Natural background level, source apportionment and health risk assessment of potentially toxic elements in multi-layer aquifers of arid area in Northwest China.

Groundwater contaminated by potentially toxic elements has become an increasing global concern for human health. Therefore, it is crucial to identify the sources and health risks of potentially toxic elements, especially in arid areas. Despite the necessity, there is a notable research gap concerning the sources and risks of these elements within multi-layer aquifers in such regions. To address this gap, 54 phreatic and 24 confined groundwater samples were collected from an arid area in Northwest China. This study aimed to trace the sources and evaluate the human health risks of potentially toxic elements by natural background level (NBL), positive matrix factorization (PMF) model, and health risk model. Findings revealed exceeding levels of potentially toxic elements existed in phreatic and confined aquifers. Source apportionment and NBL results indicated that mineral dissolution, evaporation, redox reactions, and human activities were the main factors for elevated concentrations of potentially toxic elements. High Fe and Mn concentrations were attributed to reduction environments, while F accumulation resulted from slow runoff, and irrigation from the Yellow River. Due to high F levels, more than one-third of groundwater samples (phreatic: 33.14 %, confined: 56.22 %) posed non-carcinogenic health risks to population groups. Adults displayed higher carcinogenic risks (phreatic: 19.47 %, confined: 34.16 %) than infants (phreatic: 0 %, confined: 0 %) and children (phreatic: 1.26 %, confined: 7.97 %) owing to the toxic elements of Cr. The confined aquifer presented greater health risks than the phreatic aquifer. Consequently, controlling the levels of F and Cr in multi-layered aquifers is key to reducing health risks. These findings provide valuable insights into protecting groundwater from contamination by potentially toxic elements in multi-layered aquifers worldwide.

Fluorescent probe for imaging N2H4 in plants, food, and living cells and for quantitative detection of N2H4 in soil and water using a smartphone.

Hydrazine is volatile and highly toxic, causing severe harm to water, soil, air, and organisms. Therefore, real-time detection and long-term monitoring of hydrazine are crucial for environmental protection and human health. Herein, an "OFF-ON" fluorescent probe 5-((10-ethyl-2-methoxy-10 H-phenothiazin-3-yl)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione (MPD) for hydrazine detection through a nucleophilic addition reaction was developed. MPD could exclusively identify hydrazine through colorimetric and fluorescent dual-channel responses within 30 s, which also demonstrated high sensitivity (detection limit, 12 nM) and a wide pH range (6 -12). The sensing mechanism of MPD was confirmed using theoretical calculations, where fluorescence was emitted following the recognition of hydrazine because of the disappearance of the photoinduced electron transfer (PET) process. Using a smartphone, MPD enabled the quantitative detection of hydrazine in real water samples and sandy soil. Notably, in the process of detecting hydrazine in actual water samples, the establishment of analytical methods and the completion of rapid quantitative detection only required a smartphone and built-in apps. Additionally, we showed that MPD could recognize hydrazine in various environmental samples, including plants, food, hydrazine vapors, and cells. We believe that the fluorescent probe MPD developed in this study and the established smartphone visualization platform will provide a convenient and effective tool for detecting hydrazine in environmental monitoring, food safety assessment, biological system safety, and other fields.

The value of synthetic magnetic resonance imaging in the diagnosis and assessment of prostate cancer aggressiveness.

Background: Synthetic magnetic resonance imaging (SyMRI) is a fast, standardized, and robust novel quantitative technique that has the potential to circumvent the subjectivity of interpretation in prostate multiparametric magnetic resonance imaging (mpMRI) and the limitations of existing MRI quantification techniques. Our study aimed to evaluate the potential utility of SyMRI in the diagnosis and aggressiveness assessment of prostate cancer (PCA). Methods: We retrospectively analyzed 309 patients with suspected PCA who had undergone mpMRI and SyMRI, and pathologic results were obtained by biopsy or PCA radical prostatectomy (RP). Pathological types were classified as PCA, benign prostatic hyperplasia (BPH), or peripheral zone (PZ) inflammation. According to the Gleason Score (GS), PCA was divided into groups of intermediate-to-high risk (GS ≥4+3) and low-risk (GS ≤3+4). Patients with biopsy-confirmed low-risk PCA were further divided into upgraded and nonupgraded groups based on the GS changes of the RP results. The values of the apparent diffusion coefficient (ADC), T1, T2 and proton density (PD) of these lesions were measured on ADC and SyMRI parameter maps by two physicians; these values were compared between PCA and BPH or inflammation, between the intermediate-to-high-risk and low-risk PCA groups, and between the upgraded and nonupgraded PCA groups. The risk factors affecting GS grades were identified via univariate analysis. The effects of confounding factors were excluded through multivariate logistic regression analysis, and independent predictive factors were calculated. Subsequently, the ADC+Sy(T2+PD) combined models for predicting PCA risk grade or GS upgrade were constructed through data processing analysis. The diagnostic performance of each parameter and the ADC+Sy(T2+PD) model was analyzed. The calibration curve was calculated by the bootstrapping internal validation method (200 bootstrap resamples). Results: The T1, T2, and PD values of PCA were significantly lower than those of BPH or inflammation (P≤0.001) in both the PZ or transitional zone. Among the 178 patients with PCA, intermediate-to-high-risk PCA group had significantly higher T1, T2, and PD values but lower ADC values compared with the low-risk group (P<0.05), and the diagnostic efficacy of each single parameter was similar (P>0.05). The ADC+Sy(T2+PD) model showed the best performance, with an area under the curve (AUC) 0.110 [AUC =0.818; 95% confidence interval (CI): 0.754-0.872] higher than that of ADC alone (AUC =0.708; 95% CI: 0.635-0.774) (P=0.003). Among the 68 patients initially classified as PCA in the low-risk group by biopsy, PCA in the postoperative upgraded GS group had significantly higher T1, T2, and PD values but lower ADC values than did those in the nonupgraded group (P<0.01). In addition, the ADC+Sy(T2+PD) model better predicted the upgrade of GS, with a significant increase in AUC of 0.204 (AUC =0.947; 95% CI: 0.864-0.987) compared with ADC alone (AUC =0.743; 95% CI: 0.622-0.841) (P<0.001). Conclusions: Quantitative parameters (T1, T2, and PD) derived from SyMRI can help differentiate PCA from non-PCA. Combining SyMRI parameters with ADC significantly improved the ability to differentiate between intermediate-to-high risk PCA from low-risk PCA and could predict the upgrade of low-risk PCA as confirmed by biopsy.

Serum BAFF levels are associated with the prognosis of idiopathic membranous nephropathy.

OBJECTIVE: High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear. METHODS: Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression. RESULTS: Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6-72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405-0.927; p = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202-0.648; p < 0.001). CONCLUSIONS: A high serum BAFF level is associated with severe clinical manifestations and poor disease progression in patients with iMN.

Development and validation of an 18F-FDG PET/CT-based radiomics nomogram for predicting the prognosis of patients with esophageal squamous cell carcinoma.

RATIONALE AND OBJECTIVES: The aim of this study was to develop and validate a nomogram, integrating clinical factors and radiomics features, capable of predicting overall survival (OS) in patients diagnosed with esophageal squamous cell carcinoma (ESCC). METHODS: In this study, we retrospectively analyzed the case data of 130 patients with ESCC who underwent 18F-FDG PET/CT before treatment. Radiomics features associated with OS were screened by univariate Cox regression (p < 0.05). Further selection was performed by applying the least absolute shrinkage and selection operator Cox regression to generate the weighted Radiomics-score (Rad-score). Independent clinical risk factors were obtained by multivariate Cox regression, and a nomogram was constructed by combining Rad-score and independent risk factors. The predictive performance of the model for OS was assessed using the time-dependent receiver operating characteristic curve, concordance index (C-index), calibration curve, and decision curve analysis. RESULTS: Five radiomics features associated with prognosis were finally screened, and a Rad-score was established. Multivariate Cox regression analysis revealed that surgery and clinical M stage were identified as independent risk factors for OS in ESCC. The combined clinical-radiomics nomogram exhibited C-index values of 0.768 (95% CI: 0.699-0.837) and 0.809 (95% CI: 0.695-0.923) in the training and validation cohorts, respectively. Ultimately, calibration curves and decision curves for the 1-, 2-, and 3-year OS demonstrated the satisfactory prognostic prediction and clinical utility of the nomogram. CONCLUSION: The developed nomogram, leveraging 18F-FDG PET/CT radiomics and clinically independent risk factors, demonstrates a reliable prognostic prediction for patients with ESCC, potentially serving as a valuable tool for guiding and optimizing clinical treatment decisions in the future.

131I Induced In Vivo Proteolysis by Photoswitchable azoPROTAC Reinforces Internal Radiotherapy.

Photopharmacology, incorporating photoswitches such as azobenezes into drugs, is an emerging therapeutic method to realize spatiotemporal control of pharmacological activity by light. However, most photoswitchable molecules are triggered by UV light with limited tissue penetration, which greatly restricts the in vivo application. Here, this study proves that 131I can trigger the trans-cis photoisomerization of a reported azobenezen incorporating PROTACs (azoPROTAC). With the presence of 50 µCi mL-1 131I, the azoPROTAC can effectively down-regulate BRD4 and c-Myc levels in 4T1 cells at a similar level as it does under light irradiation (405 nm, 60 mW cm-2). What's more, the degradation of BRD4 can further benefit the 131I-based radiotherapy. The in vivo experiment proves that intratumoral co-adminstration of 131I (300 µCi) and azoPROTC (25 mg kg-1) via hydrogel not only successfully induce protein degradation in 4T1 tumor bearing-mice but also efficiently inhibit tumor growth with enhanced radiotherapeutic effect and anti-tumor immunological effect. This is the first time that a radioisotope is successfully used as a trigger in photopharmacology in a mouse model. It believes that this study will benefit photopharmacology in deep tissue.

Radioactive iodine therapy for follicular thyroid cancer: a 15 years follow-up study of Chinese patients.

PURPOSE: To identify long-term predictors of distant metastases (DM) and the overall survival (OS) of follicular thyroid cancer (FTC) patients who underwent radioactive iodine (RAI) therapy. And to expand the knowledge about the clinical course and experience of RAI treatment for FTC. MATERIALS: A total of 117 FTC patients who underwent RAI therapy at our institution from 2005 to 2020 were retrospectively studied. Patient characteristics, serum stimulating thyroglobulin (sTg) and thyroglobulin antibody levels, treatment process and follow-up data were collected until 26 April 2022. RESULTS: A total of 16 patients (13.7%) were lost to follow-up. A total of 23 (19.7%) patients with DM died and all FTC without DM were still alive. DM was seen in 58.4% (59/101) of patients. The most common location for metastatic lesions was the lung. Then was bone. The mean survival time of FTC with RAI was 156 months [95% confidence interval (CI): 142-171]. Five-year and 10-year cumulative survival rates of them were 88.8% and 67.4%, respectively. As for patients with DM were 80.4% and 41.3%, respectively. Age at diagnosis [odds ratio (OR) = 1.080, P  = 0.009], RAI therapy sessions (OR = 2.959, P  = 0.001) and sTg level (OR = 1.006, P  = 0.002) were predictive of DM occurrence in FTC with RAI. In the group of FTC with DM, survival analysis showed that males were more likely to have a lower OS than females ( P  = 0.039). CONCLUSION: Age, number of RAI therapy sessions, and sTg level were predictive of the occurrence of DM in FTC patients with RAI. Sex would influence the OS of FTC patients with DM.

The RADAR technique in reconstruction of failed autologous arteriovenous fistulas due to juxta-anastomotic stenosis is equivalent to that with traditional surgery in maintenance hemodialysis patients.

OBJECTIVE: Autologous arteriovenous fistula (AVF) is recommended as superior vascular access for hemodialysis but has a high rate of failure, and juxta-anastomotic stenosis (JAS) is one of the predominant causes of fistula failure. The aim of this study was to compare the primary patency in reconstruction of failed AVFs due to JAS between the radial artery deviation and reimplantation (RADAR) technique and traditional surgery (end-vein to side-artery neo-anastomosis) in maintenance hemodialysis (MHD) patients. METHODS: A total of 1215 MHD patients with failed AVF were enrolled in this retrospective cohort study, and 614 patients with failed AVF received surgical intervention. Among these surgical interventions, 417 patients experienced AVF failure due to JAS. Finally, 25 patients who received the RADAR technique were enrolled. Controls of 50 patients received traditional surgery were randomly selected matched by age and sex. Clinical data such as age, sex, comorbidities, and blood biochemical indices were collected. Kaplan-Meier survival curves and Cox proportional hazards analyses were used to explore the difference between the RADAR group and the traditional group in reconstruction of failed AVFs. RESULTS: The RADAR group and the traditional group shared common baseline characteristics. The primary patencies of the reconstructed AVFs were 88.8%, 79.0%, 72.2%, 57.4%, and 38.3% at 12, 24, 36, 48, and 60 months among the 75 patients, respectively. Kaplan-Meier survival curve analysis demonstrated similar primary patencies in the two groups (log-rank test, p = 0.73). Compared with the traditional group, the RADAR group had no difference in predicting AVF failure after adjusting for potential confounders, with an HR of 0.92 (95% CI, 0.18-4.63). CONCLUSIONS: The primary patency of the RADAR technique and the traditional surgery in the reconstruction of failed AVFs due to JAS is almost equal in 5 years.

The influence of arm positions on mechanical dyssynchrony measured by gated myocardial perfusion imaging.

Background: In routine procedures, patient's arms are positioned above their heads to avoid potential attenuation artifacts and reduced image quality during gated myocardial perfusion imaging (G-MPI). However, it is difficult to achieve this action in the acute period following pacemaker implantation. This study aimed to explore the influence of arm positioning on myocardial perfusion imaging (MPI) in different types of heart disease. Methods: This study was conducted retrospectively. A total of 123 patients were enrolled and underwent resting G-MPI using a standard protocol with arms positioned above their heads and again with their arms at their sides. All individuals were divided into 3 groups: the normal group, the obstructive coronary artery disease (O-CAD) group, and the dilated cardiomyopathy (DCM) group. The G-MPI data were measured by QGS software and Emory Reconstruction Toolbox, including left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), end-systolic volume (ESV), extent, total perfusion deficit (TPD), summed rest score (SRS), scar burden, phase standard deviation (SD), and phase histogram bandwidth (BW). Results: In total, extent, TPD, EDV, ESV, LVEF, systolic SD, systolic BW, diastolic SD, and diastolic BW were all significantly different between the 2 arm positions (all P<0.01). On the Bland-Altman analysis, both EDV and ESV with the arm-down position were significantly underestimated (P<0.001). Meanwhile, TPD, extent, and LVEF with the arm-down position were significantly overestimated (P<0.05). Systolic SD, systolic BW, diastolic SD, and diastolic BW were systematically overestimated (P<0.001). In the DCM group (n=52), EDV, ESV, systolic SD, systolic BW, diastolic SD, and diastolic BW were identified as significantly different by the paired t-test between the 2 arm positions (P<0.05). In the O-CAD group (n=32), scar burden, ESV, LVEF, and diastolic BW were significantly different between the 2 arm positions (P<0.05). Conclusions: Systolic and diastolic dyssynchrony parameters and most left ventricular (LV) functional parameters were significantly influenced by arm position in both normal individuals and patients with heart failure (HF) with different pathophysiologies. More attention should be given to LV dyssynchrony data during clinical evaluation of cardiac resynchronization therapy (CRT) implantation procedure.

Alterations and potential roles of microbial population of pregnant mouse saliva and amniotic fluid.

PROBLEM: Prenatal exposure to intrauterine inflammation (IUI) is a crucial event in PTB pathophysiology. However, the relationship between microflora and PTB is not fully elucidated. METHOD OF STUDY: In this study, we established an intrauterine inflammation mouse model via LPS intrauterine injection. The saliva and amniotic fluid were collected for 16s RNA gene sequencing. The levels of TNF-α and IL-1ß in mouse amniotic fluid were determined by ELISA assays. RESULTS: Up to 60% of the operational taxonomic units (OTUs) in the saliva and amniotic fluid of PBS-treated mice were overlapped. LPS treatment-induced changes in the abundance of oral and amniotic fluid microorganisms. Both immune-associated probiotics, salivarius and mastitidis, were still detected in saliva (at significantly increased levels) after LPS-induced intrauterine inflammation and almost no probiotics of any type were detected in amniotic fluid, suggesting that the uterine cavity seems to be more susceptible to LPS compared to the oral cavity. Moreover, the abundance of pathogenic bacteria Escherichia coli was increased in both saliva and amniotic fluid after LPS treatment. The level of TNF-α and IL-1ß in amniotic fluid is positively related to the amniotic fluid E. coli abundance. CONCLUSIONS: The microbial composition of saliva and amniotic fluid of pregnant mice was similar. LPS-induced intrauterine inflammation decreased the consistency of microbial composition in mouse saliva and amniotic fluid, increased the abundance of E. coli in saliva and amniotic fluid, and decreased the abundance of immune-associated probiotics, especially in amniotic fluid.

ExoPD-L1: an assistant for tumor progression and potential diagnostic marker.

The proliferation and function of immune cells are often inhibited by the binding of programmed cell-death ligand 1 (PD-L1) to programmed cell-death 1 (PD-1). So far, many studies have shown that this combination poses significant difficulties for cancer treatment. Fortunately, PD-L1/PD-1 blocking therapy has achieved satisfactory results. Exosomes are tiny extracellular vesicle particles with a diameter of 40~160 nm, formed by cells through endocytosis. The exosomes are a natural shelter for many molecules and an important medium for information transmission. The contents of exosomes are composed of DNA, RNA, proteins and lipids etc. They are crucial to antigen presentation, tumor invasion, cell differentiation and migration. In addition to being present on the surface of tumor cells or in soluble form, PD-L1 is carried into the extracellular environment by tumor derived exosomes (TEX). At this time, the exosomes serve as a medium for communication between tumor cells and other cells or tissues and organs. In this review, we will cover the immunosuppressive role of exosomal PD-L1 (ExoPD-L1), ExoPD-L1 regulatory factors and emerging approaches for quantifying and detecting ExoPD-L1. More importantly, we will discuss how targeted ExoPD-L1 and combination therapy can be used to treat cancer more effectively.

Single-cell transcriptomics reveals the drivers and therapeutic targets of lymph node metastasis in lung adenocarcinoma.

Lymph node metastasis (LNM) is usually the most common metastatic pathway in lung adenocarcinoma (LUAD) and is associated with a poorer prognosis and higher possibility of recurrence. Therefore, discovering the drivers and therapeutic targets of LNM is important for early and non-invasive detection of patients with a high risk of LNM and guiding individualized therapy. Various cell constitutions of the primary tumor and lymph node microenvironment was characterized based on scRNA-seq data. The copy number variation (CNV) analysis was performed to probe clonal structures and origins of metastatic lymph nodes, and found 6q loss and 20q gain may drive LNM in LUAD. Then a LNM-related cell subset, named Scissor+ cells, was identified using the Scissor algorithm. And cell-cell communication network among Scissor+ cells and microenvironment was further analyzed. Besides, a pro-LNM signature was subsequently constructed based on 27 genes using pseudotime trajectory analysis and gene set variation analysis. The pro-LNM signature showed a significant correlation with N stage and a good predictive ability of LUAD survival. At last, we identified that erastin and gefitinib could potentially inhibit LNM by targeting Scissor+ cells based on the drug sensitivity data of the cancer cell lines, which provided new insights for LUAD therapy.

Long non-coding RNA-XLOC_002383 enhances the inhibitory effects of THP-1 macrophages on Mycobacterium avium and functions as a competing endogenous RNA by sponging miR-146a-5p to target TRAF6.

The morbidity associated with infection by Mycobacterium avium (M. avium), a type of non-tuberculous mycobacteria (NTM), has increased in recent years due to infections that are easily missed, and thus, difficult to diagnose and treat. Here, we reported that miR-146a-5p was highly expressed, and XLOC_002383 and TRAF6 were downregulated in a time- and MOI-dependent manner in THP-1 macrophages infected with M. avium. In macrophages obtained from peripheral blood mononuclear cells, the expression levels of XLOC_002383 and TRAF6 were also decreased, and miR-146a-5p expression was increased following 24 h of infection with M. avium. miR-146a-5p was a target of XLOC_002383 and TRAF6 mRNA was a target of miR-146a-5p, and XLOC_002383 regulated TRAF6 expression by adsorbing miR-146a-5p, and further increased IL-6, TNF-α, IL-1ß and iNOS levels in THP-1 macrophages. The results of qPCR and CFU assays indicated that XLOC_002383 decreased the intracellular M. avium loads. Overall, the present study demonstrated that XLOC_002383 may function as a competing endogenous RNA and interacts with miR-146a-5p to increase THP-1 macrophage inflammatory factors and microbicidal mediators iNOS. This enhanced the inhibitory effects of THP-1 macrophages on M. avium, which improved the understanding of the pathogenesis and host defenses in the process of NTM infectious diseases.

Phytophthora RxLR effector PcSnel4B promotes degradation of resistance protein AtRPS2.

Phytophthora capsici deploys effector proteins to manipulate host immunity and facilitate its colonization. However, the underlying mechanisms remain largely unclear. In this study, we demonstrated that a Sne-like (Snel) RxLR effector gene PcSnel4 is highly expressed at the early stages of P. capsici infection in Nicotiana benthamiana. Knocking out both alleles of PcSnel4 attenuated the virulence of P. capsici, while expression of PcSnel4 promoted its colonization in N. benthamiana. PcSnel4B could suppress the hypersensitive reaction (HR) induced by Avr3a-R3a and RESISTANCE TO PSEUDOMONAS SYRINGAE 2 (AtRPS2), but it did not suppress cell death elicited by Phytophthora infestin 1 (INF1) and Crinkler 4 (CRN4). COP9 signalosome 5 (CSN5) in N. benthamiana was identified as a host target of PcSnel4. Silencing NbCSN5 compromised the cell death induced by AtRPS2. PcSnel4B impaired the interaction and colocalization of Cullin1 (CUL1) and CSN5 in vivo. Expression of AtCUL1 promoted the degradation of AtRPS2 and disrupted HR, while AtCSN5a stabilized AtRPS2 and promoted HR, regardless of the expression of AtCUL1. PcSnel4 counteracted the effect of AtCSN5 and enhanced the degradation of AtRPS2, resulting in HR suppression. This study deciphered the underlying mechanism of PcSnel4-mediated suppression of HR induced by AtRPS2.

Multicenter Randomized Double-Blind Phase III Trial of Donafenib in Progressive Radioactive Iodine-Refractory Differentiated Thyroid Cancer.

PURPOSE: The phase II/III study of donafenib was initiated when there was no available treatment indicated for Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Donafenib, an oral tyrosine kinase inhibitor (TKI), showed good efficacy and tolerability in the phase II study. We aimed to further evaluate the antitumor activity and safety of donafenib in Chinese patients with RAIR-DTC. PATIENTS AND METHODS: This multicenter, double-blind, placebo-controlled, phase III study enrolled 191 patients with progressive RAIR-DTC and randomized in a ratio of 2:1 to donafenib (300 mg twice daily, n = 128) or matched placebo (n = 63). An open-label donafenib treatment period was allowed upon disease progression. The primary endpoint was progression-free survival (PFS) assessed by the independent review committee. The second endpoints include objective response rate (ORR), disease control rate (DCR), safety, etc. RESULTS: Donafenib demonstrated prolonged median PFS over placebo [12.9 vs. 6.4 months; hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.25-0.61; P < 0.0001] in Chinese patients with RAIR-DTC. Improved ORR (23.3% vs. 1.7%; P = 0.0002) and DCR (93.3% vs. 79.3%; P = 0.0044) were observed in the donafenib group over placebo. For donafenib, the most common grade ≥ 3 treatment-related adverse events (AE) included hypertension (13.3%) and hand-foot syndrome (12.5%), 42.2% underwent dose reduction or interruption, and 6.3% experienced discontinuation. CONCLUSIONS: Donafenib was well-tolerated and demonstrated clinical benefit in terms of improved PFS, ORR, and DCR in patients with RAIR-DTC. The results suggest that donafenib could be a new treatment option for patients with RAIR-DTC.

Prediction of ADMET Properties of Anti-Breast Cancer Compounds Using Three Machine Learning Algorithms.

In recent years, machine learning methods have been applied successfully in many fields. In this paper, three machine learning algorithms, including partial least squares-discriminant analysis (PLS-DA), adaptive boosting (AdaBoost), and light gradient boosting machine (LGBM), were applied to establish models for predicting the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET for short) properties, namely Caco-2, CYP3A4, hERG, HOB, MN of anti-breast cancer compounds. To the best of our knowledge, the LGBM algorithm was applied to classify the ADMET property of anti-breast cancer compounds for the first time. We evaluated the established models in the prediction set using accuracy, precision, recall, and F1-score. Compared with the performance of the models established using the three algorithms, the LGBM yielded most satisfactory results (accuracy > 0.87, precision > 0.72, recall > 0.73, and F1-score > 0.73). According to the obtained results, it can be inferred that LGBM can establish reliable models to predict the molecular ADMET properties and provide a useful tool for virtual screening and drug design researchers.

An AIE mechanism-based fluorescent probe for relay recognition of HSO3-/H2O2 and its application in food detection and bioimaging.

In view of the important physiological role of HSO3- and H2O2, it is of great significance to develop fluorescent probes to detect HSO3- and H2O2 in aqueous medium. We herein report a new fluorescent probe (E)-3-(2-(4-(1,2,2-triphenylvinyl)styryl)benzo [d]thiazol-3-ium-3-yl)propane-1-sulfonate (TPE-y) possessing benzothiazolium salt based on tetraphenylethene (TPE) moiety with aggregation-induced emission (AIE) characteristics. TPE-y can sequentially recognize HSO3- and H2O2 through colorimetric and fluorescence dual-channel response in HEPES (pH = 7.4, 1% DMSO) buffer solution, and exhibits high sensitivity and selectivity, a large Stokes shift (189 nm), as well as a wide applicable pH range. The detection limits of TPE-y and TPE-y-HSO3 for HSO3- and H2O2 are 3.52 µM and 0.15 µM, respectively. The recognition mechanism is verified by 1H NMR and HRMS methods. Furthermore, TPE-y can detect HSO3- in sugar samples, and can image exogenous HSO3- and H2O2 in living MCF-7 cells. TPE-y can relay detect HSO3- and H2O2, which is of great significance to maintain the redox balance in organisms.

The added prognostic values of baseline PET dissemination parameter in patients with angioimmunoblastic T-cell lymphoma.

To explore the prognostic values of baseline 2-deoxy-2-[18F] fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) dissemination parameter in angioimmunoblastic T-cell lymphoma (AITL) and its added values to total metabolic tumour volume (TMTV). Eighty-one AITL patients with at least two FDG-avid lesions in baseline PET/CT were retrospectively included. PET parameters including TMTV and the distance between the two lesions that are the furthest apart (Dmax) were obtained. Univariate Cox analysis showed that both Dmax and TMTV were risk factors for progression-free survival (PFS) and overall survival (OS). Multivariate Cox analysis models of different combinations showed that high Dmax (> 65.7 cm) could independently predict both PFS and OS, while high TMTV (>456.6 cm3) was only significant for OS. A concise PET model based on TMTV and Dmax can effectively risk-stratify patients. PFS and OS rates were significantly lower in patients with high Dmax and high TMTV than in patients with low Dmax and low TMTV (3-year PFS rate: 15.0% vs. 48.7%, p = 0.001; 3-year OS rate: 27.6% vs. 79.0%, p < 0.001). Dmax can directly reflect the disease dissemination characteristic and has a significant prognostic value for FDG-avid AITL patients. It has the potential to be introduced into new risk stratification models for tailored treatment.

The effects of music therapy on peripherally inserted central catheter in hospitalized children with leukemia.

To explore the effect of music therapy on children with leukemia who have peripherally inserted central catheters (PICC).In this study, we divided 107 patients undergoing PICC into music group (47 cases) and control group (60 cases). The music group received music therapy during PICC, while the control group was given no complementary treatment. The total length of catheterization, the use of sedatives and the changes of pain level and emotion level before and after PICC placement were compared between two groups.Compared with the control group, the total PICC placement time of the music group was significantly shorter (35(30-40) vs. 60(60-60); Z = -8.307; p < 0.001), and the use of sedative medications was also significantly reduced (4.35% (n = 2) vs. 91.84% (n = 45); p < 0.001). Moreover, the pain of catheterization was significantly alleviated. The median difference of pain scores of the music group was significantly less (2(1-3) vs. 5(5-5); p < 0.001). The mood of patients was also improved. The median difference of emotional scores of the music group was significantly more (5(4.75-6) vs. 3(3-3); p < 0.001) than the control group.Music therapy is effective to use in PICC. It can shorten the treatment time, reduce the use of sedative medications, and improve the children's emotion and pain response significantly, which is worth clinical application.

Comprehensive analysis of N6-methyladenosine-related lncRNAs reveals distinct hepatocellular carcinoma subtypes with immunotherapeutic implications.

Accumulating studies have demonstrated critical roles of N6-methyladenosine (m6A) modification and long noncoding RNAs (lncRNAs) in the biological processes leading to occurrence, development and chemoresistance of cancers. However, the specific identities and functional roles of lncRNAs associated with m6A modification in hepatocellular carcinoma (HCC) remain elusive. In this study, eighty-two prognostic m6A-related lncRNAs (m6A-LncRNAs) were identified in HCC datasets. Patients with HCC were classified into three subtypes (C1, C2 and C3) based on the expression of the m6A-LncRNAs. The three subtypes showed significant differences in clinical features, immune and stromal infiltration signatures, and immunotherapy sensitivity. Subclass C1 was notable for high immune and stromal cell infiltration and active immune responses, low serum α-fetoprotein (AFP) levels and high sensitivity to immune checkpoint inhibitors (ICIs). Subclass C2 showed high metabolic activities and absence of immune infiltration with favorable prognosis. Subclass C3 was associated with an exhausted immune environment, high serum AFP and poor prognosis. Notably, subclass C3 displayed high expression of immune checkpoints but failed to respond to ICIs. Finally, 12 m6A-LncRNA signatures were identified for HCC classification and validated in an external dataset. This integrated analysis indicated that the interactions between m6A methylation and lncRNAs are involved in immune and stromal cell infiltration in HCC, and may provide novel insights into precision diagnostics as well as therapeutics for HCC patients.