AbstractConcrete-filled steel tube (CFT) structures are widely used in various types of buildings and bridges. Confined concrete tube (CCFT) is a new type of structural column originally proposed in ...previous work. This paper reports the impact testing results of the CFT and carbon fiber reinforced polymer (CFRP) confined CFT stub columns under different impacting energy levels, conducted using a large-capacity drop-hammer machine. The time history curves of impacting force and deformation time history curves as well as failure patterns are investigated. The results indicate that the failure patterns are related to the impact energy. Increasing the thickness of the steel tube and providing additional transverse confinement by CFRP can enhance the impact-resistant behavior. Finally, the dynamic analysis software ANSYS/LS-DYNA is used to simulate the impact behaviors of the CFT and CCFT specimens, and the simulation results are reasonable compared with the test results.
The aim was to evaluate the changes of 16S rDNA sequencing and LC-MS metabolomics in breast cancer and explore the growth inhibition of breast cancer cells by Faecalibacterium prausnitzii.
Total 49 ...significantly different flora and 26 different metabolites were screened between two groups, and the correlation was calculated. Relative abudance of Firmicutes and Bacteroidetes were decreased, while relative abundance of verrucomicrobla, proteobacteria and actinobacteria was increased in breast cancer group. Differentially expressed metabolites were mainly enriched in pathways such as linoleic acid metabolism, retrograde endocannabinoid signaling, biosynthesis of unsaturated fatty acids, choline metabolism in cancer and arachidonic acid metabolism. Lipid upregulation was found in breast cancer patients, especially phosphorocholine. The abundance of Faecalibacterium was reduced in breast cancer patients, which was negatively correlated with various phosphorylcholines. Moreover, Faecalibacterium prausnitzii, the most well-known species in Faecalibacterium genus, could inhibit the secretion of interleukin-6 (IL-6) and the phosphorylation of Janus kinases 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) in breast cancer cells. Faecalibacterium prausnitzii also suppressed the proliferation and invasion and promoted the apoptosis of breast cancer cells, while these effects disappeared after adding recombinant human IL-6.
Flora-metabolites combined with the flora-bacteria (such as Faecalibacterium combined with phosphorocholine) might a new detection method for breast cancer. Faecalibacterium may be helpful for prevention of breast cancer. Faecalibacterium prausnitzii suppresses the growth of breast cancer cells through inhibition of IL-6/STAT3 pathway.
Bladder cancer with high expression of human epidermal growth factor receptor-2 (HER2) is related to pathological malignancy and poor prognosis. The standard care for muscle-invasive urothelial ...bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph node dissection. For HER2-positive MIBC, the efficacy of cisplatin-based NAC is unsatisfactory, and adverse reactions are inevitable or even intolerable. New regimens with higher efficiency and lower toxicity need to be explored in the neoadjuvant setting for this population.
HOPE-03 is a multi-center, open-label, single-arm, phase Ib/II study aiming to evaluate the safety and efficacy of RC48-ADC (disitamab vedotin (DV)), a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab (PD-1 antibody) as a novel neoadjuvant treatment combination in patients with HER2-positive locally advanced urothelial MIBC. Fifty-one patients with cT2-4bN0-3M0-1a pathology- and imaging-diagnosed HER2 positive (immunohistochemistry status 3+ or 2+ or 1+) MIBC were recruited. Of these patients, six were enrolled in the dose-escalation phase (three patients in the RC48-ADC 1.5 mg/kg group and three patients in the 2.0 mg/kg group), and 45 patients were enrolled in the phase II study (the expected recommended phase II dose for RC48-ADC was 2.0 mg/kg). Patients without disease progression received radical cystectomy or bladder-sparing therapies as their preference after neoadjuvant treatment. The primary endpoints were clinical complete remission rate (cCR rate; T0/Ta/Tis), pathological complete remission rate (pCR rate), and safety. The secondary endpoints were overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and quality of life.
The HOPE-03 trial provides a description of the safety profile of RC-48 and tislelizumab combination in the neoadjuvant treatment of HER2-positive locally advanced urothelial MIBC, and the efficacy is explored as well in this population.
https://www.chictr.org.cn/showproj.html?proj=137111, identifier ChiCTR2200060153.
In this article, a generalized (3 + 1)-dimensional nonlinear evolution equation (NLEE), which can be obtained by a multivariate polynomial, is investigated. Based on the Hirota bilinear method, the ...N-soliton solution and bilinear Bäcklund transformation (BBT) with explicit formulas are successfully constructed. By using BBT, two traveling wave solutions and a mixed solution of the generalized (3 + 1)-dimensional NLEE are obtained. Furthermore, the lump and the interaction solutions for the equation are constructed. Finally, the dynamic properties of the lump and the interaction solutions are described graphically.
Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare but lethal subtype of RCC. Little is known about the genomic profile of FH-deficient RCC, and the therapeutic options ...for advanced disease are limited. To this end, we performed a comprehensive genomics study to characterize the genomic and epigenomic features of FH-deficient RCC.
Integrated genomic, epigenomic, and molecular analyses were performed on 25 untreated primary FH-deficient RCCs. Complete clinicopathologic and follow-up data of these patients were recorded.
We identified that FH-deficient RCC manifested low somatic mutation burden (median 0.58 mutations per megabase), but with frequent somatic copy-number alterations. The majority of FH-deficient RCCs were characterized by a CpG sites island methylator phenotype, displaying concerted hypermethylation at numerous CpG sites in genes of transcription factors, tumor suppressors, and tumor hallmark pathways. However, a few cases (20%) with low metastatic potential showed relatively low DNA methylation levels, indicating the heterogeneity of methylation pattern in FH-deficient RCC. Moreover, FH-deficient RCC is potentially highly immunogenic, characterized by increased tumor T-cell infiltration but high expression of immune checkpoint molecules in tumors. Clinical data further demonstrated that patients receiving immune checkpoint blockade-based treatment achieved improved progression-free survival over those treated with antiangiogenic monotherapy (median, 13.3 vs. 5.1 months;
= 0.03).
These results reveal the genomic features and provide new insight into potential therapeutic strategies for FH-deficient RCC.
Background The KMT2A gene, formerly named the MLL gene, is rearranged (KMT2Ar) in 70-75% of infants, 5-6% of children and 10-15% of adult patients with B cell acute lymphoblastic leukemia (B-ALL). ...The outcome after chemotherapy of pediatric cases remains poor, and only a few studies have investigated the clinical and laboratory features, treatment response and prognosis in Chinese populations. Methods A total of 48 B-ALL children with KMT2Ar were enrolled in the study, and clinical and laboratory data were collected and analyzed by age group. The relationship between prognosis and traditional risk factors and treatment response was investigated for these patients who received chemotherapy. Results The 48 enrolled patients included 28 males and 20 females; 18 (37.50%) or 30 (62.50%) patients were an age of < 12 m (infant B-ALL) or of > 12 m at onset. An initial WBC count of 300 x 10.sup.9/L was detected in 7 (14.58%) patients; testicular leukemia (TL) or central nervous system involvement was found in 5 (10.41%) or 3 (6.25%) patients, respectively. Statistical differences were not found in the age groups of sex or initial WBC count, whereas TL was more common in the infant group (P < 0.05). 11q23 was detected in 18 patients; KMT2Ar was detected in 46 (95.83%) or 45 (93.75%) patients by FISH or multiplex RT-PCR technology, respectively; RNA-seq data were obtained for 18 patients, and 3 patients with uncommon KMT2Ar were identified. KMT2A-AFF1, KMT2A-MLLT3 and KMT2A-MLLT1 were the most common transcripts. Statistical differences were not found in treatment response by age groups, including dexamethasone induction, bone marrow (BM) smear status and minimal residual disease (MRD) level at different time points (TP), treatment-related mortality (TRM), or complete remission (CR) rate (P > 0.05); MRD levels monitored by FCM or PCR were unequal at the same TP. Four patients died of treatment, and TRM was 8.33%; 40 patients achieved CR, and the CR rate for the cohort was 83.33%. Seven patients quit, 15 patients relapsed, and the 5 yr cumulative relapse rate was 59.16 + or - 9.16%; the 5 yr prospective EFS (pEFS) for patients who were included or excluded from the TRM group was 36.86 + or - 8.48% or 40.84 + or - 9.16%, respectively. Multivariate analysis for prognosis and hazard ratio was performed for 37 patients without TRM and revealed that an initial WBC count of > 300 x 10.sup.9/L and a positive level of FCM-MRD were strongly related to a poor outcome for B-ALL patients with KMT2Ar (P < 0.05). Keywords: B cell acute lymphoblastic leukemia, KMT2A rearrangement, Pediatric, Treatment response, Minimal residual disease, Prognosis
A determinant representation of the n-fold Darboux transformation for the integrable nonlocal derivative nonlinear Schödinger (DNLS) equation is presented. Using the proposed Darboux transformation, ...we construct some particular solutions from zero seed, which have not been reported so far for locally integrable systems. We also obtain explicit breathers from a nonzero seed with constant amplitude, deduce the corresponding extended Taylor expansion, and obtain several first-order rogue wave solutions. Our results reveal several interesting phenomena which differ from those emerging from the classical DNLS equation.
Abstract
TFE3
-translocation renal cell carcinoma (
TFE3
-tRCC) is a rare and heterogeneous subtype of kidney cancer with no standard treatment for advanced disease. We describe comprehensive ...molecular characteristics of 63 untreated primary
TFE3
-tRCCs based on whole-exome and RNA sequencing.
TFE3
-tRCC is highly heterogeneous, both clinicopathologically and genotypically.
ASPSCR1-TFE3
fusion and several somatic copy number alterations, including the loss of 22q, are associated with aggressive features and poor outcomes. Apart from tumors with
MED15-TFE3
fusion, most
TFE3
-tRCCs exhibit low PD-L1 expression and low T-cell infiltration. Unsupervised transcriptomic analysis reveals five molecular clusters with distinct angiogenesis, stroma, proliferation and KRAS down signatures, which show association with fusion patterns and prognosis. In line with the aggressive nature, the high angiogenesis/stroma/proliferation cluster exclusively consists of tumors with
ASPSCR1-TFE3
fusion. Here, we describe the genomic and transcriptomic features of
TFE3
-tRCC and provide insights into precision medicine for this disease.
Objective To explore the characteristics of early motor performance in toddlers with cerebral palsy by analyzing the results of Test of Infant Motor Performance (TIMP) when they were at an age of 2 ...to 4 months. Methods A cross-sectional trial was conducted on 17 children who were followed up in the Preterm High-Risk Infant Follow-Up Clinic of the Second Affiliated Hospital of Army Medical University as high-risk premature infants and diagnosed with cerebral palsy after 1 year of age from December 2018 to December 2022. The results of their TIMP assessments at an age of 2~4 months. With the data of TIMP Chinese norm samples at the same age as controls, the Z-values were calculated and the total score of TIMP, scores of the 7 postural subgroups (including totally 42 items), and scores of these 42 items were calculated and compared between the 2 groups. Results The Z-value of the total TIMP score for the cerebral palsy infants aged 2~4 months was only -0.95±1.11, which was significantly lower than that the expec
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