A molecularly integrated grade for meningioma

BackgroundMeningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.MethodsWe evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.ResultsWe developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.ConclusionWe propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.     

原发性肝细胞癌与癌旁肝组织的雄激素受体

应用Ｓ－Ｐ免疫组化技术检测３７例手术切除并有随访资料的原发性肝细胞癌（ＨＣＣ）及其相应癌旁肝组织的雄激素受体（ＡＲ），旨在了解ＡＲ表达及其与患者预后的关系。结果表明：肝癌组织的ＡＲ阳性率（７８．３８％）显著高于癌旁肝组织（３７．８４％，Ｐ＜０．０１）。支持ＨＣＣ属雄激素依赖性肿瘤的观点。随访结果提示，肝癌组织的ＡＲ表达率与患者术后预后有关，术后半年复发组癌组织ＡＲ阳性率（８９．４７％）显著高于未复发组（５３．８５％，Ｐ＜０．０５）。检测ＡＲ可作为评价ＨＣＣ患者手术后预后的指标之一。     

中医学对代谢综合征的认识和治疗

中医学认为,代谢综合征的病因概括为先天脾胃虚弱,后天饮食不节,贪逸少劳,恣情纵欲,加之五志不遂,病机可综合为肝郁、内热、痰湿、气虚。根据本病的病因病机,采用中医辨证论治、基础方加减治疗、中成药治疗,单味药治疗及针灸疗法治疗,均可取得较满意治疗效果。     

热应激蛋白70抗体滴度作为二硫化碳接触的生物标记物的研究

目的 :了解二硫化碳接触工人的血清热应激蛋白 70 (HSP 70 )抗体滴度及探讨其作为CS2 接触的分子生物标记物的可行性。方法 :选择某化纤厂 79名工人 ,5 4名为接触组 ,2 5名为对照组。用Westernblot ELISA法对工人血清HSP 70抗体水平进行了检测。采用Logistic回归分析技术 ,分析了HSP 70抗体与CS2 接触之间的关系。结果 :抗体各滴度接触组工人血清HSP 70抗体阳性率明显高于对照组 ,有非常显著意义 (P <0 .0 1)。采用Logistic回归分析控制了因素的混杂作用后 ,这种联系仍然存在。结论 :血清HSP 70抗体滴度可反映CS2 的接触状况。以血清HSP 70抗体滴度作为分子生物学标记物 ,对CS2 接触者进行健康监护有重要意义。     

URSA患者绒毛组织中细胞凋亡及血管新生异常与miR-155表达的关系

目的:探究URSA患者绒毛组织中细胞凋亡及血管新生异常与miR-155表达的关系.方法:选择2014年1月~2015年1月来我院妇产科行清宫术后的孕妇的标本64例,其中URSA患者38例,剩余26例,将64例患者按照是否为URSA患者分为两组,即URSA组、对照组.对miR-155的表达量与细胞凋亡分子Bcl-2、Bcl-xl及血管新生分子VEGF、HIF-1α、sFlt-1的表达量记录,并与miR-155的表达量进行对比.结果:miR-155的表达量与细胞凋亡分子Bcl-2、Bcl-xl的表达量呈正相关,与血管新生分子VEGF、HIF-1α的表达量呈正相关,与sFlt-1的表达量呈负相关,且两组患者的miR-155、Bcl-2、Bcl-xl的表达量不同,URSA组显著低于对照组,且URSA组miR-155、VEGF、HIF-1α的表达量显著低于对照组,sFlt-1的表达量则显著高于对照组.结论:URSA绒毛组织中细胞的凋亡及血管新生与miR-155存在关系,且miR-155的表达量下降则会导致绒毛组织中的细胞过度凋亡.     

Berberine improves intralipid-induced insulin resistance in murine

Insulin resistance (IR) is a major metabolic risk factor even before the onset of hyperglycemia. Recently, berberine (BBR) is found to improve hyperglycemia and IR. In this study, we investigated whether BBR could improve IR independent of hyperglycemia. Acute insulin-resistant state was induced in rats by systemic infusion of intralipid (6.6%). BBR was administered via different delivery routes before or after the beginning of a 2-h euglycemic-hyperinsulinemic clamp. At the end of experiment, rats were sacrificed, gastrocnemius muscle was collected for detecting mitochondrial swelling, phosphorylation of Akt and AMPK, as well as the mitochondrial permeability regulator cyclophilin D (CypD) protein expression. We showed that BBR administration markedly ameliorated intralipid-induced IR without affecting blood glucose, which was accompanied by alleviated mitochondrial swelling in skeletal muscle. We used human skeletal muscle cells (HSMCs), AML12 hepatocytes, human umbilical vein endothelial cells, and CypD knockout mice to investigate metabolic and molecular alternations. In either HSMCs or AML12 hepatocytes, BBR (5 μM) abolished palmitate acid (PA)-induced increase of CypD protein levels. In CypD-deficient mice, intralipid-induced IR was greatly attenuated and the beneficial effect of BBR was diminished. Furthermore, we demonstrated that the inhibitory effect of BBR on intralipid-induced IR was mainly mediated by skeletal muscle, but not by intestine, liver, or microvasculature; BBR administration suppressed intralipid-induced upregulation of CypD expression in skeletal muscle. These results suggest that BBR alleviates intralipid-induced IR, which is related to the inhibition of CypD protein expression in skeletal muscle.     

血清铁死亡标记物与绝经后女性认知障碍的关系

目的 研究血清铁死亡标记物与绝经后女性认知障碍的关系。方法 选取2019年8月至2021年12月就诊的148例女性,其中生育期女性22例,围绝经期女性11例,绝经后女性115例。按照蒙特利尔认知评估量表(Montreal cognitive assessment, MoCA)将绝经后女性分为认知障碍组(n=77)和无认知障碍组(n=38),比较两组血清铁死亡标记物有无差异,应用Logistic进行多因素回归分析绝经后女性认知障碍的相关因素。通过受试者工作特征曲线(Receiver operating characteristic curve, ROC)评估相关因素对绝经后女性认知障碍的诊断价值。结果 与生育期和围绝经期女性相比,绝经后女性MoCA评分明显较低,血清ACSL4、System Xc-、GPX4、GSH、ROS、LPO及MDA水平均明显升高(均P<0.05)。与无认知障碍组相比,认知障碍组绝经后女性受教育年限短、患高血压的比例高,且血清ACSL4、System Xc_-^{、GPX4、GSH、ROS、LPO及MDA水平明显}升高 (均P<0.05)。多因素Logistic回归分析显示教育年限和血清谷胱甘肽(glutathione, GSH)与认知障碍独立相关(P<0.05),ROC曲线分析显示两者联合对预测女性是否患认知障碍具有中度诊断价值(AUC: 0.764, P<0.05)。结论 绝经后女性血清铁死亡标志物ACSL4、System Xc_-^{、GPX4、GSH、ROS、LPO及MDA水平}明显升高,其中GSH与女性认知障碍发生独立相关,与受教育年限联合有望成为绝经后女性认知障碍早期诊断的潜在标志物。     

Time-series analysis of the risk factors for haemorrhagic fever with renal syndrome: comparison of statistical models

Three conventional regression models were compared using the time-series data of the occurrence of haemorrhagic fever with renal syndrome (HFRS) and several key climatic and occupational variables collected in low-lying land, Anhui Province, China. Model I was a linear time series with normally distributed residuals; model II was a generalized linear model with Poisson-distributed residuals and a log link; and model III was a generalized additive model with the same distributional features as model II. Model I was fitted using least squares whereas models II and III were fitted using maximum likelihood. The results show that the correlations between the HFRS incidence and the independent variables measured (i.e. difference in water level, autumn crop production and density of Apodemus agrarius) ranged from -0.40 to 0.89. The HFRS incidence was positively associated with density of A. agrarius and crop production, but was inversely associated with difference in water level. The residual analyses and the examination of the accuracy of the models indicate that model III may be the most suitable in the assessment of the relationship between the incidence of HFRS and the independent variables.     

Prevalence and related factors of hyperuricaemia in Chinese children and adolescents: a pooled analysis of 11 population-based studies

Background and aimsHyperuricaemia can lead to gout and is associated with an increased risk of cardiometabolic disease. We aimed to investigate the prevalence of hyperuricaemia and its related factors in Chinese children and adolescents.MethodsWe pooled data from 11 population-based studies comprising 54,580 participants aged 3–19 years. The sex- and age-standardized prevalence of hyperuricaemia was estimated overall and by sex, age, weight status, geographic region and survey year.ResultsSerum uric acid (SUA) increased gradually from 3 to 11 years with no significant sex difference, and then increased dramatically during 11–15 years. The estimated overall prevalence of hyperuricaemia was 23.3% (26.6% in boys and 19.8% in girls, p < .001). The prevalence increased with growing age (3.7, 9.8, 15.8, 35.5 and 31.7% among children aged 3–5, 6–8, 9–11, 12–15 and 16–19 years, respectively, p for trend < .001) and with increasing weight status (18.2, 37.6, 50.6 and 64.5% among children with non-overweight, overweight, obesity and extreme obesity, respectively, p for trend < .001). The prevalence was higher in North than in South (24.2 vs. 19.7%, p < .001), and increased markedly from 16.7% during 2009–2015 to 24.8% during 2016–2019. In multivariable regression analyses, sex, age, obesity, region and survey year were independently associated with odds of hyperuricaemia.ConclusionsThe prevalence of hyperuricaemia in Chinese children and adolescents is unexpectedly high. The findings suggest an urgent need to implement effective interventions to reduce risk of hyperuricaemia in Chinese youths.

KEY MESSAGES

• Question: What is the prevalence of hyperuricaemia in Chinese children and adolescents?
• Findings: In this large pooled cross-sectional study comprising >50,000 children and adolescents aged 3–19 years, we found that the prevalence of hyperuricaemia was high in overall population and subgroups of sex, age, obesity, region and survey year.
• Meaning: Our findings indicate that hyperuricaemia is an important health problem in Chinese children and adolescents, and effective intervention strategies are needed to reduce its burden.

     

Exploring the Barriers and Motivators to Dietary Adherence among Caregivers of Children with Disorders of Amino Acid Metabolism (AAMDs): A Qualitative Study

Dietary intervention is generally accepted as the mainstay of treatment for patients with disorders of amino acid metabolism (AAMDs). However, dietary adherence to a low-protein diet is always reported as a common challenge among these patients. This study explored the perception of barriers and motivators to dietary adherence among caregivers of AAMD patients in Malaysia. Twenty caregivers of children with AAMDs receiving ongoing treatment at the genetic clinic participated in an online focus group discussion from November to December 2021. Findings showed a total of five interrelated main themes identified from focus group discussion (FGD) exploring parents’ experiences related to the management of their child’s daily diet. The barriers to dietary adherence were burden of dietary treatment, diet and dietary behavior, parenting challenges, limited knowledge related to dietary treatment, and challenges in healthcare system delivery. Key factors facilitating good dietary adherence include good knowledge of dietary treatment, parental coping strategies, social coping, and dietary behavior. In conclusion, despite the existence of several barriers to the implementation of dietary treatment, caregivers managed to use a wide range of coping strategies to overcome some, if not all, of the challenges. The important next step is to develop, in conjunction with multidisciplinary healthcare professionals, feasible implementation strategies that could address these barriers and at the same time improve the quality of life of caregivers.