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The indications for percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP) are painful vertebral compression fractures. Our study is to assess the risk–benefit ratio of PKP/PVP surgery in the patients with newly diagnosed multiple myeloma (NDMM) without receiving antimyeloma therapy. The clinical data of 426 consecutive patients with NDMM admitted to our center from February 2012 to April 2022 were retrospectively analyzed. The baseline data, postoperative pain relief, the proportion of recurrent vertebral fractures, and survival time were compared between the PKP/PVP surgical group and the nonsurgical group in the NDMM patients. Of the 426 patients with NDMM, 206 patients had vertebral fractures (206/426, 48.4%). Of these, 32 (32/206, 15.5%) underwent PKP/PVP surgery for misdiagnosis of simple osteoporosis prior to diagnosis of MM (surgical group), and the other 174 (174/206, 84.5%) did not undergo surgical treatment prior to definitive diagnosis of MM (non-surgical group). The median age of patients in the surgical and nonsurgical groups was 66 and 62 years, respectively (p = 0.01). The proportion of patients with advanced ISS and RISS stages was higher in the surgical group (ISS stage II + III 96.9% vs. 71.8%, p = 0.03; RISS stage III 96.9% vs. 71%, p = 0.01). Postoperatively, 10 patients (31.3%) never experienced pain relief and 20 patients (62.5%) experienced short-term pain relief with a median duration of relief of 2.6 months (0.2–24.1 months). Postoperative fractures of vertebrae other than the surgical site occurred in 24 patients (75%) in the surgical group, with a median time of 4.4 months postoperatively (0.4–86.8 months). Vertebral fractures other than the fracture site at the first visit occurred in 5 patients (2.9%) in the nonoperative group at the time of diagnosis of MM, with a median time of 11.9 months after the first visit (3.5–12.6 months). The incidence of secondary fractures was significantly higher in the surgical group than in the nonsurgical group (75% vs. 2.9%, p = 0.001). The time interval between the first visit and definitive diagnosis of MM was longer in the surgical group than in the nonsurgical group (6.1 months vs. 1.6 months, p = 0.01). At a median follow-up of 32 months (0.3–123 months), median overall survival (OS) was significantly shorter in the surgical group than in the nonsurgical group (48.2 months vs. 66 months, p = 0.04). Application of PKP/PVP surgery for pain relief in NDMM patients without antimyeloma therapy has a limited effect and a high risk of new vertebral fractures after surgery. Therefore, patients with NDMM may need to have their disease controlled with antimyeloma therapy prior to any consideration for PKP/PVP surgery.

The structural characteristics and immunoregulatory activities of neutral heteropolysaccharide (AVRP-N) separated from the roots of Apocynum venetum L. were extensively investigated. The results showed that the weight average molecular mass (Mw) of AVRP-N was 6.430 × 10

The use of proteasome inhibitors (PIs), new immune modulators (IMiDs), and other new drugs, as well as high-dose chemotherapy combined with autologous stem cell transplantation has considerably improved the survival of young patients with multiple myeloma (MM). However, the improvement in survival among elderly patients remains insufficient. Optimal treatment recommendation models for elderly patients with MM have not been developed especially there are quite few study in the real world.We retrospectively analyzed the treatment patterns and outcomes of 328 Chinese patients (≥65 years) with MM in a real-world setting. Patients were divided into three groups according to induction regimens.The median age of the cohort was 70 (65-86) years. The patients were divided into group 1 (PIs based regimens, n = 218), group 2 (IMiDs based regimens, n = 48) and group 3 (PIs + IMiDs, n = 62). Induction regimens in group 3 produced higher overall response rate than group 1 and 2 (85.42% vs. 71.08% vs. 66.67%, p = 0.016). The median follow-up of the cohort was 30 (interquartile range [IQR] 18-36) months. For the entire cohort median progression-free survival (PFS) was 26 (IQR 12.00-42.89) months and overall survival (OS) was 60 (IQR 40.00-67.20) months. The PFS were not significantly different among the three groups (28 months vs. 18 months vs. 26 months, p = 0.182). So were the OS (60 months vs. 59 months vs. not reached, p = 0.067). Multivariate analysis revealed that age70 year, frailty status (Geriatric vulnerability score), induction efficacy partial remission, and no maintenance treatment were independent poor prognostic factors for OS.Front-line induction regimens combining PIs and IMiDs developed more deep response than single PI or IMiD based regimens. Maintenance treatment can further improve the clinical outcome in elderly MM patients in real-world setting.

Obesity, dyslipidemia and gut dysbiosis are all linked to cardiovascular diseases. A Ganoderma meroterpene derivative (GMD) has been shown to alleviate obesity and hyperlipidemia through modulating the gut microbiota in obese mice. Here we show that GMD protects against obesity-associated atherosclerosis by increasing the abundance of Parabacteroides merdae in the gut and enhancing branched-chain amino acid (BCAA) catabolism. Administration of live P. merdae to high-fat-diet-fed ApoE-null male mice reduces atherosclerotic lesions and enhances intestinal BCAA degradation. The degradation of BCAAs is mediated by the porA gene expressed in P. merdae. Deletion of porA from P. merdae blunts its capacity to degrade BCAAs and leads to inefficacy in fighting against atherosclerosis. We further show that P. merdae inhibits the mTORC1 pathway in atherosclerotic plaques. In support of our preclinical findings, an in silico analysis of human gut metagenomic studies indicates that P. merdae and porA genes are depleted in the gut microbiomes of individuals with atherosclerosis. Our results provide mechanistic insights into the therapeutic potential of GMD through P. merdae in treating obesity-associated cardiovascular diseases.

Given the significant advancement in Bayesian inference of nuclear Equation of State (EOS) from gravitational wave and X-ray observations of neutron stars (NSs), especially since GW170817, is there a data-driven and robust empirical formula for the radius $R_{1.4}$ of canonical NSs in terms of the characteristic EOS parameters (features)? What is the single most important but currently poorly known EOS parameter for determining the $R_{1.4}$? We study these questions by extending the traditional Bayesian analysis which normally ends at presenting the marginalized posterior probability distribution functions (PDFs) of individual EOS parameters and their correlations (or sometimes only the Pearson correlation coefficients which are only reliably useful when the variables are linearly correlated while they are actually often not). Using three regression model-building methodologies: bidirectional step-wise feature selection, LASSO regression, and neural network regression on a large set of posterior EOSs and the corresponding $R_{1.4}$ values inferred from earlier comprehensive Bayesian analyses of NS observational data, we systematically and rigorously develop the most probable $R_{1.4}$ formulas with varying statistical accuracy and technical complexity. The most important EOS parameters for determining $R_{1.4}$ are found consistently in each of the feature/model selection processes to be (in order of decreasing importance): curvature $K_{sym}$, slope $L$, skewness $J_{sym}$ of nuclear symmetry energy, skewness $J_{0}$, incompressibility $K_{0}$ of symmetric nuclear matter, and the magnitude $E_{sym} (\rho_0)$ of symmetry energy at the saturation density $\rho_0$ of nuclear matter., Comment: 14 pages including 9 figures

Within an isospin- and momentum-dependent Boltzmann-Uehling-Uhlenbeck (IBUU) transport model, we investigate the hard photons emission from neutron-proton bremsstrahlung in reaction system of $^{208}Pb+^{208}Pb$ around Fermi energy. Effects of neutron skins in coordinate ($r$) space and proton skins in momentum ($k$) space on the time evolution, the angular distribution, and the transverse momentum spectra of hard photons with different energies are studied. It is shown that the emission of direct hard photons is sensitive to the neutron skin, which has larger effects for more energetic hard photons. Meanwhile, we find that the proton skins have an important influence on the emission of direct hard photons, and its effect is actually even larger than that of neutron skins. It needs to take the effect of proton skins into account when we determine the size of neutron skins by comparing transport mode predictions of hard photons with the corresponding experiment measurements.

The incidence of multidrug-resistant Gram-negative bacteria (MDR-GNB) pneumonia has increased in the last decade. If antibiotics are given only through intravenous, the antibiotic concentrations in lung tissue will be insufficient. Recently, nebulized antibiotics have shown effectiveness as an adjunctive therapy with intravenous antibiotics for resistant strains. Therefore, the goal of this study was to assess the efficacy and safety of adjunctive nebulized colistin sulfate in combination with intravenous antibiotics in patients with MDR-GNB pneumonia.A total of 203 patients who were infected with MDR-GNB pneumonia were selected. Based on whether patients received nebulized colistin sulfate, patients were divided into 2 groups: the NCIA group (nebulized colistin sulfate in combination with intravenous antibiotics) and the IA group (intravenous antibiotics without nebulized colistin sulfate). After propensity score matching (PSM) analysis, we compared the efficacy in terms of favorable clinical outcomes, the bacteria detection rate, days of hospital stay, days of intensive care unit (ICU) stay, days of mechanical ventilation (MV), antipyretic time, days of antibiotic therapy, and 28-day all-cause mortality. Safety was also compared between groups.A total of 116 patients met the criteria for evaluation, with 46 patients in the NCIA group and 70 patients in the IA group. After PSM, 31 patients were selected from each group. There were significant differences in favorable clinical outcomes on days 7 (67.7% vs. 32.3%, P=0.005) and 14 (71% vs. 41.9%, P=0.045) and the bacteria detection rate on days 7, 14, and the last day. There were also significant differences in days of hospital stay (17 vs. 23 days, P=0.01), antipyretic time (0.5 vs. 7.5 days, P=0.037), and days of antibiotic therapy (14 vs. 23 days, P=0.002). However, there were no significant differences in days of ICU stay, days of MV, and 28-day all-cause mortality. For nephrotoxicity, the NCIA group did not increase the risk of acute kidney injury (16.1% vs. 9.7%, P=0.707), only one patient (3.2%) in the NCIA group developed airway hyperresponsiveness (P=1.000).For MDR-GNB pneumonia, nebulized colistin sulfate as an adjuvant supportive treatment for intravenous antibiotics maybe can improve clinical efficacy and has high safety.

Retinitis pigmentosa (RP) is a group of genetic disorders resulting in inherited blindness due to the degeneration of rod and cone photoreceptors. The various mechanisms underlying rod degeneration primarily rely on genetic mutations, leading to night blindness initially. Cones gradually degenerate after rods are almost eliminated, resulting in varying degrees of visual disability and blindness. The mechanism of cone degeneration remains unclear. An understanding of the mechanisms underlying cone degeneration in RP, a highly heterogeneous disease, is essential to develop novel treatments of RP. Herein, we review recent advancements in the five hypotheses of cone degeneration, including oxidative stress, trophic factors, metabolic stress, light damage, and inflammation activation. We also discuss the connection among these theories to provide a better understanding of secondary cone degeneration in RP. Five current mechanisms of cone degenerations in RP Interactions among different pathways are involved in RP.

Cell Competition is a process by which neighboring cells compare their fitness. As a result, viable but suboptimal cells are selectively eliminated in the presence of fitter cells. In the early mammalian embryo, epiblast pluripotent cells undergo extensive Cell Competition, which prevents suboptimal cells from contributing to the newly forming organism. While competitive ability is regulated by MYC in the epiblast, the mechanisms that contribute to competitive fitness in this context are largely unknown. Here, we report that P53 and its pro-apoptotic targets PUMA and NOXA regulate apoptosis susceptibility and competitive fitness in pluripotent cells. PUMA is widely expressed specifically in pluripotent cellsin vitroandin vivo. We show that the p53-PUMA/NOXA pathway regulates mitochondrial membrane potential and oxidative status. We found that P53 regulates MYC levels in pluripotent cells, which connects these two Cell competition pathways, however, MYC and PUMA/NOXA levels are independently regulated by P53. We propose a model that integrates a bifurcated P53 pathway regulating both MYC and PUMA/NOXA levels and determines competitive fitness through regulation of mitochondrial activity.

AIM: To describe a novel suture approach for transscleral fixation of C-loop intraocular lenses (IOL) and to compare the surgical outcomes with the four-haptics posterior chamber (PC)-IOL technique. METHODS: We retrospectively analyzed 16 eyes of 16 patients who underwent transscleral fixation of C-loop PC-IOLs using a flapless one-knot suture technique, which were followed up for longer than 17mo. In this technique, the capsulorless IOL was suspended using a single suture for transscleral fixation of four feet. Then we compared its surgical outcomes and complications with the four-haptics PC-IOLs using the Student's t test and Chi-square test. RESULTS: Sixteen patients of 16 eyes with a mean age of 58.3±10.1y (42-76y) who received transscleral C-loop IOL implantation due to trauma, vitrectomy, or cataract surgery with inadequate capsule support showed improved visual acuity. The difference was not significant between two IOLs except the surgery time (P>0.05). The mean operation times of C-loop IOL surgery was 24.1±1.83min and 31.3±4.47min of the four-haptics PC-IOL method (P0.05). We did not detect any optic capture, IOL decentration or dislocation, suture exposed, or cystoid macular edema in patients underwent C-loop IOLs surgery. CONCLUSION: The novel flapless one-knot suture technique for transscleral fixation of C-loop IOL is a simple, reliable, and stable technique.

Thermal errors are one key impact factor on the processing accuracy of numerical control machine. This study targeted at a certain vertical processing center presents a new algorithm for predictive modeling of thermal errors in numerical control machine. This algorithm is founded on back-propagation neural networks (BPNNs) and adopts beetle antennae search (BAS) to find the best weights and thresholds of BPNNs. It avoids the local minimization due to local extremums faced by traditional BPNNs. The intermingling rate and arithmetic computation efficiency of neural network algorithms are further improved. Then, a BAS-BP thermal error prediction model is built with the machine temperature changes and thermal errors as the input data. Compared with conventional BPNNs, the BPNN after particle swarm optimization suggests the convergence rate of BAS-BP is improved by 85%, the leftover mistakes between the genuine information and the anticipated information are under 1 um, and the overall prediction precision is above 90%. Thus, the new model has high precision, high anti-disturbance ability and strong robustness.

Background Metschnikowia bicuspidata is a pathogenic yesst that can cause disease in many different economic aquatic animal species. In recent years, there was a new disease outbreak in ridgetail white prawn (Exopalaemon carinicauda) in coastal areas of Jiangsu Province China that was referred to as zombie disease by local farmers. The pathogen was first isolated and identified as M. bicuspidata. Although the pathogenicity and pathogenesis of this pathogen in other animals have been reported in some previous studies, research on its molecular mechanisms is still very limited. Therefore, a genome-wide study is necessary to better understand the physiological and pathogenic mechanisms of M. bicuspidata. Result In this study, we obtained a pathogenic strain, MQ2101, of M. bicuspidata from diseased E. carinicauda and sequenced its whole genome. The size of the whole genome was 15.98 Mb, and it was assembled into 5 scaffolds. The genome contained 3934 coding genes, among which 3899 genes with biological functions were annotated in multiple underlying databases. In KOG database, 2627 genes were annotated, which were categorized into 25 classes including general function prediction only, posttranslational modification, protein turnover, chaperones, and signal transduction mechanisms. In KEGG database, 2493 genes were annotated, which were categorized into five classes, including cellular processes, environmental information processing, genetic information processing, metabolism and organismal systems. In GO database, 2893 genes were annotated, which were mainly classified in cell, cell part, cellular processes and metabolic processes. There were 1055 genes annotated in the PHI database, accounting for 26.81% of the total genome, among which 5 genes were directly related to pathogenicity (identity ≥ 50%), including hsp90, PacC, and PHO84. There were also some genes related to the activity of the yeast itself that could be targeted by antiyeast drugs. Analysis based on the DFVF database showed that strain MQ2101 contained 235 potential virulence genes. BLAST searches in the CAZy database showed that strain MQ2101 may have a more complex carbohydrate metabolism system than other yeasts of the same family. In addition, two gene clusters and 168 putative secretory proteins were predicted in strain MQ2101, and functional analysis showed that some of the secretory proteins may be directly involved in the pathogenesis of the strain. Gene family analysis with five other yeasts revealed that strain MQ2101 has 245 unique gene families, including 274 genes involved in pathogenicity that could serve as potential targets. Conclusion Genome-wide analysis elucidated the pathogenicity-associated genes of M. bicuspidate while also revealing a complex metabolic mechanism and providing putative targets of action for the development of antiyeast drugs for this pathogen. The obtained whole-genome sequencing data provide an important theoretical basis for transcriptomic, proteomic and metabolic studies of M. bicuspidata and lay a foundation for defining its specific mechanism of host infestation.

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

Background Maintenance therapy (MT) deepens response and prolongs progression free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) after frontline regimens. Ixazomib, a 2 nd generation oral proteasome inhibitor (PI), has been approved for MT because of the convenience and tolerability. Aims We conducted this prospective multi-center study to compare the efficacy and safety of Ixazomib (I-MT) or Ixazomib plus Lenalidomide (IL-MT) to Lenalidomide (L-MT) as maintenance regimens in NDMM patients. Methods This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and registered (NCT04217967). NDMM patients were enrolled from 10 centers of North China MM Registry since September 2019. After 4 cycles of front-line induction therapy, patients who reached partial response (PR) would receive autologous stem cell transplantation (ASCT) if eligible, or keep up to 5 cycles of front regimens if ineligible, then start maintenance therapy. Patients did not reach PR would switch to a 2nd-line induction for 2-5 cycles and start MT once PR was achieved. For MT, 4mg of Ixazomib was given on day 1,8,15, and 25mg of Lenalidomide every other day on days 1-21 of a 28-day cycle. Patients in dual drug group were administrated with both Ixazomib and Lenalidomide, dose as listed above. The primary endpoint was PFS from MT. Results A total of 149 patients were enrolled, including 54 in I-MT, 65 in L-MT and 30 in IL-MT. The demographic and clinical characteristics were comparable among three groups at baseline (Table 1), including gender ratio, age, paraprotein isotype, ISS, R-ISS, response status before MT, and ASCT rate. The proportions of patients with high-risk cytogenetic abnormalities (HRCAs), defined as amplification 1q21, deletion 17p, t(4,14) and t(14,16), were comparable. The median follow-up duration since MT was 6.1, 11.1, and 5.9 months in I-MT, L-MT and IL-MT group, respectively. Disease progression developed in 9.3%, 12.3% and 10% (N=5, 8, 3, respectively) patients. The median PFS was not reached (NR) in all groups. Only one death occurred in I-MT group. There were 84%, 72.3% and 83.3% of the patients reached very good partial response (VGPR) or better before MT, while the best response rates rose to 93%, 82.3% and 90% during maintenance. The prevalence of peripheral neuropathy was 18.5% on I-MT, 10.8% on L-MT and 30% on IL-MT. Grade 2 PN occurred in 3, 1, and 0 patients, respectively. The incidence of gastrointestinal events was 11.1%, 1.5% and 20%, respectively. Grade 3-4 hematologic toxicities was 3.7%, 4.6%, and 3.3%. Infection rates were 7.4%, 6.2% and 3.3%. Skin rashes were more common in lenalidomide containing regimens (3.7%, 7.3% and 6.7%). No drug withdrawal was related to adverse events. Conclusions Due to inadequate access to melphalan and low rate of ASCT in China, there is still a gap of PFS in NDMM patients with those in western countries. We herein design this multi-centered prospective study to evaluate if dual drug MT will further strengthen response and make up the gap. Though the primary endpoint--PFS has not been reached in all treatment groups, dual MT improves response most and is quite tolerable. Figure 1. Baseline Characteristics in three groups. Abbreviations: ISS: international staging system; R-ISS: revised-ISS; HRCAs: high risk cytogenetic abnormalities. sCR: stringent complete remission. CR: complete remission. VGPR: very good partial remission. PR: partial remission. * p ＜ 0.05. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

BACKGROUND Mutations in the beta1,3-N-acetylgalactosaminyltransferase 2 (B3GALNT2) gene can lead to impaired glycosylation of α-dystroglycan, which, in turn, causes congenital muscular dystrophy (CMD). The clinical phenotypes of CMD are broad, and there are only a few reports of CMD worldwide. CASE SUMMARY This report describes the cases of two children with CMD caused by B3GALNT2 gene mutation. The main manifestations of the two cases were abnormal walking posture, language development delay, and abnormal development of the white matter. Case 2 also had unreported symptoms of meningocele and giant arachnoid cyst. Both cases had compound heterozygous mutations of the B3GALNT2 gene, each containing a truncated mutation and a missense mutation, and three of the four loci had not been reported. Nineteen patients with CMD caused by B3GALNT2 gene mutation were found in the literature. Summary and analysis of the characteristics of CMD caused by B3GALNT2 gene mutation showed that 100% of the cases had nervous system involvement. Head magnetic resonance imaging often showed abnormal manifestations, and more than half of the children had eye and muscle involvement; some of the gene-related symptoms were self-healing. CONCLUSION B3GALNT2 gene can be used as one of the candidate genes for screening CMD, cognitive development retardation, epilepsy, and multiple brain developmental malformations in infants.

Previous study demonstrated that Ganoderma meroterpene derivative (GMD) increased the abundance of butyrate-producing bacteria in gut and subsequently delivered anti-metabolic disorder effect of host. To specify the key commensal bacteria associating with the beneficial effects, we tried to isolate and compare the microbiota from the cecal samples of GMD- and vehicle-treated ob/ob mice, and further identified butyrate-producing bacterial strains. It was found that Faeciroseburia intestinalis was enriched and 11 strains affiliated to F. intestinalis were cultivated from the gut of GMD-treated mice. In vitro assay attested butyrate production by representative strain of F. intestinalis. Oral administration with F. intestinalis further demonstrated its benefits on regulating hyperglycemia and hyperlipidemia, on decreasing plasma lipopolysaccharide (LPS) and inflammation, and on improving hepatic injuries. Treatment with F. intestinalis effectively enhanced the level of gut butyrate, which subsequently ameliorated the intestinal barrier function and activated epithelial PPAR-γ signaling pathway to regulate microbiome homeostasis in gut. Our study demonstrated that the causal relationship between the butyrate-producing bacteria and the GMD's therapeutic effects and confirmed the important function of the butyrate-producing F. intestinalis in maintaining host metabolism homeostasis.

Proliferative vitreoretinopathy(PVR)is a eye disease characterized by the formation of epiretinal membranes(ERM)composed of extracellular matrix(ECM)and various types of cells in the vitreous and/or the surface of the retina through the wound repair and fibrotic process. ERM shrinks to form retinal folds and stretches the retina to cause retinal detachment(RD). Epithelial-mesenchymal transition(EMT)of retinal pigment epithelial(RPE)cells and accumulation of ECM are considered to be the main pathological mechanisms for the formation of ERM. RPE cells undergo a process named EMT induced by transforming growth factor-β(TGF-β), by which differentiated epithelial cells go through epithelial phenotypic loss, the weakness of cell-cell contact and mesenchymal phenotype expression. Fibroblast-like cells differentiated from mesenchymal cells produce ECM and other components, which forms ERM together with glial cells and fibroblasts, etc. Recent studies indicated a lot of cytokines/growth factors, transcriptional factors, and microRNA(miRNA)regulate the development of EMT in RPE cells, in which miRNA is a novel and powerful regulatory gene and plays a critical regulatory role in the EMT process of PVR. This review focuses on the current understandings of the mechanism and the interventional treatments of miRNA in PVR.

PurposeTo determine the efficacy of 1.5 T magnetic resonance imaging (MRI) for the diagnosis of anomalies of the fetal great arteries with comparison to fetal ultrasound, and to compare image quality between 1.5 T and 3.0 T MRI in fetal imaging of the great arteries.MethodsWe compared the results of postnatal exam or surgery and evaluated the application value of prenatal 1.5 T MRI in the assessment of fetal great-vessel anomalies. To further determine the diagnostic potential of 1.5 T MRI, 23 pregnant women with suspected fetal cardiovascular abnormalities who had undergone ultrasound and 3.0 T MRI were enrolled and compared, respectively.ResultsPrenatal MRI was superior to ultrasound in demonstrating aortic arch and branch abnormalities (sensitivity, 92.86% vs. 83.33%; specificity, 66.67% vs. 20%). The mean quality ratings for fetal MRI at 1.5 T was higher than 3.0 T (P Conclusions1.5 T MRI can achieve an overall assessment of fetal great-vessel anomalies, especially aortic arch and branch abnormalities. Therefore, 1.5 T MRI can be considered a supplementary imaging modality for the prenatal assessment of extracardiac great vessels malformations.

Within a Bayesian statistical framework using a Gaussian Process emulator for an isospin-dependent Boltzmann-Uehling-Uhlenbeck (IBUU) transport model simulator of heavy-ion reactions at intermediate energies, we infer from the HADES proton flow data the posterior probability distribution functions of in-medium baryon-baryon scattering cross section modification factor X with respect to free-space and the corresponding incompressibility K of nuclear matter as well as their correlation function. The mean value of X is found to be $X=1.32^{+0.28}_{-0.40}$ at 68\% confidence level, providing circumstantial evidence for enhanced baryon-braryon scattering cross sections in hot and dense nuclear matter., 12 pages including 5 figures

ObjectivePrecise risk stratification is increasingly essential in the management of multiple myeloma (MM) as some standard-risk (SR) patients still exhibit similar poor outcomes as genetically high-risk (GHR) patients in the era of novel agents. It has recently been demonstrated that functional high-risk (FHR) patients, those with suboptimal response to first-line induction therapy or early relapse within 12 months, have identifiable molecular characteristics from the SR group in the CoMMpass dataset. However, these findings lack practical validation in the real world.MethodsMM cells purified by CD138 microbeads from newly diagnosed MM (NDMM) patients received fluorescence in situ hybridization and sequencing with a 92-gene Panel. Cytogenetic abnormalities defined GHR patients with t(4;14) or t(14;16) or complete loss of functional P53 or 1q21 gain and International Staging System (ISS) stage 3. SR group was patients who did not fulfill any criteria for GHR or FHR.ResultsThere were 145 patients with NDMM, 78 in the SR group, 56 in the GHR group, and 11 in the FHR group. In the FHR group, eight patients were suboptimal responses to induction therapy, and three relapsed within 12 months. We found that male patients, patients with extra-medullary plasmacytoma (EMD), circulating clonal plasma cells (CPC) ≥0.05%, and P53 mono-allelic inactivation were significantly higher in the FHR group compared to the SR group. After a median follow-up of 21.0 months, the median progression-free survival (PFS) and overall survival (OS) were 5.0 months, 19.1 months and 36.6 months in the FHR, GHR, and SR groups, respectively. Compared to the SR group, FHR patients had a higher frequency of mutations in MKI67, ERN1, and EML4. GO analysis showed that mutations in FHR were enriched for oxidative stress, chromosomal segregation, and hypoxia tolerance.ConclusionThe FHR found in the SR NDMM patient group has unique clinical features, including being male, with EMD and CPC, and genetic characteristics of mutations affecting oxidative stress, chromosome segregation, and hypoxia tolerance. In contrast to previous reports, our data suggested that patients with P53 mono-allelic inactivation should be classified in the GHR group rather than the FHR group.

Type 2 diabetes (T2D) constitutes a worldwide health threat, and the underlying mechanism for the development and progression of T2D is complex and multifactorial. During the last decade, gut commensal bacteria have been found to play a crucial role in the regulation of T2D and related metabolic disorders. However, as a considerable component in gut microbiome, the relationship between mycobiota and T2D and related metabolic disorders remains unclear. As a proof-of-concept, we observed that the ablation of the commensal fungi in mice can protect HFD (High fat diet) induced insulin resistance and related metabolic disorders. Both ITS2 (internal transcribed spacer 2) sequencing and culture-dependent analysis show the enrichment of Candida albicans in samples from individuals with T2D (Chinese Clinical Trial Registry, ChiCTR2100042049). Repopulation with C. albicans in HFD mice accelerated insulin resistance and related disorders. Mechanically, we found the β-glucan from C. albicans mirrored the deteriorating effect of C. albicans through the dectin-1 dependent pathway. Our current findings support that gut mycobiota play an important role in the progress of T2D and indicated the preventing of gut mycobiota is a promising strategy to alleviate insulin resistance and related metabolic dysfunctions.

BackgroundOsteoporosis has already been a growing health concern worldwide. The influence of living area, lifestyle, socioeconomic, and medical conditions on the occurrence of osteoporosis in the middle-aged and elderly people in China has not been fully addressed.MethodsThe study was a multicenter cross-sectional study on the middle-aged and elderly permanent residents, which gathered information of 22,081 residents from June 2015 to August 2021 in seven representative regions of China. The bone mineral density of lumbar vertebrae and hip were determined using the dual-energy X-ray absorptiometry densitometer instruments. Serum levels of bone metabolism markers were also measured. Information about education, smoking, and chronic diseases were also collected through face-to-face interviews. Age-standardized prevalence and 95% confidence intervals (CIs) of osteopenia and osteoporosis by various criteria were estimated by subgroups and overall based on the data of China 2010 census. The relationships between the osteoporosis or osteopenia and sociodemographic variables or other factors were examined using univariate linear models and multivariable multinomial logit analyses.ResultsAfter screening, 19,848 participants (90%) were enrolled for the final analysis. The age-standardized prevalence of osteoporosis was estimated to be 33.49%(95%CI, 32.80–34.18%) in the middle-aged and elderly Chinese permanent residents, for men and women was 20.73% (95% CI, 19.58–21.87%) and 38.05% (95% CI, 37.22–38.89%), respectively. The serum concentrations of bone metabolic markers, and calcium and phosphorus metabolism were influenced by age, body mass index (BMI), gender, education level, regions, and bone mass status. Women, aged 60 or above, BMI lower than 18.5 kg/m2, low education level including middle school, primary school and no formal education as well as current regular smoking, a history of fracture were all significantly associated with a higher risk of osteoporosis and osteopenia in the middle-aged and elderly people.ConclusionsThis study revealed dramatic regional differences in osteoporosis prevalence in China, and female, aged 60 or older, low BMI, low education level, current regular smoking, and a history of fracture were associated with a high risk of osteoporosis. More prevention and treatment resources should be invested into particular population exposed to these risk factors.

Rationale and Objectives: We aim to develop a nomogram to predict overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension, according to demographic/clinical indicators such as age, creatinine, blood ammonia, indocyanine green retention rate at 15 minutes (ICG-R15) and percentage of Portal pressure gradient (PPG) decline. Materials and Methods: In this retrospective study, 296 patients with portal hypertension who received elective TIPS in Beijing Shijitan Hospital from June 2018 to June 2020 were included. These patients were randomly divided into a training cohort (n=207) and a validation cohort (n=89). According to the occurrence of OHE, patients were assigned to OHE group and non-OHE group. Both univariate and multivariate analyses were performed to determine independent variables for predicting OHE after TIPS. Accordingly, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to compare the accuracy and superiority of a novel model with conventional Child-Pugh and MELD scoring model. Results: Age (OR=1.036, 95% CI:1.002-1.070, p=0.037), Creatinine (OR=1.011, 95% CI:1.003-1.019, p=0.009), Blood ammonia (OR=1.025, 95% CI:1.006-1.044, p=0.011), ICG-R15 (OR=1.030, 95% CI:1.009-1.052, p=0.004) and Percentage decline in PPG (OR=1.068, 95% CI:1.029-1.109, p=0.001) were independent risk factors for OHE after TIPS using multifactorial analysis. A nomogram was constructed using a well-fit calibration curve for each of these five covariates. When compared to Child-Pugh and MELD score, this new nomogram has a better predictive value (C-index=0.828, 95% CI:0.761-0.896). Consistently, this finding was reproduceable in validation cohort and confirmed with DCA. Conclusion: A unique nomogram was developed to predict OHE after TIPS in patients with PHT, with a high prediction sensitivity and specificity performance than commonly applied scoring systems.

BACKGROUND Tumor dormancy is an emerging field. In recent years, the field has attracted a lot of interest. OBJECTIVE This scientometric study's objectives are to review the findings in the area of tumor dormancy research and to pinpoint potential future research hotspots. METHODS Web of Science was used to retrieve English literature on tumor dormancy published in this century. After removing irrelevant material, a complete record of each publication was saved, including the title, year of publication, author's name, nationality, affiliation, journal name, keywords, and abstract. The author, country, institution, journal, year of publication, and highly cited publications were all examined using VOSviewer. RESULTS We observed that research on tumor dormancy has increased over the past 22 years, particularly from 2015 to the present, by looking at 3167 papers that were linked to the topic. As such, the United States is a world leader in this field of study. Aguirre-Ghiso, Julio A. is the author with the most publications and citations, while Harvard University is the organization with the most publications overall. The mechanisms behind tumor dormancy, methods for treating tumor dormancy, and the relationship between tumor dormancy and bone marrow have all been the subject of research. CONCLUSIONS We think that the microenvironment of tumor dormancy and immunotherapy of tumor dormancy may be the most important study fields, but research on the mechanism and treatment of tumor dormancy has continued to gain attention.

Additional file 1: Table S1. All centers participating in the study

The occurrence of singularities where spacetime curvature becomes infinite and geodesic evolution breaks down are inevitable events in classical general relativity (GR) unless one chooses an exotic matter violating weak energy condition. These singularities show up in various physical processes, such as the gravitational collapse, the birth of the universe in the standard cosmology as well as the classical solutions of the black hole spacetimes. In the last two decades, a rigorous understanding of the dynamics of quantum spacetime and the way it resolves singularities has been achieved in loop quantum cosmology (LQC) which applies the concepts and techniques of loop quantum gravity to the symmetry reduced cosmological spacetimes. Due to the fundamental discreteness of quantum geometry derived from the quantum theory, the big bang singularity has been robustly shown to be replaced by a big bounce. Strong curvature singularities intrinsic in the classical cosmology are generically resolved for a variety of cosmological spacetimes including anisotropic models and polarized Gowdy models. Using effective spacetime description the LQC universe also provides an ultra-violet complete description of the classical inflationary scenario as well as its alternatives such as the ekpyrotic and matter bounce scenarios. In this chapter we provide a summary of singularity resolution and its physical implications for various isotropic and anisotropic cosmological spacetimes in LQC and analyze robustness of results through variant models originating from different quantization prescriptions., Comment: 48 pages, 3 figures. Invited chapter to appear in the "Handbook of Quantum Gravity", edited by Cosimo Bambi, Leonardo Modesto and Ilya Shapiro, Springer (2023)

Additional file 9: Table S7. Subgroup analysis of the relation between clinical factors and overall survival (OS)