unclear.This study aims to further explore the independent effect of excess adiposity on peak luteinizing hormone (LH) level of stimulation test in ICPP girls and the role of other related factors.A retrospective cross-sectional study was performed on 618 girls diagnosed as having ICPP,including 355 cases of normal weight,99 cases of overweight and 164 cases of obese.The results showed that obese group had more progressed Tanner stage and no significant difference (P=0.28) in LH peak was found as basal LH value was used as a covariate.The obese group had higher total testosterone (TT),adrenocorticotrophic hormone (ACTH),17-α hydroxyprogesterone (17-αOHP) and androstendione (AN),with significantly increased fasting insulin (FIN) and homeostasis model of assessment for insulin resistance index (HOMA-IR).Stratified analysis showed inconsistency of the relationship between BMI-standard deviation score (BMI-SDS) and LH peak in different Tanner stages (P for interaction=0.017).Further smoothing plot showed linear and non-linear relationship between BMI-SDS and LH peak in three Tanner stages.Then linear regression model was used to analyze the relationship between BMI-SDS and LH peak in different Tanner stages,with and without different confounding factors being adjusted.In B2 stage,BMI-SDS was negatively associated with LH peak.In B3 stage,when BMI-SDS ＜1.5,as BMI-SDS increased,the level of LH peak decreased (model Ⅰ:β=-1.8,95％ CI=-4.7 to 1.1,P=0.214).When BMI-SDS ≥1.5,BMI-SDS was significantly positively associated with LH peak (model Ⅰ:β=4.5,95％ CI=1.7 to 7.4,P=0.002).In B4 stage,when BMI-SDS ＜1.5,BMI-SDS was negatively associated with LH peak (model Ⅰ:β=-11.6,95％ CI=-22.7 to-4.5,P=0.049).When BMI-SDS ≥1.5,BMI-SDS was positively associated with LH peak (model Ⅰ:β=-4.2,95％ CI=-3.3 to 11.7,P=0.28).It is concluded that there is an independent correlation between BMI-SDS and LH peak of stimulation test in ICPP girls,their relationships are different in different Tanner stages,and the effect of BMI-SDS can be affected by adrenal androgens,estradiol and glucose metabolism parameters.

Progress in relationship between leptin and periodontitis / 口腔疾病防治

@#The in itiation and progression of periodontal disease were reported to be the results of complicated interactions between specific subgingival bacteria and host immuno-inflammatory response. As a part of the immune and defense system mechanisms of the host, leptin may have a protective effect on periodontal tissues. We summarize the latest progress in the relationship between leptin and periodontitis.

Salvianolic acid A ameliorates AGEs-induced glomerular endothelial dysfunction and protects against diabetic nephropathy / 中国药理学与毒理学杂志

OBJECTIVE Diabetic nephropathy (DN) has been one of the most common complications of diabetes and the leading cause of end-stage renal disease. Glomerular hyperfiltrationis central in earlystage of DN and leads to the progression of renal architectonic and functional abnormalities. Salvi?anolic acid A (SalA) has been proved to protect diabetic complications such as hepatic fibrosis and neuropathy. The present study was designed to investigate the effects of SalAon glomerular endothelial dysfunctionand diabetic nephropathy. METHODS Primary glomerular endothelial cells were subjected to assess permeability under injury of advanced glycation end-products (AGEs). AGEs-induced changes of RhoA/ROCK pathway and cytoskeleton rearrangement were assessed bywestern blotandimmunoflu?orescence. The beneficial effects of SalA on diabetic nephropathy were investigated in a rat model induced by high-fat and high-glucose diet combined with low dose of streptozocin (35 mg·kg- 1, ip). Renal function and architectonic changes were evaluated by biochemical assay and PAS staining. RESULTS SalA 3μMameliorated AGEs- induced glomerular endothelial permeability (P<0.05) and suppressed rearrangement of cytoskeleton through inhibiting AGE-RAGE-RhoA/ROCK pathway. SalA 1 mg · kg- 1 markedly reduced endothelium loss (P<0.01) and glomerular hyperfiltration (P<0.05) in diabetic kidney. Subsequently,SalA 1 mg·kg-1 suppressed glomerular hypertrophy and mesangial matrix expansion, eventually reduced 24 h-urinary albumin and ameliorated renal function by decreasing blood urine nitrogen (BUN), serum creatinine (Scr) and serum n-acetyl-β-d-glucosaminidase (NAG). AGEs-RAGE-Nox4-induced oxidative stress was suppressed by the treatment of SalA 1 mg·kg-1. CONCLUSION SalA ameliorated AGEs-induced glomerular endothelial hyperpermeability, and effec?tively protected against early-stage diabetic nephropathy by reducing hyperfiltration and alleviating renal structural deterioration through inhibiting AGEs and its downstream pathway. Thus, SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.

Changes of ADAMTS13 activity and vWF antigen level in patients with acute myelogenous leukemia and their significance / 中国实验血液学杂志

This study was purposed to investigate the changes of von Willebrand factor cleaving protease (ADAMTS13) activity and vWF antigen level in patients with acute myelogenous leukemia (AML) before and after treatment and evaluate their clinical significance. Seventy-three AML patients were enrolled in this study, the sodium citrate anticoagulated plasma was collected before and after their induction chemotherapy. Fluorescence resonance energy transfer substrate vWF73 (FRETS-vWF73) assay was established to detect the plasma ADAMTS13 activity while vWF antigen level was measured by ELISA. The results showed that the ADAMTS13 activity in newly diagnosed patients with AML before induction therapy was obviously lower than that in normal controls (63.3 ± 25.5)% vs (105.1 ± 37.7)(P < 0.01), while the vWF antigen level was higher than that in normal controls (226.6 ± 127.0)% vs (111.4 ± 39.7)% (P < 0.01). After standard induction chemotherapy, the ADAMTS13 activity of AML patients in complete remission period was higher than that in AML patients before therapy (P < 0.01), and was not significant difference with that in normal controls; the vWF antigen was significantly lower than that in AML patients before therapy (P < 0.01), but it still was higher than that in controls (P < 0.05). The ADAMTS13 activity in newly diagnosed AML patients complicated with infection before therapy was obviously lower than that in AML patients without infection (52.2 ± 20.6)% vs (73.9 ± 24.7)% (P < 0.01), while the vWF antigen level was significantly higher than that in AML patients without infection (262.2 ± 135.7)% vs (193.8 ± 110.2)% (P < 0.05). The ADAMTS13 activity in AML patients with disseminated intravascular coagulation (DIC) was significantly lower than that in AML patients without DIC (42.0 ± 14.5)% vs (73.4 ± 22.7)% (P < 0.01), while the vWF antigen level was obviously higher that in AML patients without DIC (274.2 ± 140.0)% vs (204.7 ± 115.5)% (P < 0.01). It is concluded that the ADAMTS13 activity in newly diagnosed AML patients befor induction therapy has been confiremed to be lower and the vWF antigen level to be higher, especially in AML patients with infection or DIC. The ADAMTS13 and vWF antigen may play a role in the pathogenesis of AML and the formation of infection and DIC.

Congenital afibrinogenemia caused by a novel insertion mutation in the FGB gene / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the genetic defect and its mechanism in a patient with congenital afibrinogenemia.</p><p><b>METHODS</b>The plasma fibrinogen activity and antigen of the patient was determined using the Clauss method and immuno-nephelometric assay, respectively. Genomic DNA was isolated from peripheral blood of the proband and his related family members. All exons and exon-intron boundaries of the three fibrinogen genes (FGA, FGB, FGG) were amplified by PCR followed by direct sequencing. Thrombin fibrin aggregation curve were detected in the plasma of the patient. Wild-type and mutation type fibrinogen vectors were constructed, and then transfected into COS-7 cells. The wild-type and mutant proteins from the culture media and cell lysates were tested by Western blot and ELISA.</p><p><b>RESULTS</b>APTT, PT, TT were significantly longer in the proband. Plasma fibrinogen activity and antigen of the patient could not be detected using the Clauss method and immuno-nephelometry, respectively. Gene analysis revealed that a novel homozygous GTTT insertion between nucleotides 2833 and 2834 in FGB exon 2 in the proband. The proband's father, mother, brother and son were heterozygous. The polymerization curves of the patient did not show a lag phase or final turbidity, compared with the normal controls. Western blot analysis showed the lack of complete half-molecules of the fibrinogen molecule and fibrinogen in patient's plasma under non-reducing conditions. It also could not detect the truncated Bβ chain under reducing conditions. Abnormal fibrinogen molecule (molecule weight>340 000) were found in transfected COS-7 cells by Western blot, which indicated that the mutation caused the abnormal intracellular fibrinogen molecule assembly. The fibrinogen band was absent in culture media transfected by the mutation. Fibrinogen levels of mutant fibrinogen were no significant different from those of wild-type fibrinogen in cell lysates by ELISA analysis [(2.47 ± 0.30) μg/ml vs (2.65±0.60) μg/ml, P=0.0889]; However, the levels of the mutant fibrinogen were statistically significant lower than those of wild type fibrinogen in culture media [(0.01 ± 0.01) μg/ml vs (3.80±0.80) μg/ml, P=0.0001].</p><p><b>CONCLUSION</b>Congenital afibrinogenemia was caused by this frameshift mutation in exon 2 of FGB. This novel mutation impaired fibrinogen assembly and secretion.</p>