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BackgroundLenvatinib is an approved first-line treatment for unresectable hepatocellular carcinoma (uHCC). We evaluated the safety and efficacy of lenvatinib versus sorafenib in patients with uHCC who deteriorated to Child-Pugh class B (CP-B) on treatment.MethodsWe retrospectively evaluated patients from REFLECT who deteriorated to CP-B versus those who remained Child-Pugh class A (CP-A) within 8 weeks after randomization. Best overall response and objective response rate (ORR) per modified Response Evaluation Criteria In Solid Tumors (mRECIST) were assessed from baseline. Progression-free survival (PFS) per mRECIST and overall survival (OS) were assessed beginning at week 8.ResultsPatients with CP-B versus CP-A classification receiving lenvatinib had ORRs of 28.3 and 42.9%, respectively; patients with CP-B versus CP-A classification receiving sorafenib had ORRs of 8.5 and 12.9%, respectively. Median PFS and OS (landmark analyses beginning at week 8) in patients receiving lenvatinib were 3.7 months [95% confidence interval (CI): 1.8-7.4] and 6.8 months (95% CI: 2.6-10.3) in the CP-B subgroup versus 6.5 months (95% CI: 5.6-7.4) and 13.3 months (95% CI: 11.6-16.1) in the CP-A subgroup, respectively. Median PFS and OS in patients receiving sorafenib were 0.5 months (95% CI: 0.1-3.6) and 4.5 months (95% CI: 2.9-6.1) in the CP-B subgroup versus 3.6 months (95% CI: 2.7-3.7) and 12.0 months (95% CI: 10.2-14.0) in the CP-A subgroup, respectively. The most common treatment-emergent adverse events in the lenvatinib cohort were hypertension (both subgroups) and decreased appetite (CP-B subgroup).ConclusionResults suggest that patients with uHCC whose liver function deteriorates to CP-B after initiation of therapy may continue to receive lenvatinib.Trial registrationClinicalTrials.gov, NCT01761266, https://clinicaltrials.gov/ct2/show/NCT01761266.

PurposeIn REFLECT, lenvatinib demonstrated an effect on overall survival (OS) by confirmation of noninferiority to sorafenib in unresectable hepatocellular carcinoma. This analysis assessed correlations between serum or tissue biomarkers and efficacy outcomes from REFLECT.Experimental designSerum biomarkers (VEGF, ANG2, FGF19, FGF21, and FGF23) were measured by ELISA. Gene expression in tumor tissues was measured by the nCounter PanCancer Pathways Panel. Pharmacodynamic changes in serum biomarker levels from baseline, and associations of clinical outcomes with baseline biomarker levels, were evaluated.ResultsFour hundred and seven patients were included in the serum analysis set (lenvatinib n = 279, sorafenib n = 128); 58 patients were included in the gene-expression analysis set (lenvatinib n = 34, sorafenib n = 24). Both treatments were associated with increases in VEGF; only lenvatinib was associated with increases in FGF19 and FGF23 at all time points. Lenvatinib-treated responders had greater increases in FGF19 and FGF23 versus nonresponders at cycle 4, day 1 (FGF19: 55.2% vs. 18.3%, P = 0.014; FGF23: 48.4% vs. 16.4%, P = 0.0022, respectively). Higher baseline VEGF, ANG2, and FGF21 correlated with shorter OS in both treatment groups. OS was longer for lenvatinib than sorafenib [median, 10.9 vs. 6.8 months, respectively; HR, 0.53; 95% confidence interval (CI), 0.33-0.85; P-interaction = 0.0397] with higher baseline FGF21. In tumor tissue biomarker analysis, VEGF/FGF-enriched groups showed improved OS with lenvatinib versus the intermediate VEGF/FGF group (HR, 0.39; 95% CI, 0.16-0.91; P = 0.0253).ConclusionsHigher baseline levels of VEGF, FGF21, and ANG2 may be prognostic for shorter OS. Higher baseline FGF21 may be predictive for longer OS with lenvatinib compared with sorafenib, but this needs confirmation.

Background and purpose: Glioma is a common malignant tumor of central nervous system with poor prognosis. Postoperative concurrent chemoradiotherapy with temozolomide (TMZ) is the main treatment for glioma. The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter can predict the sensitivity of glioma patients to TMZ treatment, however its relationship with clinical pathology and how to better predict treatment and prognosis still need further research. The purpose of this study was to analyze the status of MGMT promoter methylation (MGMTmet) in gliomas and its correlation with clinical pathological features and other common molecular abnormalities, and to explore the value of combined analysis of MGMTmet and other molecular abnormalities in predicting the prognosis of glioma and the efficacy of TMZ treatment. Methods: We retrospectively collected clinical and pathological data from 205 glioma patients diagnosed by the Department of Pathology, Fudan University Shanghai Cancer Center from July 2019 to September 2022. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect MGMTmet status. Sanger sequencing was used to detect the mutation of isocitrate dehydrogenase 1 and 2 (IDH1/2) and telomerase reverse transcriptase (TERT) genes. Fluorescence in situ hybridization (FISH) was used to detect the deletion of the short arm of chromosome 1 and the long arm of chromosome 19 (1p19q). Results: Among 205 patients, the incidence of MGMTmet was higher in female patients than in male patients. Compared to glioblastoma (47.3%), astrocytoma (74.1%) and oligodendroglioma (100.0%) were more prone to methylation of the MGMT gene promoter (P

Simultaneous localization of light to extreme spatial and spectral scales is of high importance for testing fundamental physics and various applications. However, there is a longstanding trade-off between localizing a light field in space and in frequency. Here we discover a new class of twisted lattice nanocavities based on mode locking in momentum space. The twisted lattice nanocavity hosts a strongly localized light field in a 0.048 λ3 mode volume with a quality factor exceeding 2.9 × 1011 (∼250 μs photon lifetime), which presents a record high figure of merit of light localization among all reported optical cavities. Based on the discovery, we have demonstrated silicon-based twisted lattice nanocavities with quality factor over 1 million. Our result provides a powerful platform to study light-matter interaction in extreme conditions for tests of fundamental physics and applications in nanolasing, ultrasensing, nonlinear optics, optomechanics and quantum-optical devices.

Ten years ago, three teams experimentally demonstrated the first spasers, or plasmonic nanolasers, after the spaser concept was first proposed theoretically in 2003. An overview of the significant progress achieved over the last 10 years is presented here, together with the original context of and motivations for this research. After a general introduction, we first summarize the fundamental properties of spasers and discuss the major motivations that led to the first demonstrations of spasers and nanolasers. This is followed by an overview of crucial technological progress, including lasing threshold reduction, dynamic modulation, room-temperature operation, electrical injection, the control and improvement of spasers, the array operation of spasers, and selected applications of single-particle spasers. Research prospects are presented in relation to several directions of development, including further miniaturization, the relationship with Bose-Einstein condensation, novel spaser-based interconnects, and other features of spasers and plasmonic lasers that have yet to be realized or challenges that are still to be overcome.

Here the authors develop topological polarization singular lasers that feature paired radiation channels carrying distinct topological properties which leads to single mode lasing with high external quantum efficiency.

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a rare genetic prion disease caused by a mutation in the prion protein (PRNP) gene. It is typically characterized by progressive cerebellar ataxia and slowly progressive dementia. We present a case study of the GSS from China in which a 45-year-old male with a progressive gait and balance disorder developed cerebellar ataxia onset but was misdiagnosed as spinocerebellar ataxia (SCA) for 2 years. The patient's clinical, electrophysiological, and radiological data were retrospectively analyzed. Examination revealed ataxia, dysarthria, muscle weakness, areflexia in lower limbs, including a pyramidal sign, whereas cognitive decline was insignificant. His late mother had a similar unsteady gait. An electroencephalogram (EEG) showed normal findings, and 14-3-3 protein was negative. A brain MRI was performed for global brain atrophy and ventricular enlargement. Positron emission tomography–computed tomography (PET–CT) (18F-fluoro-2-deoxy-d-glucose, FDG) images showed mild to moderate decreased glucose metabolism in the left superior parietal lobe and left middle temporal lobe. According to genetic testing, his younger brother also had the P102L variant in the PRNP gene. This single case adds to the clinical and genetic phenotypes of GSS.

ObjectivesInflammatory bowel disease (IBD) is a chronic lifelong inflammatory disease. Probiotics such as Bifidobacterium longum are considered to be beneficial to the recovery of intestinal inflammation by interaction with gut microbiota. Our goals were to define the effect of the exclusive use of BAA2573 on dextran sulfate sodium (DSS)-induced colitis, including improvement of symptoms, alleviation of histopathological damage, and modulation of gut microbiota.MethodsIn the present study, we pretreated C57BL/6J mice with Bifidobacterium longum BAA2573, one of the main components in an over-the-counter (OTC) probiotic mixture BIFOTO capsule, before modeling with DSS. 16S rDNA sequencing and liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based non-targeted metabolomic profiling were performed with the collected feces.ResultsWe found that pretreatment of Bifidobacterium longum BAA2573 given by gavage significantly improved symptoms and histopathological damage in DSS-induced colitis mice. After the BAA2573 intervention, 57 genera and 39 metabolites were significantly altered. Pathway enrichment analysis demonstrated that starch and sucrose metabolism, vitamin B6 metabolism, and sphingolipid metabolism may contribute to ameliorating colitis. Moreover, we revealed that the gut microbiome and metabolites were interrelated in the BAA2573 intervention group, while Alistipes was the core genus.ConclusionOur study demonstrates the impact of BAA2573 on the gut microbiota and reveals a possible novel adjuvant therapy for IBD patients.