Synthesis, preclinical assessment, and first-in-human study of [18F]d4-FET for brain tumor imaging.

PURPOSE: Tumor-to-background ratio (TBR) is a critical metric in oncologic PET imaging. This study aims to enhance the TBR of [18F]FET in brain tumor imaging by substituting deuterium ("D") for hydrogen ("H"), thereby improving the diagnostic sensitivity and accuracy. METHODS: [18F]d4-FET was synthesised by two automated radiochemistry modules. Biodistribution studies and imaging efficacy were evaluated in vivo  and ex vivo in rodent models, while metabolic stability and radiation dosimetry were assessed in non-human primates. Additionally, preliminary imaging evaluations were carried out in five brain tumor patients: three glioma patients underwent imaging with both [18F]d4-FET and [18F]FET, and two patients with brain metastases were imaged using [18F]d4-FET and [18F]FDG. RESULTS: [18F]d4-FET demonstrated high radiochemical purity and yield. PET/MRI in rodent models demonstrated superior TBR for [18F]d4-FET compared to [18F]FET, and autoradiography showed tumor margins that correlated well with pathological extents. Studies in cynomolgus monkeys indicated comparable in vivo stability and effective dose with [18F]FET. In glioma patients, [18F]d4-FET showed enhanced TBR, while in patients with brain metastases, [18F]d4-FET displayed superior lesion delineation compared to [18F]FDG, especially in smaller metastatic sites. CONCLUSION: We successfully synthesized the novel PET radiotracer [18F]d4-FET, which retains the advantageous properties of [18F]FET while potentially enhancing TBR for glioma imaging. Preliminary studies indicate excellent stability, efficacy, and sensitivity of [18F]d4-FET, suggesting its potential in clinical evaluations of brain tumors. TRIAL REGISTRATION: ChiCTR2400081576, registration date: 2024-03-05, https://www.chictr.org.cn/bin/project/edit?pid=206162.

Mangiferin Ameliorates CCl4-Triggered Acute Liver Injury by Inhibiting Inflammatory Response and Oxidative Stress: Involving the Nrf2-ARE Pathway.

Purpose: Acute liver injury (ALI) is characterized by inflammation and oxidative stress (OS). Although mangiferin (MGF) has antioxidant and anti-inflammatory effects, its role in ALI remains unclear. Accordingly, we investigated the MGF molecular mechanism in carbon tetrachloride (CCl4)-induced ALI in vivo and in vitro. Materials and Methods: The CCl4 was utilized to induce ALI in mice. In vivo, the therapeutic effects of MGF on CCl4-induced liver injury were evaluated through biochemical assays and histomorphological analysis. Additionally, immunohistochemistry, immunofluorescence, ELISA and Western blotting were further applied to explore the mechanism. In vitro, The CCK-8 assay and flow cytometry were employed to investigate the protective effects of MGF against CCl4-induced toxicity in HepG2 cells, while mitochondrial reactive oxygen species levels and Western blotting were used to explore the biological effects and molecular mechanisms. Results: MGF treatment resulted in a reduction in serum levels of AST and ALT, diminished concentrations of TNF-α, IL-6, and IL-1ß in liver tissue, and concurrently decreased cellular apoptosis. Furthermore, MGF pretreatment enhanced the activity of SOD and GSH while concurrently diminishing the MDA production. This study further demonstrated the upregulation of Nrf2, NQO1, and HO-1 protein expression levels, as well as the downregulation of p-p65 protein expression levels. In vitro investigations revealed that the mitigation of CCl4-induced inflammation and OS by MGF was mediated via the Nrf2- antioxidant response element (ARE) pathway, which was disrupted by ML385 in HepG2 cells. Conclusion: CCl4 can induce liver injury, while treatment with MGF mitigates ALI by inhibiting oxidative stress, inflammation, and apoptosis. The protective mechanism of MGF is mediated by the Nrf2-ARE pathway activation.

The role of islet autoantigen-specific T cells in the onset and treatment of type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM), a complex chronic disease with an intricate etiology and pathogenesis, involves the recognition of self-antigens by pancreatic islet autoantigen-specific T cells and plays crucial roles in both early- and late-stage destruction of beta cells, thus impacting disease progression. Antigen-specific T cells regulate and execute immune responses by recognizing particular antigens, playing broad roles in the treatment of various diseases. Immunotherapy targeting antigen-specific T cells holds promising potential as a targeted treatment approach. This review outlines the pathogenesis of diabetes, emphasizing the pivotal role of pancreatic islet autoantigen-specific T cells in the progression and treatment of T1DM. Exploring this avenue in research holds promise for identifying novel therapeutic targets for effectively managing diabetes.

Six new sesquineolignans from the stems of Akebia quinate and their diacylglycerol acyltransferase activity.

Six new sesquineolignans (1-6), have been isolated and elucidated from the stems of Akebia quinate together with five known analogues (7-11). Their structures were elucidated on the basis of comprehensive analysis of UV, IR, NMR, HRESIMS and CD spectroscopy experiments. All the isolates were evaluated for in vitro inhibitory activity against DGAT1 and DGAT2. Among them, compounds 1-11 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 60.4 ± 1.3 to 84.6 ± 1.3 µM. Besides, the potential binding sites of 1 were predicted by molecular docking.

Vanadate-Mediated Mismatch Configuration over the Reconstructed Nickel-Iron Electrocatalyst for Boosting Alkaline Oxygen Evolution.

During the oxygen evolution reaction (OER), catalyst candidates that can fully trigger self-reconstruction to derive active species with favorable configurations are expected to overcome the sluggish reaction kinetics. Herein, we innovatively propose the introduction of heterogeneous vanadate dopants into nickel-iron alloy precatalysts, where the crystal mismatch structure induces local electron delocalization in the hexagonal close packed alloy phase, thereby facilitating adequate electrochemical reconstruction to form (oxy)hydroxides as the real catalytic species. Simultaneously, the participation of vanadate in the reconstruction also triggers mismatch in the derived (oxy)hydroxides, reinforcing the metal-oxygen covalence, so that lattice oxygen activation is kinetically favorable and facilitates the OER via the lattice oxygen pathway. Optimized reconstructed catalyst r-NiFeVOx-NF exhibits a low overpotential of 220 mV at current densities of 10 mA cm-2 and considerably stable operation. Our study opens up opportunities for achieving robust OER performance through the design and fabrication of the mismatch catalytic configuration.

Stabilization of RRBP1 mRNA via an m6A-dependent manner in prostate cancer constitutes a therapeutic vulnerability amenable to small-peptide inhibition of METTL3.

Mounting evidence has implicated the RNA m6A methylation catalyzed by METTL3 in a wide range of physiological and pathological processes, including tumorigenesis. The detailed m6A landscape and molecular mechanism of METTL3 in prostate cancer (PCa) remains ill-defined. We find that METTL3 is overexpressed in PCa and correlates with worse patient survival. Functional studies establish METTL3 as an oncoprotein dependent on its m6A enzymatic activity in both AR+ and AR- PCa cells. To dissect the regulatory network of m6A pathway in PCa, we map the m6A landscape in clinical tumor samples using m6A-seq and identify genome-wide METTL3-binding transcripts via RIP-seq. Mechanistically, we discover RRBP1 as a direct METTL3 target in which METTL3 stabilizes RRBP1 mRNA in an m6A-dependent manner. RRBP1 positively correlates with METTL3 expression in PCa cohorts and exerts an oncogenic role in aggressive PCa cells. Leveraging the 3D structural protein-protein interaction between METTL3 and METTL14, we successfully develop two potential METTL3 peptide inhibitors (RM3 and RSM3) that effectively suppress cancer cell proliferation in vitro and tumor growth in vivo. Collectively, our study reveals a novel METTL3/m6A/RRBP1 axis in enhancing aggressive traits of PCa, which can be therapeutically targeted by small-peptide METTL3 antagonists.

Glucagon-like peptide-1 receptor agonists in neoplastic diseases.

Glucagon-like peptide-1 receptor agonist (GLP-1RA), a novel hypoglycemic agent for the treatment of type 2 diabetes, has well-known effects such as lowering blood sugar, ameliorating inflammation, reducing weight, and lowering blood lipids. It has also been shown that it can influence the proliferation and survival of cells and has a certain effect on the prognosis of some neoplastic diseases. In this study, the potential effects of GLP-1RAs on the occurrence and development of tumors were reviewed to provide new ideas for the prevention and treatment of tumors in patients.

Isoliquiritigenin as a modulator of the Nrf2 signaling pathway: potential therapeutic implications.

Nuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor responsible for cytoprotection, plays a crucial role in regulating the expression of numerous antioxidant genes, thereby reducing reactive oxygen species (ROS) levels and safeguarding cells against oxidative stress. Extensive research has demonstrated the involvement of Nrf2 in various diseases, prompting the exploration of Nrf2 activation as a potential therapeutic approach for a variety of diseases. Consequently, there has been a surge of interest in investigating the Nrf2 signaling pathway and developing compounds that can modulate its activity. Isoliquiritigenin (ISL) (PubChem CID:638278) exhibits a diverse range of pharmacological activities, including antioxidant, anticancer, and anti-tumor properties. Notably, its robust antioxidant activity has garnered significant attention. Furthermore, ISL has been found to possess therapeutic effects on various diseases, such as diabetes, cardiovascular diseases, kidney diseases, and cancer, through the activation of the Nrf2 pathway. This review aims to evaluate the potential of ISL in modulating the Nrf2 signaling pathway and summarize the role of ISL in diverse diseases prevention and treatment through modulating the Nrf2 signaling pathway.

Evaluation of the Choroid Plexus Epithelium Inflammation TLR4/NF-κB/NKCC1 Signal Pathway Activation in the Development of Hydrocephalus.

BACKGROUND: Hydrocephalus is characterized by secretion, circulation, and absorption disorder of cerebrospinal fluid (CSF) with high morbidity and complication rate. The relationship between inflammation and abnormal secretion of CSF by choroid plexus epithelium (CPE) had received more attention. In this study, we aim to detect the role of Toll-like receptor 4/nuclear factor-kappa B/Na+/K+/2Cl-cotransporter 1(TLR4/NF-κB/NKCC1) signal pathway in the development of hydrocephalus. METHOD: Hydrocephalus was induced in adult rats (8 weeks) by intracisternal kaolin injection, then pyrrolidinedithiocarbamate (PDTC) and bumetanide were administrated to the rats mode. Then the rat model was evaluated, and ventricular volume was calculated at different time points. Then CPE, cortex, preventricular tissue, and CSF were obtained. Protein expressions of TLR-4, NKCC/serine-threonine STE20/SPS1-related, proline-alanine-rich kinase (SPAK), pNKCC1, pSPAK, GFAP, AQP1, and AQP4 were measured by RT-PCR, western blot, and immunofluorescence (IF) stains in CPE, respectively. RESULT: Our data showed that inflammation factors tumor necrosis factor-(TNF-α), interleukin 18(IL-18), and glial fibrillary acidic protein (GFAP) concentrations were significantly higher in the model group than in controls. The TLR4/NF-κB/NKCC1 signal pathway were actived by NF-κB-p65, NKCC1, pNKCC1- pSPAK complex, and Aquaporin1 (AQP1) high expression. PDTC and bumetanide use can help regular TLR4/NF-κB/NKCC1 expression and reduced AQP1 expression by down-regulate NF-B-p65 and inhibiting NKCC1, respectively. As a result, the treatment groups alleviated CPE abnormal secretion and ventricle enlargement. CONCLUSION: These results confirmed that the inflammatory reaction contributes TLR4/NF-κB/NKCC1 mediated CPE abnormal secretion and consequent hydrocephalus. Regulation of TLR4/NF-κB/NKCC1 and AQP1 can prevent this process. Our study provides a strong rationale for further exploring alleviating CPE abnormal secretion as a therapeutic perspective of hydrocephalus.

CircFOXO3 upregulation mediates the radioresistance of glioblastoma by affecting cellular metabolome.

Introduction: Radioresistance remains a significant challenge in the treatment of glioblastoma multiforme (GBM), the most prevalent and lethal brain cancer in adults. Metabolic alterations are known to contribute to radioresistance by activating antioxidant responses and promoting DNA repair. However, the role of circular RNAs in this process, particularly circFOXO3, is not well understood. Methods: In this study, we investigated the expression of circFOXO3 in glioma cells exposed to radiation and in recurrent GBM tissues. We performed knockdown and overexpression experiments in vitro and in vivo to assess the effects of circFOXO3 on radiosensitivity. Metabolomic profiling was conducted to explore the metabolic changes associated with circFOXO3 overexpression following irradiation. Results: Our results showed significant upregulation of circFOXO3 in glioma cells upon radiation exposure and in recurrent GBM tissues. Knockdown of circFOXO3 increased radiosensitivity both in vitro and in vivo, whereas overexpression of circFOXO3 attenuated radiosensitivity. Metabolomic analysis revealed substantial alterations in lipid and organic compound profiles between circFOXO3-overexpressing and control groups. Additionally, circFOXO3 suppression increased proapoptotic protein levels (Caspase 7 and Bax) and decreased anti-apoptotic protein Bcl-2 levels following radiotherapy. Discussion: These findings demonstrate the pivotal role of circFOXO3 in promoting tumor radioresistance through metabolic modulation, suggesting that circFOXO3 could serve as a potential diagnostic and therapeutic target for GBM.

A smartphone-integrated deep learning strategy-assisted rapid detection system for monitoring dual-modal immunochromatographic assay.

This study focuses on the integration of a custom-built and optimally trained YOLO v5 model into a smartphone app developed with Java language. A dual-modal immunochromatographic rapid detection system based on a deep learning strategy for smartphones was developed for grade determination and predicting the concentration of aflatoxin B1 (AFB1). Innovative distance-type quantum dot microsphere fluorescent immunochromatographic chips enable semi-quantitative analysis by naked eye, and conventional colloidal gold nanoparticle colorimetric strips were also prepared. The compact and versatile hardware device making it easily integrable into smartphones of varying dimensions. Moreover, the wireless charging functionality of smartphones was to tackle power supply challenges. After optimized training, the accuracy, mAP@0.5, precision, and recall metrics of the YOLO v5 model all soared to 98 %. For the dual-modal immunochromatographic chips, the R2 values for the standard curve fits were as high as 0.993, with a broad linear range of 0.05-40 ng/mL and a standard deviation lower than 0.03 at each concentration. Finally, this system determined the grade of the AFB1 concentration with an accuracy of up to 98 % and it exhibited an ultra-sensitive quantitative detection capability with a limit of detection as low as 2.2 pg/mL, showcasing the reliability of the deep learning strategy for practical applications in smartphones. This robust technological foundation paves the way for potentially community-based, family-oriented, and personalized applications.

Oxygen Plasma Triggered Co-O-Fe Motif in Prussian Blue Analogue for Efficient and Robust Alkaline Water Oxidation.

In the context of oxygen evolution reaction (OER), the construction of high-valent transition metal sites to trigger the lattice oxygen oxidation mechanism is considered crucial for overcoming the performance limitations of traditional adsorbate evolution mechanism. However, the dynamic evolution of lattice oxygen during the reaction poses significant challenges for the stability of high-valent metal sites, particularly in high-current-density water-splitting systems. Here, we have successfully constructed Co-O-Fe catalytic active motifs in cobalt-iron Prussian blue analogs (CoFe-PBA) through oxygen plasma bombardment, effectively activating lattice oxygen reactivity while sustaining robust stability. Our spectroscopic and theoretical studies reveal that the Co-O-Fe bridged motifs enable a unique double-exchange interaction between Co and Fe atoms, promoting the formation of high-valent Co species as OER active centers while maintaining Fe in a low-valent state, preventing its dissolution. The resultant catalyst (CoFe-PBA-30) requires an overpotential of only 276 mV to achieve 1000 mA cm-2. Furthermore, the assembled alkaline exchange membrane electrolyzer using CoFe-PBA-30 as anode material achieves a high current density of 1 A cm-2 at 1.76 V and continuously operates for 250 hours with negligible degradation. This work provides significant insights for activating lattice oxygen redox without compromising structure stability in practical water electrolyzers.

Genome sequence of a ST65 hypervirulent Klebsiella pneumoniae isolate carrying mcr-8 from China.

OBJECTIVES: In this study, we report the complete genome sequence of a ST65 hypervirulent Klebsiella pneumoniae isolate carrying mcr-8 from China. The aim was to investigate its molecular characteristics and resistant mechanism. METHODS: A colistin-resistant hvKP was isolated from an inpatient in China. The whole genome was sequenced on Illumina NovaSeq 6000 and long-read ONT platforms. de novo assembly was conducted using SPAdes and Unicycler. S1 nuclease pulsed-field gel electrophoresis, Southern-blot, and antimicrobial susceptibility testing were performed. Sequence type, antimicrobial resistance and virulence-related genes were predicted from the sequence. The circular maps of multiple plasmids comparisons were drawn by the BLAST Ring Image. RESULTS: The complete genome sequence of K. pneumoniae ACESH00926 consists of one chromosome and two plasmids. ACESH00926 belongs to K2 ST65 according to the MLST scheme. ACESH00926 showed high resistance to colistin (MIC > 8 µg/mL). Several ARGs were identified, including mobile colistin-resistant gene mcr-8 which was located in an IncFIl(K)/IncFIA(HI1) type plasmid. The bigger plasmid was a pK244-like virulence plasmid. It carrying a series of virulence genes, such as the regulator of the mucoid phenotype (rmpA and rmpA2), salmochelin siderophore biosynthesis (iroB), ABC transporter (iroC), ferric aerobactin receptor (iutA), aerobactin siderophore biosynthesis protein (iucC), and aerobactin synthetase (iucA) encoded genes. And another plasmid carrying mcr-8 with a conserved genetic context (dgkA-sasA-copR-mcr-8-ccdA-ccdB-xerD-repE-parM-umuC-lexA-klcA). CONCLUSIONS: It is necessary to emphasize the necessity of monitoring a combination of colistin-resistant and hypervirulent Klebsiella pneumoniae strains in the future.

Overcoming tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade.

Lung cancer brain metastasis (LCBM) poses a significant clinical challenge due to acquired resistance to tyrosine kinase inhibitor (TKI) treatment. To elucidate its underlying mechanisms, we employed single-cell RNA sequencing analysis on surgically obtained LCBM samples with diverse genetic backgrounds and TKI treatment histories. Our study uncovers that TKI treatment elevates the immune checkpoint CTLA4 expression in T cells, promoting an immune-suppressive microenvironment. This immunomodulation is initiated by tumor-derived HMGB1 in response to TKIs. In LCBM syngeneic murine models with TKI-sensitive or TKI-resistant EGFR mutations, combining CTLA4 blockade with TKIs demonstrates enhanced efficacy over TKI monotherapy or TKIs with PD1 blockade. These findings provide insights into the TKI resistance mechanisms and highlight the potential of CTLA4 blockade in effectively overcoming TKI resistance in LCBM.

The isoflavone puerarin promotes generation of human iPSC-derived pre-oligodendrocytes and enhances endogenous remyelination in rodent models.

Puerarin, a natural isoflavone, is commonly used as a Chinese herbal medicine for the treatment of various cardiovascular and neurological disorders. It has been found to be neuroprotective via TrK-PI3K/Akt pathway, which is associated with anti-inflammatory and antioxidant effects. Myelin damage in diseases such as multiple sclerosis (MS) and ischemia induces activation of endogenous oligodendrocyte progenitor cells (OPC) and subsequent remyelination by newly formed oligodendrocytes. It has been shown that human-induced pluripotent stem cells (hiPSC)-derived OPCs promote remyelination when transplanted to the brains of disease models. Here, we ask whether and how puerarin is beneficial to the generation of hiPSC-derived OPCs and oligodendrocytes, and to the endogenous remyelination in mouse demyelination model. Our results show that puerarin increases the proportion of O4+ pre-oligodendrocytes differentiated from iPSC-derived neural stem cells. In vitro, puerarin increases proliferation of rat OPCs and enhances mitochondrial activity. Treatment of puerarin at progenitor stage increases the yielding of differentiated oligodendrocytes. In rat organotypic brain slice culture, puerarin promotes both myelination and remyelination. In vivo, puerarin increases oligodendrocyte repopulation during remyelination in mouse spinal cord following lysolethicin-induced demyelination. Our findings suggest that puerarin promotes oligodendrocyte lineage progression and myelin repair, with a potential to be developed into therapeutic agent for neurological diseases associated with myelin damage.

Comprehensive management of gestational diabetes mellitus: practical efficacy of exercise therapy and sustained intervention strategies.

Background: Gestational Diabetes Mellitus (GDM) affects 14.0% of pregnancies globally, with a 35% post-pregnancy relapse and a 60% risk of Type 2 Diabetes (T2D) within 5-10 years. Challenges in long-term management, especially postpartum, include adherence and follow-up difficulties. Methods: This study, based on a systematic review and meta-analysis, examined the practical effects of exercise therapy in the prevention, treatment, and prevention of progression from Gestational Diabetes Mellitus (GDM) to Type 2 Diabetes (T2D). Relevant research and clinical practices were retrieved from six major databases (PubMed, Scopus, Web of Science, Cochrane Library, MEDLINE, Science Direct). After analyzing the intervention effects of exercise therapy at different stages, factors favorably influencing the effectiveness of exercise intervention were identified during the more effective stages. Finally, a long-term and efficient exercise implementation plan for the comprehensive management of GDM was proposed. Results: In GDM prevention, exercise reduced the post-intervention risk by 37% compared to the control group (Relative Risk (RR)=0.63; 95% Confidence Interval (CI): 0.54 to 0.72; p=0.01). Studies on GDM treatment showed improved glucose control in the exercise group post-intervention (Mean Difference (MD)=-0.10; 95% CI: -0.16 to -0.04; p=0.04/MD=-0.27; 95% CI: -0.36 to -0.19; p<0.0001). However, exercise therapy didn't significantly affect the incidence of T2D post-GDM (RR=0.88; 95% CI: 0.69 to 1.11; p=0.39) due to challenges in quantified exercise prescriptions and the complexity of postpartum programs. Conclusion: To enhance exercise therapy effectiveness in GDM management, the study recommends adopting an integrated model emphasizing personalized pregnancy plans, postpartum strategies, and long-term support. Leveraging frequent healthcare contact during pregnancy can establish and sustain exercise habits, fostering a lifelong pattern. While the study acknowledges limitations, this approach holds potential for improving glycemic metabolism and developing healthy exercise habits in subsequent generations. Future research should include longer follow-ups to validate the practical efficacy of this approach in preventing T2D after GDM. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023463617.

Combination of intravoxel incoherent motion histogram parameters and clinical characteristics for predicting response to neoadjuvant chemoradiation in patients with locally advanced rectal cancer.

OBJECTIVE: To explore the value of histogram parameters derived from intravoxel incoherent motion (IVIM) for predicting response to neoadjuvant chemoradiation (nCRT) in patients with locally advanced rectal cancer (LARC). METHODS: A total of 112 patients diagnosed with LARC who underwent IVIM-DWI prior to nCRT were enrolled in this study. The true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and microvascular volume fraction (f) calculated from IVIM were recorded along with the histogram parameters. The patients were classified into the pathological complete response (pCR) group and the non-pCR group according to the tumor regression grade (TRG) system. Additionally, the patients were divided into low T stage (yp T0-2) and high T stage (ypT3-4) according to the pathologic T stage (ypT stage). Univariate logistic regression analysis was implemented to identify independent risk factors, including both clinical characteristics and IVIM histogram parameters. Subsequently, models for Clinical, Histogram, and Combined Clinical and Histogram were constructed using multivariable binary logistic regression analysis for the purpose of predicting pCR. The area under the receiver operating characteristic (ROC) curve (AUCs) was employed to evaluate the diagnostic performance of the three models. RESULTS: The values of D_ kurtosis, f_mean, and f_ median were significantly higher in the pCR group compared with the non-pCR group (all P < 0.05). The value of D*_ entropy was significantly lower in the pCR group compared with the non-pCR group (P < 0.05). The values of D_ kurtosis, f_mean, and f_ median were significantly higher in the low T stage group compared with the high T stage group (all P < 0.05). The value of D*_ entropy was significantly lower in the low T stage group compared with the high T stage group (P < 0.05). The ROC curves indicated that the Combined Clinical and Histogram model exhibited the best diagnostic performance in predicting the pCR patients with AUCs, sensitivity, specificity, and accuracy of 0.916, 83.33%, 85.23%, and 84.82%. CONCLUSIONS: The histogram parameters derived from IVIM have the potential to identify patients who have achieved pCR. Moreover, the combination of IVIM histogram parameters and clinical characteristics enhanced the diagnostic performance of IVIM histogram parameters.

Toripalimab combined with definitive chemoradiotherapy for locally advanced cervical squamous cell carcinoma patients (TRACE): A single-arm, phase I/II trial.

PURPOSE: This phase I/II trial (ChiCTR2000032879) assessed the safety and efficacy of toripalimab combined with chemoradiotherapy for locally advanced cervical squamous cell carcinoma. METHODS AND MATERIALS: Twenty-two patients, regardless of their programmed death ligand-1 (PD-L1) status, received toripalimab combined with concurrent chemoradiotherapy (CCRT). CCRT included cisplatin (40 mg/m2, once weekly for 5 weeks), radiotherapy (45-50.4 Gy/25-28 Fx, 5 fractions weekly), followed by brachytherapy (24-30 Gy/3-5 Fx) and toripalimab (240 mg, intravenous) on days 1, 22 and 43 during CCRT. The primary endpoints were safety and 2-year progression-free survival (PFS). The secondary endpoints included 2-year local control (LC), local regional control and overall survival (OS). RESULTS: All patients successfully completed CCRT and toripalimab treatment. Grade III and higher adverse events (AEs) were observed in 11 patients (11/22, 50%), and no patient experienced grade V AEs. The objective response rate (ORR) was 100%. At the data cutoff (June 30, 2023), the median follow-up was 31.8 months (9.5 to 37.8 months). The 2-year PFS rate was 81.8%. The 2-year LC and local regional control rates were both 95.5%, and the 2-year OS rate was 90.9%. CONCLUSIONS: Toripalimab combined with CCRT achieved good tolerance and showed promising anti-tumor effects in patients with locally advanced cervical cancer.

PCPE2: Expression of multifunctional extracellular glycoprotein associated with diverse cellular functions.

Procollagen C-endopeptidase enhancer 2, known as PCPE2 or PCOC2 (gene name, PCOLCE2) is a glycoprotein that resides in the extracellular matrix, and is similar in domain organization to PCPE1/PCPE, PCOC1 (PCOLCE1/PCOLCE). Due to the many similarities between the two related proteins, PCPE2 has been assumed to have biological functions similar to PCPE. PCPE is a well-established enhancer of procollagen processing activating the enzyme, BMP-1. However, reports show that PCPE2 has a strikingly different tissue expression profile compared to PCPE. With that in mind and given the paucity of published studies on PCPE2, this review examines the current literature citing PCPE2 and its association with specific cell types and signaling pathways. Additionally, this review will present a brief history of PCPE2's discovery, highlighting structural and functional similarities and differences compared to PCPE. Considering the widespread use of RNA sequencing techniques to examine associations between cell-specific gene expression and disease states, we will show that PCPE2 is repeatedly found as a differentially regulated gene (DEG) significantly associated with a number of cellular processes, well beyond the scope of procollagen fibril processing.

Efficacy and safety of a novel vena cava filter on pulmonary embolism prophylaxis: a prospective, multicenter, randomized, parallel, positive-controlled, noninferiority clinical trial.

Background: There are different types of vena cava filter (VCF) available in clinical practice. However, limited data exist to determine whether one type is superior to another, and no single VCF is universally recommended in clinical guidelines. The objective of this study was to investigate the safety and efficacy of a novel VCF, Octoparms, for the prevention of pulmonary embolism (PE) and to compare it with the Celect filter. Methods: This multicenter, randomized, open-label, parallel, positive-controlled, noninferiority trial was conducted in 10 centers across 6 provinces in China from October 2017 to March 2019. Patients who had confirmed lower extremity deep vein thrombosis or PE or who were at risk of PE with a clinical indication for VCF placement due to contraindication to or failure of anticoagulant therapy were included in the trial. The sample size for this trial was based on the assumption that the clinical success rate would be 95% and the noninferiority margin would be 10% for both filters. Each patient underwent baseline testing and was randomized using a web-based central system. Any additional interventions or standard treatments patients received along with the VCF placement were recorded. The primary endpoint was the overall clinical success rate, including technical and clinical success of filter placement and retrieval. The secondary endpoint was the safety of filter placement and retrieval, encompassing procedure-related and filter-related complications. Results: A total of 188 patients were included and were divided into two groups: the Octoparms group (n=94) and the Celect group (n=94). Baseline characteristics and demographics were comparable between the two groups (P>0.05). Technical and clinical success rates for filter placement were achieved in 100% (188/188) of patients. The median dwelling time was 12.0 days (range, 4-190 days). Ten VCFs were left in situ as permanent devices. Of the remaining 178 patients, technical success and clinical success rates for filter retrieval were both achieved in 100% of cases (178/178). Clinical success rates were 92.6% (87/94) for the Octoparms group and 96.8% (91/94) for the Celect group, with a difference of -4.2% (hazard ratio 2.441, 95% confidence interval 0.612-9.741; P=0.206). The lower limit was greater than the noninferiority margin of -10%. Eight patients experienced a total of eight procedure-related complications. No filter-related complications, such as migration, deformation, inferior vena cava (IVC) penetration, peripheral organ damage, or IVC stenosis/occlusion, were observed (P>0.05). Conclusions: The Octoparms filter exhibited a high rate of clinical success and a low rate of complications during placement and retrieval, demonstrating noninferiority to the Celect filter.