Clinical sequencing reveals diagnostic, therapeutic, and prognostic biomarkers for adult-type diffuse gliomas.

Diffuse gliomas in adults are highly infiltrative and largely incurable. Whole exome sequencing (WES) has been demonstrated very useful in genetic analysis. Here WES was performed to characterize genomic landscape of adult-type diffuse gliomas to discover the diagnostic, therapeutic and prognostic biomarkers. Somatic and germline variants of 66 patients with adult-type diffuse gliomas were detected by WES based on the next-generation sequencing. TCGA and CGGA datasets were included to analyze the integrated diagnosis and prognosis. Among 66 patients, the diagnosis of 9 cases was changed, in which 8 cases of astrocytoma were corrected into IDH-wildtype glioblastoma (GBM), and 1 oligodendroglioma without 1p/19q co-deletion into astrocytoma. The distribution of mutations including ATRX/TP53 differed in three cohorts. The genetic mutations in GBM mainly concentrated on the cell cycle, PI3K and RTK pathways. The mutational landscape of astrocytoma was more similar to that of GBM, with the highest frequency in germline variants. Patients with IDH-mutant astrocytoma harboring SNVs of PIK3CA and PIK3R1 showed a significantly worse overall survival (OS) than wild-type patients. AEBP1 amplification was associated with shorter OS in GBM. Our study suggests that clinical sequencing can recapitulate previous findings, which may provide a powerful approach to discover diagnostic, therapeutic and prognostic markers for precision medicine in adult-type diffuse gliomas.

Albumin-bilirubin grade as a predictor of survival in hepatocellular carcinoma patients with thrombocytopenia.

BACKGROUND: The models for assessing liver function, mainly the Child-Pugh (CP), albuminbilirubin (ALBI), and platelet-ALBI (PALBI) classifications, have been validated for use in estimating the prognosis of hepatocellular carcinoma (HCC) patients. However, thrombocytopenia is a common finding and may influence the prognostic value of the three models in HCC. AIM: To investigate and compare the prognostic performance of the above three models in thrombocytopenic HCC patients. METHODS: A total of 135 patients with thrombocytopenic HCC who underwent radical surgery were retrospectively analyzed. Preoperative scores on the CP, ALBI and PALBI classifications were estimated accordingly. Kaplan-Meier curves with log-rank tests and Cox regression models were used to explore the significant factors associated with overall survival (OS) and recurrence-free survival (RFS). RESULTS: The preoperative platelet counts were significantly different among the CP, ALBI and PALBI groups. After a median follow-up of 28 mo, 39.3% (53/135) of the patients experienced postoperative recurrence, and 36.3% (49/135) died. Univariate analysis suggested that α-fetoprotein levels, tumor size, vascular invasion, and ALBI grade were significant predictors of OS and RFS. According to the multivariate Cox regression model, ALBI was identified as an independent prognostic factor. However, CP and PALBI grades were not statistically significant prognostic indicators. CONCLUSION: The ALBI grade, rather than CP or PALBI grade, is a significant prognostic indicator for thrombocytopenic HCC patients.

Radiotherapy plus temozolomide with or without anlotinib in H3K27M-mutant diffuse midline glioma: A retrospective cohort study.

BACKGROUND: Besides the hallmark of H3K27M mutation, aberrant amplifications of receptor tyrosine kinases (RTKs) are commonly observed in diffuse midline glioma (DMG), a highly malignant brain tumor with dismal prognosis. Here, we intended to evaluate the efficacy and safety of a multitarget RTK inhibitor anlotinib in patients with H3K27M-DMG. METHODS: A total of 40 newly diagnosed H3K27M-DMG patients including 15 with anlotinib and 25 without anlotinib treatment were retrospectively enrolled in this cohort. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed and compared. RESULTS: The median PFS and OS of all patients in this cohort were 8.5 months (95% CI, 6.5-11.3) and 15.5 months (95% CI, 12.6-17.1), respectively. According to the Response Assessment in Neuro-Oncology (RANO) criteria, the disease control rate in the anlotinib group [93.3%, 95% confidence interval (CI), 70.2-98.8] was significantly higher than those without anlotinib (64%, 95% CI: 40.5-79.8, p = 0.039). The median PFS of patients with and without anlotinib was 11.6 months (95% CI, 7.8-14.3) and 6.4 months (95% CI, 4.3-10.3), respectively. Both the median PFS and OS of DMG patients treated with anlotinib were longer than those without anlotinib in the infratentorial patients (PFS: 10.3 vs. 5.4 months, p = 0.006; OS: 16.6 vs. 8.7 months, p = 0.016). Multivariate analysis also indicated anlotinib (HR: 0.243, 95% CI: 0.066-0.896, p = 0.034) was an independent prognosticator for longer OS in the infratentorial subgroup. In addition, the adverse events of anlotinib administration were tolerable in the whole cohort. CONCLUSIONS: This study first reported that anlotinib combined with Stupp regimen is a safe and feasible regimen for newly diagnosed patients with H3K27M-DMG. Further, anlotinib showed significant efficacy for H3K27M-DMG located in the infratentorial region.

Differences in survival prognosticators between children and adults with H3K27M-mutant diffuse midline glioma.

AIMS: H3K27M-mutant diffuse midline glioma (DMG) is a rare and aggressive central nervous system tumor. The biological behavior, clinicopathological characteristics, and prognostic factors of DMG have not yet been completely uncovered, especially in adult patients. This study aims to investigate the clinicopathological characteristics and identify prognostic factors of H3K27M-mutant DMG in pediatric and adult patients, respectively. METHODS: A total of 171 patients with H3K27M-mutant DMG were included in the study. The clinicopathological characteristics of the patients were analyzed and stratified based on age. The Cox proportional hazard model was used to determine the independent prognostic factors in pediatric and adult subgroups. RESULTS: The median overall survival (OS) for the entire cohort was 9.0 months. Significant differences were found in some clinicopathological characteristics between children and adults. The median OS was also significantly different between the pediatric and adult subgroups, with 7.1 months for children and 12.3 months for adults (p < 0.001). In the overall population, the multivariate analysis identified adult patients, single lesion, concurrent chemoradiotherapy/radiotherapy, and intact ATRX expression as independent favorable prognostic factors. In the age-stratified subgroups, the prognostic factors varied between children and adults, with intact ATRX expression and single lesion being independent favorable prognostic factors in adults, while infratentorial localization was significantly associated with worse prognosis in children. CONCLUSIONS: The differences in clinicopathological features and prognostic factors between pediatric and adult patients with H3K27M-mutant DMG suggest the need for further clinical and molecular stratification based on age.

Radiotherapy and radio-sensitization in H3K27M -mutated diffuse midline gliomas.

BACKGROUND: H3K27M mutated diffuse midline gliomas (DMGs) are extremely aggressive and the leading cause of cancer-related deaths in pediatric brain tumors with 5-year survival <1%. Radiotherapy is the only established adjuvant treatment of H3K27M DMGs; however, the radio-resistance is commonly observed. METHODS: We summarized current understandings of the molecular responses of H3K27M DMGs to radiotherapy and provide crucial insights into current advances in radiosensitivity enhancement. RESULTS: Ionizing radiation (IR) can mainly inhibit tumor cell growth by inducing DNA damage regulated by the cell cycle checkpoints and DNA damage repair (DDR) system. In H3K27M DMGs, the aberrant genetic and epigenetic changes, stemness genotype, and epithelial-mesenchymal transition (EMT) disrupt the cell cycle checkpoints and DDR system by altering the associated regulatory signaling pathways, which leads to the development of radio-resistance. CONCLUSIONS: The advances in mechanisms of radio-resistance in H3K27M DMGs promote the potential targets to enhance the sensitivity to radiotherapy.

Risk factors and a novel cerebral infarction extent scoring system for postoperative cerebral ischemia in patients with ischemic Moyamoya disease.

Postoperative cerebral ischemic complication is the most common complication of revascularization surgery for patients with moyamoya disease (MMD). This retrospective study was conducted on 63 patients with ischemic MMD. Postoperative ischemia occurred in 15 of the 70 revascularization operations performed for patients after surgical revascularization, translating to an incidence of 21.4%. Univariate analysis revealed that onset infarction (p = 0.015), posterior cerebral artery involvement (p = 0.039), strict perioperative management (p = 0.001), interval time between transient ischemic attack (TIA) or infarction presentation and operation (p = 0.002) and preoperatively cerebral infarction extent score (CIES) (p = 0.002) were significantly associated with postoperative cerebral ischemia. Multivariate analysis revealed that strict perioperative management (OR = 0.163; p = 0.047), and preoperatively CIES (OR = 1.505; p = 0.006) were independently associated with postoperative cerebral ischemia-related complications. After comprehensive improvement of perioperative management protocol, the incidence of symptomatic infarction declined to 7.4% (4 out of 54). Analysis of the area under the receiver operating characteristic curve (AUROC) indicated CIES was a predictor for both postoperative ischemia and high follow-up modified Rankin Scale scores. In summary, strict perioperative management and CIES were identified as independent risk factors for postoperative ischemic complications in ischemic MMD, demonstrating that comprehensive and individualized perioperative management improve postoperative outcomes in patients with MMD. Furthermore, application of CIES to evaluate pre-existing cerebral infarction can improve the management of patients.

Functional Analysis of Histone ADP-Ribosylation In Vitro and in Cells.

Gene regulation in the nucleus requires precise control of the molecular processes that dictate how, when, and which genes are transcribed. The posttranslational modification (PTM) of histones in chromatin is an effective means to link cellular signaling to gene expression outcomes. The repertoire of histone PTMs includes phosphorylation, acetylation, methylation, ubiquitylation, and ADP-ribosylation (ADPRylation). ADPRylation is a reversible PTM that results in the covalent transfer of ADP-ribose units derived from NAD+ to substrate proteins on glutamate, aspartate, serine, and other amino acids. Histones were the first substrate proteins identified for ADPRylation, over five decades ago. Since that time, histone ADPRylation has been shown to be a widespread and critical regulator of chromatin structure and function during transcription, DNA repair, and replication. Here, we describe a set of protocols that allow the user to investigate site-specific histone ADPRylation and its functional consequences in biochemical assays and in cells in a variety of biological systems. With the recent discovery that some cancer-causing histone mutations (i.e., oncohistone mutations) occur at functional sites of regulatory ADPRylation, these protocols may have additional utility in studies of oncology.

DEPDC1 as a crucial factor in the progression of human osteosarcoma.

OBJECTIVE: Novel therapeutic strategies are emerging with the increased understanding of the underlying mechanisms of human osteosarcoma. This current study tends to decipher the potentially critical role of DEP domain-containing 1 (DEPDC1), a tumor-related gene, during the progression of osteosarcoma. METHODS: Bioinformatics analysis of 25,035 genes from the National Center for Biotechnology Information (NCBI) databases was performed to screen differentially expressed genes between osteosarcoma and normal control groups, complemented by the examination of 85 clinical osteosarcoma specimens. Furthermore, the manipulation of DEPDC1 expression levels by using silencing RNA (siRNA) or lentiviral vector intervention on human osteosarcoma cells was performed to reveal its role and interactions in in vitro and in vivo settings. RESULTS: Gene expression profile analysis and immunohistochemical (IHC) examination suggested that DEPDC1 is highly expressed in human osteosarcoma cells and tumor tissue. The silencing of DEPDC1 arrested osteosarcoma cell proliferation, promoted apoptosis, and ceased tumor metastasis. Studies involving clinical human osteosarcoma cases exhibited a strong correlation of DEPDC1 over-expressed osteosarcoma specimens with a reduced patient survival rate. CONCLUSIONS: Collectively, this study demonstrated that DEPDC1 is a critical driver in the promotion of osteosarcoma progression and results in poor patient prognosis. Genetically targeting or pharmacologically inhibiting DEPDC1 may serve as a promising strategy for treating human osteosarcoma.

Radiotherapy Plus Temozolomide With or Without Nimotuzumab Against the Newly Diagnosed EGFR-Positive Glioblastoma: A Retrospective Cohort Study.

BACKGROUND: Glioblastoma (GBM) has a poor prognosis, and patients with epidermal growth factor receptor (EGFR) amplification have an even worse prognosis. Nimotuzumab is an EGFR monoclonal antibody thought to play a significant role in the treatment of GBM. This paper presents a retrospective cohort study that evaluates the clinical efficacy and safety of nimotuzumab in GBM. MATERIALS AND METHODS: A total of 56 newly diagnosed patients with EGFR-positive GBM were included in our study. The patients were divided into radiotherapy (RT) + temozolomide (TMZ) + nimotuzumab (39 patients) and RT + TMZ (17 patients) groups based on whether or not nimotuzumab was added during RT. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed. RESULTS: The median follow-up time was 27.9 months (95% confidence interval [CI], 25.1-30.8). The median PFS was 12.4 months (95% CI, 7.8-17.0) and 8.2 months (95% CI, 6.1-10.3) in the 2 groups, respectively, P = .052. The median OS was 27.3 months (95% CI, 19.0-35.6) and 16.7 months (95% CI, 11.1-22.2), respectively, P = .018. In patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter, the PFS and OS were significantly better in patients treated with nimotuzumab than in those without nimotuzumab (median PFS: 19.3 vs 6.7 months, P = .001; median OS: 20.2 vs 13.8 months, P = .026). During the treatment period, no statistically significant difference in toxicity was noted between the 2 groups. CONCLUSION: Our retrospective cohort study suggests the efficacy of Nimotuzumab combined with concurrent RT with TMZ in patients with newly diagnosed EGFR-positive GBM, and specifically those with unmethylated MGMT promoter. Further prospective studies are warranted to validate our findings. Besides, nimotuzumab demonstrated good safety and tolerability.

Advances of Electroporation-Related Therapies and the Synergy with Immunotherapy in Cancer Treatment.

Electroporation is the process of instantaneously increasing the permeability of a cell membrane under a pulsed electric field. Depending on the parameters of the electric pulses and the target cell electrophysiological characteristics, electroporation can be either reversible or irreversible. Reversible electroporation facilitates the delivery of functional genetic materials or drugs to target cells, inducing cell death by apoptosis, mitotic catastrophe, or pseudoapoptosis; irreversible electroporation is an ablative technology which directly ablates a large amount of tissue without causing harmful thermal effects; electrotherapy using an electric field can induce cell apoptosis without any aggressive invasion. Reversible and irreversible electroporation can also activate systemic antitumor immune response and enhance the efficacy of immunotherapy. In this review, we discuss recent progress related to electroporation, and summarize its latest applications. Further, we discuss the synergistic effects of electroporation-related therapies and immunotherapy. We also propose perspectives for further investigating electroporation and immunotherapy in cancer treatment.

Outcome of Endoscopic Transsphenoidal Surgery for Recurrent or Residual Pituitary Adenomas and Comparison to Non-Recurrent or Residual Cohort by Propensity Score Analysis.

Objective: To evaluate the long-term outcomes and safety of endoscopic transsphenoidal surgery (ETS) in recurrent and residual pituitary adenomas (rrPAs), as well as the predictors of gross total resection (GTR) and intraoperative CSF leakage. Furthermore, to compare outcomes and complications with non-rrPAs cohort. Methods: Clinical and radiological characteristics of patients with rrPAs who underwent ETS were collected between 2017 and 2020. Data of patients with non-rrPAs were collected from 2019 to 2020. Logistic regression analyses were performed to investigate the factors influencing gross total resection (GTR) and intraoperative CSF leakage. Between-group comparisons of outcomes and complications were performed through propensity score analysis. Results: We enrolled 73 patients with rrPAs. GTR was achieved in 41 (56.1%) cases; further, GTR or near-total resection was achieved in 93.2% of patients. The mean tumor volumes for GTR and non-GTR cases were 6.2 ±7.2 cm3 and 11.1 ±9.1 cm3, respectively. Multivariate regression analysis of the GTR rate in patients with rrPAs revealed that Knosp grade was an independent factor (odds ratio [OR] = 0.324; p=0.005). Moreover, previous transcranial surgery and non-functional pituitary adenomas were risk factors for intraoperative CSF leakage in patients with rrPAs (OR=6.450, p=0.019 and OR=7.472, p=0.012, respectively). After propensity score matching, There was no significant difference in the GTR rate between patients with rrPAs and patients with non-rrPAs. Contrastingly, patients with rrPAs had a higher rate of intraoperative CSF leakage and longer postoperative hospital stay than patients with non-rrPAs. During the follow-up, vision improved in 9 (22.0%) and 24 (62.5%) patients with rrPAs and non-rrPAs, respectively. Although there was a trend that reoperation of rrPAs involved a lower hypopituitarism recovery rate and biochemical remission rate, as well as a higher hypopituitarism rate, there was no statistically significant between-group difference. Conclusions: Knosp grade was an independent factor for GTR in endoscopic transsphenoidal surgery in patients with rrPAs. Previous transcranial surgery and non-functional PAs were risk factors for intraoperative CSF leakage. Although associated with longer hospital stay, rrPAs did not associate with lower GTR rate or more frequent postoperative complications than non-rrPAs cohort.

Changes in Thromboelastography to Predict Ecchymosis After Knee Arthroplasty: A Promising Guide for the Use of Anticoagulants.

Background: Ecchymosis is one of the worrisome complications after total knee arthroplasty (TKA) and interferes with functional rehabilitation. Current clinical guidelines do not provide individualized approaches for patients with ecchymoses. Methods: In this study, we used thromboelastography (TEG) to determine the coagulation state after TKA and to then explore markers that predict the occurrence of ecchymosis events after TKA. In our cohort, patients were divided into ecchymosis (n = 55) and non-ecchymosis (n = 137) groups according to whether ecchymosis events occurred after TKA. Rivaroxaban 10 mg/d was taken orally for thromboprophylaxis after surgery. All patients completed TEG testing. Correlation analysis was used to determine the risk factors for ecchymosis after TKA, and receiver operating characteristic (ROC) curves for variables with significant correlation were plotted. Results: In all, 55 of the 192 patients (28.65%) developed ecchymosis surrounding the surgical site. Multivariate analysis showed that hidden blood loss (OR = 1.003 and p = 0.005) and changes in the coagulation index (ΔCI) values (OR = 0.351 and p = 0.001) were risk factors for ecchymosis after TKA. Using the Youden index, 0.1805 was determined as the optimal threshold value of ΔCI for predicting the occurrence of ecchymosis, with a sensitivity of 74.55% and specificity of 72.99%. ΔCI is a promising marker as an alarm for the occurrence of ecchymosis after TKA. Trial Registration: The study was registered in the Chinese Clinical Trial Registry (ChiCTR1800017245). Registered name: The role of thrombelastography in monitoring the changes of coagulation function during perioperative period of arthroplasty. Registered 19 July 2018. http://www.chictr.org.cn/showproj.aspx?proj=29220.

Oncohistone Mutations Occur at Functional Sites of Regulatory ADP-Ribosylation.

Recent studies have identified cancer-associated mutations in histone genes that lead to the expression of mutant versions of core histones called oncohistones. Many oncohistone mutations occur at Asp and Glu residues, two amino acids known to be ADP-ribosylated (ADPRylated) by PARP1. We screened 25 Glu or Asp oncohistone mutants for their effects on cell growth in breast and ovarian cancer cells. Ectopic expression of six mutants of three different core histones (H2B, H3, and H4) altered cell growth in at least two different cell lines. Two of these sites, H2B-D51 and H4-D68, were indeed sites of ADPRylation in wild-type (unmutated) histones, and mutation of these sites inhibited ADPRylation. Mutation of H2B-D51 dramatically altered chromatin accessibility at enhancers and promoters, as well as gene expression outcomes, whereas mutation of H4-D68 did not. Additional biochemical, cellular, proteomic, and genomic analyses demonstrated that ADPRylation of H2B-D51 inhibits p300-mediated acetylation of H2B at many Lys residues. In breast cancer cell xenografts in mice, H2B-D51A promoted tumor growth, but did not confer resistance to the cytotoxic effects of PARP inhibition. Collectively, these results demonstrate that functional Asp and Glu ADPRylation sites on histones are mutated in cancers, allowing cancer cells to escape the growth-regulating effects of post-translational modifications via distinct mechanisms. SIGNIFICANCE: This study identifies cancer-driving mutations in histones as sites of PARP1-mediated ADP-ribosylation in breast and ovarian cancers, providing a molecular pathway by which cancers may subvert the growth-regulating effects of PARP1.

Hybrid-Membrane-Decorated Prussian Blue for Effective Cancer Immunotherapy via Tumor-Associated Macrophages Polarization and Hypoxia Relief.

Both tumor-associated macrophages (TAMs) and hypoxia condition severely restrict the antitumor potency during cancer immunotherapy. It is essential to overcome the two issues for improving therapeutic efficacy. In this study, a hollow mesoporous Prussian blue (HMPB) nanosystem with mannose decoration and hydroxychloroquine (HCQ) adsorption is built, to form Man-HMPB/HCQ. It can facilitate cellular internalization via mannose-receptor mediated endocytosis and induce TAM polarization via iron ion/HCQ release with HMPB degradation. The hybrid macrophage and thylakoid (TK) membrane is camouflaged on the Man-HMPB/HCQ surface, denoted as TK-M@Man-HMPB/HCQ, to reduce in vivo reticuloendothelial system uptake, enhance tumor accumulation, and mitigate hypoxia. The in vivo results indicate that TK-M@Man-HMPB/HCQ notably inhibits tumor growth, induces TAM polarization, facilitates cytotoxic T lymphocytes infiltration, and alleviates hypoxia microenvironment. The rational design may provide a new pathway to modulate the tumor microenvironment for promoting cancer immunotherapy effects.

Effectiveness and safety of tumor-treating fields therapy for glioblastoma: A single-center study in a Chinese cohort.

Objective: Tumor-treating fields (TTFields) are a new therapeutic modality for patients with glioblastoma (GBM). However, studies on survival outcomes of TTFields are rarely reported in China. This study aimed to examine the clinical efficacy and safety of TTFields therapy for GBM in China. Methods: A total of 93 patients with newly diagnosed GBM (ndGBM) and recurrent GBM (rGBM) were included in our study retrospectively. They were divided into two groups based on whether they used TTFields. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed. Results: Among the patients with ndGBM, there were 13 cases with TTFields and 39 cases with no TTFields. The median PFS was 15.3 [95% confidence interval (CI): 6.5-24.1] months and 10.6 (95% CI: 5.4-15.8) months in the two groups, respectively, with P = 0.041. The median OS was 24.8 (95% CI: 6.8-42.8) months and 18.6 (95% CI: 11.4-25.8) months, respectively, with P = 0.368. Patients with subtotal resection (STR) who used TTFields had a better PFS than those who did not (P = 0.003). Among the patients with rGBM, there were 13 cases with TTFields and 28 cases with no TTFields. The median PFS in the two groups was 8.4 (95% CI: 1.7-15.2) months and 8.0 (95% CI: 5.8-10.2) months in the two groups, respectively, with P = 0.265. The median OS was 10.6 (95% CI: 4.8-16.4) months and 13.3 (95% CI: 11.0-15.6) months, respectively, with P = 0.655. A total of 21 patients (21/26, 80.8%) with TTFields developed dermatological adverse events (dAEs). All the dAEs could be resolved or controlled. Conclusion: TTFields therapy is a safe and effective treatment for ndGBM, especially in patients with STR. However, it may not improve survival in patients with rGBM.

The typically developing pediatric foot - The data of the 1744 children in China.

BACKGROUND: The medial longitudinal arch (MLA) improves with age in childhood. However, it still causes parents to worry that children have flat feet. Due to the lack of a standard to quantitatively assess the arch development in kids at certain age, the pediatricians judge the flat feet by experience, causing many cases to be overtreated. The aim of this study was to plot the distribution of MLA parameters in children. METHODS: Children without lower limb deformity and lower limb pain were recruited from 12 primary schools and kindergartens in Chongqing province-level city. Foot length (FL) and navicular height (NH) was measured manually, arch index (AI) and arch volume (AV) were measured with the Foot Plantar Scanner. Each parameter was measured in both weight-bearing and non-weight-bearing positions. Significant differences were also compared between the measurements of consecutive years. RESULTS: This study was the first to use a three-dimensional laser surface scanner to measure the MLA parameters of children aged 3-12 years in China. 1744 children (871 girls, 873 boys) participated in this study. FL, NH, AI and AV varied significantly with age in both the weight-bearing and non-weight-bearing positions. These parameters have significant differences between the weighted and non-weighted positions (p < 0.05). CONCLUSIONS: The age distribution characteristics of these parameters indicated that the MLA improves with age. The establishment of a developmental scale for the children's MLA is necessary.

Contrast-enhanced ultrasound imaging for intestinal lymphoma.

BACKGROUND: Intestinal lymphoma is a rare tumor. Contrast-enhanced ultrasound (CEUS) findings of intestinal lymphoma have not been reported previously, and the relationship between CEUS and clinicopathological features and prognostic factors is still unknown. AIM: To describe the B-mode US and CEUS features of intestinal lymphoma and investigate the correlation of CEUS and histopathological features. METHODS: This was a single-center retrospective study. Eighteen patients with histologically confirmed intestinal lymphoma underwent B-mode US and CEUS examinations between October 2016 and November 2019. We summarized the features of B-mode US and CUES imaging of intestinal lymphoma and compared the frequency of tumor necrosis in intestinal lymphomas with reference to different pathological subtypes (aggressive or indolent) and clinical stage (early or advanced). The time-intensity curve parameters of CEUS were also compared between patients with normal and elevated serum lactate dehydrogenase. RESULTS: In B-mode imaging, four patterns were observed in intestinal lymphoma: Mass type (12/18, 66.7%), infiltration type (1/18, 5.6%), mesentery type (4/18, 22.2%) and mixed type (1/18, 5.6%). All cases were hypoechoic and no cystic areas were detected. On CEUS, most cases (17/18, 94.4%) showed arterial hyperechoic enhancement. All cases showed arterial enhancement followed by venous wash out. A relatively high rate of tumor necrosis (11/18, 61.1%) was observed in this study. Tumor necrosis on CEUS was more frequent in aggressive subtypes (10/13, 76.9%) than in indolent subtypes (1/5, 20.0%) (P = 0.047). There were no correlations between tumor necrosis and lesion size and Ann Arbor stage. There was no significant difference in time-intensity curve parameters between normal and elevated lactate dehydrogenase groups. CONCLUSION: B-mode US and CEUS findings of intestinal lymphoma are characteristic. We observed a high rate of tumor necrosis, which appeared more frequently in aggressive pathological subtypes of intestinal lymphoma.

Astragalus polysaccharide attenuates LPS-related inflammatory osteolysis by suppressing osteoclastogenesis by reducing the MAPK signalling pathway.

Bacterial products can stimulate inflammatory reaction and activate immune cells to enhance the production of inflammatory cytokines, and finally promote osteoclasts recruitment and activity, leading to bone destruction. Unfortunately, effective preventive and treatment measures for inflammatory osteolysis are limited and usually confuse the orthopedist. Astragalus polysaccharide (APS), the main extractive of Astragali Radix, has been widely used for treating inflammatory diseases. In the current study, in vitro and in vivo experimental results demonstrated that APS notably inhibited osteoclast formation and differentiation dose-dependently. Moreover, we found that APS down-regulated RANKL-related osteoclastogenesis and levels of osteoclast marker genes, such as NFATC1, TRAP, c-FOS and cathepsin K. Further underlying mechanism investigation revealed that APS attenuated activity of MAPK signalling pathways (eg ERK, JNK and p38) and ROS production induced by RANKL. Additionally, APS was also found to suppress LPS-related inflammatory osteolysis by decreasing inflammatory factors' production in vivo. Overall, our findings demonstrate that APS effectively down-regulates inflammatory osteolysis due to osteoclast differentiation and has the potential to become an effective treatment of the disorders associated with osteoclast.

Compositional evolution of nanoscale zero valent iron and 2,4-dichlorophenol during dechlorination by attapulgite supported Fe/Ni nanoparticles.

Transformation of chloro-organic compounds by nFe(0) has been studied extensively, but limited study exists on the transformation and fate of nFe(0) during the dechlorination of chloro-organics even though such knowledge is important in predicting its surface chemistry, particularly, toxicity in the environment. In this study, the nFe(0) core became hollowed, collapsed and gradually corroded into poorly crystallized ferrihydrite (Fe5O3(OH)9) at the pristine reaction time, which later gave rise to lath-like lepidocrocite (γ-FeOOH), acicular goethite (α-FeOOH) and cubic magnetite (Fe3O4) by the end of the reaction time (120 min). Also, dechlorination of 2,4-DCP into 2-CP, 4-CP and phenol was achieved within 120 min. The rapid dechlorination of 2,4-DCP and transformation of nFe(0) could not be achieved significantly without doping Ni on nFe(0) and supporting on attapulgite. The schematic representation of the transformation and compositional evolution of nFe(0) in A-nFe/Ni was proposed. These findings are critical in understanding the compositional evolution and the fate of nFe(0) upon reaction with chloro-organics and can provide guidance for more efficient uses of the nFe(0) reactivity towards the target contaminants in groundwater remediation.

Remimazolan inhibits glioma cell growth and induces apoptosis through down-regulation of NF-κB pathway.

Glioma alone accounts for 30% of various kinds of primary brain tumors and is the highest cause of mortality associated with intracranial malignant cancers. In the present study, Suzuki-coupling products of remimazolan were synthesized and investigated for anti-neoplastic property against glioma cells. RFMSP treatment for 48 hr suppressed viabilities of U-118MG and U87MG cells in dose dependent manner. Exposure of primary astrocytes to RFMSP at 2-20 µM concentration range minimally affected viabilities. RFMSP treatment at 5 µM doses raised apoptotic cell count to 53.8 ± 2.3% and 48.2 ± 1.8%, respectively in U-118MG and U87MG cells. Treatment of the cells with RFMSP induced nuclear condensation and subsequent fragmentation. In RFMSP treated U-118MG and U87MG cells, NF-κB p65 expression was markedly suppressed compared to the control cells. Additionally, RFMSP treatment decreased the ratio of nuclear to total NF-κB p65 level in both the cell lines. Treatment of U-118MG and U87MG cells with 5 µM RFMSP for 48 hr caused a marked down-regulation in survivin and XIAP levels. Treatment with RFMSP promoted Bax expression and suppressed Bcl-2 level. The caspase-9 and -3 activation was markedly induced by RFMSP treatment in U-118MG and U87MG cells compared to the control cells. In summary, the RFMSP synthesized by Suzuki-coupling of RFMSP inhibited glioma cell survival via DNA damage mediated apoptosis. The anti-glioma potential of RFMSP involved down-regulation of NF-κB expression, targeted survivin & XIAP levels and induced caspase activation in glioma cells. Therefore, RFMSP may be studied further as therapeutic agent for the treatment of glioma.