熊磊教授基于“脾为痰源”辨治儿童癫痫临证思路探赜

熊磊教授以理脾为本，将治痰贯穿始终。根据小儿脾常不足、肾常虚、肝常有余的生理特点，癫痫发作期治疗主以涤痰开窍，辅以理气健脾，同时配合活血化瘀通窍与平肝息风潜阳。主要选方为柴芍温胆汤、天麻钩藤饮、桃红四物汤加减；缓解期则以补肾养肝为主，兼以健脾化痰，主要选方为杞菊地黄丸合定痫丸加减，取得较好临床疗效。     

Mesenchymal neoplasms with NTRK and other kinase gene alterations

Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications.     

Standardisierte Kontrastmittelsonographie (CEUS) in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin (CEUS-Akut)

Die Anaesthesiologie -     

Study on the Value of Ultrasound Elastography Combined with Plasma miRNA Expression in the Early Detection of Breast Cancer

Background: Breast cancer (BC) is the most common malignant tumor in women, and its morbidity and mortality are increasing each year, due to the lack of specific clinical symptoms in the early stage of BC, and the lack of diagnostic methods for early breast cancer. Therefore, identifying an effective diagnostic method for early BC has become urgent. Materials and Methods: Breast lesions with a histological diagnosis that were examined by ultrasonic elastography (UE) in our department from June 2020 to December 2021 were reviewed. qRT-PCR was performed to measure the expression levels of miR-144-5p and miR-26b-5p in the plasma of patients with BC. The receiver operating characteristics (ROC) curve and area under the curve (AUC) were used to investigate the potential diagnostic value of miR- 144-5p, miR-26b-5p and the elastographic score in BC. Results: The ultrasonic elastography score(UES) was found to be significantly upregulated in BC compared with that in benign breast lesions, and the AUC, sensitivity and specificity were 0.809, 0.717 and 0.806 for distinguishing BC from benign breast lesions, respectively. miR-144-5p and miR-26b- 5p were found to be upregulated in the plasma of BC patients, and miR-144-5p+miR-26b-5p had 0.781 sensitivity and 0.780 specificity for the diagnosis of BC. Furthermore, we found that the diagnostic performance of miR-144-5p and miR-26b-5p combined with UES for BC had 0.913 sensitivity and 0.890 specificity. Conclusions: The combination of plasma miR-144-5p, miR-26b-5p and UES has a very high clinical application value for the early detection of BC.     

Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Pre-COVID-19 Social Determinants of Health Among Mexican Migrants in Los Angeles and New York City and Their Increased Vulnerability to Unfavorable Health Outcomes During the COVID-19 Pandemic

Journal of Immigrant and Minority Health - COVID-19 has disproportionally affected underrepresented minorities (URM) and low-income immigrants in the United States. The aim of the study is to...