Objective To summarize the clinical characteristics,treatment outcomes,and prognostic factors of children with non-metastatic Ewing's sarcoma(ES).Methods A retrospective analysis was conducted on the clinical data of 41 children with non-metastatic ES diagnosed and treated at the Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018.All patients underwent chemotherapy based on the RMS-2009 protocol of the center,and local treatment such as surgery and/or radiotherapy was performed according to risk grouping.The Kaplan-Meier method was used to calculate the overall survival(OS)and event-free survival(EFS)rates.Univariate prognostic analysis was performed using the log-rank test,and multivariate analysis was conducted with Cox regression.Results Of the 41 children,21 were male and 20 were female.The median age at diagnosis was 7.7 years(range:1.2-14.6 years).The median follow-up time for patients with event-free survival was 68.1 months(range:8.1-151.7 months).As of the last follow-up,33 patients were in complete remission,and the overall 5-year EFS and OS rates were(78±6)％and(82±6)％,respectively.Univariate analysis by the log-rank test showed that a tumor diameter ≥8 cm,time from diagnosis to start of local treatment ≥16 weeks,and incomplete surgical resection were associated with poor prognosis(P＜0.05).Multivariate Cox regression analysis indicated that incomplete surgical resection(HR=8.381,95％CI:1.681-41.801,P=0.010)was an independent risk factor for poor prognosis in children with ES.Secondary tumors occurred in 2 cases.Conclusions A comprehensive treatment strategy incorporating chemotherapy,surgery,and radiotherapy can improve the prognosis of children with ES.Poor prognosis is associated with an initial tumor diameter ≥8 cm,while complete surgical resection and early initiation of local treatment can improve outcomes.[Chinese Journal of Contemporary Pediatrics,2024,26(4):365-370]

ObjectiveTo explore the mechanism of Dendrobium huoshanense polysaccharide （DHP） against inflammatory damage of neurons in Parkinson's disease （PD） model. MethodSH-SY5Y cells were randomized into blank group， model group， and DHP group. The survival rate of cells was measured by thiazole blue（MTT） assay， and the levels of lactate dehydrogenase （LDH）， reactive oxygen species （ROS）， malondialdehyde （MDA）， and superoxide dismutase （SOD） were measured by colorimetric analysis. BV-2 microglia were classified into blank group， model group， DHP group， and MCC950 group （positive control group）， and enzyme-linked immunosorbent assay （ELISA） was applied to detect the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18）. The expression of NOD-like receptor protein 3 （NLRP3）， adaptor protein apoptosis-associated dot protein （ASC）， cysteine aspartic protease-1 （Caspase-1）， and IL-1β was measured by Western blot. A total of 50 C57BL/6 mice were randomized into blank group， model group， DHP low-dose （100 mg·kg^-1） group， DHP equivalent-dose （350 mg·kg^-1） group， and MCC950 group （positive control group）， 10 mice in each group. The motor balance and coordination of C57BL/6 mice were observed by beam walking test， tail suspension test and rotarod test. The levels of Iba-1 and tyrosine hydroxylase （TH） were detected by immunofluorescence staining. The damage of dopaminergic neurons in the substantia nigra was detected by FJB staining. The levels of inflammatory factors such as IL-1β， IL-18， and TNF-α in mouse midbrain tissues were detected by ELISA and the protein levels of NLRP3， ASC， Caspase-1， and IL-1β protein were measured by Western blot. ResultCompared with the blank group， the SH-SY5Y model group showed decreased cell survival， increased levels of LDH， ROS， and MDA （P<0.05）， and decreased levels of SOD （P<0.05）. Compared with the model group， the DHP group demonstrated increased cell survival， decreased levels of LDH， ROS， and MDA （P<0.01）， and increased level of SOD （P<0.01）. Compared with the blank group， BV-2 model group had high levels of IL-1β， IL-18， and TNF-α （P<0.05） and high protein expression of NLRP3， Caspase-1， IL-1β， and ASC （P<0.05）. Compared with the model group， DHP and MCC950 groups demonstrated low levels of IL-1β， IL-18， and TNF-α （P<0.01） and low protein expression of NLRP3， Caspase-1， IL-1β， and ASC （P<0.01）. Compared with the blank group， the C57BL/6 model group displayed long time to pass the balance wood （P<0.05）， short time spent on the rod in the rotarod test （P<0.05）， high levels of IL-1β， IL-18， and TNF-α （P<0.05） and expression of Iba-1 in the midbrain substantia nigra （P<0.05）， low TH expression （P<0.05）， more positive neurons in the FJB staining （P<0.05）， and high expression of NLRP3， Caspase-1， ASC， and IL-1β proteins （P < 0.05）. Compared with the model group， the mice in the DHP and MCC950 groups had short time to pass the balance beam （P<0.01）， long time spent on the rod （P<0.01）， low levels of IL-1β， IL-18， and TNF-α （P<0.01）， low Iba-1 expression in midbrain substantia nigra （P<0.01）， high TH expression （P<0.01）， and small number of positive neurons in the midbrain substantia nigra （P<0.01）. The expression of NLRP3， ASC， and IL-1β proteins was lower in the MCC950 group （P<0.01）， and the expression of NLRP3， ASC， Caspase-1 and IL-1β proteins was lower in the DHP equivalent-dose group （P<0.01） than in the model group. ConclusionDHP has anti-oxidative stress effect. It regulates the expression of NLRP3 inflammasome and inhibits the overactivation of microglia， thereby alleviating the neuroinflammatory injury in PD and exerting the neuroprotective effect.

Humans ; Brentuximab Vedotin ; Ki-1 Antigen ; Antineoplastic Agents ; Immunoconjugates/therapeutic use* ; Lymphoma/drug therapy*

Next-generation sequencing has revolutionized family-based association tests for rare variants. As the lower power of genome wide association study for detecting casual rare variants, methods aggregating effects of multiple variants have been proposed, such as burden tests and variance component tests. This paper summarizes the methods of rare variants association test that can be applied for family data, introduces their principles, characteristics and applicable conditions and discusses the shortcomings and the improvement of the present methods.
Computer Simulation ; Family Relations ; Genetic Association Studies ; Genetic Variation ; Genome-Wide Association Study/methods* ; Humans

Objective: To summarize the clinical features, management and outcome of superior vena cava syndrome (SVCS) associated with mediastinal malignancy in children. Methods: Clinical data of 42 children of SVSC associated with mediastinal malignancy in Shanghai Children's Medical Center from January 2015 to December 2021 were collected and analyzed retrospectively. The clinical manifestations, pathological diagnosis, disease diagnosis process, and prognosis were summarized. Results: Among 42 children of SVCS associated with mediastinal malignancy, there were 31 males and 11 females. The age at diagnosis was 8.5 (1.9, 14.9) years. Cough and wheezing (33 cases, 79%), orthopnea (19 cases, 45%) and facial edema (18 cases, 43%) occurred most commonly. T-cell lymphoblastic lymphoma (T-LBL) was the most frequent pathological diagnosis (25 cases, 60%), followed by T-cell acute lymphoblastic leukemia (T-ALL) (7 cases, 17%), anaplastic large cell lymphoma (4 cases, 10%) and diffuse large B-cell lymphoma (2 cases, 5%), peripheral T-lymphoma, Hodgkin lymphoma, Ewing's sarcoma and germ cell tumor (1 case each). Pathological diagnosis was confirmed by bone marrow aspiration or thoracentesis in 14 cases, peripheral lymph node biopsy in 6 cases, and mediastinal biopsy in 22 cases. Twenty-seven cases (64%) had local anesthesia. Respiratory complications due to mediastinal mass developed in 3 of 15 cases who received general anesthesia. Of the 42 cases, 27 cases had sustained remission, 1 case survived with second-line therapy after recurrence, and 14 cases died (2 cases died of perioperative complications and 12 cases died of recurrence or progression of primary disease). The follow-up time was 36.7 (1.2, 76.1) months for 27 cases in continuous complete remission. The 3-year overall survival (OS) and events free survival (EFS) rates of 42 children were 59% (95%CI 44%-79%) and 58% (95%CI 44%-77%) respectively. Conclusions: SVCS associated with mediastinal malignancy in children is a life-threatening tumor emergency with high mortality. The most common primary disease is T-LBL. The most common clinical symptoms and signs are cough, wheezing, orthopnea and facial edema. Clinical management should be based on the premise of stable critical condition and confirm the pathological diagnosis through minimal invasive operation.
Child ; China ; Cough ; Edema ; Female ; Humans ; Male ; Mediastinal Neoplasms/diagnosis* ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Respiratory Sounds ; Retrospective Studies ; Superior Vena Cava Syndrome/therapy*

Youth is the core force of social and economic development, once the occurrence of youth stroke will place a heavy burden on society and family. However, the prevention and control of stroke in China is mainly aimed at middle-aged and elderly patients, the part of young stroke is relatively easy to be ignored. This article focuses on the characteristics, research progress, prevention and control status of young stroke, pointing out the importance of centering on the prevention and treatment of young stroke. At the same time, it hopes that the industry can concentrate on the prevention and treatment of young stroke, making precise policies in the future, and developing secondary prevention guidelines for the causes or risk factors of young stroke, so as to improve comprehensive stroke prevention and control system. On this basis, the health level of the whole population will be improved, and the life expectancy of residents will be extended, thus promoting the realization of the strategic goal of "Healthy China 2030".
Adolescent ; Aged ; China/epidemiology* ; Health Status ; Humans ; Life Expectancy ; Middle Aged ; Policy ; Stroke/prevention & control*

Autism spectrum disorder (ASD), a representative disease of children's neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.

OBJECTIVE: Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot (RDS), was developed based on a classical prescription of traditional Chinese medicine (TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019 (COVID-19), have been shown. However, the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS. METHODS: To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, and cluster analysis; further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS. RESULTS: For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent-target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-constituent-disease network. Twelve disease pathways attributed to the Lung-Large Intestine meridians, with six and five attributed to the Kidney-Urinary Bladder and Stomach-Spleen meridians, respectively. One-hundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-2 3-chymotrypsin-like protease (3CL), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3CL inhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode, the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches. CONCLUSION RDS acts primarily in the Lung-Large Intestine, Kidney-Urinary Bladder and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS's dual effects of health-strengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.
Antiviral Agents ; chemistry ; therapeutic use ; Betacoronavirus ; chemistry ; enzymology ; Coronavirus Infections ; drug therapy ; prevention & control ; virology ; Cysteine Endopeptidases ; chemistry ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Humans ; Mass Spectrometry ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Pandemics ; prevention & control ; Pneumonia, Viral ; drug therapy ; prevention & control ; virology ; Protein Interaction Maps ; Viral Nonstructural Proteins ; chemistry

BACKGROUND: A novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, has been rapidly spreading around the world. This study investigates the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Zhejiang Province who did or did not have a history of Wuhan exposure. METHODS: We collected data from medical records of confirmed COVID-19 patients in Zhejiang Province from Jan. 17 to Feb. 7, 2020 and analyzed epidemiological, clinical, and treatment data of those with and without recorded recent exposure in Wuhan. RESULTS: Patients in the control group were older than those in the exposure group ((48.19±16.13) years vs. (43.47±13.12) years, P<0.001), and more were over 65 years old (15.95% control vs. 5.60% exposure, P<0.001). The rate of clustered onset was also significantly higher in the control group than in the exposure group (31.39% vs. 18.66%, P<0.001). The symptom of a sore throat in patients in the exposure group was significantly higher than that in the control group (17.30% vs. 10.89%, P=0.01); however, headache in the exposure group was significantly lower than that in the control group (6.87% vs. 12.15%, P=0.015). More patients in the exposure group had a significantly lower level of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) than those in the control group. There was no significant difference in any degree of COVID-19 including mild, severe, and critical between the two groups. CONCLUSIONS From the perspective of epidemiological and clinical characteristics, there was no significant difference between COVID-19 patients with and without Wuhan exposure history.
Adolescent ; Adult ; Aged ; Aspartate Aminotransferases ; blood ; Betacoronavirus ; Case-Control Studies ; Child ; Child, Preschool ; China ; epidemiology ; Coronavirus Infections ; epidemiology ; physiopathology ; therapy ; Female ; Humans ; Infant ; Infant, Newborn ; L-Lactate Dehydrogenase ; blood ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; epidemiology ; physiopathology ; therapy ; Retrospective Studies ; Young Adult

OBJECTIVE: To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes. METHODS: The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables. RESULTS: The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120－0.407), 0.404 (95%CI: 0.135－0.673), and 0.799 (95%CI: 0.590－1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120－1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181－0.788, P<0.05). CONCLUSION Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.
Blood Pressure ; Chronic Disease ; Female ; Heart Rate ; Humans ; Hypertension ; Male ; Middle Aged ; Pedigree