Insights into dynamic evolution of glucuronofucogalactoglucan from water extract of Agrocybe cylindracea during maturation.

This study explored the physicochemical properties and structural characteristics of Agrocybe cylindracea polysaccharides at four developmental stages, as well as their dynamic evolution during maturation. Results showed that the polysaccharides from A. cylindracea water extract exhibited similar structural characteristics across all four maturity stages, despite a significant reduction in yields. Four water-soluble heteroglycans, including one high molecular weight (ACPM-Et50-I) and three low molecular weight (ACPM-Et50-II, ACPM-Et60, ACPM-Et80), were isolated from A. cylindracea at each maturity stage. ACPM-Et50-I was identified as branched heterogalactans, while ACPM-Et60 and ACPM-Et80 were branched heteroglucans. However, ACPM-Et50-II was characterized as a branched glucuronofucogalactoglucan at the tide-turning stage but a glucuronofucoglucogalactan at the pileus expansion stage due to the increase of its α-(1 â†’ 6)-D-Galp. In general, although the structural skeletons of most A. cylindracea heteroglycans were similar during maturation as shown by their highly consistent glycosyl linkages, there were still differences in the distribution of some heteroglucans. This work has for the first time reported a glucuronofucogalactoglucan in A. cylindracea and its dynamic evolution during maturation, which may facilitate the potential application of A. cylindracea in food and biomedicine industries.

Prehabilitation of surgical patients: a bibliometric analysis from 2005 to 2023.

BACKGROUND: Good preoperative conditions help patients to counteract surgical injury. Prehabilitation is a multimodal preoperative management strategy, including physical, nutritional, psychological, and other interventions, which can improve the functional reserve of patients and enhance postoperative recovery. The purpose of this study is to show the evolution trend and future directions of research related to the prehabilitation of surgical patients. METHODS: The global literature regarding prehabilitation was identified from The Web of Science Core Collection database. Bibliometric methods of the Bibliometrix package of R (version 4.2.1) and VOSviewer were used to analyze publication trends, cooperative networks, study themes, and co-citation relationships in the field. RESULTS: A total of 638 publications were included and the number of publications increased rapidly since 2016, with an average annual growth rate of 41.0%. "Annals of Surgery", "British Journal of Surgery" and "British Journal of Anesthesia" were the most cited journals. Experts from the USA, Canada, the UK, and the Netherlands contributed the most in this field, and an initial cooperative network among different countries and clinical teams was formed. Malnutrition, older patients, frailty, and high-risk patients were the hotspots of recent studies. However, among the top 10 cited articles, the clinical effects of prehabilitation were conflicting. CONCLUSION: This bibliometric review summarized the most influential publications as well as the publication trends and clarified the progress and future directions of prehabilitation, which could serve as a guide for developing evidence-based practices.

FSCME: A Feature Selection Method Combining Copula Correlation and Maximal Information Coefficient by Entropy Weights.

Feature selection is a critical component of data mining and has garnered significant attention in recent years. However, feature selection methods based on information entropy often introduce complex mutual information forms to measure features, leading to increased redundancy and potential errors. To address this issue, we propose FSCME, a feature selection method combining Copula correlation (Ccor) and the maximum information coefficient (MIC) by entropy weights. The FSCME takes into consideration the relevance between features and labels, as well as the redundancy among candidate features and selected features. Therefore, the FSCME utilizes Ccor to measure the redundancy between features, while also estimating the relevance between features and labels. Meanwhile, the FSCME employs MIC to enhance the credibility of the correlation between features and labels. Moreover, this study employs the Entropy Weight Method (EWM) to evaluate and assign weights to the Ccor and MIC. The experimental results demonstrate that FSCME yields a more effective feature subset for subsequent clustering processes, significantly improving the classification performance compared to the other six feature selection methods. The source codes of the FSCME are available online at https://github.com/CDMBlab/FSCME.

Identification of Family-Specific Features in Cas9 and Cas12 Proteins: A Machine Learning Approach Using Complete Protein Feature Spectrum.

The recent development of CRISPR-Cas technology holds promise to correct gene-level defects for genetic diseases. The key element of the CRISPR-Cas system is the Cas protein, a nuclease that can edit the gene of interest assisted by guide RNA. However, these Cas proteins suffer from inherent limitations such as large size, low cleavage efficiency, and off-target effects, hindering their widespread application as a gene editing tool. Therefore, there is a need to identify novel Cas proteins with improved editing properties, for which it is necessary to understand the underlying features governing the Cas families. In this study, we aim to elucidate the unique protein features associated with Cas9 and Cas12 families and identify the features distinguishing each family from non-Cas proteins. Here, we built Random Forest (RF) binary classifiers to distinguish Cas12 and Cas9 proteins from non-Cas proteins, respectively, using the complete protein feature spectrum (13,494 features) encoding various physiochemical, topological, constitutional, and coevolutionary information on Cas proteins. Furthermore, we built multiclass RF classifiers differentiating Cas9, Cas12, and non-Cas proteins. All the models were evaluated rigorously on the test and independent data sets. The Cas12 and Cas9 binary models achieved a high overall accuracy of 92% and 95% on their respective independent data sets, while the multiclass classifier achieved an F1 score of close to 0.98. We observed that Quasi-Sequence-Order (QSO) descriptors like Schneider.lag and Composition descriptors like charge, volume, and polarizability are predominant in the Cas12 family. Conversely Amino Acid Composition descriptors, especially Tripeptide Composition (TPC), predominate the Cas9 family. Four of the top 10 descriptors identified in Cas9 classification are tripeptides PWN, PYY, HHA, and DHI, which are seen to be conserved across all Cas9 proteins and located within different catalytically important domains of the Streptococcus pyogenes Cas9 (SpCas9) structure. Among these, DHI and HHA are well-known to be involved in the DNA cleavage activity of the SpCas9 protein. Mutation studies have highlighted the significance of the PWN tripeptide in PAM recognition and DNA cleavage activity of SpCas9, while Y450 from the PYY tripeptide plays a crucial role in reducing off-target effects and improving the specificity in SpCas9. Leveraging our machine learning (ML) pipeline, we identified numerous Cas9 and Cas12 family-specific features. These features offer valuable insights for future experimental and computational studies aiming at designing Cas systems with enhanced gene-editing properties. These features suggest plausible structural modifications that can effectively guide the development of Cas proteins with improved editing capabilities.

Immunodeviation towards T cell-mediated immune response in the testes of LPS-induced mouse epididymo-orchitis.

The testicular consequences of acute epididymo-orchitis remain largely unelucidated in long-term damage, which might be a neglected factor for male infertility. In this study, the differential phenotype of testicular immune cell subpopulations in lipopolysaccharide (LPS)-induced mouse epididymo-orchitis were analyzed by flow cytometry on day 1, day 7, and day 28. The number of macrophages, neutrophils, and myeloid-derived suppressor cells (MDSCs) steadily decreased in the testes with inoculation. Total F4/80-CD11c+ dendritic cells (DCs) maintained a relatively stable level, whereas conventional type 1 dendritic cells (cDC1) increased gradually from day 1 to day 28. There was a lower number of CD4+ and CD8+ T cells at day 1 and day 7, and they had similar results with a ceiling level at day 28. The testes displayed a higher level of CD3+ T cells but a lower frequency of macrophages, cDC2, and neutrophils at 28 days post-inoculation compared with the epididymis. In summary, our data indicates acute epididymo-orchitis could lead to long-term damage in the testes, which is characterized by CD3+ T cell (including CD4+ and CD8+ T cells)-mediated immune responses.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Construction of a Bifunctional Redox-Site Conjugated Covalent-Organic Framework for Photoinduced Precision Trapping of Uranyl Ions.

The performance of covalent-organic frameworks (COFs) for the photocatalytic extraction of uranium is greatly limited by the number of adsorption sites. Herein, inspired by electronegative redox reactions, we designed a nitrogen-oxygen rich pyrazine connected COF (TQY-COF) with multiple redox sites as a platform for extracting uranium via combining superaffinity and enhanced photoinduction. The preorganized bisnitrogen-bisoxygen donor configuration on TQY-COF is entirely matched with the typical geometric coordination of hexavalent uranyl ions, which demonstrates high affinity (tetra-coordination). In addition, the presence of the carbonyl group and pyrazine ring effectively stores and controls electron flow, which efficaciously facilitates the separation of e-/h+ and enhances photocatalytic performance. The experimental results show that TQY-COF removes up to 99.8% of uranyl ions from actual uranium mine wastewater under the light conditions without a sacrificial agent, and the separation coefficient reaches 1.73 × 106 mL g-1 in the presence of multiple metal ions, which realizes the precise separation in the complex environment. Importantly, DFT calculations further elucidate the coordination mechanism of uranium and demonstrate the necessity of the presence of N/O atoms in the photocatalytic adsorption of uranium.

The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC.

Accumulating evidence indicated that HHEX participated in the initiation and development of several cancers, but the potential roles and mechanisms of HHEX in hepatocellular carcinoma (HCC) were largely unclear. Cancer stem cells (CSCs) are responsible for cancer progression owing to their stemness characteristics. We reported that HHEX was a novel CSCs target for HCC. We found that HHEX was overexpressed in HCC tissues and high expression of HHEX was associated with poor survival. Subsequently, we found that HHEX promoted HCC cell proliferation, migration, and invasion. Moreover, bioinformatics analysis and experiments verified that HHEX promoted stem cell-like properties in HCC. Mechanistically, ABI2 serving as a co-activator of transcriptional factor HHEX upregulated SLC17A9 to promote HCC cancer stem cell-like properties and tumorigenesis. Collectively, the HHEX-mediated ABI2/SLC17A9 axis contributes to HCC growth and metastasis by maintaining the CSC population, suggesting that HHEX serves as a promising therapeutic target for HCC treatment.

Dexmedetomidine with different concentrations added to local anesthetics in erector spinae plane block: a meta-analysis of randomized controlled trials.

Background: Dexmedetomidine has been used as a perineural local anesthetic (LA) adjuvant to facilitate the potency of erector spinal plane block (ESPB). This quantitative review aimed to evaluate whether perineural dexmedetomidine for ESPB can improve the effects of analgesia compared to LA alone. Methods: Randomized controlled trials (RCTs) that investigated the addition of dexmedetomidine to LA compared to LA alone in ESPB were included. The pain scores, duration of sensory block, the time to first analgesia requirement, postoperative morphine consumption, rescue analgesia, and dexmedetomidine-related side effects were analyzed and combined using random-effects models. Results: A total of 823 patients from 13 RCTs were analyzed. Dexmedetomidine was used at the concentration of 0.5 µg/kg in three trials and 1 µg/kg in nine trials, and both in one trial. Both concentrations of dexmedetomidine perineurally administrated significantly reduced the rest VAS scores postoperatively at 12 h (0.5 µg/kg dexmedetomidine: MD = -0.86; 95% CI: -1.59 to -0.12; p = 0.02; 1 µg/kg dexmedetomidine: MD = -0.49; 95% CI: -0.83 to -0.16; p = 0.004), and 24 h (0.5 µg/kg dexmedetomidine: MD = -0.43; 95% CI: -0.74 to -0.13; p = 0.005; 1 µg/kg dexmedetomidine: MD = -0.62; 95% CI: -0.84 to -0.41; p < 0.00001). Both concentrations of dexmedetomidine added in LAs improved the dynamic VAS scores postoperatively at 12 h (0.5 µg/kg dexmedetomidine: MD = -0.55; 95% CI: -0.95 to -0.15; p = 0.007; 1 µg/kg dexmedetomidine: MD = -0.66; 95% CI: -1.05 to -0.28; p = 0.0006) and 24 h (0.5 µg/kg dexmedetomidine: MD = -0.52; 95% CI: -0.94 to -0.10; p = 0.01; 1 µg/kg dexmedetomidine: MD = -0.46; 95% CI: -0.75 to -0.16; p = 0.002). Furthermore, perineural dexmedetomidine prolonged the duration of the sensory block and the time to first analgesia requirement, reduced postoperative morphine consumption, and lowered the incidence of rescue analgesia and chronic pain. Conclusion: The meta-analysis showed that using perineural dexmedetomidine at either 0.5 µg/kg or 1 µg/kg doses in ESPB can effectively and safely enhance pain relief. Systematic review registration: PROSPERO (CRD42023424532: https://www.crd.york.ac.uk/PROSPERO/).

Intolerance of uncertainty and negative emotions among high school art students during COVID-19 pandemic: a moderated mediation analysis.

Objectives: A number of high school art students experience negative emotions during their preparation for the art college entrance examination, characterized by worries and fear of uncertainty. Therefore, how individual difference factors, such as intolerance of uncertainty, affect the negative emotions of students needs to be examined. Inspired by the integrative model of uncertainty tolerance, the current study seeks to explain the association between intolerance of uncertainty and negative emotions by testing the potential mediating role of psychological capital and the moderating role of family functioning. Patients and methods: A total of 919 Chinese high school art students (Mage = 18.50 years, range = 16-22) participated from November 2022 to December 2022. Convenience sampling strategies were used. The participants were asked to complete the measures of intolerance of uncertainty scale, psychological capital questionnaire, depression anxiety stress scale, and family adaptability and cohesion evaluation scale. The data were analyzed using Pearson's r correlations and moderated mediation analysis. Results: Results showed that intolerance of uncertainty was positively associated with negative emotions but negatively associated with psychological capital, which in turn, was negatively associated with negative emotions. Psychological capital mediated the indirect link of intolerance of uncertainty with negative emotions. Family functioning buffered the impact of psychological capital on negative emotions. Conclusion: This study can enhance our understanding of the intolerance of uncertainty on negative emotions and provide insights on interventions for high school art students' negative emotions for educators. The interventions targeting intolerance of uncertainty, psychological capital and family functioning may be beneficial in reducing the effect of intolerance of uncertainty on negative emotions faced by high school art students.

The cumulative impact of temperature and nitrogen availability on the potential nitrogen fixation and extracellular polymeric substances secretion by Dolichospermum.

Nitrogen-fixing cyanobacteria not only cause severe blooms but also play an important role in the nitrogen input processes of lakes. The production of extracellular polymeric substances (EPS) and the ability to fix nitrogen from the atmosphere provide nitrogen-fixing cyanobacteria with a competitive advantage over other organisms. Temperature and nitrogen availability are key environmental factors in regulating the growth of cyanobacteria. In this study, Dolichospermum (formerly known as Anabaena) was cultivated at three different temperatures (10 °C, 20 °C, and 30 °C) to examine the impact of temperature and nitrogen availability on nitrogen fixation capacity and the release of EPS. Initially, confocal laser scanning microscopy (CLSM) and the quantification of heterocysts at different temperatures revealed that lower temperatures (10 °C) hindered the differentiation of heterocysts under nitrogen-deprived conditions. Additionally, while heterocysts inhibited the photosynthetic activity of Dolichospermum, the secretion of EPS was notably affected by nitrogen limitation, particularly at 30 °C. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of nitrogen-utilizing genes (ntcA and nifH) and EPS synthesis-related genes (wzb and wzc). The results indicated that under nitrogen-deprived conditions, the expression of each gene was upregulated, and there was a significant correlation between the upregulation of nitrogen-utilizing and EPS synthesis genes (P < 0.05). Our findings suggested that Dolichospermum responded to temperature variation by affecting the formation of heterocysts, impacting its potential nitrogen fixation capacity. Furthermore, the quantity of EPS released was more influenced by nitrogen availability than temperature. This research enhances our comprehension of interconnections between nitrogen deprivation and EPS production under the different temperatures.

Nonlinear Photon Generations from Subwavelength Whispering-Gallery-Mode Resonator.

The strong light localization and long photon lifetimes in whispering gallery mode (WGM) microresonators, benefiting from a high-quality (Q) factor and a small mode volume (V), could significantly enhance light-matter interactions, enabling efficient nonlinear photon generation and paving the way for exploring novel on-chip optical functionalities. However, the leakage of energy from bending losses severely limits the improvement of the Q factor for subwavelength WGM microresonators. Here, we demonstrated an integrated self-suspended WGM microresonator that combines external rings and bridges with a microdisk on a platform of silicon on insulator, achieving about one-hundred-fold enhancement in the Q factor and an ultrasmall mode volume of 2.67(/λnSi)3 as predicted by numerical simulations. We experimentally confirmed the improved performance of the subwavelength WGM resonator with the dramatic enhancement of third-harmonic generation and second-harmonic generation on this device. Our work is anticipated to enhance light-matter interactions on small-footprint microresonators and boost the development of efficient integrated nonlinear and quantum photonics.

Survey of Rickettsia species in hematophagous arthropods from endemic areas for Japanese spotted fever in China.

Japanese spotted fever (JSF) is caused by Rickettsia japonica, mainly vectored by hard ticks. However, whether R. japonica can be transmitted by other arthropods remains unknown. Moreover, it is of interest to investigate whether other Rickettsia species cause spotted fever in endemic areas. In this study, a survey of Rickettsia species was performed in hematophagous arthropods (mosquitoes, tabanids, and ticks) from endemic areas for JSF in Hubei Province, central China. The results showed that the diversity and prevalence of Rickettsia species in mosquitoes are low, suggesting that mosquitoes may not be the vector of zoonotic Rickettsia species. A novel Rickettsia species showed a high prevalence (16.31%, 23/141) in tabanids and was named "Candidatus Rickettsia tabanidii." It is closely related to Rickettsia from fleas and mosquitoes; however, its pathogenicity in humans needs further investigation. Five Rickettsia species were identified in ticks. Rickettsia japonica, the agent of JSF, was detected only in Haemaphysalis longicornis and Haemaphysalis hystricis, suggesting that they may be the major vectors of R. japonica. Notably, two novel species were identified in H. hystricis ticks, one belonging to the spotted fever group and the other potentially belonging to the ancestral group. The latter one named "Candidatus Rickettsia hubeiensis" may provide valuable insight into the evolutionary history of Rickettsia.

Charge-transfer-driven ultrasensitive SERS sensing in a two-dimensional titanium carbonitride MXene.

Two-dimensional (2D) MXenes stand out as promising platforms for surface-enhanced Raman scattering (SERS) sensing owing to their metallic feature, various compositions, high surface area, compatibility with functionalization, and ease of fabrication. In this work, we report a high-performance 2D titanium carbonitride (Ti3CN) MXene SERS substrate. We reveal that the abundant electronic density of states near the Fermi level of Ti3CN MXene boosts the efficiency of photo-induced charge transfer at the interface of Ti3CN/molecule, resulting in significant Raman enhancement. The SERS sensitivity of Ti3CN MXene is further promoted through a 2D morphology regulation and molecular enrichment strategies. Moreover, prohibited drugs are detectable on this substrate, presenting the potential of trace-amount analysis on Ti3CN MXene. This work provides a deep insight of the SERS mechanisms of Ti3CN MXene and broadens the practical application of transition metal carbonitride MXene SERS substrates.

Post-marketing safety concerns with elagolix: a disproportionality analysis of the FDA adverse event reporting system.

OBJECTIVE: Elagolix is approved for the treatment of moderate-to-severe pain associated with endometriosis. However, the long-term safety of elagolix in a large sample of real-world patients is unknown. METHODS: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) reports were collected and analyzed from January 2019 to June 2023. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed in data mining to quantify the signals of elagolix-related adverse events (AEs). RESULTS: After removing the non-drug-related AE signals, we detected several AE signals such as hot flushes, bone pain, suicidal ideation, depression, and increased liver enzymes, which were known during the clinical trial phase. In addition to this, we detected several unexpected important AEs that were not mentioned in the drug insert, including cystitis interstitial, parosmia, and epiploic appendagitis. The median onset time of elagolix-associated AEs was 28.5 days. CONCLUSION: Our study provides a comprehensive picture of the safety of elagolix in the post-marketing setting, while also identifying potential new AE signals. These findings emphasize the importance of continued monitoring of the potential risks of elagolix.

Dendritic boron and nitrogen doped high-entropy alloy porous carbon fibers for high-efficiency hydrogen evolution reaction.

Among various electrocatalysts, high-entropy alloys (HEAs) have gained significant attention for their unique properties and excellent catalytic activity in the hydrogen evolution reaction (HER). However, the precise synthesis of HEA catalysts in small sizes remains challenging, which limits further improvement in their catalytic performance. In this study, boron- and nitrogen-doped HEA porous carbon nanofibers (HE-BN/PCNF) with an in situ-grown dendritic structure were successfully prepared, inspired by the germination and growth of tree branches. Furthermore, the dendritic fibers constrained the growth of HEA particles, leading to the synthesis of quantum dot-sized (1.67 nm) HEA particles, which also provide a pathway for designing HEA quantum dots in the future. This work provides design ideas and guiding suggestions for the preparation of borated HEA fibers with different elemental combinations and for the application of dendritic nanofibers in various fields.

Transcutaneous auricular vagal nerve stimulation for consciousness recovery in patients with prolonged disorders of consciousness (TAVREC): study protocol for a multicenter, triple-blind, randomized controlled trial in China.

INTRODUCTION: Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC). METHODS AND ANALYSIS: The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 µs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073950.

Elevated serum levels of soluble B-cell maturation antigen as a prognostic biomarker for multiple myeloma.

Serum B-cell maturation antigen (sBCMA) levels can serve as a sensitive biomarker in multiple myeloma (MM). In the research setting, sBCMA levels can be accurately detected by enzyme-linked immunosorbent assay (ELISA), but the approach has not been approved for clinical use. Here, we used a novel chemiluminescence method to assess sBCMA levels in 759 serum samples from 17 healthy donors and 443 patients with plasma cell (PC) diseases including AL amyloidosis, POEMS syndrome and MM. Serum BCMA levels were elevated 16.1-fold in patients with newly diagnosed MM compared to healthy donors and rare PC diseases patients. Specifically, the sBCMA levels in patients with progressive disease were 64.6-fold higher than those who showed partial response or above to treatment. The sBCMA level also correlated negatively with the response depth of MM patients. In newly diagnosed and relapsed MM patients, survival was significantly longer among those subjects whose sBCMA levels are below the median levels compared with those above the median value. We optimized the accuracy of the survival prediction further by integrating sBCMA level into the Second Revised International Staging System (R2-ISS). Our findings provide evidence that the novel chemiluminescence method is sensitive and practical for measuring sBCMA levels in clinical samples and confirm that sBCMA might serve as an independent prognostic biomarker for MM.

Impact of Platelet-to-HDL-Cholesterol Ratio on Long-Term Mortality in Coronary Artery Disease Patients with or Without Type 2 Diabetes: Insights from a Chinese Multicenter Cohort.

Background: Inflammation contributes to the initiation and advancement of both coronary atherosclerosis and type 2 diabetes mellitus (T2DM). Recent evidence has underscored the platelet-to-HDL-cholesterol ratio (PHR) as a promising inflammatory biomarker closely linked to the severity of coronary artery disease (CAD). Nevertheless, the risk of adverse clinical outcomes remains unclear among CAD patients with varying PHR levels and glycemic status. Methods: A total of 56,316 CAD patients were enrolled, primarily focusing on mortality outcomes. Patients were categorized into four subgroups based on median baseline PHR values and glycemic status: lower PHR (PHR-L) and higher PHR (PHR-H) with or without T2DM. Cox proportional hazard model and subgroup analysis were employed to investigate the association between PHR and glycemic status with mortality. Results: Over a median 5.32-year follow-up, 8909 (15.8%) patients experienced all-cause mortality, with 3873 (6.9%) deaths attributed to cardiovascular causes. Compared to individuals in PHR-L/non-DM, those in PHR-H/non-DM, PHR-L/DM and PHR-H/DM groups exhibited a higher risk of all-cause death [adjusted hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06-1.18; HR 1.21, 95% CI 1.14-1.29; HR 1.43, 95% CI 1.34-1.52, respectively], as well as cardiac mortality [HR 1.19, 95% CI 1.08-1.30; HR 1.58, 95% CI 1.44-1.74; HR 1.89, 95% CI 1.72-2.07, respectively]. Cox proportional hazard model also revealed the highest mortality risk among patients in PHR-H/DM compared to other groups (P <0.05). Restricted cubic spline regression analysis revealed a positive linear association between PHR and all-cause as well as cardiac mortality (P for non-linearity >0.05) after adjustment. Additionally, subgroup analysis indicated consistent effects on cardiac mortality within diverse subsets. Conclusion: In this real-world observational cohort analysis, elevated PHR levels joint with T2DM were related to adverse long-term clinical outcomes in CAD patients. PHR levels may serve as a valuable tool for identifying high-risk individuals within this specific group. Trial Registration: The Cardiorenal ImprovemeNt II registry NCT05050877.