Chronic neutropenia in childhood: experience of a tertiary center

Abstract Objective: To assess the prevalence of chronic neutropenia (CN) and the clinical profile of patients with CN aged up to 18 years, followed in the pediatric hematology, rheumatology, or immunology outpatient clinic of a tertiary medical center from May 1, 2018, to 30 April 2019. Methods: Retrospective observational study carried out by collecting data from the patient's medical charts. CN was defined as absolute neutrophil count (ANC) below 1.5 × 109/L lasting over three months. Autoimmune neutropenia (AIN) was defined by clinical criteria and an over twofold increase in ANC after glucocorticoid stimulation. AIN was considered secondary when associated with autoimmune or immunoregulatory disorders. Wilcoxon and Fisher's exact tests were used to compare variables; the significance level was 5 %. Results: A total of 1,039 patients were evaluated; 217 (20 %) presented CN. Twenty-one (2 %) had AIN, classified as primary in 57 % of the cases. The average age at the onset of symptoms was 38.6 months. During follow-up, patients had 4.2 infections on average; frequency was higher among patients with secondary AIN (p = 003). Isolated neutropenia occurred in 43 % of the patients with AIN. Neutropenia resolved in eight (38 %) of the 21 patients with AIN within 19.6 months on average. Eight patients with secondary AIN met the criteria for Inborn Errors of Immunity. Conclusion: AIN prevalence was 2 %. Most cases were first evaluated by a pediatric immunologist or rheumatologist rather than a pediatric hematologist. This study highlights the need for a multidisciplinary approach involving a pediatric immunologist, rheumatologist, and hematologist.

Tuberculosis Extrapulmonar como Linfopatía Cervical: Revisión Sistemática y Presentación de Caso Clínico

La tuberculosis es una infección bacteriana causada por Mycobacterium tuberculosis que afecta a millones de personas en todo el mundo. Aunque principalmente se manifiesta en los pulmones, también puede afectar otras partes del cuerpo, como la regiónes de la cabeza y el cuello. Aunque es poco común, se han reportado casos de tuberculosis en glándulas parótidas, tonsilas palatinas y seno piriforme. La forma más común de tuberculosis extrapulmonar en esta región es la linfadenopatía superficial, que afecta principalmente los nódulos linfáticos del territorio cervical anterior. Los linfonodos afectados por tuberculosis presentan características específicas en la ecografía, lo que puede ayudar en el diagnóstico. El diagnóstico de tuberculosis extrapulmonar se realiza mediante pruebas como la citología por aspiración con aguja fina (PAAF) o la reacción en cadena de la polimerasa (PCR). Estas pruebas permiten detectar la presencia de Mycobacterium tuberculosis en los tejidos afectados. El tratamiento de la tuberculosis implica el uso de antibióticos antituberculosos durante un periodo prolongado. Es importante seguir el tratamiento completo para asegurar la erradicación de las bacterias y prevenir la recurrencia de la enfermedad. En este artículo, se presenta una revisión sistemática de la literatura de tuberculosis extrapulmonar en la región de la cabeza y cuello y un caso de un paciente sexo masculino de 81 años de edad, que se presentó con un aumento de volumen submandibular izquierdo de 3 semanas de evolución, con hipótesis diagnóstica de submaxilitis idiopática. Presentaba múltiples adenopatías supraclaviculares, mediastínicas e hiliares, y en conjunto a scanner, biopsias, cultivos y test dio resultados positivos para tuberculosis que se manifestó de forma extrapulmonar.

Tuberculosis is a bacterial infection caused by Mycobacterium tuberculosis that affects millions of people around the world. Although it manifests primarily in the lungs, it can also affect other parts of the body, such as the head and neck regions. Although rare, cases of tuberculosis in the parotid glands, palatine tonsils, and piriform sinus have been reported. The most common form of extrapulmonary tuberculosis in this region is superficial lymphadenopathy, which mainly affects the nodules of the anterior cervical area. Lymph nodes affected by tuberculosis present specific characteristics on ultrasound, which can help in diagnosis. The diagnosis of extrapulmonary tuberculosis is made through tests such as fine needle aspiration cytology (FNAC) or polymerase chain reaction (PCR), which allow the presence of Mycobacterium tuberculosis in the affected tissues to be detected. Treatment of tuberculosis involves the use of anti-tuberculosis antibiotics for long periods of time. It is important to follow the complete treatment to ensure the eradication of bacteria and prevent recurrence of the disease. In this article, we present a systematic review of the literature on extrapulmonary tuberculosis in the head and neck region and case of an 81-year-old male patient, who presented with a 3-week increase in left submandibular volume with a diagnostic hypothesis of idiopathic submaxilitis. The patient had multiple supraclavicular, mediastinal and hilar lymphadenopathy; following scan, biopsies, and cultures, the patient tested positive for tuberculosis that manifested extrapulmonarily.

Hipertensión portal no cirrótica por enfermedad vascular porto-sinusoidal: presentación de un caso y revisión de la literatura / Non-cirrhotic portal hypertension due to porto-sinusoidal vascular disease: Case presentation and literature review

La enfermedad vascular porto-sinusoidal es una causa infrecuente de hipertensión portal no cirrótica, fue descrita recientemente y es poco diagnosticada por el desconocimiento entre los médicos. Se considera en casos de hipertensión portal clínicamente significativa, en ausencia de cirrosis. El diagnóstico se basa en los hallazgos de la biopsia. El pronóstico de la enfermedad es mejor que el de los pacientes cirróticos, y el tratamiento es similar al de la hipertensión portal y al de las complicaciones que presentan los pacientes con cirrosis. Se presenta el caso de una paciente con várices esofágicas con estudios de imágenes no compatibles con cirrosis y hallazgos específicos en la biopsia de enfermedad vascular porto-sinusoidal. Este caso muestra el ejercicio diagnóstico en un caso de enfermedad vascular porto-sinusoidal de una paciente de Colombia, así como el resultado de las intervenciones terapéuticas y la evolución en el tiempo.

Porto-sinusoidal vascular disease is an uncommon cause of non-cirrhotic portal hypertension. It was recently described and is rarely diagnosed due to lack of knowledge among doctors. It is considered in cases of clinically significant portal hypertension in the absence of cirrhosis, and the diagnosis is based on biopsy findings. The prognosis of the disease is better than that of cirrhotic patients, and the treatment is similar to that of portal hypertension, including the management of complications associated with cirrhosis. We present the case of a patient with esophageal varices, whose imaging studies were not compatible with cirrhosis, alongside specific biopsy findings of porto-sinusoidal vascular disease. This case illustrates the diagnostic process in a patient from Colombia with portosinusoidal vascular disease, as well as the outcomes of therapeutic interventions and the patient´s evolution over time.

Escoliosis idiopática del adolescente / Adolescent idiopathic scoliosis

La escoliosis idiopática del Adolescente (EIA) es una deformidad tridimensional de la columna vertebral que aqueja de diversas formas la condición de vida de quien la padece, afectando el desarrollo físico y psicológico del paciente. Proponemos evaluar el resultado clínico, radiológico y el componente de calidad de vida de pacientes tratados quirúrgicamente con EIA, en el servicio de Neurocirugía, Hospital Jesús Yerena del Lídice. Se evaluó patrón de la curva, clasificación según Lenke, ángulo de Cobb pre y postquirúrgico, edad de tratamiento quirúrgico, gradode corrección, calidad de vida según cuestionario SRS-22 pre y postquirúrgica, valoración funcional mediante la escala de discapacidad de Oswestry (ODI) y complicaciones postoperatorias. Se estudiaron 22 casos (95 % femenino), el principal grupo etario fue de 11-14 años (55 %), la escoliosis tipo 1 fue la predominante (60 %), el ángulo de Cobb inicial fue mayor a 50° (50 %) y la madurez esquelética principal fue Risser 3 (55 %). La edad de resolución quirúrgica predominante fue entre 15-18 años (60 %), el grado de corrección postoperatorio fue de 75-100 % (73 %) y la densidad de los tornillos pediculares fue de 1.4-1.7 (64 %). En el cuestionario SRS-22, hubo mayor afectación en las dimensiones de autoimagen con una media de 1.8 y la valoración por ODI mostró un índice de incapacidad mínima, que fue mejorando en los controles sucesivos. Nuestra principal complicación fueron las infecciones (36 %). Concluimos que la cirugía correctiva temprana en la EIA ofrece a una mejoría clínica, radiológica y de la calidadde vida de estos paciente(AU)

Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine that affects the living condition of those who suffer from it in various ways, affecting the physical and psychological development of the patient. We propose to evaluate the clinical and radiological outcome and the quality-of-life component of patients treated surgically with EIA, in the Neurosurgery Service, Hospital Jesús Yerena del Lídice. Curve pattern, Lenke classification, pre-and post-surgical Cobb angle, age at surgical treatment, degree of correction, quality of life according to pre-and post-surgical SRS-22 questionnaire, functional assessment using the Oswestry Disability Scale (ODI) and postoperative complications were evaluated. 22 cases were studied (95% female), the main age group was 11-14 years (55%), type 1 scoliosis was predominant (60%), the initial Cobb angle was greater than 50° (50%) and the main skeletal maturity was Risser 3 (55%). The predominant age of surgical resolution was between 15-18 years (60%), the degree of postoperative correction was 75-100% (73%) and the density of pedicle screws was 1.4-1.7 (64%). In the SRS-22 questionnaire, there was greater impairment in the self-image dimensions with a mean of 1.8 and the ODI assessment showed aminimal disability index, which improved in successive controls. Our main complication was infections (36%). We conclude that early corrective surgery in AIS offers clinical, radiological and quality of life improvement for these patient(AU)

Valores de referencia para el 1-minute sit-to-stand test en pacientes pediátricos con artritis idiopática juvenil / Reference values for the 1-minute sit-to-stand test in pediatric patients with juvenile idiopathic arthritis

Introducción: los niños con artritis idiopática juvenil (AIJ) experimentan períodos de dolor e inmovilidad que afectan sus capacidades condicionales. Objetivos: describir los valores de referencia para el 1-minute Sit-to-Stand Test(1-STS; test de 1 minuto de sentarse y pararse) en niños con AIJ como evaluación de la capacidad aeróbico-funcional y de la fuerza muscular de los miembros inferiores (MMII).Materiales y métodos: se realizó un estudio observacional que incluyó a 15 niños con AIJ de entre 5 y 16 años. Se evaluó su rendimiento en el 1-STS. Resultados: se encontró una correlación positiva significativa entre el 1-STS y el test de la marcha de 6 minutos (r=0,56; p=0,03), como con el índice de capacidad funcional (CAPFUN) (r=0,54; p=0,03). No se observaron correlaciones significati-vas entre el Childhood Health Assessment Questionnaire (CHAQ) y el 1-STS (r=-0,21; p=0,44), tampoco con el Juvenile Arthritis Disease Activity Score (JADAS-10) (p=0,83). Conclusiones: el 1-STS parece prometedor para medir la capacidad aeróbi-co-funcional y la fuerza muscular de los miembros inferiores en niños con AIJ oligoarticular.

Introduction: children with juvenile idiopathic arthritis (JIA) experience periods of pain and immobility that affect their physical capacities. Objectives: to describe reference values for the 1-minute sit to stand test (1-STS) in children with JIA as an assessment of aerobic-functional capacity and lower limb muscle strength.Materials and methods: an observational study was conducted, including 15 children with JIA aged between 5 and 16 years. Their performance in the 1-STS was assessed. Results: a significant positive correlation was found between the 1-STS and the 6-Minute Walk Test (r=0,56; p=0,03), as well as with the Functional Capacity Index (CAPFUN) (r=0,54; p=0,03). No significant correlations were observed between the Childhood Health Assessment Questionnaire (CHAQ) and the 1-STS (r=-0,21; p=0,44), nor with the Juvenile Arthritis Disease Activity Score (JADAS-10) (p=0,83). Conclusions: the 1-STS appears promising for assessing aerobic-functional capacity and lower limb muscle strength in children with oligoarticular JIA.

Valores de referencia para el 1-minute sit-to-stand test en pacientes pediátricos con artritis idiopática juvenil / Reference values for the 1-minute sit-to-stand test in pediatric patients with juvenile idiopathic arthritis

Resumen Introducción: los niños con artritis idiopática juvenil (AIJ) experimentan períodos de dolor e inmovilidad que afectan sus capacidades condicionales. Objetivos: describir los valores de referencia para el 1-minute Sit-to-Stand Test (1-STS; test de 1 minuto de sentarse y pararse) en niños con AIJ como evaluación de la capacidad aeróbico-funcional y de la fuerza muscular de los miembros inferiores (MMII). Materiales y métodos: se realizó un estudio observacional que incluyó a 15 niños con AIJ de entre 5 y 16 años. Se evaluó su rendimiento en el 1-STS. Resultados: se encontró una correlación positiva significativa entre el 1-STS y el test de la marcha de 6 minutos (r=0,56; p=0,03), como con el índice de capacidad funcional (CAPFUN) (r=0,54; p=0,03). No se observaron correlaciones significativas entre el Childhood Health Assessment Questionnaire (CHAQ) y el 1-STS (r=-0,21; p=0,44), tampoco con el Juvenile Arthritis Disease Activity Score (JADAS-10) (p=0,83). Conclusiones: el 1-STS parece prometedor para medir la capacidad aeróbico-funcional y la fuerza muscular de los miembros inferiores en niños con AIJ oligoarticular.

Abstract Introduction: children with juvenile idiopathic arthritis (JIA) experience periods of pain and immobility that affect their physical capacities. Objectives: to describe reference values for the 1-minute sit to stand test (1-STS) in children with JIA as an assessment of aerobic-functional capacity and lower limb muscle strength. Materials and methods: an observational study was conducted, including 15 children with JIA aged between 5 and 16 years. Their performance in the 1-STS was assessed. Results: a significant positive correlation was found between the 1-STS and the 6-Minute Walk Test (r=0,56; p=0,03), as well as with the Functional Capacity Index (CAPFUN) (r=0,54; p=0,03). No significant correlations were observed between the Childhood Health Assessment Questionnaire (CHAQ) and the 1-STS (r=-0,21; p=0,44), nor with the Juvenile Arthritis Disease Activity Score (JADAS-10) (p=0,83). Conclusions: the 1-STS appears promising for assessing aerobic-functional capacity and lower limb muscle strength in children with oligoarticular JIA.

Imaging study on thoracic and lumbar physiological curvature in adolescent idiopathic scoliosis / 中国骨伤

OBJECTIVE@#To observe the alteration of thoracic and lumbar physiological curvature in adolescent idiopathic scoliosis(AIS) and the difference of physiological curvature between different types of scoliosis.@*METHODS@#A retrospective analysis was conducted on 305 adolescent patients taken full spine X-ray in our hospital from January 2017 to December 2021. The patients were divided into normal group and scoliosis group. The normal group was composed of 179 patients, 79 males and 100 females, aged 10 to 18 years old with an average of (12.84±2.10) years old, with cobb agle less than 10 degrees. The scoliosis group was composed of 126 patients, 33 males and 93 females, aged 10 to 18 years old with an average of (13.92±2.20) years old. The gender, age, Risser sign, thoracic kyphosis(TK) and lumbar lordosis(LL) in 2 groups were compared, and the TK and LL were also compared between different genders, different degrees of scoliosis and different segments of scoliosis.@*RESULTS@#The female ratio(P=0.001) and age (P<0.001) in scoliosis group were higher than them in normal group; the ratio of low-grade ossification was higher in normal group than in scoliosis group(P=0.038). TK was significantly smaller in scoliosis group than in normal group(P<0.001), but there was no significant difference in LL between the 2 groups(P=0.147). There were no significant difference in TK and LL between male and female. The TK was significantly bigger in mild AIS patients than in moderate AIS patients(P<0.05), but there was no significant difference in LL between mild and moderate patients(P>0.05). The TK and LL in different segments scoliosis were not found significant difference.@*CONCLUSION@#The physiological curvature of thoracic and lumbar spine is independent of gender. The thoracic physiological curvature becomes smaller in AIS patients, but lumbar curvature remains unchanged. The thoracic physiological curvature in mild AIS patients is greater than that in moderate AIS patients, but the lumbar curvature is almost unchanged between mild and moderate scoliosis and is similar with that in normal adolescent. The alteration of thoracic and lumbar physiological curvature in AIS patients may be related to relative anterior spinal overgrowth, and the specific detailed mechanism needs to be further studied.

Improvement of Lung Function in Rats with Idiopathic Pulmonary Fibrosis by Shengxiantang via Regulating Cell Senescence Mediated by Wnt3a/β-catenin Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Shengxiantang （SXT） on cell senescence mediated by wingless/integrated （Wnt）3a/β-catenin pathway in rats with idiopathic pulmonary fibrosis （IPF） and reveal the possible mechanism in improving lung function of IPF rats. MethodA total of 32 SPF level SD rats were randomly divided into sham group， model group， pirfenidone group， and SXT group. The IPF rat model was established by intratracheal instillation of bleomycin （0.005 g·kg-1）. The following day after surgery， rats in the SXT group were given the aqueous solution of SXT granules （0.78 g·kg-1）， and the pirfenidone group was given pirfenidone suspension （0.05 g·kg-1）. The other groups were given deionized water （10 mL·kg-1） for 28 consecutive days. Lung tissue was collected after the lung function was measured. The pathological changes of the lung tissue were observed by hematoxylin-eosin （HE） and Masson staining， and then the Szapiel score and Ashcroft score were performed. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect telomere length. Western blot was applied to detect the expressions of epithelial-mesenchymal transformation （EMT） markers ［α-smooth muscle actin （α-SMA） and E-cadherin］， telomere reverse transcriptase （TRET）， aging-related proteins （p53 and p21）， senescence-associated secretory phenotype ［interleukin-6 （IL-6） and matrix metalloproteinase-1 （MMP-1）］， and key proteins of Wnt signaling pathway ［Wnt3a， glycogen synthase kinase-3β （GSK-3β）， β-catenin， Cyclin D1， and c-Myc］. ResultCompared with those in the Sham group， peak expiratory flow （PEF） and minute ventilation volume （MV） in the model group were significantly decreased （P<0.01）， and the frequency of respiratory （f） was significantly increased （P<0.01）. The Szapiel score， Ashcroft score， and protein expression of α-SMA， p53， p21， IL-6， MMP-1， Wnt3a， GSK3β， β-catenin， Cyclin D1， and c-Myc were increased （P<0.01）. The expressions of E-cadherin and TERT， as well as telomere length were significantly decreased （P<0.01）. Compared with those in the model group， PEF and MV in the SXT group were significantly increased （P<0.01）， while f was significantly decreased （P<0.01）. The Szapiel score， Ashcroft score， and protein expression of α-SMA， p53， p21， IL-6， MMP-1， Wnt3a， GSK3β， β-catenin， Cyclin D1， and c-Myc were significantly decreased （P<0.05， P<0.01）. Nevertheless， the expression of E-cadherin and TERT， as well as telomere length were significantly increased （P<0.01）. ConclusionSXT presents a significant protective effect on lung function in IPF rats， and the prescription may act on the Wnt3a/β-catenin signaling pathway to regulate cell senescence induced by TERT to inhibit EMT.

A unicenter real-world study of the correlation factors for complete clinical response in idiopathic inflammatory myopathies / 北京大学学报(医学版)

Objective:To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies(IIMs)patients receiving conventional treatment.Methods:Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were in-cluded.The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics,laboratory features,peripheral blood lymphocytes,immunological indicators,and therapeutic drugs.Results:Among the 635 patients included,518 patients finished the follow-up,with an average time of 36.8 months.The total complete clinical response rate of IIMs was 50.0％(259/518).The complete clinical response rate of dermatomyositis(DM),anti-synthetase syn-drome(ASS)and immune-mediated necrotizing myopathy(IMNM)were 53.5％,48.9％and 39.0％,respectively.Fever(P=0.002)and rapid progressive interstitial lung disease(RP-ILD)(P=0.014)were observed much more frequently in non-complete clinical response group than in complete clinical re-sponse group.The aspartate transaminase(AST),lactate dehydrogenase(LDH),D-dimer,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP)and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group.As for the treat-ment,the percentage of glucocorticoid received and intravenous immunoglobin(IVIG)were significantly higher in non-complete clinical response group than in complete clinical response group.Risk factor analysis showed that IMNM subtype(P=0.007),interstitial lung disease(ILD)(P=0.001),eleva-ted AST(P=0.012),elevated serum ferritin(P=0.016)and decreased count of CD4+T cells in peripheral blood(P=0.004)might be the risk factors for IIMs non-complete clinical response.Conclu-sion:The total complete clinical response rate of IIMs is low,especially for IMNM subtype.More effec-tive intervention should be administered to patients with ILD,elevated AST,elevated serum ferritin or decreased count of CD4+T cells at disease onset.

Advances in enthesitis-related arthritis / 国际儿科学杂志

Enthesitis related arthritis（ERA）is one of the subtypes of juvenile idiopathic arthritis（JIA）. It is a group of diseases characterized by arthritis，inflammation，axial lesions，and human leucocyte antigen-B27 positive. In the previous classification criteria，ERA does not include all of the subsets of juvenile spondyloarthritis（JSpA）. Based on an evidence-based approach，the Pediatric Rheumatology International trials Organization developed the latest classification criteria in 2019，and proposed the classification criteria of ERA/SpA，to distinguish it from other subtypes of JIA. The new definition added the term spondylitis，included imaging criteria，and adopted a new definition of back pain. The pathogenesis，evolution of classification criteria and prognosis of spondyloarthritis are described in this paper，in order to improve the level of diagnosis and treatment of patients with axial joint involvement，so as to improve the prognosis.

Analysis of therapeutic effect of thalidomide on refractory systemic onset juvenile idiopathic arthritis / 国际儿科学杂志

Objective:To analyze and summarize the efficacy and safety of thalidomide in the treatment of refractory systemic juvenile idiopathic arthritis（sJIA）.Methods:The clinical data of ten patients with refractory sJIA admitted to Department of Nephrology and Immunology in Children's Hospital of Hebei Province from January 2015 to March 2022 were collected，and the clinical manifestations，efficacy and safety of thalidomide in the treatment of refractory sJIA were analyzed retrospectively. Systemic juvenile arthritis disease activity score（sJADAS）was used to evaluate the efficacy of the treatment. Statistical analysis was performed by repeated measurements using general linear models.Results:Among the 10 children（4 males and 6 females）with refractory sJIA，the average age of onset was（7.5±3.3）years. Seven patients were complicated with macrophage activation syndrome at an early stage of disease.The average course of disease was（4.4±1.7）years，and the longest course of disease was 8.3 years. Before the application of thalidomide，all the 10 children experienced relapses（ranging from 2 to 10 times）. The indices of 10 children treated with thalidomide at 6 months and 12 months were compared with those before treatment. Peripheral blood leukocytes［（10.19±3.67）×10 9/L，（8.53±2.83）×10 9/L vs.（16.11±7.81）×10 9/L， F=7.918，11.084， P=0.020，0.009］，C-reactive protein［19.13（0.38，35.21）mg/L，8.05（0.10，18.00）mg/L vs. 59.34（24.20，131.90）mg/L， F=7.030，12.731， P=0.026，0.006］，sJADAS scores［6.00（1.50，12.50）scores，3.00（0，12.50）scores vs. 20.00（11.50，28.00）scores， F=14.710，17.870， P=0.004，0.002］were decreased significantly. The doses of prednisone［0.13（0，0.45）mg/（kg·d），0.02（0，0.06）mg/（kg·d）vs. 0.42（0.16，1.47）mg/（kg·d）， F=5.890，7.623， P=0.041，0.022］were significantly decreased.All the differences were statistically significant. Prednisone was successfully discontinued in 7 cases. Tocilizumab was gradually withdrawn in 3 cases，and tocilizumab administration interval was prolonged in 1 case. None of the 10 children had serious adverse reactions. Conclusion:Thalidomide is clinically effective in the treatment of sJIA，and can reduce the required dose of prednisone and prolong the tocilizumab free remission.

Prediction model of therapeutic effect on children with idiopathic short stature based on vitamin K2,IGFBP-3 and Omentin-1 / 国际检验医学杂志

Objective To investigate the relationship between vitamin K2,insulin-like growth factor bind-ing protein 3(IGFBP-3),Omentin-1 and the therapeutic effect on children with idiopathic short stature(ISS),and to build a prediction model.Methods A total of 242 ISS children in Jinan Second Maternal and Child Health Hospital from 2019 to 2021 were selected.All of them received recombinant human growth hormone(rhGH)treatment and were divided into effective group and ineffective group according to the therapeutic effect after 12 months of treatment.The general data,vitamin K2,IGFBP-3 and Omentin-1 in the two groups were analyzed.The influencing factors of ISS children's therapeutic effect were analyzed by Logistic regression model and decision tree model.The predictive performance of two models was analyzed by using receiver oper-ating characteristic(ROC)curve.Results There were statistically significant differences in 25-hydroxy vita-min D[25(OH)D],parathyroid hormone(PTH),thyroid stimulating hormone(TSH),vitamin K2,IGFBP-3,Omentin-1,rhGH dosage and weekly outdoor exercise time between the two groups(P＜0.05).Logistic re-gression showed that PTH(OR=7.011,95％CI:2.456-20.014),vitamin K2(OR=0.605,95％CI:.0.465-0.788),IGFBP-3(OR=0.458,95％CI:0.321-0.654),Omentin-1(OR=0.514,95％CI:0.389-0.679)and rhGH dose(OR=0.563,95％CI:0.445-0.712)]were the influential factors for treatment ineffectiveness in ISS children(P＜0.05).The decision tree model showed that vitamin K2,IGFBP-3 and Omentin-1 were the factors influencing the therapeutic effect of ISS,and IGFBP-3 had the most significant impact.ROC curve re-sults showed that the area under the curve of decision tree model and Logistic regression model were 0.922 and 0.908,respectively,with good classification effect.Conclusion The therapeutic effect of ISS children is in-fluenced by factors such as vitamin K2,IGFBP-3,Omentin-1,and so on,and IGFBP-3 has the most significant impact.Logistic regression model and decision tree model could complement each other so as to provide refer-ence for improving the therapeutic effect of ISS children from different aspects.

Constitution of children with idiopathic central precocious puberty and rapidly progressive early development / 国际中医中药杂志

Objective:Exploratory study on the relationship between TCM syndrome types, TCM constitution and clinical symptoms of idiopathic central precocious puberty children and rapidly progressive early development children in Shanghai, so as to provide a basis for early intervention and syndrome differentiation and treatment.Methods:A cross-sectional study and retrospectively enrolled. Through questionnaire survey, the basic information, clinical symptoms and TCM constitution of children diagnosed with idiopathic central precocious puberty and rapidly progressive early development were collected from the Pediatric Endocrinology Clinic of Affiliated Shuguang Hospital of Shanghai University of Traditional Chinese Medicine from July to August 2022, and the correlation between the distribution, differentiation and clinical symptoms of TCM constitution in children with idiopathic central precocious puberty and children with rapidly progressive precocious puberty in Shanghai were explored through data analysis.Results:① Fast progressive early development children with higher BMI and age than idiopathic central precocious puberty were statistically significant ( P<0.05), and no significant difference in the sex composition ratio between the two groups. ② Among children with idiopathic central precocious puberty and children with rapid progressive early development, the proportion of liver depression fire syndrome was the highest, 59.15% (42/71) and 46.51% (60/129) respectively, and the proportion of Qi depression was the highest, 35.21% (25/71) and 36.43% (47/129) respectively. However, there was no significant difference in the TCM syndrome types and physical distribution of the two groups. ③ The TCM syndrome types of 200 precocious children weres correlated with physical distribution, among which Yin deficiency fire flourishing syndrome was significantly associated with Yin deficiency, liver stagnation fire syndrome was significantly correlated with qi depression, and phlegm dampness obstruction syndrome was significantly correlated with phlegm dampness and Yang deficiency ( P<0.01). ④ A total of 200 children with precocious puberty were more female than male, male BMI was higher than female, and the BMI of children with precocious puberty was higher than other syndrome types, and the differences were statistically significant ( P<0.01). Liver stasis fire syndrome was the highest proportion between boys and girls, but there was no obvious difference in TCM syndrome types between different genders. The highest proportion of breast pain in clinical symptoms was 22.19% (69/311). Conclusion:Children with idiopathic central precocious puberty and rapidly progressive early development children have differences in age and BMI, with no obvious difference in gender composition, TCM syndrome type and physical distribution, but there is a correlation between TCM syndrome type and physical constitution of precocious puberty children.

Study on the Distribution Characteristics of Traditional Chinese Medicine Syndrome Types in Girls with Idiopathic Central Precocious Puberty from Hainan Province / 广州中医药大学学报

Objective To investigate the distribution characteristics of traditional Chinese medicine(TCM)syndromes in girls with idiopathic central precocious puberty(ICPP)from Hainan province.Methods A total of 216 cases of ICPP girls admitted to Hainan Women and Children's Medical Centre from January 2019 to December 2021 were retrospectively collected.The frequency statistics and grading of TCM syndromes in the included ICPP girls were carried out,and the distribution characteristics of TCM syndromes were discussed on the basis of the analysis of the three TCM syndrome types of yin deficiency and fire exuberance syndrome,qi and blood insufficiency syndrome and incoordination between heart and kidney syndrome.Results(1)The age of ICPP onset in 216 girls were between 4 and 10 years old,with an average onset age of(7.15±1.06)years.The highest incidence rate of ICPP was found in the girls aged over 7 years old while less than 8 years old,which was 49.54%.(2)Of the three TCM syndrome types,yin deficiency and fire exuberance syndrome accounted for the highest proportion(147 cases,68.06%),followed by the qi and blood insufficiency syndrome(41 cases,18.98%)and the incoordination between heart and kidney syndrome(28 cases,12.96%).(3)The common 16 TCM symptoms(frequency＞25.0%)in descending order of frequency were aversion to heat and night sweating,feverish sensation in soles and palms,breast distension and pain,irritability,thready and rapid pulse,dry stools,dry throat and mouth,hot flushes,excessive intake of fat and sweet food,red tongue with less fur,depression,mental weakness,flushed cheeks,insomnia and dreaminess,red tongue with yellow fur,and bitterness and dryness in the mouth.(4)The distribution of the age in ICPP girls with various syndromes was as follows:yin deficiency and fire exuberance syndrome and qi and blood insufficiency syndrome were more common in the ICPP girls aged over 7 years old while less than 8 years old(accounting for 58.50%and 51.22%),and incoordination between heart and kidney syndrome was more common in ICPP girls aged over 8 years old while less than 9 years old(accounting for 89.29%).Conclusion Yin deficiency and fire exuberance syndrome is the common TCM syndrome that accounts for the highest proportion in ICPP girls from Hainan province.The study of the distribution of TCM syndromes in girls with precocious puberty will be helpful for the observation of the early clinical symptoms of precocious puberty and early diagnosis of the disease,and can provide clues and evidence for the clinical diagnosis and medication for girls with ICPP.

Effects of lncRNA FEZF1-AS1 on proliferation,migration and invasion through regulating EZH2 of lung interstitial cells / 基础医学与临床

Objective To investigate the effects of long non-coding RNA FEZ family zinc finger 1 antisense RNA 1(lncRNA FEZF1-AS1)on enhancer of zeste homolog 2(EZH2)in regulation of proliferation,migration,invasion and epithelial-mesenchymal transition(EMT)of pulmonary interstitial cells and its mechanism.Methods The A549 cells human lung adenocarcinoma cell line were divided into control group and model group[model cells were induced into lung interstitial cells after being treated with transforming growth factor β1(TGF-β1)20 ng/mL for 48 h].The protein expression of E-cadherin,N-cadherin and vimentin in each group was detected by Western blot.The expression of lncRNA FEZF1-AS1 and EZH2 in the two groups was detected by RT-qPCR.Cells in the trans-fection group were divided into si NC group,lncRNA FEZF1-AS1+OE vector group and si lncRNA FEZF1-AS1+OE EZH2 group.Cell proliferation was examined by CCK-8 method,cell migration was detected by cell scratch,and cell invasion was detected by Transwell assays.The protein expression of E-cadherin,N-cadherin,vimentin and EZH2 in each group was detected by Western blot.The direct binding effect of FEZF1-AS1 and EZH2 was deter-mined by RNA immuno-precipitation(RIP).Results Compared with the control group,the protein expression level of E-cadherin in the model group was significantly decreased(P＜0.05),and the protein expression of N-cadherin and vimentin was significantly increased(P＜0.05).Compared with the control group,the expression level of lncRNA FEZF1-AS1 and EZH2 genes was significantly increased in the model group(P＜0.05).Compared with si NC group,the proliferation,migration and invasion ability of si lncRNA FEZF1-AS1+OE vector group were decreased,the ex-pression of E-cadherin protein was increased while the expression of N-cadherin,vimentin and EZH2 was decreased(P＜0.05).Compared with si lncRNA FEZF1-AS1+OE vector group,the proliferation,invasion and migration of si lncRNA FEZF1-AS1+OE EZH2 group were increased(P＜0.05).E-cadherin expression was decreased,while N-cad-herin,vimentin and EZH2 expressions were increased(P＜0.05).RIP experiment further confirmed that lncRNA FEZF1-AS1 had direct binding effect with EZH2.Conclusions LncRNA FEZF1-AS1 can promote the proliferation,invasion,metastasis and EMT process of pulmonary fibrosis cells by regulating EZH2.

Expression of Serum Vaspin and SFRP5 in Children with Idiopathic Nanosomia and Their Diagnostic Value / 现代检验医学杂志

Objective To explore the expression level of visceral adipose tissue-derived serine protease inhibitor(Vaspin)and secreted frizzled-related protein5(SFRP5)in the serum of children with idiopathic short stature(ISS)and its diagnostic value.Methods 70 children with ISS diagnosed in the First Hospital of Zhangjiakou from December 2021 to February 2023 were selected as the disease group,while 72 healthy volunteer children who underwent physical examination were collected as the control group.Immunoluminescence was applied to detect the expression level of VASPIN,Enzyme-linked immunosorbent assay(ELISA)was applied to detect the expression level of SFRP5 the clinical data of children in two groups were analyzed.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum Vaspin and SFRP5 for ISS,multivariate Logistic regression was used to analyze the influencing factors of ISS.Results Compared with the control group,the serum Vaspin level in the disease group was obviously increased(2.89±0.92 ng/ml vs 1.81±0.42 ng/ml),while the SFRP5 level was obviously reduced(10.22±2.84 pg/ml vs 13.21±3.53 pg/ml),the differences were statistically significant(t=9.040,5.552,all P＜0.05).The weight,height,body mass index(BMI)and proportion of sexual development stage II～V of children in the disease group were obviously lower than those in the control group,and the differences were statistically significant(t=7.687,6.330,5.559,7.024,all P＜0.05).The area under ROC curve showed that the AUC of Vaspin and SFRP5 and their combined detection in the diagnosis of ISS were 0.768,0.849 and 0.925,respectively,the combined diagnosis efficacy of Vaspin and SFRP5 was better than that of serum Vaspin and SFRP5 alone(Z =3.829,P＜0.001;Z =2.141,P=0.032).Multivariate Logistic regression analysis showed that BMI(OR=0.508,95%CI:0.260～0.991),Vaspin(OR=3.458,95%CI:1.125～10.631)and SFRP5(OR=0.378,95%CI:0.153～0.935)were the influencing factors for ISS(all P＜0.05).Conclusion The expression level of Vaspin in the serum of children with ISS is obviously increased,while the expression level of SFRP5 is obviously reduced.The two are influencing factors of ISS,and the combined detection of their expression levels has certain value in the diagnosis of ISS.

The mechanism of miR-10b targeting TGFBR1/SMAD3 pathway on chondrocyte proliferation and hypertrophy in idiopathic short stature / 天津医药

Objective To investigate the effect and mechanism of microRNA-10b(miR-10b)on idiopathic short stature(ISS).Methods A total of 54 children with ISS and 54 healthy children were collected.The serum expression of miR-10b was detected by RT-qPCR,and the relationship between serum miR-10b expression and clinical data of children with ISS was analyzed.miR-10b inhibitor,si-TGFBR1 and their negative control transfection C28/I2 cells were used.CCK-8 experimental detection was used to detect C28/I2 cell proliferation.Western blot assay was used to detect gnome related transcription factor 2(RUNX2),collagen type X alpha 1 chain(COL10A1),transforming growth factor beta receptor 1(TGFBR1),SMAD3 and pSMAD3 protein expression.The target of miR-10b was screened in StarBase database,and the targeting relationship between miR-10b and TGFBR1 was verified by dual luciferase reporter gene assay.Results The serum expression of miR-10b was higher in the ISS group than that of the healthy control group,and the higher the miR-10b expression,the more obvious the decrease of child height,IGF-1 and alkaline phosphatase(P＜0.05).Compared with the NC group,the cell proliferation ability and RUNX2,COL10A1,TGFBR1,and pSMAD3 protein expression were up-regulated in the miR-10b inhibitor group(P＜0.05).StarBase database suggested that miR-10b had a binding site of TGFBR1,and dual luciferase reporter gene assay confirmed that TGFBR1 interacted with miR-10b(P＜0.05).Compared with the si-NC group,the expression of TGFBR1 was down-regulated and the cell proliferation ability was decreased in the si-TGFBR1 group(P＜0.05).Conclusion miR-10b inhibits chondrocyte proliferation and hypertrophy in idiopathic short stature by targeting TGFBR1/SMAD3 pathway.

The effect of lncRNA FEZF1-AS1 targeting regulation of miR-200c-3p on biological behaviors of human lung fibroblasts / 天津医药

Objective To investigate the effect of FEZ family zinc finger 1-antisense RNA 1(LncRNA FEZF1-AS1)targeting regulation of miR-200c-3p expression on biological behaviors of human lung fibroblasts(HLF).Methods Transforming growth factor β1(TGF-β1)was used to induce the transformation of HLF into myofibroblasts,which were divided into the Blank group and the model group(HLF+TGF-β1 group).According to different transfection plasmid,cells were divided into the Blank group,the TGF-β1+Si LncRNA FEZF1-AS1 NC group and the TGF-β1+Si LncRNA FEZF1-AS1 group.The protein expressions of α-SMA,Collagen Ⅰ and Vimentin were detected by Western blot assay.The expressions of LncRNA FEZF1-AS1 and miR-200c-3p were detected by quantitative real-time PCR(qRT-PCR).Cell proliferation ability was detected by CCK-8 method,migration ability was detected by cell scratch experiment and invasion ability was detected by Transwell assay.The targeting relationship between FEZF1-AS1 and miR-200c-3p was detected by dual-luciferase reporter assay.Results Compared with the Blank group,protein expressions of α-SMA,Collagen Ⅰ,Vimentin and the expression of LncRNA FEZF1-AS1 were increased in the HLF+TGF-β1 group(P＜0.05),and the expression of miR-200c-3p was decreased(P＜0.05).Compared with the TGF-β1+Si LncRNA FEZF1-AS1 NC group,cell proliferation,migration,invasion ability,LncRNA FEZF1-AS1 expression,protein expressions of α-SMA,Collagen Ⅰ and Vimentin were decreased in the TGF-β1+Si LncRNA FEZF1-AS1 group(P＜0.05),and the expression of miR-200c-3p was increased(P＜0.05).There were binding sites between miR-200c-3p and FEZF1-AS1 gene sequence.Conclusion LncRNA FEZF1-AS1 promotes the formation and progression of idiopathic pulmonary interstitial fibrosis by inhibiting miR-200c-3p.

Correlation between coronal pressure variation and coronal imbalance in adolescent idiopathic scoliosis patients / 中国组织工程研究

BACKGROUND:The distribution of horizontal pressure in adolescent idiopathic scoliosis can be used to evaluate the coronal imbalance.Currently,there are no reports on the characteristics of coronal pressure distribution and its correlation with coronal imbalance. OBJECTIVE:To explore the correlation between coronal pressure variation and coronal imbalance in adolescent idiopathic scoliosis patients. METHODS:A total of 39 adolescent idiopathic scoliosis patients who met the inclusion and exclusion criteria in Lianyungang First People's Hospital from March 2021 to June 2022 were selected as the adolescent idiopathic scoliosis group,and 30 matched healthy volunteers were recruited from the outpatient department as the control group.The horizontal position pressure,folding position pressure,coefficient of variation,and global and trunk pressure variation were measured by the TBED Postural Couch evaluation system.In the adolescent idiopathic scoliosis group,full-length spine radiographs were taken to measure Cobb angle,coronal balance,apical vertebral deviation and Nash-Moe rotation.The characteristics of coronal pressure variation and its correlation with coronal imbalance were analyzed. RESULTS AND CONCLUSION:(1)Compared with the control group,there was no statistically significant difference in the horizontal position pressure and folding position pressure in the adolescent idiopathic scoliosis group(P>0.05),but the global pressure variation and coefficient of variation were significantly increased(all P<0.05).(2)There were differences in both sides of the trunk of the adolescent idiopathic scoliosis group and the control group(P<0.05),and the convex side pressure variation in the adolescent idiopathic scoliosis group was higher than the concave side pressure variation in the left and right side pressure variation in the control group(all P<0.05).(3)The variation of the convex side pressure of the trunk in adolescent idiopathic scoliosis patients was positively correlated with coronal balance intensity(r=0.692,P<0.05),moderately positively correlated with Cobb angle and apical vertebral deviation(r=0.499,0.595,all P<0.05),and weakly correlated with Nash-Moe grade(r=0.377,P<0.05).The variation of the concave side pressure of the trunk was moderately positively correlated with coronal balance(r=0.410,P<0.05),and the rest was weakly correlated or not correlated(P>0.05).(4)These findings indicate that pressure variation may be used as an adjoint assessment tool in patients with mild to moderate scoliosis.

Visualization analysis of research hotspots and trends in adolescent idiopathic scoliosis / 中国组织工程研究

BACKGROUND:Adolescent idiopathic scoliosis is the most common scoliosis deformity,accounting for about 80%of all scoliosis.Its pathogenesis is unknown.In recent years,the incidence rate has shown an obvious upward trend,which seriously threatens the physical and mental health of adolescents. OBJECTIVE:To perform the visualization analysis of the relevant literature on adolescent idiopathic scoliosis in recent 20 years through the Bibliometrics method,and explore the research hotspots and trends in this field to provide references for further research. METHODS:The relevant articles included in the Web of Science core collection database from January 1,2002 to December 31,2021 were searched by computer.The scientific knowledge map was drawn by CiteSpace 5.8.R3 software.The cooperation network,co-citation network,keyword co-occurrence,burst,clustering and timeline map were visually analyzed. RESULTS AND CONCLUSION:A total of 5245 papers were included.In the past 20 years,the annual publication volume has shown a fluctuating upward trend.The analysis of the cooperation network shows that the author with the most publications is Qiu Yong;the institution is Nanjing University;the country is USA.The author with the highest intermediary centrality is Lowe TG;the institution is Childrens Hosp Philadelphia,and the country is Switzerland.The co-citation network analysis exhibits that the author with the highest frequency of citations is Lenke LG;the document is Weinstein SL,2013,N Engl J Med;the journal is Spine,and the author with the highest intermediary centrality is Suk SI,and the cited document is Danielsson AJ,2001,Eur Spine J;the cited journal is Spine.Keyword analysis displays that the research hotspots mainly focus on conservative treatment,imaging parameters,pathogenesis,and genome-wide associations.Through the visualization analysis of the literature in this research field,this study clarifies the context of the research in this field,reveals the research hotspots and trends in this field,and provides research ideas and methods for many scholars.