Methyl CpG binding protein 2 regulates CYP27A1-induced myometrial contraction during preterm labor.

Persistent and intense uterine contraction is a risk factor for preterm labor. We previously found that Methyl-CpG binding protein 2 (MeCP2), as a target of infection-related microRNA miR-212-3p, may play an inhibitory role in regulating myometrium contraction. However, the molecular mechanisms by which MeCP2 regulates myometrial contraction are still unknown. In this study, we found that MeCP2 protein expression was lower in myometrial specimens obtained from preterm labor cases, compared to those obtained from term labor cases. Herein, using RNA sequence analysis of global gene expression in human uterine smooth muscle cells (HUSMCs) following siMeCP2, we show that MeCP2 silence caused dysregulation of cholesterol metabolism pathway. Notably, MeCP2 silence resulted in the upregulation of CYP27A1, the key enzyme involved in regulating cholesterol homeostasis, in HUSMCs. Methylation Specific PCR (MSP), Chromatin Immunoprecipitation (ChIP) and dual luciferase reporter gene technology indicated that MeCP2 could bind to the methylated CYP27A1 promoter region and repress its transcription. Administration of siCYP27A1 in an LPS-induced preterm labor mouse model delayed the onset of preterm labor. Human preterm myometrium and the LPS-induced preterm labor mouse model both showed lower expression of MeCP2 and increased expression of CYP27A1. These results demonstrated that aberrant upregulation of CYP27A1 induced by MeCP2 silencing is one of the mechanisms facilitating inappropriate myometrial contraction. CYP27A1 could be exploited as a novel therapeutic target for preterm birth.

Prognostic Value of Preoperative MRI-derived 3D Quantitative Tumor Arterial Burden in Patients with Hepatocellular Carcinoma Receiving Transarterial Chemoembolization.

Purpose To investigate the association of tumor arterial burden (TAB) on preoperative MRI with transarterial chemoembolization refractoriness (TACER) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). Materials and Methods This retrospective study included patients with HCC who underwent repeated transarterial chemoembolization (TACE) treatments between January 2013 and December 2020. HCC was confirmed with pathology or imaging, and patients with other tumors, lost follow-up, or with a combination of other treatments were excluded. TACER was defined as viable lesions of more than 50% or increase in tumor number after two or more consecutive TACE treatments, continuous elevation of tumor markers, extrahepatic spread, or vascular invasion. TAB assessed with preoperative MRI was divided into high and low groups according to the median. A Cox proportional hazards model was used to determine the predictors of TACER and PFS. Results A total of 355 patients (median age, 61 years [IQR, 54-67]; 306 [86.2%] men, 49 [13.8%] women) were included. During a median follow-up of 32.7 months, the high TAB group had significantly faster TACER and decreased PFS than the low TAB group (all log-rank P < .001). High TAB was the strongest independent predictor of TACER and PFS in multivariable Cox regression analyses (hazard ratio [HR], 2.23 [95% CI: 1.51, 3.29]; HR, 2.30 [95% CI: 1.61, 3.27], respectively), especially in patients with Barcelona Clinic Liver Cancer stage A or a single tumor. The restricted cubic spline plot demonstrated that the HR of TACER and PFS continuously increased with increasing TAB. Conclusion High preoperative TAB at MRI was a risk factor for faster refractoriness and progression in patients with HCC treated with TACE. Keywords: Interventional-Vascular, MR Angiography, Hepatocellular Carcinoma, Transarterial Chemoembolization, Progression-free Survival, MRI Supplemental material is available for this article. © RSNA, 2024.

MicroRNA-322-5p protects against myocardial infarction through targeting BTG2.

BACKGROUND: Numerous studies have explored the therapeutic potential of microRNA (miR) in myocardial infarction (MI) treatment. This study focuses on the role of miR-322-5p in MI, particularly in its regulatory interaction with B-cell translocation gene 2 (BTG2). MATERIALS AND METHODS: Expression levels of miR-322-5p and BTG2 were assessed in a rat MI model. Adenovirus altering miR-322-5p or BTG2 expression were administered to MI rats. Evaluation included cardiac function, inflammation, myocardial injury, pathological changes, apoptosis, and NF-κB pathway-related genes in MI rats post-targeted treatment. The miR-322-5p and BTG2 targeting relationship was investigated. RESULTS: MI rats exhibited low miR-322-5p and high BTG2 expression in the myocardial tissues. Restoration of miR-322-5p enhanced cardiac function, alleviated inflammation and myocardial injury, mitigated pathological changes and apoptosis, and deactivated the NF-κB pathway in MI rats. BTG2 expression was negatively-regulated by miR-322-5p. Overexpressed BTG2 counteracted miR-322-5p-induced cardioprotection on MI rats. CONCLUSION: This study provides evidence that miR-322-5p protects against MI by suppressing BTG2 expression.

Radiomics and machine learning based on preoperative MRI for predicting extrahepatic metastasis in hepatocellular carcinoma patients treated with transarterial chemoembolization.

Purpose: To develop and validate a radiomics machine learning (Rad-ML) model based on preoperative MRI to predict extrahepatic metastasis (EHM) in hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE) treatment. Methods: A total of 355 HCC patients who received multiple TACE procedures were split at random into a training set and a test set at a 7:3 ratio. Radiomic features were calculated from tumor and peritumor in arterial phase and portal venous phase, and were identified using intraclass correlation coefficient, maximal relevance and minimum redundancy, and least absolute shrinkage and selection operator techniques. Cox regression analysis was employed to determine the clinical model. The best-performing algorithm among eight machine learning methods was used to construct the Rad-ML model. A nomogram combining clinical and Rad-ML parameters was used to develop a combined model. Model performance was evaluated using C-index, decision curve analysis, calibration plot, and survival analysis. Results: In clinical model, elevated neutrophil to lymphocyte ratio and alpha-fetoprotein were associated with faster EHM. The XGBoost-based Rad-ML model demonstrated the best predictive performance for EHM. When compared to the clinical model, both the Rad-ML model and the combination model performed better (C-indexes of 0.61, 0.85, and 0.86 in the training set, and 0.62, 0.82, and 0.83 in the test set, respectively). However, the combined model's and the Rad-ML model's prediction performance did not differ significantly. The most influential feature was peritumoral waveletHLL_firstorder_Minimum in AP, which exhibited an inverse relationship with EHM risk. Conclusions: Our study suggests that the preoperative MRI-based Rad-ML model is a valuable tool to predict EHM in HCC patients treated with TACE.

EMDL-ac4C: identifying N4-acetylcytidine based on ensemble two-branch residual connection DenseNet and attention.

Introduction: N4-acetylcytidine (ac4C) is a critical acetylation modification that has an essential function in protein translation and is associated with a number of human diseases. Methods: The process of identifying ac4C sites by biological experiments is too cumbersome and costly. And the performance of several existing computational models needs to be improved. Therefore, we propose a new deep learning tool EMDL-ac4C to predict ac4C sites, which uses a simple one-hot encoding for a unbalanced dataset using a downsampled ensemble deep learning network to extract important features to identify ac4C sites. The base learner of this ensemble model consists of a modified DenseNet and Squeeze-and-Excitation Networks. In addition, we innovatively add a convolutional residual structure in parallel with the dense block to achieve the effect of two-layer feature extraction. Results: The average accuracy (Acc), mathews correlation coefficient (MCC), and area under the curve Area under curve of EMDL-ac4C on ten independent testing sets are 80.84%, 61.77%, and 87.94%, respectively. Discussion: Multiple experimental comparisons indicate that EMDL-ac4C outperforms existing predictors and it greatly improved the predictive performance of the ac4C sites. At the same time, EMDL-ac4C could provide a valuable reference for the next part of the study. The source code and experimental data are available at: https://github.com/13133989982/EMDLac4C.

Calcium dobesilate attenuates renal ischemia-reperfusion injury in a mouse model.

BACKGROUND: Calcium dobesilate (CaD) is a microvascular protective agent that can significantly improve kidney function by reducing urinary protein, serum creatinine, and urea nitrogen levels. The effects of CaD on ischemia-reperfusion-induced acute kidney injury (AKI) were investigated in this study. METHOD: In this study, The Balb/c mice were randomly divided into (1) sham group, (2) I/R group, (3) I/R group + CaD (50 mg/kg) and (4) I/R group + CaD (500 mg/kg). After treatment, serum creatinine and urea nitrogen were detected. The levels of superoxide dismutase (SOD) and malonaldehyde (MDA) were examined. Then, the effects of CaD H2O2-damaged HK-2 cells were investigated, as reflected by the results of cell viability, reactive oxygen species (ROS) level, apoptosis and markers of kidney injury. RESULTS: The results showed that CaD treatment effectively attenuated the renal functions, pathological changes, and oxidative stress in I/R-induced AKI mice. It effectively reduced ROS production and improved MMP and apoptosis in H2O2-damaged HK-2 cells. The increased expression of apoptosis-related proteins and kidney injury biomarkers were significantly ameliorated after CaD treatment. CONCLUSION: Overall, CaD effectively ameliorated renal injury by eliminating ROS and demonstrated in vivo and in vitro for I/R-induced AKI. CaD has been shown to be a promising therapeutic agent for the treatment of I/R-induced AKI.

Efficacy and safety of lenvatinib plus PD-1 inhibitor with or without transarterial chemoembolization in unresectable hepatocellular carcinoma.

PURPOSE: To compare the clinical benefit and tolerability of triple therapy of lenvatinib, programmed death 1 (PD-1) inhibitor, and transarterial chemoembolization (TACE) versus dual therapy of lenvatinib and PD-1 inhibitor in unresectable hepatocellular carcinoma (HCC) patients. METHODS: Between October 2018 and September 2021, patients with unresectable HCC who received triple therapy of lenvatinib, PD-1 inhibitor, and TACE or dual therapy of lenvatinib and PD-1 inhibitor participated in this study. The efficacy was evaluated by survival and therapeutic response, and the tolerability was evaluated by the frequency and severity of key adverse events (AEs). RESULTS: In total, 118 eligible patients with unresectable HCC who received combination therapy were included in this study. Among them, 60 patients received triple therapy of lenvatinib, PD-1 inhibitor, and TACE (L-P-T group), and 58 eligible patients received dual therapy of lenvatinib and PD-1 inhibitor (L-P group). Patients who received triple therapy had better overall survival (OS) [median, 29.0 vs. 17.8 months, p < 0.01] and progression-free survival (PFS) [median, 16.2 vs. 10.2 months, p < 0.01] than those who received dual therapy. The objective response rate (76.7 vs. 44.9%, p < 0.01) and disease control rate (96.7 vs. 75.9%, p < 0.01) in the L-P-T group were higher than in the L-P group, respectively. Multivariate analyses revealed that the treatment option and BCLC stage were independent prognostic factors for OS, while treatment option and tumor number were independent prognostic factors for PFS. The incidence and severity of AEs in the L-P-T group were comparable to those in the L-P group (any grade, 95.0 vs. 94.8%, p = 1.00; grade ≥ 3, 30.0 vs. 27.6%, p = 0.93). CONCLUSION: Triple therapy of lenvatinib, PD-1 inhibitor, and TACE may achieve more favorable survival benefits than dual therapy of lenvatinib and PD-1 inhibitor in unresectable HCC patients with manageable safety profiles.

Dually Amplified Electrochemical Aptasensor for Endotoxin Detection via Target-Assisted Electrochemically Mediated ATRP.

As the entering of bacterial endotoxin into blood can cause various life-threatening pathological conditions, the screening and detection of low-abundance endotoxin are of great importance to human health. Taking advantage of signal amplification by target-assisted electrochemically mediated atom transfer radical polymerization (teATRP), we illustrate herein a simple and cost-effective electrochemical aptasensor capable of detecting endotoxin with high sensitivity and selectivity. Specifically, the aptamer receptor was employed for the selective capture of endotoxin, of which the glycan chain was then decorated with ATRP initiators via covalent coupling between the diol sites and phenylboronic acid (PBA) group, followed by the recruitment of ferrocene signal reporters via the grafting of polymer chains through potentiostatic eATRP under ambient temperature. As the glycan chain of endotoxin can be decorated with hundreds of ATRP initiators while the further grafting of polymer chains through eATRP can recruit hundreds to thousands of signal reporters to each initiator-decorated site, the teATRP-based strategy allows for the dual amplification of the detection signal. This dually amplified electrochemical aptasensor has the ability to sensitively and selectively detect endotoxin at a concentration as low as 1.2 fg/mL, and its practical applicability has been further demonstrated using human serum samples. Owing to the simplicity, high efficiency, biocompatibility, and inexpensiveness of the teATRP-based amplification strategy, this electrochemical aptasensor holds great application potential in the sensitive and selective detection of low-abundance endotoxin and many other glycan chain-containing bio-targets.

Association between depressive symptoms and lung function in the United States adults without pulmonary diseases: A cross-sectional study from NHANES.

BACKGROUND: Depression is a severe and common mental disorder. The association between depressive symptoms and lung function remains unclear. To determine whether depressive symptoms are associated with lung function in U.S. adults without pulmonary diseases. METHODS: A cross-sectional study of National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2012 were used to estimate the relationship between depressive symptoms and lung function. Depressive symptoms were determined by a participant's score on the Patient Health Questionnaire-9. Forced Expiratory Volume 1st Second (FEV1) Forced Vital Capacity (FVC) were determined by the spirometry. Weighted multivariate linear regression was used to analyze this relationship and subgroup analyses were performed. RESULTS: Of 8027 participants, 576 (7.18 %) participants with depression. Depression group had significant lower FEV1 and FVC than non-depression group. After adjustment for all covariates, there was a significant negative association between depressive symptoms and FVC (ß -4.84, 95 % CI -9.10 to -0.57), especially in non-Hispanic White people (ß -9.03, 95 % CI -14.38 to -3.69). There was no independent association between depressive symptoms and FEV1 in all participants, whereas the association was significant in non-Hispanic White people (ß -4.91, 95 % CI -9.50 to -0.32). CONCLUSIONS: High depressive symptoms were independently associated with decline of FVC among U.S. adults without pulmonary diseases, especially in non-Hispanic White people. In addition, although it was not independently associated with FEV1 in all participants, depressive symptom score was also negatively associated with FEV1 in non-Hispanic White people.

Targeting ADAM10 in Renal Diseases.

ADAM10 is part of the ADAM superfamily containing cell surface proteins with special structures and potential adhesion and protease domains. This paper provides a review of the specific effects of ADAM10 in kidney development as well as its relations with renal diseases. ADAM10 plays an important role in developing tissues and organs and the pathogenesis of multiple diseases. The catalytic mechanism of ADAM10 on kidney-related molecules, including Notch, epidermal growth factor receptors, tumor necrosis factor-α, CXCL16, E-cadherin, cell adhesion molecule 1, meprin and klotho. ADAM10 is also closely associated with the progress of glomerular diseases, acute kidney injury and renal fibrosis. It probably is a good therapeutic target for renal diseases.

DLC-ac4C: A Prediction Model for N4-acetylcytidine Sites in Human mRNA Based on DenseNet and Bidirectional LSTM Methods.

Introduction: N4 acetylcytidine (ac4C) is a highly conserved nucleoside modification that is essential for the regulation of immune functions in organisms. Currently, the identification of ac4C is primarily achieved using biological methods, which can be time-consuming and labor-intensive. In contrast, accurate identification of ac4C by computational methods has become a more effective method for classification and prediction. Aim: To the best of our knowledge, although there are several computational methods for ac4C locus prediction, the performance of the models they constructed is poor, and the network structure they used is relatively simple and suffers from the disadvantage of network degradation. This study aims to improve these limitations by proposing a predictive model based on integrated deep learning to better help identify ac4C sites. Methods: In this study, we propose a new integrated deep learning prediction framework, DLC-ac4C. First, we encode RNA sequences based on three feature encoding schemes, namely C2 encoding, nucleotide chemical property (NCP) encoding, and nucleotide density (ND) encoding. Second, one-dimensional convolutional layers and densely connected convolutional networks (DenseNet) are used to learn local features, and bi-directional long short-term memory networks (Bi-LSTM) are used to learn global features. Third, a channel attention mechanism is introduced to determine the importance of sequence characteristics. Finally, a homomorphic integration strategy is used to limit the generalization error of the model, which further improves the performance of the model. Results: The DLC-ac4C model performed well in terms of sensitivity (Sn), specificity (Sp), accuracy (Acc), Mathews correlation coefficient (MCC), and area under the curve (AUC) for the independent test data with 86.23%, 79.71%, 82.97%, 66.08%, and 90.42%, respectively, which was significantly better than the prediction accuracy of the existing methods. Conclusion: Our model not only combines DenseNet and Bi-LSTM, but also uses the channel attention mechanism to better capture hidden information features from a sequence perspective, and can identify ac4C sites more effectively.

Boronate Affinity-Amplified Electrochemical Aptasensing of Lipopolysaccharide.

As lipopolysaccharide (LPS) is closely associated with sepsis and other life-threatening conditions, the point-of-care (POC) detection of LPS is of significant importance to human health. In this work, we illustrate an electrochemical aptasensor for the POC detection of low-abundance LPS by utilizing boronate affinity (BA) as a simple, efficient, and cost-effective amplification strategy. Briefly, the BA-amplified electrochemical aptasensing of LPS involves the tethering of the aptamer receptors and the BA-mediated direct decoration of LPS with redox signal tags. As the polysaccharide chain of LPS contains hundreds of cis-diol sites, the covalent crosslinking between the phenylboronic acid group and cis-diol sites can be harnessed for the site-specific decoration of each LPS with hundreds of redox signal tags, thereby enabling amplified detection. As it involves only a single-step operation (∼15 min), the BA-mediated signal amplification holds the significant advantages of unrivaled simplicity, rapidness, and cost-effectiveness over the conventional nanomaterial- and enzyme-based strategies. The BA-amplified electrochemical aptasensor has been successfully applied to specifically detect LPS within 45 min, with a detection limit of 0.34 pg/mL. Moreover, the clinical utility has been validated based on LPS detection in complex serum samples. As a proof of concept, a portable device has been developed to showcase the potential applicability of the BA-amplified electrochemical LPS aptasensor in the POC testing. In view of its simplicity, rapidness, and cost-effectiveness, the BA-amplified electrochemical LPS aptasensor holds broad application prospects in the POC testing.

Electrochemical Detection of Femtomolar DNA via Boronate Affinity-Mediated Decoration of Polysaccharides with Electroactive Tags.

In view of their high efficiency and cost-effectiveness, polymers are of great promise as carriers for signal tags in amplified detection. Herein, we present a polysaccharide-amplified method for the electrochemical detection of a BRCA1 breast cancer gene-derived DNA target at the femtomolar levels. Briefly, peptide nucleic acid (PNA) with a complementary sequence was tethered as the capture probe for the DNA target, to which carboxyl group-containing polysaccharides were then attached via facile phosphate-Zr(IV)-carboxylate crosslinking, followed by the decoration of polysaccharide chains with electroactive ferrocene (Fc) signal tags via affinity coupling between a cis-diol site and phenylboronic acid (PBA) group. As the polysaccharide chain contains hundreds of cis-diol sites, boronate affinity can enable the site-specific decoration of each polysaccharide chain with hundreds of Fc signal tags, efficiently transducing each target capture event into the decoration of many Fc signal tags. As polysaccharides are cheap, renewable, ubiquitous, and biodegradable natural biopolymers, the use of polysaccharides for signal amplification offers the benefits of high efficiency, cost-effectiveness, excellent biocompatibility, and environmental friendliness. The linear range of the polysaccharide-amplified method for DNA detection was demonstrated to be from 10 fM to 10 nM (R2 = 0.996), with the detection limit as low as 2.9 fM. The results show that this method can also discriminate single base mismatch with satisfactory selectivity and can be applied to DNA detection in serum samples. In view of these merits, the polysaccharide-amplified PNA-based electrochemical method holds great promise in DNA detection with satisfactory sensitivity and selectivity.

Electrochemically Controlled Atom Transfer Radical Polymerization for Electrochemical Aptasensing of Tumor Biomarkers.

Tumor biomarkers are of great value in the liquid biopsy of malignant tumors. In this work, a simple and cost-friendly electrochemical aptasensor was presented for the highly sensitive and selective detection of glycoprotein tumor biomarkers. The DNA aptamer-modified electrode was used as the sensing interface to specifically capture the target glycoprotein tumor biomarkers, to which the alkyl halide initiators for atom transfer radical polymerization (ATRP) were then attached via the esterification crosslinking between the boronic acid group and the cis-dihydroxyl sites of the conjugated oligosaccharide chains on glycoprotein tumor biomarkers followed by the growth of long-chain polymers through electrochemically controlled ATRP (eATRP) to efficiently recruit the ferrocene detection tags. As there are tens to hundreds of cis-dihydroxyl sites on a glycoprotein tumor biomarker for attaching ATRP initiators while each long-chain polymer can recruit hundreds to thousands of ferrocene detection tags, a significantly high current signal can be generated even in the presence of ultralow-abundance targets. Hence, the eATRP-based electrochemical aptasensor is capable of sensitively and selectively detecting glycoprotein tumor biomarkers. Using alpha-fetoprotein as the model target, the limit of detection was demonstrated to be 0.32 pg/mL. Moreover, the aptasensor has been successfully applied to detect glycoprotein tumor biomarkers in human serum samples. In view of its high sensitivity and selectivity, simple operation, and cost-friendliness, the eATRP-based electrochemical aptasensor shows great promise in the glycoprotein-based liquid biopsy of malignant tumors, even at the early stage of development.

Coronary Intervention Guided by Quantitative Flow Ratio vs Angiography in Patients With or Without Diabetes.

BACKGROUND: The clinical utility of the quantitative flow ratio (QFR), a novel angiography-based index for the functional assessment of coronary stenoses, has recently been demonstrated in patients undergoing percutaneous coronary intervention (PCI). OBJECTIVES: This study aimed to ascertain whether the beneficial outcomes of QFR guidance for lesion selection during PCI is affected by diabetes status. METHODS: This substudy from the FAVOR III China trial, in which diabetes was one of the prespecified factors for stratified randomization, compared clinical outcomes of QFR-guided vs angiography-guided PCI lesion selection according to the presence of diabetes. The primary endpoint was the 1-year risk of major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization). RESULTS: Among 3,825 patients enrolled, 1,295 (33.9%) had diabetes, 347 (26.8%) of whom were treated with insulin. Baseline characteristics were well balanced between treatment arms in both diabetic and nondiabetic patients. Compared with standard angiography-based lesion selection, the QFR-guided strategy consistently reduced the risk of 1-year MACE in both diabetic patients (6.2% vs 9.6%; HR: 0.64; 95% CI: 0.43-0.95) and nondiabetic patients (5.6% vs 8.3%; HR: 0.66; 95% CI: 0.49-0.89) (Pinteraction = 0.88). Among patients in whom PCI was deferred after QFR, the risk of 1-year MACE was similar in patients with and without diabetes (4.5% vs 6.2%; P = 0.51). CONCLUSIONS: A QFR-guided lesion selection strategy improves PCI outcomes compared with standard angiography guidance in patients both with and without diabetes. (The Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease [FAVOR III China Study]; NCT03656848).

Efficacy and safety of atezolizumab plus bevacizumab combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma.

Background: Atezolizumab plus bevacizumab has been proved to have promising antitumor activity and tolerable safety in patients with unresectable hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) also demonstrated high response rates and favorable survival for patients with advanced HCC. This study aimed to explore the preliminary clinical efficacy and safety of atezolizumab plus bevacizumab combined with HAIC for patients with treatment-naive advanced HCC. Methods: Between October 2020 and September 2021, patients with advanced HCC who initially received atezolizumab plus bevacizumab combined with HAIC of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) from three hospitals in China were reviewed for eligibility. The efficacy was evaluated by tumor response rate and survival, and the safety was evaluated by the frequency of key adverse events (AEs). Results: In total, 52 eligible patients with advanced HCC who received triple therapy were included in this study. The objective response rates (ORRs) based on mRECIST and RECIST1.1 criteria were 67.3% and 44.2%, respectively. The median progression-free survival (PFS) of patients was 10.6 months (95% CI, 8.37-13.8), and the overall survival (OS) was not reached. Extrahepatic metastasis was an independent risk factor associated with PFS. All AEs were controlled and no treatment-related deaths occurred. Conclusion: Atezolizumab plus bevacizumab combined with HAIC-FOLFOX had a significant therapeutic effect and manageable AEs in patients with advanced HCC, which may be a potential treatment option for advanced HCC.

Boronate Affinity-Based Electrochemical Aptasensor for Point-of-Care Glycoprotein Detection.

As a class of oligosaccharide chain-containing proteins, glycoproteins are of great value in screening and early diagnosis of malignant tumors and other major diseases. Herein, we report a universal boronate affinity-based electrochemical aptasensor for point-of-care glycoprotein detection. Aptasensing of glycoproteins involves the specific recognition and capture of target glycoproteins by end-tethered nucleic acid aptamers and the site-specific labeling of ferrocene tags via the phenylboronic acid (PBA)-based boronate affinity interactions because the cis-diol sites of oligosaccharide chains on glycoproteins can selectively react with the PBA receptor groups to form cyclic phenylborates in aqueous basic media. Due to the presence of hundreds to thousands of cis-diol sites on a glycoprotein, a large number of ferrocene tags can be recruited for the signal-on aptasensing of glycoproteins at a low-abundance level, eliminating the need for extra amplification strategies. As a result, the boronate affinity-based electrochemical aptasensor is highly sensitive and selective for glycoprotein detection and tolerant to the false-positive results. The detection limit for α-fetoprotein (AFP) is 0.037 ng/mL, with a linear response ranging from 0.1 to 100 ng/mL. In addition to the merits of simple operation, short assay time, and low detection cost, the aptasensor is applicable to the detection of glycoproteins in serum samples and the point-of-care detection using disposable flexible electrodes. Overall, this work provides a universal and promising platform for the point-of-care detection of glycoproteins, holding great potential in screening and early diagnosis of glycoprotein-related malignant tumors and other major diseases.

Boronate-Affinity Cross-Linking-Based Ratiometric Electrochemical Detection of Glycoconjugates.

Despite the widespread application of the boronate-affinity cross-linking (BAC) in the separation, enrichment, and sensing of glycoconjugates, it remains a huge challenge to integrate the BAC into the selective electrochemical detection of glycoconjugates due to the poor selectivity of the BAC. Herein, we demonstrate a BAC-based ratiometric electrochemical method for the simple, low-cost, and highly sensitive and selective detection of glycoconjugates. Briefly, the methylene blue (MB)-tagged nucleic acid aptamer is exploited as the recognition element to selectively capture target glycoconjugate, to which a large number of ferrocene (Fc) tags are subsequently labeled via the BAC between the phenylboronic acid (PBA) group and the cis-diol site of the oligosaccharide chains on the captured targets. Using the MB tag as the internal reference and the Fc tag as the reporter of the target capture, the dual-signal output enables the ratiometric detection. Due to the presence of a high density of the cis-diol sites on a glycoconjugate, sufficiently high sensitivity can be obtained even without using any amplification strategies. Using glycoprotein mucin 1 (MUC1) as the model target, the signal ratio (IFc/IMB) exhibits good linearity over the range from 0.05 to 50 U/mL, with a detection limit of 0.021 U/mL. In addition to the high sensitivity and selectivity, the results of the analysis of MUC1 in serum samples are acceptable. By virtue of its simplicity, cost-effectiveness, and high robustness and reproducibility, this BAC-based ratiometric electrochemical method holds great promise in the highly sensitive and selective detection of glycoconjugates.

Microwave ablation versus parathyroidectomy for the treatment of primary hyperparathyroidism: a cohort study.

OBJECTIVE: To compare the clinical outcomes between microwave ablation (MWA) and parathyroidectomy (PTX) for the treatment of primary hyperparathyroidism (pHPT). MATERIALS AND METHODS: This retrospective study enrolled 212 patients with pHPT treated by either MWA (MWA group) or PTX (PTX group) from January 2015 to October 2020. The baseline data were balanced through propensity score matching. Clinical cure was evaluated by the Kaplan-Meier method and compared between the MWA and PTX groups. The risk factors related to persistent or recurrent pHPT were screening out using a Cox proportional hazards regression model. RESULTS: After propensity score matching, a total of 174 patients were enrolled in the present study, with 87 patients in each group. During the follow-up period (median, 28.5 months), there were no differences between the two groups regarding the clinical cure (hazard ratio, 1.71; 95% confidence interval: 0.81-3.62; p = .155), persistent pHPT rate (13.8% vs. 10.3%, p = .643), recurrent pHPT rate (6.9% vs. 3.4%, p = .496), or major complications (6.9% vs. 3.4%, p = .496). MWA resulted in a shorter procedure time (30 min vs. 60 min), smaller incision length (0.1 cm vs. 7 cm) and slightly higher costs (25745 CNY vs. 24111 CNY) (all p < .001). High levels of preoperative intact parathyroid hormone (p = .01) and multiple pHPT nodules (p < .001) were independent risk factors for recurrent and persistent pHPT in the two groups. CONCLUSION: MWA and PTX have comparable clinical outcomes for pHPT. MWA has a shorter procedure time and smaller incision length. KEY POINTS: • There were no differences in terms of clinical cure, persistent pHPT, recurrent pHPT, or major complications between MWA and PTX in the treatment of pHPT. • MWA is minimally invasive and results in a shorter procedure time. • Multiple nodules and high levels of iPTH were the independent risk factors for recurrent and persistent pHPT.

Biologically Mediated RAFT Polymerization for Electrochemical Sensing of Kinase Activity.

The assay of kinase activity with ultrahigh sensitivity is important to medical diagnostics and drug discovery. Herein, we report the biologically mediated RAFT polymerization (BMRP) and its potential use as an efficient amplification strategy in the ultrasensitive electrochemical sensing of kinase activity. In BMRP, the reversible addition-fragmentation chain-transfer (RAFT) process is initiated and sustained by the reduced form of coenzyme I (i.e., NADH), which can efficiently mediate the direct fragmentation of thiocarbonylthio (TCT) compounds (or the TCT-capped dormant chains) to produce an initiating/propagating radical under mild conditions. Due to the absence of exogenous radicals, the notorious radical termination in RAFT equilibrium can be greatly suppressed. For the sensing of kinase activity, the recognition peptides, without carboxyl groups, are immobilized via the Au-S self-assembly. After phosphorylation, TCT compounds (as RAFT agents) are tethered to the enzymatically generated phosphate groups via the carboxylate-Zr(IV)-phosphate (CZP) linkage. Subsequently, the BMRP of ferrocenylmethyl methacrylate (FcMMA) results in the labeling of each phosphate group with hundreds to thousands of Fc tags, thereby greatly amplifying the sensing signal. Obviously, the BMRP-based strategy is biologically friendly, highly efficient, uncomplicated, and quite low-cost. The detection limit of 1.85 mU/mL has been achieved toward the selective sensing of the cAMP-dependent protein kinase (PKA). Moreover, the proposed kinase sensor is applicable to inhibitor screening and kinase activity sensing in serum samples. By virtue of its low cost, high sensitivity and selectivity, and uncomplicated operation, the proposed kinase sensor holds great potential in medical diagnostics and drug discovery.