Impact of implementation of 2019 European respiratory distress syndrome guidelines on bronchopulmonary dysplasia in very preterm infants.

BACKGROUND: To evaluate the impact of implementation of 2019 European respiratory distress syndrome (RDS) guidelines on the incidence of bronchopulmonary dysplasia (BPD). METHOD: We retrospectively collected the clinical data of very preterm infants (VPIs) born before 32 gestational weeks from January 1st 2018 to December 31st 2021. VPIs were divided into group A and group B according to their birth date which was before or at/after January 1st 2020, when the 2019 European RDS guidelines were introduced. BPD is considered as primary outcome. We statistically analyzed all the data, and we compared the general characteristics, ventilation support, medication, nutrition and the outcomes between the two groups. RESULTS: A total of 593 VPIs were enrolled, including 380 cases in group A and 213 cases in group B. There were no statistic differences regarding to gender ratio, gestational age, birth weight and delivery mode between the two groups. Compared with group A, group B showed higher rate of antenatal corticosteroid therapy (75.1% vs. 65.5%). The improvement of ventilation management in these latter patients included lower rate of invasive ventilation (40.4% vs. 50.0%), higher rate of volume guarantee (69.8% vs. 15.3%), higher positive end expiratory pressure (PEEP) [6 (5, 6) vs. 5 (5, 5) cmH2O] and higher rate of synchronized nasal intermittent positive pressure ventilation (sNIPPV) (36.2% vs. 5.6%). Compared with group A, group B received higher initial dose of pulmonary surfactant [200 (160, 200) vs. 170 (130, 200) mg/Kg], shorter antibiotic exposure time [13 (7, 23) vs. 17 (9, 33) days], more breast milk (86.4% vs. 70.3%) and earlier medication for hemodynamically significant patent ductus arteriosus (hsPDA) treatment [3 (3, 4) vs. 8 (4, 11) days] (p < 0.05). As the primary outcome, the incidence of BPD was significantly decreased (16.9% vs. 24.2%) (p < 0.05), along with lower extrauterine growth retardation (EUGR) rate (39.0% vs. 59.7%), while there were no statistic differences regarding to other secondary outcomes, including mortality, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of preterm (ROP) and necrotizing enterocolitis (NEC). However, in the subgroups of infants less than 28 gestational weeks or infants less than 1,000 g, the incidence of BPD was not significantly decreased (p > 0.05). CONCLUSIONS: After implementation of 2019 European RDS guidelines, the overall incidence of BPD was significantly decreased in VPIs. Continuous quality improvement is still needed in order to decrease the incidence of BPD in smaller infants who are less than 28 gestational weeks or less than 1,000 g.

Multiple-Effect Combined Hydrogels: "Temporal Regulation" Treatment of Osteosarcoma-Associated Bone Defects with Switchable Hyperthermia and Bioactive Agents.

Achieving the clinically staged treatment of osteosarcoma-associated bone defects encounters the multiple challenges of promptly removing postoperative residual tumor cells and bacterial infection, followed by bone reconstruction. Herein, a core/shell hydrogel with multiple-effect combination is designed to first exert antitumor and antibacterial activities and then promote osteogenesis. Specifically, doxorubicin (DOX) is loaded by magnesium-iron-based layered double hydroxide (LDH) to prepare LDOX, which is introduced into a thermo-sensitive hydrogel to serve as an outer shell of the core/shell hydrogel, meanwhile, LDH-contained liquid crystal hydrogel, abbreviated as LCgel-L, is served as an inner core. At the early stage of treatment, the dissociation of the outer shell triggered by moderate hyperthermia led to the thermo-sensitive release of LDOX, which can be targeted for the release of DOX within tumor cells, thereby promptly removing postoperative residual tumor cells based on the synergistic effect of photothermal therapy (PTT) and DOX, and postoperative bacterial infection can also be effectively prevented by PTT simultaneously. More importantly, the dissociation of the outer shell prompted the full exposure of the inner core, which will exert osteogenic activity based on the synergy of liquid crystal hydrogel as well as LDH-induced mild hyperthermia and ion effects, thereby enabling "temporal regulation" treatment of osteosarcoma-associated bone defects. This study provides a valuable insight for the development of osteosarcoma-associated bone repair materials.

Viromics reveals two novel viruses of the family Closteroviridae in Codiaeum variegatum plant with leaf variegation symptoms.

Codiaeum variegatum is a valuable ornamental plant with distinct bright yellowing and golden spots on dark green leaves, which resemble virus symptoms. To investigate the factors, especially viral agents, associated with the variegated leaf color of Codiaeum variegatum, we performed virome profiling of a single C. variegatum 'Gold Dust' leaf sample collected from Hainan, China using ribosomal RNA-depleted total RNA sequencing on an Illumina NovaSeq 6000 platform. Two novel viruses, with two variants each, belonging to the family Closteroviridae were detected and characterized: Croton golden spot-associated virus C variants 1 and 2 (CGSaVC-v1, and CGSaVC-v2) of the genus Crinivirus and Croton golden spot-associated virus A variants 1 and 2 (CGSaVA-v1 and CGSaVA-v2) of the genus Ampelovirus. Transmission electron microscopy showed long, flexuous, filamentous virus particles approximately 15 nm in diameter and 760-770 nm in length. Molecular screening of ninety-seven variegated individual plant leaves showed a high prevalence of CGSaVA-v1 (90.7%), CGSaVA-v2 (75.3 %), CGSaVC-v1 (70.1%), and CGSaVC-v2 (47.4%), while asymptomatic leaves near the meristem tip were mostly free of the target viruses. To our knowledge, this is the first study to demonstrate the significant association between closterovirids and the golden spots. The findings provide novel insights into the genetic diversity of the family Closteroviridae and inform future germplasm conservation and new cultivar development of Codiaeum Variegatum.

Community assessment of methods to deconvolve cellular composition from bulk gene expression.

We evaluate deconvolution methods, which infer levels of immune infiltration from bulk expression of tumor samples, through a community-wide DREAM Challenge. We assess six published and 22 community-contributed methods using in vitro and in silico transcriptional profiles of admixed cancer and healthy immune cells. Several published methods predict most cell types well, though they either were not trained to evaluate all functional CD8+ T cell states or do so with low accuracy. Several community-contributed methods address this gap, including a deep learning-based approach, whose strong performance establishes the applicability of this paradigm to deconvolution. Despite being developed largely using immune cells from healthy tissues, deconvolution methods predict levels of tumor-derived immune cells well. Our admixed and purified transcriptional profiles will be a valuable resource for developing deconvolution methods, including in response to common challenges we observe across methods, such as sensitive identification of functional CD4+ T cell states.

Hyperoxia exposure promotes endothelial-mesenchymal transition and inhibits regulatory T cell function in human pulmonary microvascular endothelial cells.

Objective: This study aims to investigate the effects of hyperoxia exposure on TGF-ß1-induced endothelial-mesenchymal transition (EndoMT) and regulatory T cell (Treg)-mediated immunomodulation in human pulmonary microvascular endothelial cells (HPMECs), which could provide a theoretical basis for further studies of the pathogenesis of bronchopulmonary dysplasia (BPD). Methods: A BPD cell model was established by exposing HPMECs to hyperoxia. Flow cytometry was used to isolate CD4 + CD3 + CD25 + CD127- Tregs from the peripheral blood samples of preterm infants. HPMECs were divided into four groups based on whether they were exposed to hyperoxia and/or co-cultured with Tregs. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to test the expression levels of TGF-ß1, α-SMA, Foxp3, IL-10, and reactive oxygen species (ROS). Results: The results showed that the expression levels of TGF-ß1 and α-SMA in HPMECs increased at 24 h, 48 h, and 72 h of hyperoxia exposure. In the co-culture group of HPMECs and Tregs, Foxp3 and IL-10 expressions decreased at 48 h and 72 h of hyperoxia exposure. ROS expression increased in the hyperoxia group of HPMECs at 24 h, 48 h, and 72 h of hyperoxia exposure, which were higher than those in the hyperoxia group of HPMECs and Tregs. Conclusion: These findings suggest that hyperoxia exposure promotes EndoMT in HMPECs and inhibits the immunosuppressive effect of Tregs. Despite this, Tregs still seem could protect HPMECs from oxidative stress injury.

Alveolar epithelial cells mitigate neutrophilic inflammation in lung injury through regulating mitochondrial fatty acid oxidation.

Type 2 alveolar epithelial (AT2) cells of the lung are fundamental in regulating alveolar inflammation in response to injury. Impaired mitochondrial long-chain fatty acid ß-oxidation (mtLCFAO) in AT2 cells is assumed to aggravate alveolar inflammation in acute lung injury (ALI), yet the importance of mtLCFAO to AT2 cell function needs to be defined. Here we show that expression of carnitine palmitoyltransferase 1a (CPT1a), a mtLCFAO rate limiting enzyme, in AT2 cells is significantly decreased in acute respiratory distress syndrome (ARDS). In mice, Cpt1a deletion in AT2 cells impairs mtLCFAO without reducing ATP production and alters surfactant phospholipid abundance in the alveoli. Impairing mtLCFAO in AT2 cells via deleting either Cpt1a or Acadl (acyl-CoA dehydrogenase long chain) restricts alveolar inflammation in ALI by hindering the production of the neutrophilic chemokine CXCL2 from AT2 cells. This study thus highlights mtLCFAO as immunometabolism to injury in AT2 cells and suggests impaired mtLCFAO in AT2 cells as an anti-inflammatory response in ARDS.

[Role and mechanism of epithelial-mesenchymal transition in a rat model of bronchopulmonary dysplasia induced by hyperoxia exposure]. / 上皮-间å è´¨è½¬åŒ–åœ¨é«˜æ°§è¯±å¯¼å¤§é¼ æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯æ¨¡åž‹ä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To investigate the role and mechanism of epithelial-mesenchymal transition (EMT) in a rat model of bronchopulmonary dysplasia (BPD). METHODS: The experiment consisted of two parts. (1) Forty-eight preterm rats were randomly divided into a normoxia group and a hyperoxia group, with 24 rats in each group. The hyperoxia group was exposed to 85% oxygen to establish a BPD model, while the normoxia group was kept in room air at normal pressure. Lung tissue samples were collected on days 1, 4, 7, and 14 of the experiment. (2) Rat type II alveolar epithelial cells (RLE-6TN) were randomly divided into a normoxia group (cultured in air) and a hyperoxia group (cultured in 95% oxygen), and cell samples were collected 12, 24, and 48 hours after hyperoxia exposure. Hematoxylin-eosin staining was used to observe alveolarization in preterm rat lungs, and immunofluorescence was used to detect the co-localization of surfactant protein C (SPC) and α-smooth muscle actin (α-SMA) in preterm rat lung tissue and RLE-6TN cells. Quantitative real-time polymerase chain reaction and protein immunoblotting were used to detect the expression levels of EMT-related mRNA and proteins in preterm rat lung tissue and RLE-6TN cells. RESULTS: (1) Compared with the normoxia group, the hyperoxia group showed blocked alveolarization and simplified alveolar structure after 7 days of hyperoxia exposure. Co-localization of SPC and α-SMA was observed in lung tissue, with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 7 and 14 days of hyperoxia exposure compared to the normoxia group. In the hyperoxia group, the mRNA and protein levels of TGF-ß1, α-SMA, and N-cadherin were increased, while the mRNA and protein levels of SPC and E-cadherin were decreased at 7 and 14 days of hyperoxia exposure compared to the normoxia group (P<0.05). (2) SPC and α-SMA was observed in RLE-6TN cells, with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 24 and 48 hours of hyperoxia exposure compared to the normoxia group. Compared to the normoxia group, the mRNA and protein levels of SPC and E-cadherin in the hyperoxia group were decreased, while the mRNA and protein levels of TGF-ß1, α-SMA, and E-cadherin in the hyperoxia group increased at 48 hours of hyperoxia exposure (P<0.05). CONCLUSIONS: EMT disrupts the tight connections between alveolar epithelial cells in a preterm rat model of BPD, leading to simplified alveolar structure and abnormal development, and is involved in the development of BPD. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 765-773.

The relationship between the psychological resilience and post-traumatic growth of college students during the COVID-19 pandemic: a model of conditioned processes mediated by negative emotions and moderated by deliberate rumination.

BACKGROUND: The mental health of university students during the COVID-19 pandemic has attracted the attention of researchers. For the present study researchers constructed a mediation model to explore the relationship between psychological resilience and post-traumatic growth, the mediating role of negative emotions and the moderating role of deliberate rumination in students. METHODS: The Psychological Resilience Scale, Posttraumatic Growth Inventory, Depression-Anxiety-Stress Scale (DASS-21) and Event Related Rumination Inventory were used in a survey of 881 college students. The data were analyzed using SPSS 26.0 and the PROCESS plugin (version 3.3). RESULTS: (1) Psychological resilience is positively related with post-traumatic growth. Deliberate rumination is positively related to psychological resilience, posttraumatic growth, and negative emotions. Psychological resilience, post-traumatic growth and negative emotions are negatively related. (2) Negative emotions mediated the relationship between psychological resilience and post-traumatic growth. (3) Deliberate rumination plays a moderating role in psychological resilience affecting negative emotions. Deliberate rumination plays a moderating role in the extent to which psychological resilience influences PTG through negative emotions. CONCLUSIONS: Psychological resilience affects post-traumatic growth directly and also indirectly through negative emotions. With the increase of mental resilience, the level of negative emotion tended to decrease. When individuals are experiencing negative emotions, high levels of active rumination are more likely to promote post-traumatic growth. This study helps to explore the factors affecting the mental health of college students during the epidemic, thus providing guidance for appropriate mental health interventions.

FerroLigandDB: A Ferroptosis Ligand Database of Structure-Activity Relations.

Ferroptosis is an iron-dependent programmed cell death characterized by lipid peroxidation that is linked to the pathophysiological processes in many diseases, such as neurodegenerative diseases, cancers, ischemia-reperfusion injuries, and organ damages. Many proteins are associated with ferroptosis signal transduction pathways. Novel chemical compounds are demanded to explore and regulate these pathways. Therefore, a ferroptosis ligand database, which holds relations among chemical structures, targets, bioactivities, and diseases, is needed for discovering and designing new ferroptosis regulators. This work reports FerroLigandDB, a manually curated database for small-molecular ferroptosis regulators. The database comprises 466 ferroptosis inducer entries (with 380 unique molecular structures) and 539 ferroptosis inhibitor entries (with 468 unique molecular structures) (note: one compound can be recorded as multiple entries due to the different assays). Each ferroptosis ligand entry is detailed with compound IDs, structure attributes, bioactivity values, test objects, target information, associated diseases, and references. The fields in the FerroLigandDB database implicitly contain relationships among chemical structures, bioactivities, targets, and diseases. Thus, FerroLigandDB is a comprehensive resource for scientists to design and discover novel ferroptosis regulators. The user interface of FerroLigandDB is implemented with query features and data visualization facilities. With compound identifiers, the compounds are linked to the records of other chemoinformatics databases (such as PubChem and SciFinder). The FerroLigandDB database is freely accessible at http://ferr.gulab.org.cn/.

Orthogonal Radical and Cationic Single-Unit Monomer Insertions for Engineering Polymer Architectures.

The single-unit monomer insertion (SUMI), derived from living/controlled polymerization, can be directly functionalized at the end or within the chain of polymers prepared by living/controlled polymerization, offering potential applications in the preparation of polymers with complex architectures. Many scenarios demand the simultaneous incorporation of monomers suitable for different polymerization methods into complex polymers. Therefore, it becomes imperative to utilize SUMI technologies with diverse mechanisms, especially those that are compatible with each other. Here, we reported the orthogonal SUMI technique, seamlessly combining radical and cationic SUMI approaches. Through the careful optimization of monomer and chain transfer agent pairs and adjustments to reaction conditions, we can efficiently execute both radical and cationic SUMI processes in one pot without mutual interference. The utilization of orthogonal SUMI pairs facilitates the integration of radical and cationic reversible addition-fragmentation chain transfer (RAFT) polymerization in various configurations. This flexibility enables the synthesis of diblock, triblock, and star polymers that incorporate both cationically and radically polymerizable monomers. Moreover, we have successfully implemented a mixing mechanism of free radicals and cations in RAFT step-growth polymerization, resulting in the creation of a side-chain sequence-controlled polymer brushes.

Universal crRNA Acylation Strategy for Robust Photo-Initiated One-Pot CRISPR-Cas12a Nucleic Acid Diagnostics.

Spatiotemporal regulation of clustered regularly interspaced short palindromic repeats (CRISPR) system is attractive for precise gene editing and accurate molecular diagnosis. Although many efforts have been made, versatile and efficient strategies to control CRISPR system are still desirable. Here, we proposed a universal and accessible acylation strategy to regulate the CRISPR-Cas12a system by efficient acylation of 2'-hydroxyls (2'-OH) on crRNA strand with photolabile agents (PLGs). The introduction of PLGs confers efficient suppression of crRNA function and rapid restoration of CRISPR-Cas12a reaction upon short light exposure regardless of crRNA sequences. Based on this strategy, we constructed a universal PhotO-Initiated CRISPR-Cas12a system for Robust One-pot Testing (POIROT) platform integrated with recombinase polymerase amplification (RPA), which showed two orders of magnitude more sensitive than the conventional one-step assay and comparable to the two-step assay. For clinical sample testing, POIROT achieved high-efficiency detection performance comparable to the gold-standard quantitative PCR (qPCR) in sensitivity and specificity, but faster than the qPCR method. Overall, we believe the proposed strategy will promote the development of many other universal photo-controlled CRISPR technologies for one-pot assay, and even expand applications in the fields of controllable CRISPR-based genomic editing, disease therapy, and cell imaging.

Identifying eleven new ferroptosis inhibitors as neuroprotective agents from FDA-approved drugs.

With increasing evidence that ferroptosis is associated with diverse neurological disorders, targeting ferroptosis offers a promising avenue for developing effective pharmaceutical agents for neuroprotection. In this study, we identified ferroptosis inhibitors as neuroprotective agents from US Food and Drug Administration (FDA)-approved drugs. 1176 drugs have been screened against erastin-induced ferroptosis in HT22 cells, resulting in 89 ferroptosis inhibitors. Among them, 26 drugs showed significant activity with EC50 below10 µM. The most active ferroptosis inhibitor is lumateperone tosylate at nanomolar level. 11 drugs as ferroptosis inhibitors were not reported previously. Further mechanistic studies revealed that their mechanisms of actions involve free radical scavenging, Fe2+ chelation, and 15-lipoxygenase inhibition. Notably, the active properties of some drugs were firstly revealed here. These ferroptosis inhibitors increase the chemical diversity of ferroptosis inhibitors, and offer new therapeutic possibilities for the treatments of related neurological diseases.

3D Printing Drug-Free Scaffold with Triple-Effect Combination Induced by Copper-Doped Layered Double Hydroxides for the Treatment of Bone Defects.

Tissue-engineered poly(l-lactide) (PLLA) scaffolds have been widely used to treat bone defects; however, poor biological activities have always been key challenges for its further application. To address this issue, introducing bioactive drugs or factors is the most commonly used method, but there are often many problems such as high cost, uncontrollable and monotonous drug activity, and poor bioavailability. Here, a drug-free 3D printing PLLA scaffold with a triple-effect combination induced by surface-modified copper-doped layered double hydroxides (Cu-LDHs) is proposed. In the early stage of scaffold implantation, Cu-LDHs exert a photothermal therapy (PTT) effect to generate high temperature to effectively prevent bacterial infection. In the later stage, Cu-LDHs can further have a mild hyperthermia (MHT) effect to stimulate angiogenesis and osteogenic differentiation, demonstrating excellent vascularization and osteogenic activity. More importantly, with the degradation of Cu-LDHs, the released Cu2+ and Mg2+ provide an ion microenvironment effect and further synergize with the MHT effect to stimulate angiogenesis and osteogenic differentiation, thus more effectively promoting the healing of bone tissue. This triple-effect combined scaffold exhibits outstanding antibacterial, osteogenic, and angiogenic activities, as well as the advantages of low cost, convenient procedure, and long-term efficacy, and is expected to provide a promising strategy for clinical repair of bone defects.

The utility of long non-coding RNAs in chronic obstructive pulmonary disease: a comprehensive analysis.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality in the world. However, there are some patients who are not diagnosed early and correctly through routine methods because of inconspicuous or serious symptoms. This study aims to assess the diagnostic role of long non-coding RNA (lncRNA) in COPD. METHODS: We searched literature from electronic databases, after excluding non-COPD literature, the bibliometric analysis was performed, and VOSviewer software was used to represent the data analyzed. Literature evaluating the diagnostic test accuracy of lncRNA for COPD was eligible, and the QUADAS-2 checklist was used to evaluate the quality. The pooled sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (sROC) were used to analyze the overall diagnostic performance. Subgroup and meta-regression analyses were performed to explore the heterogeneity, and a funnel plot was assessed for publication bias. Also, lncRNAs related to COPD were identified and explored for their potential biological function. RESULTS: An increased annual growth rate of literature on this subject from 2016 focused on COPD, humans, RNA, and lncRNA. The meta-analysis enrolled 17 literature indicated that the SEN, SPE, and DOR differentiating COPD patients from normal controls (NCs) were 0.86 (95% CI [0.80, 0.90]), 0.78 (95% CI [0.67, 0.86]), and 21.59 (95% CI [11.39, 40.91]), respectively. Meanwhile, lncRNAs had the ability to distinguish acute exacerbations of COPD (AECOPD) patients from COPD; the SEN, SPE, and DOR were 0.75 (95% CI [0.62, 0.85]), 0.81 (95% CI [0.71, 0.89]), and 13.02 (95% CI [7.76, 21.85]), respectively. The area under the sROC were calculated to be greater than 0.8 at least. Subgroup and meta-regression analysis showed that the types of specimens and dysregulated lncRNAs might affect the diagnostic accuracy. The funnel plot showed there was a certain publication bias. 41 lncRNAs related to COPD were identified and mainly located in the nucleus and cytoplasm, associated with proliferation, invasion, and prognosis. These lncRNA-binding proteins were involved in the spliceosome, Rap1 signaling pathway, MAPK signaling pathway, and so on. CONCLUSION: LncRNA suggests potential diagnostic biomarkers and therapeutic targets for COPD patients.

Virome Profiling, New Virus Identification and the Prevalence and Distribution of Viruses Infecting Chieh-Qua (Benincasa hispida Cogn. var. chieh-qua How) in China.

The cucurbit vegetable chieh-qua (Benincasa hispida var. chieh-qua How) is an important crop in South China and southeast Asian countries. Viral diseases cause substantial loss of chieh-qua yield. To identify the viruses that affect chieh-qua in China, ribosomal RNA-depleted total RNA sequencing was performed using chieh-qua leaf samples with typical viral symptoms. The virome of chieh-qua comprises four known viruses (melon yellow spot virus (MYSV), cucurbit chlorotic yellows virus (CCYV), papaya ringspot virus (PRSV) and watermelon silver mottle virus (WSMoV) and two novel viruses: cucurbit chlorotic virus (CuCV) in the genus Crinivirus and chieh-qua endornavirus (CqEV) in the genus Alphaendornavirus. The complete genomes of the two novel viruses in chieh-qua and three other isolates of CuCV in pumpkin, watermelon and cucumber were determined and the recombination signals of pumpkin and watermelon isolates of CuCV were detected. A reverse transcriptase PCR indicated that the dominant viruses of chieh-qua in Hainan are MYSV (66.67%) and CCYV (55.56%), followed by CuCV (27.41%), WSMoV (7.41%), cucumber mosaic virus (8.15%), zucchini yellow mosaic virus (6.67%), PRSV (6.67%) and CqEV (35.56%). Our findings support diagnostic and prevalence studies of viruses infecting chieh-qua in China, enabling sustainable control strategies for cucurbit viruses worldwide.

Using an In-Sample Addition of Medronic Acid for the Analysis of Purine- and Pyrimidine-Related Derivatives and Its Application in the Study of Lung Adenocarcinoma A549 Cell Lines by LC-MS/MS.

Intracellular purine- and pyrimidine-related derivatives are vital molecules for preserving genetic information and are essential for cellular bioenergetics and signal transduction. This study developed a practical liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying intracellular purine- and pyrimidine-related derivatives. To solve the distorted peak shape related to di- and triphosphate nucleotides, in-sample addition of medronic acid and ammonium phosphate was performed. Using the BEH-amide column, the results showed that adding 0.5 mM medronic acid to the sample significantly improved the peak shape without causing an obvious ion suppressive effect. Method validation confirmed that the coefficients of determination (R2) values for linearity evaluation were above 0.94 for all analytes. The intraday and interday accuracies ranged from 85.1 to 128.4%, with the precision below 16.6%. The validated method was successfully applied in characterizing the alterations of purine- and pyrimidine-related derivatives in the A549 cell line with perturbed mitochondrial fission or blockade of the electron transport chain. Collectively, this study demonstrates that the strategy of in-sample medronic acid addition is effective in improving the quantification of intracellular purine- and pyrimidine-related derivatives. We believe that our proposed platform can facilitate the development of novel drugs targeting purine and pyrimidine metabolism in the future.

The effect of research on life satisfaction in middle-aged and older adults: physical disability and physical activity as a parallel and serial mediation analysis.

BACKGROUND AND OBJECTIVE: Maintaining the life satisfaction of frail middle-aged and older adults when they experience physical disability, lower activity status, or complex conditions that are related to each other is now an urgent issue. Therefore, the purpose of this study was to provide evidence for the impact of frailty in middle-aged and older adults on life satisfaction under the simultaneous occurrence and correlation of physical disability and physical activity status. METHODS: Data from the 2015 Taiwan Longitudinal Study in Ageing (TLSA) were analyzed by PROCESS in SPSS to explore three different mediation models (N = 4,421). The first was a parallel mediation model for exploring life satisfaction in middle-aged and older adults with frailty through physical disability or physical activity. The second was a serial mediation model for examining physical disability and physical activity in causal chains linked with a specific direction of flow and to test all combinations. The third was a moderated mediation model for testing whether the indirect effect of frailty status on life satisfaction through physical disability or physical activity was moderated by age stratification. RESULTS: Physical disability and physical activity partially mediated the relationship between frailty status and life satisfaction (IEOVERALL = -0.196, 95% CI: -0.255 to -0.139). The causal path with the highest indirect effect was found to be that between frailty and physical disability; increased frailty led to higher physical disability, which in turn affected physical activity, leading to lower life satisfaction (IE = 0.013, 95% CI: 0.008 to 0.019). The different stratifications by age significantly increased the mediating effect of physical activity (Index of Moderated Mediation = -0.107, SE = 0.052, 95% CI: -0.208 to -0.005) but did not reduce the mediating effect of physical disability. CONCLUSION: This study provides evidence that physical activity and physical disability influence the development of frailty. It also has a significant impact on the life satisfaction of middle-aged and older adults.

Rare Pattern of Myelodysplastic Syndrome (MDS) with Serum Monoclonal Immunoglobulin: Case Report.

Background: Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by bone marrow dysplasia, ineffective hematopoiesis, and cytopenias. Monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients have a high risk of secondary MDS or acute myeloid leukemia (AML) compared to healthy persons, and chemotherapy or transplantation may result in secondary treatment-related MDS. Methods: A patient was diagnosed with both MDS and MGUS, which was treated using thalidomide, dexamethasone, and danazol. A follow-up blood test was conducted to determine leukocyte and hemoglobin levels. Results: Immunoprotein electrophoresis showed M protein peak with IgA+ κ components. Nuclear cells proliferated actively in bone marrow aspirates. Bone marrow analysis suggested a myelodysplastic syndrome with myeloblastoma (MDS-RS) and a new plasmacytoma. The immunophenotype was shown as follows: R5 cells (red) are about 15.5%. Among the CD38+CD45 cells, about 95.9% of cKappa cells and 1.7% of cLambda cells are considered as plasmacytoma. Gene detection showed that the patient carried 14 gene mutations, and karyotype analysis showed that they had normal male chromosome structure. The patient was diagnosed as MDS and MGUS, and finally discharged after treatment with thalidomide (75 mg daily), dexamethasone (3 mg daily), and danazol (200 mg twice daily). Within 1 year, the disease has stabilized. Conclusion: The combination of plasma cell disease and myeloid malignancy may increase mortality. This is uncommon and may be easily misdiagnosed if not detected early. When a myeloid neoplasm tests positive for MDS and serum M protein, clinicians should evaluate for other plasma cell disease.

[Research Progress of Regulatory T Cells in the Pathogenesis of Multiple Myeloma --Review].

The multiple myeloma (MM), the second most common hematologic malignancy, is malignant proliferative disease of plasma cells. Although the application of many targeted drugs has significantly prolonged the survival time of MM patients, it is still an incurable disease. In recent years, the immunosuppression caused by interaction between tumor microenvironment(TME) and tumor cells has attracted people's attention gradually. As a kind of immunosuppressive cells in TME, regulatory T cells (Treg) play an important role in the progress of MM. Treg is related to the proliferation and metastasis of tumors, and can lead to the progress of MM by promoting the angiogenesis and generating immunosuppressive TME. In this review, we briefly summarized the latest research progress on the impact of Treg on the pathogenesis of MM.

Efficacy of ultrasound-guided acupotomy for knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This systematic review aimed to evaluate the effectiveness and safety of ultrasound-guided acupotomy (UGAT) therapy in the treatment of patients with knee osteoarthritis (KOA). METHODS: We conducted online researches in the databases including PubMed, the Cochrane Library, EMBASE, China national knowledge infrastructure, China biomedical literature database, and Wan Fang data. All data were collected until January 1, 2022. Relevant randomized controlled trials on the effectiveness of UGAT for the treatment of KOA were included. Meta-analyses were carried out by RevMan 5.3 software. Evidence quality was evaluated by the grading of recommendations, assessment development, and evaluation. RESULTS: Eight studies including 543 participants were analyzed in this study. The pooled analysis indicated that UGAT was significantly more efficient than the control group in decreasing the visual analogue scale score (mean difference = -0.81, 95% confidence interval (CI) = [-1.15, -0.47], P < .00001, 8 studies), improving knee function on the Lysholm knee score (mean difference = 8.26, 95% CI = [1.56, 14.97], P = .02, 2 studies), and increasing clinical effective rate (relative risk = 1.14, 95% CI = [1.06, 1.23], P = .0005, 6 studies). For adverse events, UGAT was also associated with lower incidence of adverse event (odds ratio = 0.27, 95% CI = [0.12, 0.63], P = .002, 4 studies) compared to traditional acupotomy. CONCLUSION: Current evidence suggested that UGAT therapy was effective and safe in the clinical treatments of KOA, thus could be suggested in the clinical managements of KOA. However, considering the unsatisfactory quality of the available trials, more large-scale, and better quality randomized controlled trials were recommend in future.