Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells.

BACKGROUND: Dysregulation of immune surveillance is tightly linked to the development of metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC); however, its underlying mechanisms remain unclear. Herein, we aimed to determine the role of interleukin-21 receptor (IL-21R) in MASH-driven HCC. METHODS: The clinical significance of IL-21R was assessed in human HCC specimens using immunohistochemistry staining. Furthermore, the expression of IL-21R in mice was assessed in the STAM model. Thereafter, two different MASH-driven HCC mouse models were applied between IL-21R-deficient mice and wild type controls to explore the role of IL-21R in MASH-driven HCC. To further elucidate the potential mechanisms by which IL-21R affected MASH-driven HCC, whole transcriptome sequencing, flow cytometry and adoptive lymphocyte transfer were performed. Finally, flow cytometry, enzyme-linked immunosorbent assay, immunofluorescent staining, chromatin immunoprecipitation assay and western blotting were conducted to explore the mechanism by which IL-21R induced IgA+ B cells. RESULTS: HCC patients with high IL-21R expression exhibited poor relapse-free survival, advanced TNM stage and severe steatosis. Additionally, IL-21R was demonstrated to be upregulated in mouse liver tumors. Particularly, ablation of IL-21R impeded MASH-driven hepatocarcinogenesis with dramatically reduction of lipid accumulation. Moreover, cytotoxic CD8+ T lymphocyte activation was enhanced in the absence of IL-21R due to the reduction of immunosuppressive IgA+ B cells. Mechanistically, the IL-21R-STAT1-c-Jun/c-Fos regulatory axis was activated in MASH-driven HCC and thus promoted the transcription of Igha, resulting in the induction of IgA+ B cells. CONCLUSIONS: IL-21R plays a cancer-promoting role by inducing IgA+ B cells in MASH-driven hepatocarcinogenesis. Targeting IL-21R signaling represents a potential therapeutic strategy for cancer therapy.

Ultrasound-based radiomics-clinical nomogram for noninvasive prediction of residual cancer burden grading in breast cancer.

PURPOSE: To assess the predictive value of an ultrasound-based radiomics-clinical nomogram for grading residual cancer burden (RCB) in breast cancer patients. METHODS: This retrospective study of breast cancer patients who underwent neoadjuvant therapy (NAC) and ultrasound scanning between November 2020 and July 2023. First, a radiomics model was established based on ultrasound images. Subsequently, multivariate LR (logistic regression) analysis incorporating both radiomic scores and clinical factors was performed to construct a nomogram. Finally, Receiver operating characteristics (ROC) curve analysis and decision curve analysis (DCA) were employed to evaluate and validate the diagnostic accuracy and effectiveness of the nomogram. RESULTS: A total of 1122 patients were included in this study. Among them, 427 patients exhibited a favorable response to NAC chemotherapy, while 695 patients demonstrated a poor response to NAC therapy. The radiomics model achieved an AUC value of 0.84 in the training cohort and 0.83 in the validation cohort. The ultrasound-based radiomics-clinical nomogram achieved an AUC value of 0.90 in the training cohort and 0.91 in the validation cohort. CONCLUSIONS: Ultrasound-based radiomics-clinical nomogram can accurately predict the effectiveness of NAC therapy by predicting RCB grading in breast cancer patients.

Molecular insights into the catabolism of dibutyl phthalate in Pseudomonas aeruginosa PS1 based on biochemical and multi-omics approaches.

A comprehensive understanding of the molecular mechanisms underlying microbial catabolism of dibutyl phthalate (DBP) is still lacking. Here, we newly isolated a bacterial strain identified as Pseudomonas aeruginosa PS1 with high efficiency of DBP degradation. The degradation ratios of DBP at 100-1000 mg/L by this strain reached 80-99 % within 72 h without a lag phase. A rare DBP-degradation pathway containing two monobutyl phthalate-catabolism steps was proposed based on intermediates identified by HPLC-TOF-MS/MS. In combination with genomic and transcriptomic analyses, we identified 66 key genes involved in DBP biodegradation and revealed the genetic basis for a new complete catabolic pathway from DBP to Succinyl-CoA or Acetyl-CoA in the genus Pseudomonas for the first time. Notably, we found that a series of homologous genes in Pht and Pca clusters were simultaneously activated under DBP exposure and some key intermediate degradation related gene clusters including Pht, Pca, Xyl, Ben, and Cat exhibited a favorable coexisting pattern, which contributed the high-efficient DBP degradation ability and strong adaptability to this strain. Overall, these results broaden the knowledge of the catabolic diversity of DBP in microorganisms and enhance our understanding of the molecular mechanism underlying DBP biodegradation.

Low Levels of Metrnl are Linked to the Deterioration of Diabetic Kidney Disease.

Objective: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Metrnl is a secreted protein that plays an important role in kidney disease. The aim of this study was to investigate DKD-related factors and the correlation between serum Metrnl levels and the severity of DKD. Methods: Ninety-six type 2 diabetes mellitus (T2DM) patients and 45 DKD patients were included in the study. A range of parameters were measured simultaneously, including waist-to-hip ratio (WHR), body mass index (BMI), urinary albumin/creatinine ratio (UACR), monocyte-lymphocyte ratio (MLR), albumin/globulin (A/G), liver and kidney function, blood lipid profile, islet function, and others. Subsequently, the related factors and predictive significance of DKD were identified. The correlation between the relevant factors of DKD and serum Metrnl levels with DKD was evaluated. Results: The duration of the disease (OR: 1.12, 95% CI: 1.01-1.24, P=0.031), hypertension (OR: 4.86, 95% CI: 1.16-20.49, P=0.031), fasting blood glucose (OR: 1.23, 95% CI: 1.03-1.48, P=0.025), WHR (OR: 2.53, 95% CI: 1.03-6.22, P=0.044), and MLR (OR: 1.91, 95% CI: 1.18-3.08, P=0.008) are independent risk factors for DKD (P < 0.05). Conversely, A/G (OR: 0.13, 95% CI: 0.02-0.76, P=0.024) and Metrnl (OR: 0.99, 95% CI: 0.98-1.00, P=0.001) have been identified as protective factors against DKD. Furthermore, the level of Metrnl was negatively correlated with the severity of DKD (rs=-0.447, P<0.001). The area under receiver operating characteristic (ROC) curves for the diagnostic accuracy of Metrnl for DKD is 0.765 (95% CI: 0.686-0.844). Conclusion: The duration of the disease, hypertension, fasting blood glucose, WHR, and MLR are major risk factors for DKD. Metrnl and A/G are protective factors for DKD. Serum Metrnl concentrations are inversely correlated with DKD severity.

Investigation and analysis of the status of myopia and related behavior in children and adolescents in Northeast Sichuan.

PURPOSE: In this study, we examined the current status of myopia among primary and secondary school children in northeastern Sichuan to analyze the factors connected to myopia and provide data support and a theoretical foundation for the prevention and control of myopia. METHODS: Using a cross-sectional study and a comprehensive sampling survey, 34,138 students aged 5-19 years were screened for refraction in 22 primary and secondary schools in Langzhong, and 4000 behavioral questionnaires were delivered at random. After evaluation and rational problem-solving, a total of 3764 valid questionnaires were obtained. SPSS 23.0 statistical software was used for data analysis. RESULTS: The percentage of myopia among primary and secondary school students in Langzhong was 65.61%, with female students having a higher rate than male students ( P < 0.05); 52.81% of primary school students, 86.26% of secondary school students, and 88.17% of high school students had myopia. The incidence of myopia detection increased with school age ( P < 0.001), indicating a correlation between age and myopia prevalence. The prevalence of myopia was mainly low (40.53%) and moderate myopia (19.89%). The prevalence of high myopia (5.19%) was relatively high. The prevalence of myopia among female students (5.54%) was greater than that in male students ( P < 0.05) and increased with age ( P < 0.001). The proportion of students who wore eyeglasses was 24.36%, with a larger proportion of female students (25.93%) than male students (22.61%) ( P < 0.001). In addition, the rate of eyeglass use increased with school age ( P < 0.001). A logistic regression analysis revealed that higher grade point averages, female gender, and long-term usage of electronic items were risk factors for myopia. The results of the questionnaire survey revealed that students in this region were under immense pressure to perform well academically, spent a lot of time engaged in near-work activities, and had a low rate of myopia awareness; 24.43% of the students had not had a vision examination in the previous year, indicating that parents did not pay sufficient attention to eye health. CONCLUSION: The incidence of myopia among children and teenagers is high in Northeast Sichuan, and the outlook for addressing the problem is bleak. Therefore, it is critical to improve vision monitoring and eye health education.

Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence.

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD+ loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD+ loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.

Ultrasound characteristics of breast fibromatosis mimicking carcinoma.

PURPOSE: To explore the value of ultrasound (US) characteristics in diagnosing breast fibromatosis (BF) and evaluate their differences from breast carcinoma. METHODS: A total of 121 patients with BF (n = 24, 29 lesions) or invasive ductal carcinoma (IDC) (n = 97, 102 lesions) of the breast were included. Their clinical and US findings were recorded and analyzed. RESULTS: The mean age of BF was younger than that of IDC (28.75 ± 5.55 vs. 50.19 ± 9.87, p < 0.001). The mean size of the BF was smaller than that of IDC (2.09 ± 0.91 vs. 2.71 ± 1.20, p = 0.011). Compared to IDC, BF had more frequency of posterior echo attenuation (p < 0.001), less frequency of peripheral hyperechoic halo (p = 0.002), calcification (p = 0.001), US reported axillary lymph node positive (p = 0.025), and grade 2-3 vascularity (p < 0.001). The Breast Imaging Reporting and Data System categorized BF at a lower level than IDC (p < 0.001). After adjusting for age, the peripheral hyperechoic halo, posterior echo feature, and vascularity could independently identify the differences between these two entities. CONCLUSION: Some differences were observed between BF and IDC in terms of patient age, lesion size, and US characteristics.

[Comparative study of purgative pharmacological effects and mechanisms of Moringa oleifera leaves and Rhei Radix et Rhizoma].

Moringa oleifera leaves are known for their "Virechana"(purgative) effect in Ayurvedic medicine in India. This study compared the purgative effects and mechanisms of M. oleifera leaves with the reference Rhei Radix et Rhizoma to establish a foundation for the further application of M. oleifera leaves in traditional Chinese medicine(TCM). Using network pharmacology and molecular docking methods, this study identified the material basis, common targets, and signaling pathways through which Rhei Radix et Rhizoma and M. oleifera leaves exerted their purgative pharmacological effects. A low-fiber diet-induced constipation mouse model was established to measure fecal parameters and small intestinal propulsion rate, and histological changes in the colon were observed using HE staining. Relative expression levels of relevant genes and target proteins were assessed using RT-qPCR and immunohistochemistry, respectively. The results showed that mapping the targets of Rhei Radix et Rhizoma and M. oleifera leaves onto the biological process network of constipation revealed close proximity, indicating that they may exert their therapeutic effects on constipation through similar biological processes. Molecular docking results indicated that compounds such as sennoside C and isoquercitrin could target serine/threonine protein kinases(AKT1) and mitogen-activated protein kinase 3(MAPK3), thereby affecting MAPK and calcium signaling pathways to promote defecation. Animal experiments demonstrated that both M. oleifera leaves and Rhei Radix et Rhizoma increased the number of fecal pellets and water content in constipated mice, improved small intestine motility, colon mucosal thickness, and muscle layer thickness, upregulated the gene expression levels of AKT1 and MAPK3 in the colon, and downregulated the expression of AQP3 protein. These findings suggest that M. oleifera leaves and Rhei Radix et Rhizoma share similarities in their therapeutic efficacy and mechanisms for treating constipation. Using Rhei Radix et Rhizoma as a reference can provide a better understanding of the characteristics of the "Virechana"(purgative) effect of M. oleifera leaves in TCM.

[Research progress in pathogenesis and traditional Chinese medicines treatment of ischemic stroke-related headache].

Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.

A nomogram incorporating clinical, conventional ultrasound and shear wave elastography findings for distinguishing pleomorphic adenoma from Warthin's tumor of the major salivary glands.

OBJECTIVE: Pre-operative differentiation between pleomorphic adenoma (PA) and Warthin's tumor (WT) of the major salivary glands is crucial for treatment decisions. The purpose of this study was to develop and validate a nomogram incorporating clinical, conventional ultrasound (CUS) and shear wave elastography (SWE) features to differentiate PA from WT. METHODS: A total of 113 patients with histological diagnosis of PA or WT of the major salivary glands treated at Fujian Medical University Union Hospital were enrolled in training cohort (n = 75; PA = 41, WT = 34) and validation cohort (n = 38; PA = 22, WT = 16). The least absolute shrinkage and selection operator (LASSO) regression algorithm was used for screening the most optimal clinical, CUS, and SWE features. Different models, including the nomogram model, clinic-CUS (Clin+CUS) and SWE model, were built using logistic regression. The performance levels of the models were evaluated and validated on the training and validation cohorts, and then compared among the three models. RESULTS: The nomogram incorporating the clinical, CUS and SWE features showed favorable predictive value for differentiating PA from WT, with the area under the curves (AUCs) of 0.947 and 0.903 for the training cohort and validation cohort, respectively. Decision curve analysis showed that the nomogram model outperformed the Clin+CUS model and SWE model in terms of clinical usefulness. CONCLUSIONS: The nomogram had good performance in distinguishing major salivary PA from WT and held potential for optimizing the clinical decision-making process.

[Traditional application and modern research progress on new foreign medicinal resources].

Chinese medicinal resources are the material basis for the survival and development of traditional Chinese medicine(TCM)and the sustainable development of Chinese medicinal resources is also an important project for the modernization of TCM in China. With the increasing demand for Chinese medicinal resources in China, over-exploitation has destroyed Chinese medicinal resources, resulting in a shortage of many natural medicinal resources in China and making the sustainable development of TCM in trouble. The introduced new foreign medicinal resources have become effective supplement and replacement for Chinese medicinal resources to some extent. However, the development and utilization of new foreign medicinal resources in China are different. To fully understand the development of new foreign medicinal resources in China, this paper, taking 43 new foreign medicinal resources such as Acacia nilotica as objects, sorted out the introduction forms and policies of new foreign medicinal resources, overviewed its current development status in China, summarized the application experience of new foreign medicinal resources in the place of origin, as well as the research progress and problems of new foreign medicinal resources in China and abroad, and analyzed the research situation, which can enrich Chinese medicinal resources and other uses, promote the sustainable development of Chinese medicinal resources, and provide ideas for further development and research of new foreign medicinal resources.

Contrast-Enhanced Ultrasound Imaging: Novel Method for the Evaluation of Chronic Alcohol-Induced Testicular Damage.

OBJECTIVE: The goals of this study were to determine whether contrast-enhanced ultrasound (CEUS) imaging could be used for assessment of chronic alcohol-induced testicular damage (CAITD) and to explore the relationships between the laboratory and pathological findings of CAITD and the quantitative parameters of CEUS. METHODS: Thirty-six rabbits were randomly divided into a chronic ethanol exposure (CEE) group and negative control (NC) group, which were further randomly divided into six groups with equal numbers of rabbits by period of exposure (30 d, 60 d, 90 d). All rabbits underwent conventional US and CEUS imaging at the end of the induction period. Blood and histological specimens were collected for laboratory and pathological examination. RESULTS: The peak intensity (PI) and area under the curve (AUC) for the CEUS parameters decreased as CAITD progressed (p < 0.05). Both PI and AUC were positively correlated with the Johnsen score (r= 0.945 and 0.898, respectively, all p values <0.001) and the mean epithelium thickness of the seminiferous tubule (METST) (r= 0.927 and 0.881, respectively, all p values <0.001) of the testis, and negatively correlated with the serum levels of endothelin-1 (ET-1) (r = -0.940 and -0.899, respectively, all p values <0.001) and nitric oxide (NO) (r = -0.894 and -0.954, respectively, all p values <0.001), as well as the testicular tissue content of malondialdehyde (MDA) (r = -0.894 and -0.945, respectively, all p values <0.001). CONCLUSION: CEUS imaging can be used for monitoring organ perfusion of the testis to quantify the development of CAITD.

Metrnl deficiency retards skin wound healing in mice by inhibiting AKT/eNOS signaling and angiogenesis.

Meteorin-like (Metrnl) is a novel secreted protein with various biological activities. In this study, we investigated whether and how Metrnl regulated skin wound healing in mice. Global Metrnl gene knockout mice (Metrnl-/-) and endothelial cell-specific Metrnl gene knockout mice (EC-Metrnl-/-) were generated. Eight-mm-diameter full-thickness excisional wound was made on the dorsum of each mouse. The skin wounds were photographed and analyzed. In C57BL/6 mice, we observed that Metrnl expression levels were markedly increased in skin wound tissues. We found that both global and endothelial cell-specific Metrnl gene knockout significantly retarded mouse skin wound healing, and endothelial Metrnl was the key factor affecting wound healing and angiogenesis. The proliferation, migration and tube formation ability of primary human umbilical vein endothelial cells (HUVECs) were inhibited by Metrnl knockdown, but significantly promoted by addition of recombinant Metrnl (10 ng/mL). Metrnl knockdown abolished the proliferation of endothelial cells stimulated by recombinant VEGFA (10 ng/mL) but not by recombinant bFGF (10 ng/mL). We further revealed that Metrnl deficiency impaired VEGFA downstream AKT/eNOS activation in vitro and in vivo. The damaged angiogenetic activity in Metrnl knockdown HUVECs was partly rescued by addition of AKT activator SC79 (10 µM). In conclusion, Metrnl deficiency retards skin wound healing in mice, which is related to impaired endothelial Metrnl-mediated angiogenesis. Metrnl deficiency impairs angiogenesis by inhibiting AKT/eNOS signaling pathway.

Rapid Point-of-Care Assay by SERS Detection of SARS-CoV-2 Virus and Its Variants.

Addressing the spread of coronavirus disease 2019 (COVID-19) has highlighted the need for rapid, accurate, and low-cost diagnostic methods that detect specific antigens for SARS-CoV-2 infection. Tests for COVID-19 are based on reverse transcription PCR (RT-PCR), which requires laboratory services and is time-consuming. Here, by targeting the SARS-CoV-2 spike protein, we present a point-of-care SERS detection platform that specifically detects SARS-CoV-2 antigen in one step by captureing substrates and detection probes based on aptamer-specific recognition. Using the pseudovirus, without any pretreatment, the SARS-CoV-2 virus and its variants were detected by a handheld Raman spectrometer within 5 min. The limit of detection (LoD) for the pseudovirus was 124 TU µL-1 (18 fM spike protein), with a linear range of 250-10,000 TU µL-1. Moreover, this assay can specifically recognize the SARS-CoV-2 antigen without cross reacting with specific antigens of other coronaviruses or influenza A. Therefore, the platform has great potential for application in rapid point-of-care diagnostic assays for SARS-CoV-2.

[Formation and development of "Xiang thinking" in traditional Chinese medicine].

"Xiang thinking" is the main thinking mode in traditional Chinese medicine(TCM) with both philosophical and scientific connotations, and has an important influence on the emergence and development of TCM. This study systematically expounded the philosophical connotation and characteristics of "Xiang thinking", and its application in the construction of TCM theory, clinical syndrome differentiation and treatment, the formation of medicinal properties, and interpretation of efficacy of Chinese medicine. "Xiang thinking" in TCM develops and changes continuously with practical application, and its historical evolution can be summarized into three stages, i.e., "Ying Xiang(corresponding to Xiang)" "Fa Xiang(following Xiang)", and "Bian Xiang(differentiating Xiang)". The understanding of Xiang is based on the means and methods of human observation of things and the backgrounds of the philosophy, science, and development. The result of comparison depends on the depth and breadth of Xiang. In the real world, Xiang is showing new construction characteristics with multiple dimensions and levels. Therefore, this study proposed the thinking of "Bian Xiang", which is expected to provide a thinking approach that can realize the transformation from "Xiang thinking" to scientific research for the exploration and innovative research on life origin in the field of contemporary and TCM.

Short-term effects of wildfire on soil arthropods in a semi-arid grassland on the Loess Plateau.

Fires lead to dramatic shifts in ecosystems and have a large impact on the biota. Soil organisms, especially soil fauna, are often used as indicators of environmental change. At present, minimal attention has been paid to using soil fauna as an indicator of environmental change after a fire. Here, a field survey of burnt herbaceous vegetation in semi-arid areas was conducted to determine the response of soil arthropods to fire and their short-term recovery after fire. Overall, the abundance and biomass of soil arthropods was more sensitive to fire than the number of groups. The number of soil arthropod groups, especially the dominant groups (mites and springtails), was not significantly affected by wildfires. At the unburned site, soil arthropod abundance showed significant seasonal shifts that may be related to the vegetation properties, temperature, and precipitation caused by seasonal changes. In contrast, soil arthropods at the burnt sites showed a delayed recovery and had only reached 56%-82%, 17%-54%, and 91%-190% of the biomass in the unburnt forest at the 3, 6, and 9 months after the burning event. Our findings of soil arthropod abundance changes in the present study suggest that fire-induced changes in soil and vegetation properties (e.g., AN, LT, and VC) were crucial factors for the changes in soil arthropod abundance in this semi-arid grassland. We conclude that fire disturbance reduces the seasonal sensitivity of soil arthropods by altering their habitat. This study furthers our understanding of wildfire impact recovery by documenting the short-term temporal dynamics of soil arthropods.

Individualized combination therapies based on whole-exome sequencing displayed significant clinical benefits in a glioblastoma patient with secondary osteosarcoma: case report and genetic characterization.

BACKGROUND: The incidence of osteosarcoma as a secondary neoplasm in glioblastoma patient is extremely rare. The genetic characteristic still remains unclear until now. CASE DESCRIPTION: We reported a 47-year-old female patient with multiple intracranial disseminations and infiltrations (splenium of the corpus callosum and lateral ventricular wall) of a rapid progressive glioblastoma underwent occipital craniotomy and total resection of all the enhancing lesions. Whole-exome sequencing and pathological examination revealed glioblastoma, IDH1 wild type, PTEN deficient, TERT mutated, NF1mutated, MGMT unmethylated. After surgery, the patient received combined therapeutic regimen of TTFields (tumor-treating fields) plus pembrolizumab plus temozolomide and TTFields plus everolimus, which displayed significant clinical benefits. During the combined therapeutic course, an extremely rare secondary malignant neoplasm occurred, femur MR and pathological detection of biopsy tissue demonstrated osteosarcoma. The result of whole-exome sequencing revealed 7 germline mutated genes (EPAS1, SETD2, MSH3, BMPR1A, ERCC4, CDH1, AR). Bioinformatic analysis showed the two germline mutations (MSH3 and ERCC4) induced deficiency in the DNA repair machinery, which resulting in the accumulation of mutations and may generate neoantigens contributing to the development of a secondary osteosarcoma in this case. CONCLUSION: Individualized combination therapies based on whole-exome sequencing displayed significant clinical benefits in this case. Germline MSH3 and ERCC4 mutation may induce a secondary osteosarcoma in glioblastoma patients.

[Simultaneous determination of glucosinolates and flavonoids in leaves of Moringa oleifera by quantitative analysis of multi-components by single-marker (QAMS)].

To establish a method for simultaneously determining the content of four glucosinolates and five flavonoids in leaves of Moringa oleifera via quantitative analysis of multi-components by single-marker(QAMS) and verify the feasibility and applicability of the established method. The glucosinolates and flavonoids were analyzed via Waters Acquity UPLC HSS T_3 column(2.1 mm × 100 mm, 1.8 µm). The gradient elution was carried out with the mobile phase composed of 0.1% formic acid-acetonitrile and 0.3% formic acid at the flow rate of 0.4 mL·min~(-1) and the column temperature of 40 ℃. The wavelengths for the detection of glucosinolates and flavonoids were 225 nm and 260 nm, respectively. With 4-O-(α-L-rhamnoyloxy)-benzyl glucosinolate and vecenin-2 as internal reference substances, the relative correction factors of four glucosinolates and five flavonoids were respectively calculated for determining the content of the 9 ingredients in leaves of M. oleifera. To verify the accuracy and feasibility of QAMS, we used internal standard method(ISM) and external standard method(ESM) to determine the content of glucosinolates and flavonoids, respectively. The t-test results showed that there was no significant difference in the content of glucosinolates obtained by ISM and QAMS methods or in the content of flavonoids obtained by ESM and QAMS methods. The content of glucosinolates and flavonoids varied among M. oleifera of different varieties and from different producing areas. The total glucosinolates and total flavonoids had the highest content in the Indian variety while the lowest content in the variety ■Honghe No. 1'. The established QAMS method is rapid, simple and accurate and can be used for simultaneous determination of glucosinolates and flavonoids in the leaves of M. oleifera. This study provides experimental data for the quality control and utilization of M. oleifera leaves.