Efficacy of transcutaneous electrical nerve stimulation combined with mirabegron therapy compared with mirabegron monotherapy for overactive bladder: a prospective randomized controlled study.

PURPOSE: The objective was to evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) combined with mirabegron therapy compared with mirabegron monotherapy in the treatment of female patients with overactive bladder (OAB). METHODS: In this randomized controlled study, 100 female outpatients with OAB were screened. Among these patients, 86 who met the inclusion criteria were randomly divided into the TENS combined with mirabegron treatment group and mirabegron monotherapy treatment group, with 43 patients in each group. The voiding diary, Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Symptom Bother Score (OAB-q SBS), total health-related quality of life (OAB-q HRQoL), and treatment satisfaction-visual analog scale (TS-VAS) score before and after treatment were recorded to evaluate the efficacy of OAB treatment. Seventy-nine of the 86 patients (40 in the TENS plus mirabegron group and 39 in the mirabegron monotherapy group) completed 12 weeks of treatment. RESULTS: TENS combined with mirabegron therapy was superior to mirabegron monotherapy in improving the primary endpoints, including the daily number of micturition episodes and the daily MVV/micturition and secondary endpoints, including the daily number of urgency episodes, the OABSS, the OAB-q SBS, the HRQoL score and TS-VAS score. There were no statistically significant differences in urgency urinary incontinence and nocturia between the groups. Some minor adverse effects were observed, including muscle pain, local paresthesia and constipation. CONCLUSIONS: The combination of TENS and mirabegron was more effective than mirabegron alone in the treatment of female patients with OAB. TRIAL REGISTRATION NUMBER: ChiCTR2400080528 (31.01.2024, retrospectively registered).

USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

An electrochemiluminescent dual-signal immunosensor based on a Ru(bpy)32+-doped silica nanoparticle/copper nanocluster composite for okadaic acid detection.

In this study, a sensitive dual-signal electrochemiluminescence (ECL) immunosensor was developed for okadaic acid (OA) detection utilizing copper nanoclusters (CuNCs) and Ru(bpy)32+-doped silica nanoparticles (RuSiNPs). Interestingly, the CuNCs could simultaneously enhance both cathodic (-0.95 V) and anodic (+1.15 V) ECL signals of RuSiNPs, forming a dual-signal ECL sensing platform. Further, RuSiNPs@CuNCs were used as immunomarkers by covalently conjugating them with an anti-OA monoclonal antibody (mAb) to form probes. Finally, dual ECL signals of the immunosensor were fabricated and showed good linear relationships with OA concentrations in the range of 0.05-70 ng mL-1, having a median inhibitory concentration (IC50) of 1.972 ng mL-1 and a limit of detection of 0.039 ng mL-1. Moreover, the constant ratio of the cathodic and anodic ECL peaks achieved self-calibration of the detection signal and improved the reliability of the results. Finally, we successfully applied the ECL sensor to detect OA in spiked oyster samples.

Remediation of Cr(VI)-contaminated soil by CS/PPy coupling with Microbacterium sp. YL3.

In this research, a new material, chitosan/polypyrrole (CS/PPy), was synthesized and linked with the Cr(VI)-reducing bacterial strain YL3 to treat Cr(VI)-polluted soil. The findings demonstrated that the synergistic application of strain YL3 and CS/PPy achieved the greatest reduction (99.6 %). During the remediation process, CS/PPy served as a mass-storage and sustained release agent in the soil, which initially decreased the toxic effects of high concentrations of Cr(VI) on strain YL3, thereby enhancing the Cr(VI) reduction efficiency of strain YL3. These combined effects significantly mitigated Cr(VI) stress in the soil and restored enzyme activities. Furthermore, wheat growth in the treated soil also significantly improved. High-throughput sequencing of the microorganisms in the treated soil revealed that CS/PPy was not only effective at removing Cr(VI) but also at preserving the original microbial diversity of the soil. This suggests that the combined treatment using strain YL3 and CS/PPy could rehabilitate Cr(VI)-contaminated soil, positioning CS/PPy as a promising composite material for future bioremediation efforts in Cr(VI)-contaminated soils.

Synergistic pathogenicity of vertically transmitted chicken infectious anemia virus and avian leukosis virus subgroup J coinfection in chickens.

Avian leukemia virus subgroup J (ALV-J) and chicken infectious anemia virus (CIAV) can be vertically transmitted; however, the pathogenicity of vertically transmitted coinfection with these 2 pathogens has not been studied. In this study, we created a model of chick morbidity in which chicks carried either ALV-J, CIAV, or both viruses via embryo inoculation. Thereafter, we analyzed the effects of vertically transmitted coinfection with CIAV and ALV-J on the pathogenicity of ALV-J and performed a purification assay based on hatching, mortality viremia positivity, and detection of fecal ALV-p27 antigen rates, and body weight. The hatching rate of the ALV-J+CIAV group was 68.57%, lower than those of the single infection and control groups. The survival curve showed that the mortality rates of the CIAV and ALV-J coinfection groups were higher than those of the single infection and control groups. Body weight statistics showed that coinfection aggravated the 7-d growth inhibition effect. The results of ALV-p27 antigen detection in cell culture supernatants showed that the positivity rates of the ALV-J and ALV-J+CIAV groups were 100% at all ages and 0% in the control group. The results of ALV-p27 antigen detection by anal swabs showed that the positivity rates of the ALV-J group were 92.86, 90.90, 88.89, and 93.33% at all ages, and that the ALV-J p27 positivity detection rate of anal swabs was lower than that of plasma virus isolation. The immune organ index of the ALV-J+CIAV group was significantly or very significantly lower than those of the single infection and control groups. The immune organ viral load showed that coinfection with CIAV and ALV-J promoted the proliferation of ALV-J and CIAV in immune organs. Coinfection with ALV-J and CIAV reduced chicken embryo hatchability and increased chick mortality and growth inhibition relative to their respective single infections. Additionally, coinfection with ALV-J + CIAV was even more detrimental in inducing immune organ atrophy (e.g., the thymus, spleen, and bursa), and promoted individual virus replication during coinfection.

Association of Lipoprotein(a) Levels With Myocardial Infarction in Patients With Low-Attenuation Plaque.

BACKGROUND: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. OBJECTIVES: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). METHODS: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. RESULTS: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. CONCLUSIONS: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.

Development of a cell adhesion-based prognostic model for multiple myeloma: Insights into chemotherapy response and potential reversal of adhesion effects.

Multiple myeloma (MM) is a hematologic malignancy notorious for its high relapse rate and development of drug resistance, in which cell adhesion-mediated drug resistance plays a critical role. This study integrated four RNA sequencing datasets (CoMMpass, GSE136337, GSE9782, and GSE2658) and focused on analyzing 1706 adhesion-related genes. Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes, including KIF14, TROAP, FLNA, MSN, LGALS1, PECAM1, and ALCAM, which demonstrated the strongest associations with poor overall survival (OS) in MM patients. To comprehensively evaluate the impact of cell adhesion on MM prognosis, an adhesion-related risk score (ARRS) model was constructed using Lasso Cox regression analysis. The ARRS model emerged as an independent prognostic factor for predicting OS. Furthermore, our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs, protein kinase inhibitors, and drugs targeting the PI3K/Akt/mTOR signaling pathway. Nevertheless, we identified promising drug candidates, such as tirofiban, pirenzepine, erlotinib, and bosutinib, which exhibit potential in reversing this resistance. In vitro, experiments employing NCIH929, RPMI8226, and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs. By employing siRNA-mediated knockdown of the key ARRS model gene KIF14, we observed suppressed proliferation of NCIH929 cells, along with decreased adhesion to BMSCs and fibronectin. This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM. Additionally, potential molecular mechanisms underlying adhesion-related resistance are proposed, along with viable strategies to overcome such resistance. These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.

Retinal structure and vessel density changes in cerebral small vessel disease.

Background: Cerebral small vessel disease (CSVD) attaches people's attention in recent years. In this study, we aim to explore retinal structure and vessel density changes in CSVD patients. Methods: We collected information on retinal metrics assessed by optical coherence tomography (OCT) and OCT angiography and CSVD characters. Logistic and liner regression was used to analyze the relationship between retinal metrics and CSVD. Results: Vessel density of superficial retinal capillary plexus (SRCP), foveal density- 300 length (FD-300), radial peripapillary capillary (RPC) and thickness of retina were significantly lower in CSVD patients, the difference only existed in the thickness of retina after adjusted relevant risk factors (OR (95% CI): 0.954 (0.912, 0.997), p = 0.037). SRCP vessel density showed a significant downward trend with the increase of CSVD scores (ß: -0.087, 95%CI: -0.166, -0.008, p = 0.031). SRCP and FD-300 were significantly lower in patients with lacunar infarctions and white matter hypertensions separately [OR (95% CI): 0.857 (0.736, 0.998), p = 0.047 and OR (95% CI): 0.636 (0.434, 0.932), p = 0.020, separately]. Conclusion: SRCP, FD-300 and thickness of retina were associated with the occurrence and severity of total CSVD scores and its different radiological manifestations. Exploring CSVD by observing alterations in retinal metrics has become an optional research direction in future.

Identification and validation of mitophagy-related signatures as a novel prognostic model for colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in the world. Mitophagy is associated with tumorigenesis and development of malignancy. However, the specific role of mitophagy has yet not been systematically explored in CRC. Methods: The RNA-sequencing dataset of CRC from The Cancer Genome Atlas (TCGA) and microarray data of gene expression profiles of CRC from Gene Expression Omnibus (GEO) were downloaded. Mitophagy-related gene sets were obtained from the Pathway Unification database. The package "limma" was used for differential gene expression analysis. Kaplan-Meier (KM) survival analyses were utilized to evaluate the prognostic value of the mitophagy regulators. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate the infiltrating immune cells and the activity of immune response. The ConsensusClusterPlus algorithm was used to determine mitophagy-related subtypes. Principal component analysis (PCA) was used to create composite measurement of mitophagy scores. The R packages "survminer" and "ReGlot" were used to plot the nomogram and calibration curves. Results: Integrated analysis of the GEO and TCGA databases revealed some common differentially expressed genes (DEGs) in CRC. MFN2, UBB, PINK1, and PRKN were significantly downregulated in CRC samples as compared to normal samples, and other genes were significantly upregulated in CRC samples. KM survival analyses showed that high expression of ATG12 and MAP1LC3B predicted a poor prognosis, whereas high expression of TOMM22 and TOMM40 predicted a better prognosis. Mitophagy showed significant correlation with immune-related pathways in CRC samples. We identified 2 distinct CRC subtypes with different mitophagy accumulation, of which subtype B had better prognosis and immune activity. The mitophagy score may be employed as a new and efficient clinical predictor in conjunction with other clinical indicators to predict the prognosis of CRC patients. Conclusions: We systematically investigated the CRC heterogeneity with reference to mitophagy based on bioinformatics analyses, and the findings of this study might provide some guidance for future research into potential biomarkers for diagnosis and prognosis prediction of CRC patients.

Galvanic replacement-induced preparation of bloom-like Pt23Ni77 for methanol coupled efficient hydrogen production.

Galvanic replacement reaction (GRR) leverages the difference in metal reduction potentials to regulate the structure of nanomaterials. The crucial aspect of constructing highly active catalysts lies in the precise manipulation of both the oxidative dissolution of sacrificial template metals and reductive deposition of alternate metals. Herein, we investigated the morphological transformation of metal Ni as a sacrificial template in the presence of different amounts of H2PtCl6 solution and the Pt4+ substitution of Ni to achieve the redistribution of elements on the catalyst surface, which provides superior performance in both the methanol oxidation reaction (MOR) and hydrogen evolution reaction (HER). The uniform distribution of Pt on a three-dimensional transition metal Ni substrate allows for the complete exposure of the noble metal to the catalyst surface. This distribution increases the reaction area, facilitating easy access for reactants and promoting electron transfer. Meanwhile, Pt (1.39 Å) has a larger atomic radius compared to Ni (1.24 Å), and the substitution reaction in the transition metal phase induces strong compressive strain, which effectively regulates the electronic structure of Ni.

A universal nucleic acid detection platform combing CRISPR/Cas12a and strand displacement amplification with multiple signal readout.

Rapid and sensitive detection of nucleic acids has become crucial in various fields. However, most current nucleic acid detection methods can only be used in specific scenarios, such as RT-qPCR, which relies on fluorometer for signal readout, limiting its application at home or in the field due to its high price. In this paper, a universal nucleic acid detection platform combing CRISPR/Cas12a and strand displacement amplification (CRISPR-SDA) with multiple signal readout was established to adapt to different application scenarios. Nucleocapsid protein gene of SARS-CoV-2 (N gene) and hepatitis B virus (HBV) DNA were selected as model targets. The proposed strategy achieved the sensitivity of 53.1 fM, 0.15 pM, and 1 pM for N gene in fluorescence mode, personal glucose meter (PGM) mode and lateral flow assay (LFA) mode, respectively. It possessed the ability to differentiate single-base mismatch and the presence of salmon sperm DNA with a mass up to 105-fold of the targets did not significantly interfere with the assay signal. The general and modular design idea made CRISPR-SDA as simple as building blocks to construct nucleic acid sensing methods to meet different requirements by simply changing the SDA template and selecting suitable signal report probes, which was expected to find a breadth of applications in nucleic acids detection.

Reversible single-crystal-to-single-crystal transition in Gd(III) metal-organic frameworks induced by heat and solvents with a significant magnetocaloric effect.

The design and synthesis of a Gd(III) metal-organic framework with the formula [Gd4(BTDI)3(DMF)4]n (JXUST-40, H4BTDI = 5,5'-(benzo[c][1,2,5]thiadiazole-4,7-diyl)diisophthalic acid) are reported hererin. Interestingly, a reversible single-crystal-to-single-crystal transition between JXUST-40 and {[Gd4(BTDI)3(H2O)4]·6H2O}n (JXUST-40a) was achieved under the stimulation of heat and solvents. Both JXUST-40 and JXUST-40a exhibited good stability when soaked in common solvents and aqueous solutions with pH values of 1-12. Magnetic studies showed that JXUST-40a has a larger magnetocaloric effect with -ΔSmaxm = 26.65 J kg-1 K-1 at 2 K and 7 T than JXUST-40 due to its larger magnetic density. Structural analyses indicated that the coordinated solvent molecules play a crucial role in the coordination environment around the Gd(III) ions and the change in the framework, ultimately leading to the changes in the pore size and magnetism between JXUST-40 and JXUST-40a. In addition, both isomorphic [Dy4(BTDI)3(DMF)4]n (JXUST-41) and {[Dy4(BTDI)3(H2O)4]·6H2O}n (JXUST-41a) displayed slow magnetic relaxation behaviour.

Intracerebral hemorrhage-induced brain injury in mice: The role of peroxiredoxin 2-Toll-like receptor 4 inflammatory axis.

BACKGROUND: Peroxiredoxin 2 (Prx2), an intracellular protein that regulates redox reactions, released from red blood cells is involved in inflammatory brain injury after intracerebral hemorrhage (ICH). Toll-like receptor 4 (TLR4) may be crucial in this process. This study investigated the role of the Prx2-TLR4 inflammatory axis in brain injury following experimental ICH in mice. METHODS: First, C57BL/6 mice received an intracaudate injection of autologous arterial blood or saline and their brains were harvested on day 1 to measure Prx2 levels. Second, mice received an intracaudate injection of either recombinant mouse Prx2 or saline. Third, the mice were co-injected with autologous arterial blood and conoidin A, a Prx2 inhibitor, or vehicle. Fourth, the mice received a Prx2 injection and were treated with TAK-242, a TLR4 antagonist, or saline (intraperitoneally). Behavioral tests, magnetic resonance imaging, western blot, immunohistochemistry/immunofluorescence staining, and RNA sequencing (RNA-seq) were performed. RESULTS: Brain Prx2 levels were elevated after autologous arterial blood injection. Intracaudate injection of Prx2 caused brain swelling, microglial activation, neutrophil infiltration, neuronal death, and neurological deficits. Co-injection of conoidin A attenuated autologous arterial blood-induced brain injury. TLR4 was expressed on the surface of microglia/macrophages and neutrophils and participated in Prx2-induced inflammation. TAK-242 treatment attenuated Prx2-induced inflammation and neurological deficits. CONCLUSIONS: Prx2 can cause brain injury following ICH through the TLR4 pathway, revealing the Prx2-TLR4 inflammatory axis as a potential therapeutic target.

G-4 inhibits triple negative breast cancer by inducing cell apoptosis and promoting LCN2-dependent ferroptosis.

Compound G-4 is a derivate of cyclin-dependent kinase inhibitor Rocovitine and showed strong sensitivity to triple negative breast cancer (TNBC) cells. In this study, the antitumor activity, mechanism and possible targets of G-4 in TNBC were investigated. Flow cytometry and immunoblotting showed that G-4 not only arrested the S phase of the cell cycle, but also induced apoptosis in TNBC cells via the mitochondrial pathway through inhibiting epidermal growth factor receptor (EGFR), AKT and MAPK pathways. In addition, G-4 induced the iron-mutagenesis process in TNBC cells and down-regulated differentially expressed gene lipid carrier protein 2 (LCN2) by RNA-seq. Moreover, G-4 elevated levels of cytosolic reactive oxygen species (ROS), lipid ROS, Fe and malondialdehyde (MDA), but decreased levels of superoxide dismutase (SOD) and glutathione (GSH), consistent with the effects of iron-mutagenic agonists Erastin and RSL3, which were inhibited by the iron inhibitor ferrostatin-1 (Fer-1). Furthermore, a LCN2 knockdown cell model was established by siRNA transfection, the IC50 of G-4 was increased nearly 100-fold, accompanied by a trend of no ferroptosis characteristic index. The results indicated that G-4 suppressed the malignant phenotype of TNBC, induced apoptosis by inhibiting EGFR pathway and promoted LCN2-dependent ferroptosis.

Spem2, a novel testis-enriched gene, is required for spermiogenesis and fertilization in mice.

Spermiogenesis is considered to be crucial for the production of haploid spermatozoa with normal morphology, structure and function, but the mechanisms underlying this process remain largely unclear. Here, we demonstrate that SPEM family member 2 (Spem2), as a novel testis-enriched gene, is essential for spermiogenesis and male fertility. Spem2 is predominantly expressed in the haploid male germ cells and is highly conserved across mammals. Mice deficient for Spem2 develop male infertility associated with spermiogenesis impairment. Specifically, the insufficient sperm individualization, failure of excess cytoplasm shedding, and defects in acrosome formation are evident in Spem2-null sperm. Sperm counts and motility are also significantly reduced compared to controls. In vivo fertilization assays have shown that Spem2-null sperm are unable to fertilize oocytes, possibly due to their impaired ability to migrate from the uterus into the oviduct. However, the infertility of Spem2-/- males cannot be rescued by in vitro fertilization, suggesting that defective sperm-egg interaction may also be a contributing factor. Furthermore, SPEM2 is detected to interact with ZPBP, PRSS21, PRSS54, PRSS55, ADAM2 and ADAM3 and is also required for their processing and maturation in epididymal sperm. Our findings establish SPEM2 as an essential regulator of spermiogenesis and fertilization in mice, possibly in mammals including humans. Understanding the molecular role of SPEM2 could provide new insights into future therapeutic treatment of human male infertility and development of non-hormonal male contraceptives.

Application of plasma metagenomic next-generation sequencing improves prognosis in hematology patients with neutropenia or hematopoietic stem cell transplantation for infection.

Introduction: Metagenomic next-generation sequencing (mNGS) is a novel technique for detecting pathogens. This retrospective study evaluated the diagnostic value of mNGS using plasma for infections in hematology patients and its impact on clinical treatment and prognosis in different subgroups of hematology patients. Methods: A total of 153 hematology patients with suspected infection who underwent mNGS using plasma were enrolled in the study. Their clinical histories, conventional microbiological test (CMT) results, mNGS results, treatment and prognosis were retrospectively analyzed. Results: In 153 plasma samples, mNGS yielded a higher positivity rate than CMT (total: 88.24% vs. 40.52%, P<0.001; bacteria: 35.95% vs. 21.57%, P < 0.01; virus: 69.93% vs. 21.57%, P<0.001; fungi: 20.26% vs. 7.84%, P<0.01). mNGS had a higher positivity rate for bacteria and fungi in the neutropenia group than in the non-neutropenia group (bacteria: 48.61% vs. 24.69%, P<0.01; fungi: 27.78% vs. 13.58%, P<0.05). mNGS demonstrated a greater advantage in the group of patients with hematopoietic stem cell transplantation (HSCT). Both the 3-day and 7-day efficacy rates in the HSCT group were higher than those in the non-HSCT group (3-day: 82.22% vs. 58.65%, P < 0.01; 7-day: 88.89% vs. 67.31%, P < 0.01), and the 28-day mortality rate was lower in the HSCT group than in the non-HSCT group (6.67% vs. 38.89%, P < 0.000). The neutropenia group achieved similar efficacy and mortality rates to the non-neutropenia group (7-day efficiency rate: 76.39% vs. 71.43%, P > 0.05; mortality rate: 29.17% vs. 29.63%, P > 0.05) with more aggressive antibiotic adjustments (45.83% vs. 22.22%, P < 0.01). Conclusion: mNGS can detect more microorganisms with higher positive rates, especially in patients with neutropenia. mNGS had better clinical value in patients with hematopoietic stem cell transplantation (HSCT) or neutropenia, which had a positive effect on treatment and prognosis.

Clinical and diagnostic values of metagenomic next-generation sequencing for infection in hematology patients: a systematic review and meta-analysis.

OBJECTIVES: This meta-analysis focused on systematically assessing the clinical value of mNGS for infection in hematology patients. METHODS: We searched for studies that assessed the clinical value of mNGS for infection in hematology patients published in Embase, PubMed, Cochrane Library, Web of Science, and CNKI from inception to August 30, 2023. We compared the detection positive rate of pathogen for mNGS and conventional microbiological tests (CMTs). The diagnostic metrics, antibiotic adjustment rate and treatment effective rate were combined. RESULTS: Twenty-two studies with 2325 patients were included. The positive rate of mNGS was higher than that of CMT (blood: 71.64% vs. 24.82%, P < 0.001; BALF: 89.86% vs. 20.78%, P < 0.001; mixed specimens: 82.02% vs. 28.12%, P < 0.001). The pooled sensitivity and specificity were 87% (95%CI: 81-91%) and 59% (95%CI: 43-72%), respectively. The reference standard/neutropenia and research type/reference standard may be sources of heterogeneity in sensitivity and specificity, respectively. The pooled antibiotic adjustment rate according to mNGS was 49.6% (95% CI: 41.8-57.4%), and the pooled effective rate was 80.9% (95% CI: 62.4-99.3%). CONCLUSION: mNGS has high positive detection rates in hematology patients. mNGS can guide clinical antibiotic adjustments and improve prognosis, especially in China.

Resourcization of Argillaceous Limestone with Mn3O4 Modification for Efficient Adsorption of Lead, Copper, and Nickel.

Argillaceous limestone (AL) is comprised of carbonate minerals and clay minerals and is widely distributed throughout the Earth's crust. However, owing to its low surface area and poorly active sites, AL has been largely neglected. Herein, manganic manganous oxide (Mn3O4) was used to modify AL by an in-situ deposition strategy through manganese chloride and alkali stepwise treatment to improve the surface area of AL and enable its utilization as an efficient adsorbent for heavy metals removal. The surface area and cation exchange capacity (CEC) were enhanced from 3.49 to 24.5 m2/g and 5.87 to 31.5 cmoL(+)/kg with modification, respectively. The maximum adsorption capacities of lead (Pb2+), copper (Cu2+), and nickel (Ni2+) ions on Mn3O4-modified argillaceous limestone (Mn3O4-AL) in mono-metal systems were 148.73, 41.30, and 60.87 mg/g, respectively. In addition, the adsorption selectivity in multi-metal systems was Pb2+ > Cu2+ > Ni2+ in order. The adsorption process conforms to the pseudo-second-order model. In the multi-metal system, the adsorption reaches equilibrium at about 360 min. The adsorption mechanisms may involve ion exchange, precipitation, electrostatic interaction, and complexation by hydroxyl groups. These results demonstrate that Mn3O4 modification realized argillaceous limestone resourcization as an ideal adsorbent. Mn3O4-modified argillaceous limestone was promising for heavy metal-polluted water and soil treatment.

Metformin adverse event profile: a pharmacovigilance study based on the FDA Adverse Event Reporting System (FAERS) from 2004 to 2022.

BACKGROUND: Metformin has the potential for treating numerous diseases, but there are still many unrecognized and unreported adverse events (AEs). METHODS: We selected data from the United States FDA Adverse Event Reporting System (FAERS) database from the first quarter (Q1) of 2004 to the fourth quarter (Q4) of 2022 for disproportionality analysis to assess the association between metformin and related adverse events. RESULTS: In this study 10,500,295 case reports were collected from the FAERS database, of which 56,674 adverse events related to metformin were reported. A total of 643 preferred terms (PTs) and 27 system organ classes (SOCs) that were significant disproportionality conforming to the four algorithms simultaneously were included. The SOCs included metabolic and nutritional disorders (p = 0.00E + 00), gastrointestinal disorders (p = 0.00E + 00) and others. PT levels were screened for adverse drug reaction (ADR) signals such as acute pancreatitis (p = 0.00E + 00), melas syndrome, pemphigoid (p = 0.00E + 00), skin eruption (p = 0.00E + 00) and drug exposure during pregnancy (p = 0.00E + 00). CONCLUSION: Most of our results were consistent with the specification, but some new signals of adverse reactions such as acute pancreatitis were not included. Therefore, further studies are needed to validate unlabeled adverse reactions and provide important support for clinical monitoring and risk identification of metformin.

Relocation of lower pole renal stones helps improve the stone-free rate during flexible ureteroscopy with a low complication rate.

OBJECTIVE: To compare the efficacy and safety of relocating the lower pole stones to a favorable pole during flexible ureteroscopy with in situ lithotripsy for the treatment of 10-20 mm lower pole stone (LPS). METHODS: This study was a prospective analysis of patient outcomes who underwent an FURS procedure for the treatment of 10-20 mm lower pole renal stones from January 2020 to November 2022. The patients were randomized into a relocation group or in situ group. The LPSs were relocated into a calyx, during lithotripsy in the relocation group was performed, whereas the in situ group underwent FURS without relocation. All the procedures were performed by the same surgeon. The patients' demographic data, stone characteristics, perioperative parameters and outcomes, stone-free rate (SFR), complications, and overall costs were assessed retrospectively. RESULTS: A total of 90 patients were enrolled and analyzed in this study (45 per group) with no significant differences between the two groups in terms of age, gender, BMI, diabetes, hypertension, stone size, number, laterality, composition, and density. The mean operation time, total energy consumption, postoperative stay, and complications were similar between the groups. Both groups had similar SFR at 1 day postoperative follow-up (p = 0.091), while the relocation group achieved significantly higher SFR 3 months later (97.8% vs 84.4%, p = 0.026). The relocation group also had a significantly higher WisQol score than the in situ group (126.98 vs 110.18, p < 0.001). CONCLUSION: A satisfactory SFR with a relatively low complication rate was achieved by the relocation technique during the FURS procedure.