Role of 8-hydroxyguanine DNA glycosidase 1 deficiency in exacerbating diabetic cardiomyopathy through the regulation of insulin resistance.

Diabetic cardiomyopathy (DCM) is a heart failure syndrome, and is one of the major causes of morbidity and mortality in diabetes. DCM is mainly characterized by ventricular dilation, myocardial hypertrophy, myocardial fibrosis and cardiac dysfunction. Clinical studies have found that insulin resistance is an independent risk factor for DCM. However, its specific mechanism of DCM remains unclear. 8-hydroxyguanine DNA glycosylase 1(OGG1)is involved in DNA base repair and the regulation of inflammatory genes. In this study, we show that OGG1 was associated with the occurrence of DCM. for the first time. The expression of OGG1 was increased in the heart tissue of DCM mice, and OGG1 deficiency aggravated the cardiac dysfunction of DCM mice. Metabolomics show that OGG1 deficiency resulted in obstruction of glycolytic pathway. At the molecular level, OGG1 regulated glucose uptake and insulin resistance by interacting with PPAR-γ in vitro. In order to explore the protective effect of exogenous OGG1 on DCM, OGG1 adeno-associated virus was injected into DCM mice through tail vein in the middle stage of the disease. We found that the overexpression of OGG1 could improve cardiac dysfunction of DCM mice, indicating that OGG1 had a certain therapeutic effect on DCM. These results demonstrate that OGG1 is a new molecular target for the treatment of DCM and has certain clinical significance.

Pitfalls of ultrasound for deep vein thrombosis of the lower extremities.

Venous ultrasound is the primary, widely accepted diagnostic tool to assess deep vein thrombosis (DVT) in the lower extremities. However, other focal lesions in the lower extremities can be identified on ultrasound. The sonographic appearance of these abnormalities may overlap the thrombosis, which included vascular tumors, Baker's cyst, hematoma, cancer thrombosis, and peripheral nerve tumors. This essay derives from cases diagnosed in our centers and published literature, with images available for illustrations, which may help to improve the clinical management of these findings.

Impact of Microbubble Degradation and Flow Velocity on Subharmonic-aided Pressure Estimation (SHAPE): An Experimental Investigation.

OBJECTIVE: This study aimed to investigate the impact of microbubble degradation and flow velocity on Sub-Harmonic Aided Pressure Estimation (SHAPE), and to explore the correlation between subharmonic amplitude and pressure as a single factor. METHODS: We develop an open-loop vascular phantom platform system and utilize a commercial ultrasound machine and microbubbles for subharmonic imaging. Subharmonic amplitude was measured continuously at constant pressure and flow velocity to assess the impact of microbubble degradation. Flow velocity was varied within a range of 4-14 cm/s at constant pressure to investigate its relationship to subharmonic amplitude. Furthermore, pressure was varied within a range of 10-110 mm Hg at constant flow velocity to assess its isolated effect on subharmonic amplitude. RESULTS: Under constant pressure and flow velocity, subharmonic amplitude exhibited a continuous decrease at an average rate of 0.221 dB/min, signifying ongoing microbubble degradation during the experimental procedures. Subharmonic amplitude demonstrated a positive correlation with flow velocity, with a variation ratio of 0.423 dB/(cm/s). Under controlled conditions of microbubble degradation and flow velocity, a strong negative linear correlation was observed between pressure and subharmonic amplitude across different Mechanical Index (MI) settings (all R2 > 0.90). The sensitivity of SHAPE was determined to be 0.025 dB/mmHg at an MI of 0.04. CONCLUSION: The assessment of SHAPE sensitivity is affected by microbubble degradation and flow velocity. Excluding the aforementioned influencing factors, a strong linear negative correlation between pressure and subharmonic amplitude was still evident, albeit with a sensitivity coefficient lower than previously reported values.

[Reliability Thermal Design, Simulation and Experimental Verification of Electronic Monitoring Unit for Magnetic Resonance System].

The monitoring unit used in the nuclear magnetic resonance system, as an important unit of the system, faces a high thermal risk during its entire life cycle. This paper ensures the high efficiency and reliability of the thermal design of the product module from the two dimensions of structural design and device derating design. In order to reduce the risk of thermal design of electronic modules and comprehensively verify the effectiveness of thermal design of electronic modules, the design verification is carried out by combining simulation and experiment. In the simulation process, by establishing a thermal simulation model at the circuit board level, the crustal temperature of the core device is numerically calculated, and the index is compared with the thermal design index value and the test value, on the one hand, to verify the correctness of the simulation model. On the other hand, the validity of thermal design is verified. In the testing process, a thermal test platform for product modules is built, and the thermal characteristics test values of the core components of the module under extreme electrical conditions are obtained, and the corresponding conversion methods are used to predict the thermal performance and thermal design margin of the product at different altitudes. The results show that the electronic module can meet the thermal design requirements in terms of structural design and derating design of core components, and can ensure that the product module can work safely and reliably during the entire life cycle of the NMR system.

Nanoparticle-Based Immunotherapy for Reversing T-Cell Exhaustion.

T-cell exhaustion refers to a state of T-cell dysfunction commonly observed in chronic infections and cancer. Immune checkpoint molecules blockading using PD-1 and TIM-3 antibodies have shown promising results in reversing exhaustion, but this approach has several limitations. The treatment of T-cell exhaustion is still facing great challenges, making it imperative to explore new therapeutic strategies. With the development of nanotechnology, nanoparticles have successfully been applied as drug carriers and delivery systems in the treatment of cancer and infectious diseases. Furthermore, nanoparticle-based immunotherapy has emerged as a crucial approach to reverse exhaustion. Here, we have compiled the latest advances in T-cell exhaustion, with a particular focus on the characteristics of exhaustion that can be targeted. Additionally, the emerging nanoparticle-based delivery systems were also reviewed. Moreover, we have discussed, in detail, nanoparticle-based immunotherapies that aim to reverse exhaustion, including targeting immune checkpoint blockades, remodeling the tumor microenvironment, and targeting the metabolism of exhausted T cells, etc. These data could aid in comprehending the immunopathogenesis of exhaustion and accomplishing the objective of preventing and treating chronic diseases or cancer.

8-Oxoguanine DNA glycosylase protects cells from senescence via the p53-p21 pathway.

Cellular senescence is an important factor leading to pulmonary fibrosis. Deficiency of 8-oxoguanine DNA glycosylase (OGG1) in mice leads to alleviation of bleomycin (BLM)-induced mouse pulmonary fibrosis, and inhibition of the OGG1 enzyme reduces the epithelial mesenchymal transition (EMT) in lung cells. In the present study, we find decreased expression of OGG1 in aged mice and BLM-induced cell senescence. In addition, a decrease in OGG1 expression results in cell senescence, such as increases in the percentage of SA-ß-gal-positive cells, and in the p21 and p-H2AX protein levels in response to BLM in lung cells. Furthermore, OGG1 promotes cell transformation in A549 cells in the presence of BLM. We also find that OGG1 siRNA impedes cell cycle progression and inhibits the levels of telomerase reverse transcriptase (TERT) and LaminB1 in BLM-treated lung cells. The increase in OGG1 expression results in the opposite phenomenon. The mRNA levels of senescence-associated secretory phenotype (SASP) components, including IL-1α, IL-1ß, IL-6, IL-8, CXCL1/CXCL2, and MMP-3, in the absence of OGG1 are obviously increased in A549 cells treated with BLM. Interestingly, we demonstrate that OGG1 binds to p53 to inhibit the activation of p53 and that silencing of p53 reverses the inhibition of OGG1 on senescence in lung cells. Additionally, the augmented cell senescence is shown in vivo in OGG1-deficient mice. Overall, we provide direct evidence in vivo and in vitro that OGG1 plays an important role in protecting tissue cells against aging associated with the p53 pathway.

OGG1 promoted lung fibrosis by activating fibroblasts via interacting with Snail1.

One of abundant DNA lesions induced by reactive oxygen species is 8-oxoguanine (8-oxoG), which compromises genetic instability. 8-oxoG is recognized by the DNA repair protein 8-oxoguanine DNA glycosylase-1 (OGG1) that not only participates in base excision repair but also involves in transcriptional regulation.OGG1 has an important role inIdiopathic Pulmonary Fibrosis (IPF) processing and targeting fibroblasts is a major strategy for the treatment of pulmonary fibrosis, but whether OGG1 activate fibroblast is not clear. In this study, we show that OGG1 expression level is increased at the fibroblast activation stage in mouse lungs induced by bleomycin (BLM) treatment. OGG1 promoted the expression level of fibroblast activation markers (CTGF, fibronectin, and collagen 1) in a pro-fibrotic gene transcriptional regulation pathway via interacting with Snail1, which dependent on 8-oxoG recognition. Global inhibition of OGG1 at the middle stage of lung fibrosis also relieved BLM-induced lung fibrosis in mice. Our results suggest that OGG1 is a target for inhibiting fibroblast activation and a potential therapeutic target for IPF.

Two zinc finger proteins, VdZFP1 and VdZFP2, interact with VdCmr1 to promote melanized microsclerotia development and stress tolerance in Verticillium dahliae.

BACKGROUND: Melanin plays important roles in morphological development, survival, host-pathogen interactions and in the virulence of phytopathogenic fungi. In Verticillum dahliae, increases in melanin are recognized as markers of maturation of microsclerotia which ensures the long-term survival and stress tolerance, while decreases in melanin are correlated with increased hyphal growth in the host. The conserved upstream components of the VdCmr1-regulated pathway controlling melanin production in V. dahliae have been extensively identified, but the direct activators of this pathway are still unclear. RESULTS: We identified two genes encoding conserved C2H2-type zinc finger proteins VdZFP1 and VdZFP2 adjacent to VdPKS9, a gene encoding a negative regulator of both melanin biosynthesis and microsclerotia formation in V. dahliae. Both VdZFP1 and VdZFP2 were induced during microsclerotia development and were involved in melanin deposition. Their localization changed from cytoplasmic to nuclear in response to osmotic pressure. VdZFP1 and VdZFP2 act as modulators of microsclerotia melanization in V. dahliae, as confirmed by melanin biosynthesis inhibition and supplementation with the melanin pathway intermediate scytalone in albino strains. The results indicate that VdZFP1 and VdZFP2 participate in melanin biosynthesis by positively regulating VdCmr1. Based on the results obtained with yeast one- and two-hybrid (Y1H and Y2H) and bimolecular fluorescence complementation (BiFC) systems, we determined the melanin biosynthesis relies on the direct interactions among VdZFP1, VdZFP2 and VdCmr1, and these interactions occur on the cell walls of microsclerotia. Additionally, VdZFP1 and/or VdZFP2 mutants displayed increased sensitivity to stress factors rather than alterations in pathogenicity, reflecting the importance of melanin in stress tolerance of V. dahliae. CONCLUSIONS: Our results revealed that VdZFP1 and VdZFP2 positively regulate VdCmr1 to promote melanin deposition during microsclerotia development, providing novel insight into the regulation of melanin biosynthesis in V. dahliae.

Vibration-enhanced disposable electroanalytical platform for selective analysis of tryptophan in fruits based on molecular imprinting.

Although electrochemical detection based on molecular imprinting polymers (MIP) could dramatically improve the selectivity, the procedure is time-consuming because of the essential incubation step. In addition, current MIP electrochemical detections were not suitable for analysis of microliter-level sample solutions, limiting their applications for real samples. This investigation aims at applying vibration to enhance efficiency of MIP electrochemical detection of 20 µL sample solutions. MIP analysis of Tryptophan (Trp) was used as the model with disposable MIP electrodes prepared by electrochemical polymerization of o-phenylenediamine on carbon ink coated on stainless steel sheets. The MIP electrode was integrated in a 3D-printed analytical device for vibration-enhanced electrochemical detection of Trp. Our results showed that this vibration-enhanced strategy could significantly increase electrochemical responses of Trp at the same incubation time. Such improvement might be attributed to the enhanced mass transfer at the surface of the working electrode brought by vibration. It needs to be emphasized that this strategy is suitable for analysis of sample solutions with the volume of microliters, which is superior to normal stirring in MIP electrochemical detection. Our approach could be successfully utilized for differentiation of Trp in different fruits, opening more opportunities for MIP electrochemical detection of real samples. The enhanced efficiency by vibration could pave foundation for extensive practical MIP detection of sample solutions at the level of microliters.

The performance of duplex ultrasonography for the assessment of renal artery stenosis in Takayasu's arteritis patients.

BACKGROUND: This study intends to analyze the hemodynamic parameters of the renal artery in patients with Takayasu's arteritis (TAK) to explore the diagnostic efficacy of duplex ultrasonography in assessing the involved renal artery in TAK patients. METHODS: One hundred fifteen TAK patients with 314 renal arteries were retrospectively analyzed, who were admitted to Peking Union Medical College Hospital between 2017 and 2022. These patients underwent both renal artery ultrasonography and angiography within a 4-week period. Specifically, the study compared seven ultrasonic parameters across groups categorized by the severity of renal artery stenosis (RAS), including noninvolvement, < 50% stenosis, 50-69% stenosis, and 70-99% stenosis. Receiver operating characteristic (ROC) curves were employed to determine the optimal threshold values for renal artery peak systolic velocity (RPSV), renal-aortic PSV ratio (RAR), and renal-interlobar PSV ratio (RIR) in order to diagnose various degrees of RAS in TAK patients. RESULTS: Statistically significant differences were observed in RAR and RIR among the four groups (all P < 0.05). However, no statistically significant differences were found in RPSV and AT between the moderate stenosis group (50-69% stenosis) and the severe stenosis group (70-99% stenosis). The discrimination of interlobar PSV (IPSV) and interlobar RI (IRI) was not significant, and IEDV did not show statistical significance among the four groups. For TAK patients, the recommended thresholds of RPSV for the diagnosis of renal artery involvement (RAI), ≥ 50% RAS, and ≥ 70% RAS were determined to be 143 cm/s, 152 cm/s, and 183 cm/s, respectively. The sensitivities, specificities, and accuracies of these thresholds were all found to be greater than 80%. Additionally, the optimal thresholds of RIR for detecting RAI, ≥ 50% RAS, and ≥ 70% RAS were determined to be 4.6, 5.6, and 6.4, respectively, with satisfactory diagnostic efficiencies. The areas under the curve (AUCs) for RPSV and RIR were calculated to be 0.908 and 0.910, respectively, for the diagnosis of ≥ 50% RAS, and 0.876 and 0.882 for the diagnosis of ≥ 70% RAS. When the aortic PSV is greater than or equal to 140 cm/s, the RAR exhibits inadequate diagnostic efficacy. Conversely, when the aortic PSV is less than 140 cm/s, a RAR value of 2.2 or higher can be employed as the diagnostic threshold for identifying RAS of 70% or greater, with a sensitivity of 84.00%, specificity of 89.93%, and an overall accuracy of 89.08%. CONCLUSION: In the present study, it has been demonstrated that RPSV and RIR possess substantial diagnostic value as ultrasonic parameters for diagnosing RAS in TAK patients. Furthermore, when assessing the diagnostic efficacy of RAR, it is crucial to consider the severity of aortic stenosis as a determining factor.

Diagnostic experience of intravenous leiomyomatosis with emphasis on conventional ultrasonography imaging: a single-center study.

Objective: Intravenous leiomyomatosis (IVL) is a rare and aggressive tumor type that has the potential to extend into the inferior vena cava (IVC) and is susceptible to be misdiagnosed and neglected. Despite its clinical significance, there is a paucity of research that has focused on the specific manifestations of IVL on ultrasonography. Therefore, this study aims to systematically analyze the specific ultrasound features of IVL and augment its diagnostic accuracy. Materials and method: Prospective inclusion was granted to patients admitted to our hospital between December 2016 and March 2021 for an IVC-occupying lesion. Multi-modal ultrasonography, encompassing gray-scale and color Doppler, was conducted. Lesions were categorized as IVL or non-IVL based on pathological or follow-up data. Two ultrasound sonographers with over 5 years of experience read and recorded ultrasound data for all lesions, which were subsequently comparatively analyzed to identify specific signs of IVL. Results: A total of 284 patients diagnosed with IVC-occupying lesions were included in the study. The lesion types comprised of IVL (n=67, 23.6%), IVC thrombus (n=135, 47.5%), tumor thrombus of renal carcinoma involving the IVC (n=35, 12.4%), tumor thrombus of liver carcinoma involving the IVC (n=24, 8.5%), leiomyosarcoma of the IVC (n=14, 4.9%), and tumor thrombus of adrenocortical adenocarcinoma (n=9, 4.1%). The presence of "sieve hole" and "multi-track" signs was observed in 20 IVL lesions under the grey-scale modality, while both signs were absent in the non-IVL group (P<0.01). The study found no statistically significant differences in the presentation of "sieve hole" and "multi-track" signs under the grey-scale and color Doppler modalities in cases of intravascular lithotripsy (IVL) (P>0.05). Using these two signs as diagnostic criteria for IVL, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), miss rate, misdiagnosis rate, and accuracy were determined to be 29.9%, 100%, 100%, 82.2%, 70.1%, 0, and 83.5%, respectively (AUC ROC=0.649; 95%CI: 0.537-0.761). Conclusion: IVL exhibits distinct ultrasound presentations, including "sieve hole" and "multi-track" signs, which demonstrate high specificity and accuracy as diagnostic indicators. Furthermore, these signs are corroborated by pathological evidence and effectively distinguish IVL from other lesions occupying the IVC.

Differential Analysis of Korean and Chinese Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) Spore Powder by Infrared Spectroscopy with Stoichiometry.

To investigate the differences between Korean Ganoderma lucidum spore powder (KP), broken-spo-roderm KP (BSKP), Chinese traditional G. lucidum spore powder (CP), and broken-sporoderm CP (BSCP), they were identified by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), second derivative infrared spectroscopy (SD-IR), dual-index sequence analysis (DISA) and X-ray diffraction (XRD). SEM showed that there were no significant differences in microstructure between the two kinds of spore powders. FT-IR spectra showed that the four spore powders appeared with characteristic peaks of 3400, 3006, 2925, 1745, 1535, 1454, 1249, 1074, 1049, and 896 cm-1, respectively, they were contained the characteristic peaks of total triterpenes, polysaccharides and fatty acids. DISA showed that the same species of spore powders, the overall similarity of before and broken the sporoderm was high with minor differences and there were no differences between the different kinds of spore powders. Similarity analysis showed that the four spore powders were in high agreement and were no differences. The polysaccharide, total triterpene, spore oil and protein content of the four spore powders were determined separately. The results showed that the active ingredients content of the batch of KP were lower than that of CP, that of BSKP were lower than that of BSCP, while the active ingredients content of both broken-sporoderm spore powders were higher than that of before broken-sporoderm. It is inferred that the structure of the main chemical and component of KP is the same as that of CP. This study provides a reference for the future development and application of G. lucidum.

Basic characterization, antioxidant and immunomodulatory activities of polysaccharides from sea buckthorn leaves.

The polysaccharides from Sea buckthorn leaves (SBLPs) were extracted by hot water and purified by DEAE cellulose, then separated into six polysaccharides (SBLP-S) by DEAE-52 column. Six separated polysaccharides were characterized by Ultraviolet Spectroscopy, Infrared Spectrum, High Performance Liquid Chromatographic and Congo red analysis. The antioxidant activity and immunological activity were investigated in vitro. The results revealed that the monosaccharide composition of SBLP-S-1, SBLP-S-2, SBLP-S-3, SBLP-S-5 and SBLP-S-6 contained Man, GlcN, Rib, Rha, GluA, GalA, Glu, Gal, Xyl, Ara and Fuc, among them, rare glucosamine was found. And SBLP-S-4 contained all above components except GlcN and GluA. FT-IR showed that SBLP-S were sulfated polysaccharide containing uronic acid. Molecular weights of SBLP-S were 338.659, 401.305, 599.849, 393.904, 626.895 and 176.862 kDa. The Congo-red test indicated that SBLP-S-2, SBLP-S-4, SBLP-S-5, and SBLP-S-6 had triple helix conformation. Crude polysaccharides had the strong scavenging activities on DPPH radicals, ABTS radicals and hydroxyl radicals. The six polysaccharides had the activity of immune stimulation on RAW264.7 cell. SBLP-S-2 promoted the phagocytosis best and SBLP-S-6 promoted the NO production best. The results suggested that SBLPs could be used as potential antioxidants and immunomodulatory agents in pharmaceutical and functional food fields.

Rationality of FIGO 2018 IIIC restaging of cervical cancer according to local tumor size: A cohort study.

INTRODUCTION: FIGO 2018 IIIC remains controversial for the heterogeneity of its prognoses. To ensure a better management of cervical cancer patients in Stage IIIC, a revision of the FIGO IIIC version classification is required according to local tumor size. MATERIAL AND METHODS: We retrospectively enrolled cervical cancer patients of FIGO 2018 Stages I-IIIC who had undergone radical surgery or chemoradiotherapy. Based on the tumor factors from the Tumor Node Metastasis staging system, IIIC cases were divided into IIIC-T1, IIIC-T2a, IIIC-T2b, and IIIC-(T3a+T3b). Oncologcial outcomes of all stages were compared. RESULTS: A total of 63 926 cervical cancer cases were identified, among which 9452 fulfilled the inclusion criteria and were included in this study. Kaplan-Meier pairwise analysis showed that: the oncology outcomes of I and IIA were significantly better than of IIB, IIIA+IIIB, and IIIC; the oncology outcome of IIIC-(T1-T2b) was significantly better than of IIIA+IIIB and IIIC-(T3a+T3b); no significant difference was noted between IIB and IIIC-(T1-T2b), or IIIC-(T3a+T3b) and IIIA+IIIB. Multivariate analysis indicated that, compared with IIIC-T1, Stages T2a, T2b, IIIA+IIIB and IIIC-(T3a+T3b) were associated with a higher risk of death and recurrence/death. There was no significant difference in the risk of death or recurrence/death between patients with IIIC-(T1-T2b) and IIB. Also, compared with IIB, IIIC-(T3a+T3b) was associated with a higher risk of death and recurrence/death. No significant differences in the risk of death and recurrence/death were noted between IIIC-(T3a+T3b) and IIIA+IIIB. CONCLUSIONS: In terms of oncology outcomes of the study, FIGO 2018 Stage IIIC of cervical cancer is unreasonable. Stages IIIC-T1, T2a, and T2b may be integrated as IIC, and it might be unnecessary for T3a/T3b cases to be subdivided by lymph node status.

Smartphone-based interventions in the secondary prevention of cardiovascular disease: A meta-analysis.

BACKGROUND: A variety of reviews have indicated the effectiveness of smartphone-based interventions in preventing secondary cardiovascular disease (CVD). However, few studies have focused on clinical outcomes. OBJECTIVE: This meta-analysis aimed to evaluate the potential benefits of application interventions and short message service (SMS) interventions on CVD outcomes. METHODS: Electronic databases were searched to identify randomized controlled trials (RCT) investigating an application or SMS intervention for secondary CVD prevention. Primary outcomes included major adverse cardiovascular events (MACE), cardiovascular death, and cardiac hospitalization. Secondary outcomes were cardiovascular risk factors (BMI, blood pressure, and cholesterol). RESULTS: A total of 26 RCTs were included, with 16 investigating applications and 10 assessing SMS. Overall, there was no significant difference in MACE, cardiovascular death, and cardiac hospitalization when comparing application interventions with usual care, as well as comparing SMS with usual care. Subgroup analysis revealed that patients who received applications without a medical interface had a significantly lower incidence of MACE (OR = 0.56; 95% CI: 0.33, 0.98). Participants who received applications with a medical interface showed a tendency towards higher rates of cardiac hospitalization (OR = 2.03; 95% CI: 0.85, 4.87). Significant reduction in waist circumference (SMD =-0.80; 95% CI: -1.58, -0.03) was found in application interventions compared to usual care; while significant reductions in SBP (SMD =-0.08; 95% CI: -0.15, -0.01) and TC (SMD =-0.31; 95% CI: -0.57, -0.08) were found in SMS interventions compared to usual care. CONCLUSION: Smartphone-based interventions, including applications and SMS, have the potential to benefit the secondary prevention of CVD. Applications may reduce the incidence of cardiovascular-related adverse events, while SMS interventions may improve cardiovascular risk factors.

Vibration for enhancement of electrochemical analysis of biomolecules in a droplet on the rough surface of a disposable working electrode.

Although electrochemical detection of microliters-level solutions is attractive for analysis of low-amount biological samples, its performance could be weakened by limited mass transfer due to low Reynolds number and laminar flow. Herein we designed a 3D-printed electroanalytical device to apply vibration for improvement of mass transfer during electrochemical detection. In our approach, the droplet-size sample solution containing Indole-3-acetic acid (IAA, as a model) was directly applied on the effective surface of a disposable working electrode. We demonstrated that vibration could enhance electrochemical responses of IAA more on the rough surface than on the smooth surface of the working electrodes. After optimization, the sensitivity for electrochemical detection of a 20-µL droplet under vibration with the voltage of 7 V increased more than 100% compared with the static condition. The enhanced electrochemical responses brought by vibration could be achieved reproducibly, which could be ascribed to improved mass transfer. Our strategy could be practically applied for differentiation of IAA in different tissues of Marchantia polymorpha with enhanced responses. This study suggested that vibration might become a simple and effective method to improve mass transfer in analysis of microliter-volume solutions, which might be extended for more biochemical assays.

The correlation between the costs and clinical benefits of PD-1/PD-L1 inhibitors in malignant tumors: An evaluation based on ASCO and ESMO frameworks.

Background: Life expectancy for patients with malignant tumors has been significantly improved since the presence of the programmed cell death protein-1/programmed cell death protein ligand-1 (PD-1/PD-L1) inhibitors in 2014, but they impose heavy financial burdens for patients, the healthcare system and the nations. The objective of this study was to determine the survival benefits, toxicities, and monetary of programmed cell death protein-1/programmed cell death protein ligand-1 inhibitors and quantify their values. Methods: Randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitors for malignant tumors were identified and clinical benefits were quantified by American Society of Clinical Oncology Value Framework (ASCO-VF) and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). The drug price in Micromedex REDBOOK was used to estimate monthly incremental drug costs (IDCs) and the correlation between clinical benefits and incremental drug costs of experimental and control groups in each randomized controlled trial, and the agreement between two frameworks were calculated. Results: Up to December 2022, 52 randomized controlled trials were included in the quantitative synthesis. All the randomized controlled trials were evaluated by American society of clinical oncology value framework, and 26 (50%) met the American society of clinical oncology value framework "clinical meaningful value." 49 of 52 randomized controlled trials were graded by European society for medical oncology magnitude of clinical benefit scale, and 30 (61.2%) randomized controlled trials achieved European Society for Medical Oncology criteria of meaningful value. p-values of Spearman correlation analyses between monthly incremental drug costs and American society of clinical oncology value framework/European society for medical oncology magnitude of clinical benefit scale scores were 0.9695 and 0.3013, respectively. In addition, agreement between two framework thresholds was fair (κ = 0.417, p = 0.00354). Conclusion: This study suggests that there might be no correlation between the cost and clinical benefit of programmed cell death protein-1/programmed cell death protein ligand-1 inhibitors in malignancy, and the same results were observed in subgroups stratified by drug or indication. The results should be a wake-up call for oncologists, pharmaceutical enterprises and policymakers, and meanwhile advocate the refining of American Society of Clinical Oncology and European Society for Medical Oncology frameworks.

Comparative Efficacy of Secukinumab Versus Tumor Necrosis Factor Inhibitors for the Treatment of Takayasu Arteritis.

OBJECTIVE: Tumor necrosis factor (TNF) alpha and interleukin-17 (IL-17) are thought to be involved in the pathogenesis of Takayasu arteritis (TAK), and TNF inhibitors (TNFi) are recommended for the treatment of TAK. The present study was undertaken to investigate the efficacy of secukinumab, an IL-17A monoclonal antibody, compared to treatment with TNFi. METHODS: This was a prospective, single-center, open-label cohort study. Patients with active TAK who did not respond to treatment with glucocorticoids combined with 2 immunosuppressive agents were treated with either secukinumab or TNFi as an add-on therapy without an increased dosage of glucocorticoids. A complete response was defined as complete resolution of signs and symptoms of active disease, normal values of inflammatory markers, no progression on imaging of involved arteries, and dose of glucocorticoid <15 mg/day. A partial response was similarly defined as a complete response except with an erythrocyte sedimentation rate <40 mm/hour and C-reactive protein level of <20 mg/liter. RESULTS: Nineteen patients in the secukinumab group and 34 patients in the TNFi group were enrolled. The demographic data and inflammatory markers of the 2 groups were comparable at baseline. Complete response and partial response for patients treated with secukinumab and TNFi were 31.6% and 58.8% (P = 0.057), respectively, at 3 months and 52.6% and 64.7%, respectively, at 6 months (P = 0.389). CONCLUSION: Our findings suggest that secukinumab and TNFi are effective for patients with TAK who do not respond to oral glucocorticoids and conventional immunosuppressive agents, with similar response rates at 3 and 6 months.