National tertiary public hospital performance appraisal: Using FOCUS-PDCA to improve external quality assessment.

PURPOSE: To innovatively use the FOCUS-PDCA quality improvement strategy to establish an external quality assessment (EQA) working group to continuously improve EQA performance, an important indicator of the national tertiary public hospital performance appraisal. METHODS: The project was carried out at the National Center for Clinical Laboratories. Using FOCUS-PDCA, which combines problem-focused steps (FOCUS) and improvement steps (PDCA), a project team was established to carry out improvement work. Root cause analysis was carried out to analyze the problems in quality control from EQA project application to results analysis and an improvement plan was implemented according to the steps of FOCUS-PDCA. The project was executed in three cycles from 2019 to 2021 to obtain more satisfactory results. RESULTS: After implementing three cycles of FOCUS-PDCA, the EQA participation rate increased from 66.5% in 2018 to 100% in 2021, and the EQA pass rate increased from 94.9% in 2018 to 99.3% in 2021. Consequently, the hospital moved into the top 50 in performance assessment for the first time in 2020 and ranked 27th in 2021. CONCLUSION: The use of the FOCUS-PDCA quality improvement strategy can improve the EQA performance of national tertiary public hospitals and help them achieve satisfactory results in the national examination.

[Research Progress of Iron Metabolism in Disease Progression and Drug Resistance of Multiple Myeloma--Review].

Iron metabolism is involved in the development and drug resistance of many malignancies, including multiple myeloma (MM). Based on recent studies on iron metabolism and MM, this paper reviews the relationship between iron metabolism and disease process of MM in terms of iron overload leading to ferroptosis in MM cells, the role of iron deficiency in oxidative respiration and proliferation of MM cells, and the interaction between ferroptosis and autophagy in the disease process. The mechanisms by which iron metabolism-related substances lead to MM cells' resistance to proteasome inhibitors (PI) through inducing redox imbalance and M2 macrophage polarization are also briefly described, aiming to provide a theoretical basis for the application of iron metabolism-related drugs to the clinical treatment of MM patients.

Matrix metalloproteinases and tissue inhibitors in multiple myeloma: promote or inhibit?

Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) play a vital role in the pathogenesis of multiple myeloma (MM), especially for tumor invasion and osteolytic osteopathy. By breaking down extracellular matrix (ECM) components and releasing the proteins composing the ECM and growth factors, as well as their receptors, MMPs affect tissue integrity and promote cancer cell invasion and metastasis. A vital pathophysiological characteristic of MM is the progress of osteolytic lesions, which are brought on by interactions between myeloma cells and the bone marrow microenvironment. MMPs, certainly, are one of the fundamental causes of myeloma bone disease due to their ability to degrade various types of collagens. TIMPs, as important regulators of MMP hydrolysis or activation, also participate in the occurrence and evolution of MM and the formation of bone disease. This review focuses on the role of MMP-1, MMP-2, MMP-7, MMP-9, MMP-13, MMP-14, and MMP-15 and the four types of TIMPs in the invasion of myeloma cells, angiogenesis, osteolytic osteopathy, to offer some novel perspectives on the clinical diagnostics and therapeutics of MM.

An NIR Fluorescence Turn-on and MRl Bimodal Probe for Concurrent Real-time in vivo Sensing and Labeling of ß-Galactosidase.

To realize sensing and labeling biomarkers is quite challenging in terms of designing multimodal imaging probes. In this study, we developed a novel ß-galactosidase (ß-gal) activated bimodal imaging probe that combines near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI) to enable real-time visualization of activity in living organisms. Upon ß-gal activation, Gal-Cy-Gd-1 exhibits a remarkable 42-fold increase in NIR fluorescence intensity at 717 nm, allowing covalent labeling of adjacent target enzymes or proteins and avoiding molecular escape to promote probe accumulation at the tumor site. This fluorescence reaction enhances the longitudinal relaxivity by approximately 1.9 times, facilitating high-resolution MRI. The unique features of Gal-Cy-Gd-1 enable real-time and precise visualization of ß-gal activity in live tumor cells and mice. The probe's utilization aids in identifying in situ ovarian tumors, offering valuable assistance in the precise removal of tumor tissue during surgical procedures in mice. The fusion of NIR fluorescence and MRI activation through self-immobilizing target enzymes or proteins provides a robust approach for visualizing ß-gal activity. Moreover, this approach sets the groundwork for developing other activatable bimodal probes, allowing real-time in vivo imaging of enzyme activity and localization.

Monitoring Hg2+ and MeHg+ poisoning in living body with an activatable near-infrared II fluorescence probe.

Noninvasively imaging mercury poisoning in living organisms is critical to understanding its toxicity and treatments. Especially, simultaneous fluorescence imaging of Hg2+ and MeHg+in vivo is helpful to disclose the mysteries of mercury poisoning. The key limitation for mercury imaging in vivo is the low imaging signal-to-background ratio (SBR) and limited imaging depth, which may result in unreliable detection results. Here, we designed and prepared a near-infrared II (NIR II) emissive probe, NIR-Rh-MS, leveraging the "spirolactam ring-open" tactic of xanthene dyes for in situ visualization of mercury toxicity in mice. The probe produces a marked fluorescence signal at 1015 nm and displays good linear responses to Hg2+ and MeHg+ with excellent sensitivity, respectively. The penetration experiments elucidate that the activated NIR-II fluorescence signal of the probe penetrates to a depth of up to 7 mm in simulated tissues. Impressively, the probe can monitor the toxicity of Hg2+ in mouse livers and the accumulation of MeHg+ in mouse brains via intravital NIR-II imaging for the first time. Thus, we believe that detecting Hg2+ and MeHg+ in different organs with a single NIR-II fluorescence probe in mice would assuredly advance the toxicologic study of mercury poisoning in vivo.

Gut microbiome in multiple myeloma: Mechanisms of progression and clinical applications.

The gut commensal microbes modulate human immunity and metabolism through the production of a large number of metabolites, which act as signaling molecules and substrates of metabolic reactions in a diverse range of biological processes. There is a growing appreciation for the importance of immunometabolic mechanisms of the host-gut microbiota interactions in various malignant tumors. Emerging studies have suggested intestinal microbiota contributes to the progression of multiple myeloma. In this review, we summarized the current understanding of the gut microbiome in MM progression and treatment, and the influence of alterations in gut microbiota on treatment response and treatment-related toxicity and complications in MM patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, we discussed the impact of gut microbiota-immune system interactions in tumor immunotherapy, focusing on tumor vaccine immunotherapy, which may be an effective approach to improve anti-myeloma efficacy.

[Clinical Role of M Protein in Multiple Myeloma and Lymphoma --Review].

M protein is often expressed in multiple myeloma and also can be detected in several lymphoma such as Waldenstrm macroglobulinaemia. M protein level can reflect the malignant degree and even genetic abnormality of multiple myeloma and lymphoma to some extent to predict the progress of the diseases, and the therapeutic response and prognosis of the disease can be evaluated by monitoring the M protein level and its change degree. This article reviews the role of M protein in the progression and prognosis of multiple myeloma and lymphoma, and discusses the differences in M protein expression between multiple myeloma and lymphoma, in order to provide new insights for clinical diagnosis, monitoring and evaluation of therapeutic effect.

[Research Progress of Intercellular Mitochondrial Transfer in the Development of Hematological Malignant Tumors --Review].

In recent years, studies have found that mitochondrial transfer between leukemic cells and different types of cells in their bone marrow microenvironment, especially mesenchymal stem cells, plays a key role in the occurrence, development and drug resistance of hematological malignant tumors. This paper mainly introduces the role and latest research progress of mitochondrial transfer in acute and chronic myeloid leukemia, acute lymphoblastic leukemia and multiple myeloma, and briefly describes the mechanism of drug resistance caused by mitochondrial transfer in leukemic cells during chemotherapy. The aim is to provide a new idea and theoretical basis for using intercellular mitochondrial transfer as a potential therapeutic target.

A narrative review for platelets and their RNAs in cancers: New concepts and clinical perspectives.

Recent years have witnessed a growing body of evidence suggesting that platelets are involved in several stages of the metastatic process via direct or indirect interactions with cancer cells, contributing to the progression of neoplastic malignancies. Cancer cells can dynamically exchange components with platelets in and out of blood vessels, and directly phagocytose platelets to hijack their proteome, transcriptome, and secretome, or be remotely regulated by metabolites or microparticles released by platelets, resulting in phenotypic, genetic, and functional modifications. Moreover, platelet interactions with stromal and immune cells in the tumor microenvironment lead to alterations in their components, including the ribonucleic acid (RNA) profile, and complicate the impact of platelets on cancers. A deeper understanding of the roles of platelets and their RNAs in cancer will contribute to the development of anticancer strategies and the optimization of clinical management. Encouragingly, advances in high-throughput sequencing, bioinformatics data analysis, and machine learning have allowed scientists to explore the potential of platelet RNAs for cancer diagnosis, prognosis, and guiding treatment. However, the clinical application of this technique remains controversial and requires larger, multicenter studies with standardized protocols. Here, we integrate the latest evidence to provide a broader insight into the role of platelets in cancer progression and management, and propose standardized recommendations for the clinical utility of platelet RNAs to facilitate translation and benefit patients.

A ratiometric photoelectrochemical microsensor based on a small-molecule organic semiconductor for reliable in vivo analysis.

Photoelectrochemical (PEC) sensing has been developing quickly in recent years, while its in vivo application is still in the infancy. The complexity of biological environments poses a high challenge to the specificity and reliability of PEC sensing. We herein proposed the concept of small-molecule organic semiconductor (SMOS)-based ratiometric PEC sensing making use of the structural flexibility as well as readily tunable energy band of SMOS. Xanthene skeleton-based CyOH was prepared as a photoactive molecule, and its absorption band and corresponding PEC output can be modulated by an intramolecular charge transfer process. As such, the target mediated shift of absorption offered the opportunity to construct a ratiometric PEC sensor. A proof-of-concept probe CyOThiols was synthesized and assembled on a Ti wire electrode (TiWE) to prepare a highly selective microsensor for thiols. Under two monochromatic laser excitation (808 nm and 750 nm), CyOThiols/TiWE offered a ratiometric signal (j 808/j 750), which exhibited pronounced capacity to offset the disturbance of environmental factors, guaranteeing its reliability for application in vivo. The ratiometric PEC sensor achieved the observation of bio-thiol release induced by cytotoxic edema and fluctuations of thiols in drug-induced epilepsy in living rat brains.

Circulating miRNAs as Auxiliary Diagnostic Biomarkers for Multiple Myeloma: A Systematic Review, Meta-Analysis, and Recommendations.

Multiple myeloma (MM) is a hematologic malignancy characterized by aberrant expansion of monoclonal plasma cells with high mortality and severe complications due to the lack of early diagnosis and timely treatment. Circulating miRNAs have shown potential in the diagnosis of MM with inconsistent results, which remains to be fully assessed. Here we updated a meta-analysis with relative studies and essays published in English before Jan 31, 2021. After steps of screening, 32 studies from 11 articles that included a total of 627 MM patients and 314 healthy controls were collected. All data were analyzed by REVMAN 5.3 and Stata MP 16, and the quality of included literatures was estimated by Diagnostic Accuracy Study 2 (QUADAS-2). The pooled area under the curve (AUC) shown in summary receiver operating characteristic (SROC) analyses of circulating miRNAs was 0.87 (95%CI, 0.81-0.89), and the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.79, 0.86, 5, 0.27, 22, respectively. Meta-regression and subgroup analysis exhibited that "miRNA cluster", patient "detailed stage or Ig isotype" accounted for a considerable proportion of heterogeneity, revealing the importance of study design and patient inclusion in diagnostic trials; thus standardized recommendations were proposed for further studies. In addition, the performance of the circulating miRNAs included in MM prognosis and treatment response prediction was summarized, indicating that they could serve as valuable biomarkers, which would expand their clinical application greatly. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=234297, PROSPERO, identifier (CRD42021234297).

Flexible Designing Strategy to Construct Activatable NIR-II Fluorescent Probes with Emission Maxima beyond 1200 nm.

Activatable second near-infrared (NIR-II) fluorescent probes that can be lighted up by specific targets have attracted great attention because of their high specificity and resolution, which hold great promise in deep-tissue imaging. However, such probes were relatively rarely reported so far, and the emission maximum is still limited (mainly located at 900-1000 nm). To solve the problem, herein, we proposed a flexible strategy to modulate the emission wavelength of NIR-II fluorescent probes, and four proof-of-concept probes (WH-1, WH-2, WH-3, and WH-4) based on D-π-A molecular skeleton were obtained. These probes can be activated by H2S and the emission maximum located from 925 to 1205 nm, which was attributed to the cooperation of elongating the π-conjugated system and enhancing the electron-donating ability of the donor region. In these probes, WH-3 exhibited the combination of long excitation/emission (925/1140 nm) and moderate quantum yield as well as high sensitivity toward H2S, enabling us to track and image H2S in vivo with high contrast. We expected that such a molecular design strategy will become an important approach to developing activatable NIR-II fluorescent probes with long emission.

Design of Activatable NIR-II Molecular Probe for In Vivo Elucidation of Disease-Related Viscosity Variations.

A clear elucidation of a disease-related viscosity change in vivo is significant yet highly challenging as well. Fluorescence imaging in the second near-infrared region (NIR-II, 1000-1700 nm) has gained increasing attention for observation in living organisms, but a viscosity-activatable fluorescent probe emitting at this region remains a vacancy. Herein, we report the first panel of a viscosity-activated NIR-II emissive fluorescent probe WD-X. By embedding different substituents into the WD-X platform and screening, we obtained an ideal probe, WD-NO2, which displayed the best combination of properties, including a 31-fold fluorescence enhancement in response to viscosity, insensitivity to environments (pH, polarity), and relatively high quantum yield (1.6% in glycerol). WD-NO2 was successfully applied to track the variation of viscosity in diabetes-induced liver injury in vivo.

Simultaneous imaging of mitochondrial viscosity and hydrogen peroxide in Alzheimer's disease by a single near-infrared fluorescent probe with a large Stokes shift.

It has been speculated that both the intracellular viscosity and H2O2 level in Alzheimer's disease (AD) brains are higher than that in healthy brains, but direct evidence from living beings is scarce. Herein, we report a NIR emissive fluorescent probe with a large Stokes shift for the associated detection of mitochondrial viscosity and H2O2 in live rat brains with AD for the first time.

A Red Emissive Two-Photon Fluorescence Probe Based on Carbon Dots for Intracellular pH Detection.

Intracellular pH is closely related with many biological processes, including cellular proliferation, apoptosis, endocytic processes, signal transduction, and enzymatic activity. The use of fluorescent probes has become an essential method for intracellular pH detection, but existing fluorescent probes have substantial limitations, such as requiring tedious synthetic preparation, suffering from an inappropriate response range and insufficiently long emission wavelength. In this work, a red emissive two-photon fluorescence probe based on carbon dots (pH-CDs) is fabricated using a facile one-pot hydrothermal method for the monitoring of intracellular pH. pH-CDs possess a variety of superior properties, including high selectivity, excellent photostability, and low cytotoxicity. Furthermore, they exhibit a pH-sensitive response in the range of 1.0-9.0 and a linear range of 3.5-6.5, which is desirable for tracking the pH value in living cells. It is demonstrated that the pH-dependent fluorescence signal is regulated via switching between aggregation and disaggregation of CDs. More importantly, pH-CDs can be successfully applied to sense and visualize pH fluctuation in cells, tissue, and zebrafish. These findings suggest that the as-prepared pH-CDs probe has significant potential for practical application in living systems.