Lenalidomide or bortezomib as maintenance treatment remedy the inferior impact of high-risk cytogenetic abnormalities in non-transplant patients with newly diagnosed multiple myeloma: a real-world multi-centered study in China

Maintenance treatment is a pivotal part in the whole process management of multiple myeloma (MM), which further deepens response and improves survival. However, evidence of maintenance in non-transplant MM patients is inadequate in real-world practice. Here, we retrospectively analyzed the efficacy and survival of 375 non-transplant MM patients from 11 centers between 2010 and 2021 in north China. After a median of seven cycles of front-line regimens, there were 141, 79, and 155 patients receiving lenalidomide maintenance (L-MT), bortezomib maintenance (B-MT), or thalidomide maintenance (T-MT), respectively. Patients on L-MT and B-MT had significantly greater proportions of high-risk cytogenetic abnormalities (HRCAs) detected by fluorescence in situ hybridization (FISH), which was defined as 1q21 gain, 17p deletion, adverse immunoglobulin heavy chain (IgH) translocations. Although the progression-free survival (PFS) and overall survival (OS) were comparable among the three groups, L-MT and B-MT remedied the negative impact of HRCAs on survival (PFS of patients with HRCAs vs. patients without HRCAs: L-MT, 26.9 vs. 39.2 months, p=0.19; B-MT, 20.0 vs. 29.7 months, p=0.36; OS not reached in all groups). Patients with HRCAs in the T-MT group presented inferior clinical outcomes compared to standard-risk patients (PFS, 12.1 vs. 22.8 months, p=0.02, HR=1.8, 95% CI 1.0–3.4; OS, 54.9 months vs. NR, p<0.001, HR=3.2, 95% CI 1.5–7.0). Achieving complete response (CR) after induction therapy led to superior PFS compared to other degrees of response, regardless of maintenance medication. Furthermore, maintenance duration over 24 months correlated with favorable survival. Due to the large gap of transplant eligibility in China, optimizing maintenance therapy is important for non-transplant MM patients. In this real-world multi-centered study, our findings suggest that clinicians prefer to prescribe lenalidomide or bortezomib as maintenance therapy in high-risk settings, which are superior to thalidomide in non-transplant MM patients. Achievement of CR and maintenance duration over 2 years are positive factors that influence survival

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Enhanced Proton Conductivity of Sulfonated Hybrid Poly(arylene ether ketone) Membranes by Incorporating an Amino–Sulfo Bifunctionalized Metal–Organic Framework for Direct Methanol Fuel Cells

Novel side-chain-type sulfonated poly­(arylene ether ketone) (SNF-PAEK) containing naphthalene and fluorine moieties on the main chain was prepared in this work, and a new amino–sulfo-bifunctionalized metal–organic framework (MNS, short for MIL-101-NH₂-SO₃H) was synthesized via a hydrothermal technology and postmodification. Then, MNS was incorporated into a SNF-PAEK matrix as an inorganic nanofiller to prepare a series of organic–inorganic hybrid membranes (MNS@SNF-PAEK-XX). The mechanical property, methanol resistance, electrochemistry, and other properties of MNS@SNF-PAEK-XX hybrid membranes were characterized in detail. We found that the mechanical strength and methanol resistances of these hybrid membranes were improved by the formation of an ionic cross-linking structure between −NH₂ of MNS and −SO₃H on the side chain of SNF-PAEK. Particularly, the proton conductivity of these hybrid membranes increased obviously after the addition of MNS. MNS@SNF-PAEK-3% exhibited the proton conductivity of 0.192 S·cm^–1, which was much higher than those of the pristine membrane (0.145 S·cm^–1) and recast Nafion (0.134 S·cm^–1) at 80 °C. This result indicated that bifunctionalized MNS rearranged the microstructure of hybrid membranes, which could accelerate the transfer of protons. The hybrid membrane (MNS@SNF-PAEK-3%) showed a better direct methanol fuel cell performance with a higher peak power density of 125.7 mW/cm² at 80 °C and a higher open-circuit voltage (0.839 V) than the pristine membrane

Higher Serum Neuropeptide Y Levels Are Associated with Metabolically Unhealthy Obesity in Obese Chinese Adults: A Cross-Sectional Study

Objective. Neuropeptide Y (NPY), an orexigenic peptide known to cause hyperphagia, has been involved in the occurrence and development of obesity. However, differences in the distribution of serum NPY levels in obese phenotypes (including metabolically unhealthy obesity (MUO) phenotype and metabolically healthy obesity (MHO) phenotype) and the association of NPY with MUO phenotype have not been unequivocally established. We therefore determined associations of serum NPY levels with MUO phenotype in obese Chinese adults. Methods. A cross-sectional study was conducted from 400 obese adults in Hunan province, who underwent a health examination in the Second Xiangya Hospital, and 164 participants were finally enrolled in the study and divided into MHO and MUO groups. Serum NPY levels were examined; univariate and multivariate analyses as well as smooth curve fitting analyses were conducted to measure the association of NPY serum levels with the MUO phenotype. Results. Serum NPY levels were significantly elevated in the MUO group compared with the MHO group ((667.69±292.90) pg/mL vs. (478.89±145.53) pg/mL, p<0.001). A threshold and nonlinear association between serum NPY levels and MUO was found (p=0.001). When serum NPY levels exceeded the turning point (471.5 pg/mL), each 10 pg/mL increment in the NPY serum level was significantly associated with an 18% increased odds ratio of MUO phenotype (OR: 1.18, 95% CI: 1.07–1.29, p=0.0007) after adjusted for confounders. Conclusions. Higher NPY serum levels were positively correlated with MUO phenotype in obese Chinese adults

Single-cell transcriptome analysis reveals T population heterogeneity and functions in tumor microenvironment of colorectal cancer metastases

Cell mediated immune escape, a microenvironment factor, induces tumorigenesis and metastasis. The purpose of this study was to display the characteristics of T cell populations in immune microenvironments for colorectal cancer (CRC) metastasis. Unsupervised cluster analysis was conducted to identify functionally distinct T cell clusters from 3,003 cells in peripheral blood and 4,656 cells in tissues. Subsequently, a total of 8 and 4 distinct T cell population clusters were identified from tumor tissue and peripheral blood, respectively. High levels of CD8+TEX, CD4+TRM, TH1-like T cells, CD8+TEM, tumor-Treg from tissues, and CD4+TN from peripheral blood are essential components of immune microenvironment for the prediction of CRC metastasis. Moreover, exhausted T cells are characterized by higher expression of multiple inhibitory receptors, including PDCD1 and LAG3. Some genes such as PFKFB3, GNLY, circDCUN1D4, TXNIP and NR4A2 in T cells of cluster were statistically different between CRC metastasis and non-metastasis. The ligand-receptor interactions identified between different cluster cells and metastases-related DEGs identified from each cluster revealed that the communications of cells, alterations of functions, and numbers of T subsets may contribute to the metastasis of CRC. The mutation frequency of KiAA1551, ATP8B4 and LNPEP in T cells from tissues and SOR1 from peripheral blood were higher in metastatic CRC than that in non-metastatic CRC. In conclusion, the discovery of differential genes in T cells may provide potential targets for immunotherapy of CRC metastasis and relevant insights into the clinical prediction and prognosis of CRC metastasis

Prevalence of hepatitis C virus infection among key populations in China: A systematic review

Background and aim: Chronic hepatitis C is a major global health challenge. China has the world’s largest burden of hepatitis C and related liver disease, with several groups having an increased risk of acquiring hepatitis C virus (HCV) infection. We undertook a systematic review in Chinese and English literature to determine the seroprevalence of anti-HCV among men who have sex with men (MSM), sex workers, people who use drugs (PWUD) and migrant workers in China. Methods: We searched three Chinese databases (CNKI, Wanfang and Chongqing VIP Information) and four English databases (Pubmed, EMBASE, Global Health and CINAHL) for studies published between 2010 and 2015. Included were 89 studies for MSM, 112 for sex workers, 11 for migrant workers, 94 for people who inject drugs (PWID) and 67 for non-injectors. Random-effect models pooled estimates of anti-HCV seroprevalence in each population and a meta-regression model examined the relationship between anti-HCV seroprevalence and injecting drug use. Results: The overall pooled seroprevalence of anti-HCV among MSM was 0.67% (CI 95 0.51–0.86); for sex workers 0.65% (CI 95 0.53–0.77); for migrant workers 0.48 (CI 95 0.20–0.85); for IDUs 72.41% (CI 95 68.71–75.97); among non-injectors 25.07% (CI 95 21.51%–28.80%). Our meta-regression model predicted that the seroprevalence of anti-HCV among PWID increased by 8.6% for each 10% increase seroprevalence of reporting ever having injected drugs. Conclusions: Overall, seroprevalence of HCV infection is high among PWUD, especially those who inject. Lower HCV seroprevalence (<1%) was found among MSM, sex workers and migrant workers. Our estimates for IDU seroprevalence are higher than that from the national surveillance system, though estimates for other at-risk populations are similar. Keywords: Hepatitis, China, People who inject drugs, Hepatitis C virus, Men who have sex with men, Sex workers, Seroprevalenc