Postoperative ctDNA detection predicts relapse but has limited effects in guiding adjuvant therapy in resectable stage I NSCLC

BackgroundTo date, identifying resectable stage I non-small cell lung cancer (NSCLC) patients likely to benefit from adjuvant therapy (ADT) remains a major challenge. Previous studies suggest that circulating tumor DNA (ctDNA) is emerging as a promising biomarker for NSCLC. However, the effectiveness of ctDNA detection in guiding ADT for resectable stage I NSCLC patients remains elusive. This study aimed to elucidate the role of ctDNA detection in estimating prognosis and guiding ADT for resectable stage I NSCLC patients.MethodsIndividual patient data and ctDNA results data were collected from 270 patients across four independent cohorts. The detection of ctDNA was conducted at 3 days to 1 month after surgery. The endpoint for this study was relapse-free survival (RFS) and overall survival (OS).ResultsOf the 270 resectable stage I NSCLC patients, 9 patients with ctDNA-positive and 261 patients with ctDNA-negative. We found that the risk of recurrence was significantly lower in the ctDNA-negative group compared to the ctDNA-positive group(HR=0.11, p<0.0001). However, there is no difference in the risk of death between the two groups (p =0.39). In the ctDNA-positive group, there were no significant differences in RFS between patients who received ADT and patients who did not receive ADT (p =0.58). In the ctDNA-negative group, those who received ADT had a worse RFS in comparison with those who did not receive ADT (HR=2.36, p =0.029). No difference in OS was seen between patients who received ADT and patients who did not receive ADT in both the ctDNA-positive group and the ctDNA-negative group (All p values>0.05). Furthermore, there was no difference in RFS and OS between patients who received chemotherapy-based or tyrosine kinase inhibitor-based ADT and patients who did not receive ADT in both the ctDNA-positive group and the ctDNA-negative group (All p values>0.05).ConclusionsPostoperative ctDNA detection can be a prognostic marker to predict recurrence but has limited effects in guiding ADT for resectable stage I NSCLC. Future prospective investigations are needed to verify these results

Endoscopic endonasal surgery for non-invasive pituitary neuroendocrinology tumors with incomplete pseudocapsule

BackgroundPituitary neuroendocrinology tumors (PitNETs) with pseudocapsule can be effectively removed by the pseudocapsule-based extracapsular resection technique. In the areas without pseudocapsule, the tumor cells can spread into the adjacent tissues at the cellular level, which brings a great challenge to achieving total tumor resection.MethodsOur surgical strategy for PitNETs with an incomplete pseudocapsule is to combine the pseudocapsule-based extracapsular resection technique with the intensive excision technique for the removal of the tumor. Specifically, the pseudocapsule-based extracapsular resection technique is applied in the areas with pseudocapsule, while in the areas without pseudocapsule, the intensive excision technique bounded by adjacent normal structures is adopted. Moreover, a pathological examination was performed to determine the situations of pseudocapsule and tumor cell remnant.ResultsAll growth hormone-secreting PitNETs achieved biochemical remission after surgery. There was no deterioration of pituitary functions postoperatively, and the preoperative hypopituitarism had improved in all patients postoperatively. In total, two cases suffered a transient diabetes insipidus, and intraoperative cerebrospinal fluid leakage was observed in two cases but no postoperative cerebrospinal fluid leakage in all cases. There was no recurrence during the follow-up. The fragmental pseudocapsule and small tumor remnants were found in the majority of suspicious tissues by histological staining.ConclusionThe effectiveness and safety of the surgical strategy were preliminarily explored for removing PitNETs without incomplete pseudocapsules. In overview, the pseudocapsule-based extracapsular resection technique is applied in areas with pseudocapsule, while the intensive excision bounded by adjacent normal structures is adopted in other areas

The LAMOST Complete Spectroscopic Survey of Pointing Area (LaCoSSPAr) in the Southern Galactic Cap I. The Spectroscopic Redshift Catalog

We present a spectroscopic redshift catalog from the LAMOST Complete Spectroscopic Survey of Pointing Area (LaCoSSPAr) in the Southern Galactic Cap (SGC), which is designed to observe all sources (Galactic and extra-galactic) by using repeating observations with a limiting magnitude of $r=18.1~mag$ in two $20~deg^2$ fields. The project is mainly focusing on the completeness of LAMOST ExtraGAlactic Surveys (LEGAS) in the SGC, the deficiencies of source selection methods and the basic performance parameters of LAMOST telescope. In both fields, more than 95% of galaxies have been observed. A post-processing has been applied to LAMOST 1D spectrum to remove the majority of remaining sky background residuals. More than 10,000 spectra have been visually inspected to measure the redshift by using combinations of different emission/absorption features with uncertainty of $\sigma_{z}/(1+z)<0.001$. In total, there are 1528 redshifts (623 absorption and 905 emission line galaxies) in Field A and 1570 redshifts (569 absorption and 1001 emission line galaxies) in Field B have been measured. The results show that it is possible to derive redshift from low SNR galaxies with our post-processing and visual inspection. Our analysis also indicates that up to 1/4 of the input targets for a typical extra-galactic spectroscopic survey might be unreliable. The multi-wavelength data analysis shows that the majority of mid-infrared-detected absorption (91.3%) and emission line galaxies (93.3%) can be well separated by an empirical criterion of $W2-W3=2.4$. Meanwhile, a fainter sequence paralleled to the main population of galaxies has been witnessed both in $M_r$/$W2-W3$ and $M_*$/$W2-W3$ diagrams, which could be the population of luminous dwarf galaxies but contaminated by the edge-on/highly inclined galaxies ($\sim30\%$).Comment: 19 pages, 14 figures, 2 MRT, accepted by ApJ

Chemistry of new particle formation and growth events during wintertime in suburban area of Beijing : Insights from highly polluted atmosphere

The high frequency of new particle formation (NPF) events observed under polluted atmospheric conditions is still poorly understood. To improve our understanding of NPF and its effects, the particle number size distribution (3-1000 nm) and submicron particle chemical composition were measured from 4 November 2017 to 17 January 2018 in suburban Beijing. During this intense campaign, 22 NPF events were identified with a frequency of 29%, including 11 cases that occurred under "clean" conditions (C-NPF) and 11 cases that occurred under "polluted" conditions (P-NPF). The observed formation rate (J(3)) and condensation sink were 4.6-148.9 cm(-3).s(-1) and 0.01-0.07 s(-1), and the majority of NPF events occurred when the condensation sink (CS) values below 0.03 s(-1), indicating that condensation vapor likely constitutes the critical limiting factor for NPF events. The correlations between log J(3) and [H2SO4] that close to previous CLOUD experimental results in the majority of NPF events (68%) suggest the high nucleation rates (up to 100 cm(-3).s(-1)) would be attributed by the amines that enhancing sulfuric acid nucleation, while the reminding cases (32%) possibly attributed to the H2SO4-NH3 clustering mechanism, which is supported by the theoretical expectations for H2SO4 nucleation with NH3 simulated by the MALTE_BOX model. The observed growth rate varied from 4.9 to 37.0 mm.h(-1), with the dominant contribution (>60%) from sulfuric acid during the early phases of growth (similar to 4 nm), which was also sufficient to explain the observed Q(GR) for 50 nm)Peer reviewe

Seoul Virus and Hantavirus Disease, Shenyang, People’s Republic of China

This outbreak was caused by the virus circulating in local wild rats through infection of laboratory rats

Homoharringtonine exhibits potent anti-tumor effect and modulates DNA epigenome in acute myeloid leukemia by targeting SP1/TET1/5hmC

Homoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), homoharringtonine potently inhibits cell growth/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression in vivo, and substantially prolongs survival of mice bearing murine or human AML. Strikingly, homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1/TET1 axis, and TET1 depletion mimics homoharringtonine’s therapeutic effects in AML. Our further 5hmC-seq and RNA-seq analyses, followed by a series of validation and functional studies, suggest that FLT3 is a critical down-stream target of homoharringtonine/SP1/TET1/5hmC signaling, and suppression of FLT3 and its downstream targets (e.g. MYC) contributes to the high sensitivity of FLT3-mutated AML cells to homoharringtonine. Collectively, our studies uncover a previously unappreciated DNA epigenome-related mechanism underlying the potent antileukemic effect of homoharringtonine, which involves suppression of the SP1/TET1/5hmC/FLT3/MYC signaling pathways in AML. Our work also highlights the particular promise of clinical application of homoharringtonine to treat human AML with FLT3 mutations, which accounts for more than 30% of total cases of AML

Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma.

Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) has a dismal prognosis. A better understanding of tumor evolution holds the key to developing more effective treatment. Here we study GBM\u27s natural evolutionary trajectory by using rare multifocal samples. We sequenced 61,062 single cells from eight multifocal IDH wild-type primary GBMs and defined a natural evolution signature (NES) of the tumor. We show that the NES significantly associates with the activation of transcription factors that regulate brain development, including MYBL2 and FOSL2. Hypoxia is involved in inducing NES transition potentially via activation of the HIF1A-FOSL2 axis. High-NES tumor cells could recruit and polarize bone marrow-derived macrophages through activation of the FOSL2-ANXA1-FPR1/3 axis. These polarized macrophages can efficiently suppress T-cell activity and accelerate NES transition in tumor cells. Moreover, the polarized macrophages could upregulate CCL2 to induce tumor cell migration. SIGNIFICANCE: GBM progression could be induced by hypoxia via the HIF1A-FOSL2 axis. Tumor-derived ANXA1 is associated with recruitment and polarization of bone marrow-derived macrophages to suppress the immunoenvironment. The polarized macrophages promote tumor cell NES transition and migration. This article is highlighted in the In This Issue feature, p. 2711

Aggregation-Induced Emission (AIE), Life and Health

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health