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Twenty 3-acyloxymaltol/ethyl maltol derivatives (7a-j and 8a-j) were synthesized and evaluated in vitro for their anti-oomycete activity against Phytophthora capsici, respectively. Among all of twenty derivatives, more than half of the compounds 7f, 7h, 8a-h and 8j had anti-oomycete activity higher than the positive control zoxamide (EC50 = 22.23 mg/L), and the EC50 values of 18.66, 20.32, 12.80, 16.18, 10.59, 14.98, 16.80, 10.36, 15.32, 12.64, and 13.59 mg/L, respectively. Especially, compounds 8c and 8f exhibited the best anti-oomycete activity against P. capsici with EC50 values of 10.59 and 10.36 mg/L, respectively. Overall, hydroxyl group of maltol/ethyl maltol is important active modification site. [ABSTRACT FROM AUTHOR]

Background: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. Methods: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. Results: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0–1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2–1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. Conclusions: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. ClinicalTrials.gov Identifier: NCT03472508 (Registration Date: March 21, 2018). [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress. Methods: A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-β to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers' expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-β with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected. Results: In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding. Conclusion: The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Background: This study aims to thoroughly study the connection between congenital heart disease (CHD) and neurodevelopmental disorders (NDDs) through observational and Mendelian randomization (MR) designs. Methods: This observational study uses data from the National Survey of Children's Health (2020–2021). Multivariable logistic regression and propensity score matching (PSM) were performed to analyze the association. PSM was used to minimize bias for covariates such as age, race, gender, maternal age, birth weight, concussion or brain injury, preterm birth, cerebral palsy, Down syndrome, and other inherited conditions. In MR analyses, inverse variance-weighted measures, weighted median, and MR-Egger were employed to calculate causal effects. Results: A total of 85,314 children aged 0–17 were analyzed in this study. In regression analysis, CHD (p = 0.04), the current heart condition (p = 0.03), and the severity of current heart condition (p < 0.05) had a suggestive association with speech or language disorders. The severity of current heart condition (p = 0.08) has a potential statistically significant association with attention deficit hyperactivity disorder(ADHD). In PSM samples, ADHD(p = 0.003), intellectual disability(p = 0.012), and speech or language disorders(p < 0.001) were all significantly associated with CHD. The severity of current heart condition (p < 0.001) also had a significant association with autism. MR analysis did not find causality between genetically proxied congenital cardiac malformations and the risk of NDDs. Conclusions: Our study shows that children with CHD have an increased risk of developing NDDs. Heart conditions currently and severity of current heart conditions were also significantly associated with these NDDs. In the future, we need to try more methods to clarify the causal relationship between CHD and NDDs. [ABSTRACT FROM AUTHOR]

Introduction: Immune microenvironment plays an important role in the occurrence and development of acute myeloid leukemia (AML). Studies assessing the prognostic significance of bone marrow (BM) lymphocyte subsets' frequencies at diagnosis in patients with AML were limited. Methods: Fresh BM samples collected from 97 adult AML patients at diagnosis were tested for lymphocyte, T, CD4+T, CD8+T, γδT, NK, and B cell frequencies using multi‐parameter flow cytometry. Results: Low frequencies of lymphocytes, T, CD4+T, and CD8+T cells were associated with significantly lower rates of one‐course complete remission (CR) (all p < 0.05). Moreover, the frequency of CD4+T cells independently predicted one‐course CR achievement (p = 0.021). Low frequencies of T and CD8+T cells were significantly associated with lower relapse‐free survival (RFS) rates (p = 0.032; 0.034), respectively, and a low frequency of CD8+T cells was associated with a significantly lower overall survival (OS) rate (p = 0.028). Combination of frequency of CD8+T cells and ELN risk stratification showed that patients with ELN‐intermediate/adverse risk + high CD8+T cell frequency had a similar RFS rate to those with ELN‐favorable risk + high CD8+T cell frequency and those with ELN‐favorable risk + low CD8+T cell frequency (p = 0.88; 0.76), respectively. The RFS rate of patients with ELN intermediate/adverse risk + low CD8+T cell frequency was significantly lower than that of all aforementioned patients (p = 0.021; 0.0007; 0.028), respectively. Conclusion: The frequencies of BM lymphocyte subsets at diagnosis predicted clinical outcomes and could help improve risk stratification in AML. [ABSTRACT FROM AUTHOR]

Guided by 1H NMR spectroscopic experiments using the characteristic enol proton signals as probes, three pairs of new tautomeric cinnamoylphloroglucinol-monoterpene adducts (1–3) were isolated from the buds of Cleistocalyx operculatus. Their structures with absolute configurations were established by spectroscopic analysis, modified Mosher's method, and quantum chemical electronic circular dichroism calculation. Compounds 1–3 represent a novel class of cinnamoylphloroglucinol-monoterpene adducts featuring an unusual C-4–C-1′ linkage between 2,2,4-trimethyl-cinnamyl-β-triketone and modified linear monoterpenoid motifs. Notably, compounds 1–3 exhibited significant in vitro antiviral activity against respiratory syncytial virus (RSV). [ABSTRACT FROM AUTHOR]

Simple Summary: Epithelial ovarian cancer (EOC) is the fifth-leading cause of cancer-related deaths in women worldwide and the most lethal gynecologic malignancy. Seventy-five percent of patients are diagnosed at an advanced stage, accompanied by extensive pelvic and abdominal metastases, and thus have a poor prognosis. We first screened for critical genes in EOC in the GEO database. LLGL2 was upregulated in ovarian cancer tissue, while low expression of LLGL2 was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients, implying that LLGL2 may function as a tumor suppressor gene. Our data demonstrated that overexpression of LLGL2 inhibited the ovarian cancer cell migration and invasion abilities in vivo and in vitro. Mechanistically, LLGL2 altered the intracellular localization and function of ACTN1 by interacting with ACTN1 and regulating cytoskeleton remodeling to inhibit the invasion and metastasis of ovarian cancer cells. Epithelial ovarian cancer is the most lethal gynecological malignant tumor. Although debulking surgery, chemotherapy, and PARP inhibitors have greatly improved survival, the prognosis for patients with advanced EOC without HRD is still poor. LLGL2, as a cell polarity factor, is involved in maintaining cell polarity and asymmetric cell division. In the study of zebrafish development, LLGL2 regulated the proliferation and migration of epidermal cells and the formation of cortical F-actin. However, the role of LLGL2 in ovarian cancer has not been described. Our study found, through bioinformatics analysis, that low expression of LLGL2 was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients. Functional experiments that involved LLGL2 overexpression and knockdown showed that LLGL2 inhibited the migration and invasion abilities of ovarian cancer cells in vitro, without affecting their proliferation. LLGL2-overexpressing mice had fewer metastatic implant foci than the controls in vivo. Mechanistically, immunoprecipitation combined with mass spectrometry analysis suggested that LLGL2 regulated cytoskeletal remodeling by interacting with ACTN1. LLGL2 altered the intracellular localization and function of ACTN1 without changing its protein and mRNA levels. Collectively, we uncovered that LLGL2 impaired actin filament aggregation into bundles by interacting with ACTN1, which led to cytoskeleton remodeling and inhibition of the invasion and metastasis of ovarian cancer cells. [ABSTRACT FROM AUTHOR]

This study aimed to explore the magnetic resonance imaging (MRI) features of dual-phenotype hepatocellular carcinoma (DPHCC) and their diagnostic value.The data of 208 patients with primary liver cancer were retrospectively analysed between January 2016 and June 2021. Based on the pathological diagnostic criteria, 27 patients were classified into the DPHCC group, 113 patients into the noncholangiocyte-phenotype hepatocellular carcinoma (NCPHCC) group, and 68 patients with intrahepatic cholangiocarcinoma (ICC) were classified into the ICC group. Two abdominal radiologists reviewed the preoperative MRI features by a double-blind method. The MRI features and key laboratory and clinical indicators were compared between the groups. The potentially valuable MRI features and key laboratory and clinical characteristics for predicting DPHCC were identified by univariate and multivariate analyses, and the odds ratios (ORs) were recorded. In multivariate analysis, tumour without capsule (P = 0.046, OR = 9.777), dynamic persistent enhancement (P = 0.006, OR = 46.941), and targetoid appearance on diffusion-weighted imaging (DWI) (P = 0.021, OR = 30.566) were independently significant factors in the detection of DPHCC compared to NCPHCC. Serum alpha-fetoprotein (AFP) > 20 µg/L (P = 0.036, OR = 67.097) and prevalence of hepatitis B virus (HBV) infection (P = 0.020, OR = 153.633) were independent significant factors in predicting DPHCC compared to ICC. The differences in other tumour marker levels and imaging features between the groups were not significant. In MR enhanced and diffusion imaging, tumour without capsule, persistent enhancement and DWI targetoid findings, combined with AFP > 20 µg/L and HBV infection-positive laboratory results, can help to diagnose DPHCC and differentiate it from NCPHCC and ICC. These results suggest that clinical, laboratory and MRI features should be integrated to construct an AI diagnostic model for DPHCC. [ABSTRACT FROM AUTHOR]

Background: Implant-related infections are a challenging complication of orthopedic surgery, primarily due to the formation of bacterial biofilms on the implant surface. An antibacterial coating for titanium implants was developed to provide novel insights into the prevention and treatment of implant-related infections. Methods: Titanium plates were coated with TiO2 nanotubes by anodization, and iodine was doped onto the coating via electrophoretic deposition. The obtained plates were characterized using a range of analytical techniques. Subsequently, Staphylococcus aureus was inoculated onto the surfaces of untreated titanium plates (control group), TiO2-nanocoated titanium plates (TiO2 group), and iodine-doped TiO2-nanocoated titanium plates (I-TiO2 group) to compare their antibacterial properties. Results: Twenty-four hour in vitro antimicrobial activity test of the I-TiO2 group against Staphylococcus aureus was superior to those of the other groups, and this difference was statistically significant (P < 0.05). Conclusions: This coating technology provides a new theoretical basis for the development of anti-infective implants against Staphylococcus aureus in orthopedics. [ABSTRACT FROM AUTHOR]

Objective: Accurate quantification of the root surface area (RSA) plays a decisive role in the advancement of periodontal, orthodontic, and restorative treatment modalities. In this study, we aimed to develop a dynamic threshold-based computer-aided system for segmentation and calculation of the RSA of isolated teeth on cone-beam computed tomography (CBCT) and to assess the accuracy of the measured data. Method: We selected 24 teeth to be extracted, including single-rooted and multi-rooted teeth, from 22 patients who required tooth extraction. In the experimental group, we scanned 24 isolated teeth using CBCT with a voxel size of 0.3 mm. We designed a computer-aided system based on a personalized dynamic threshold algorithm to automatically segment the roots of 24 isolated teeth in CBCT images and calculate the RSA. In the control group, we employed digital intraoral scanner devices to perform optical scanning on 24 isolated teeth and subsequently manually segmented the roots using 3-matic software to calculate the RSA. We used the paired t-test (P < 0.05) and Bland-Altman plots to analyze the consistency of the two measurement methods. Results: The results of the paired t-test showed that there was no significant difference in the RSAs obtained using the dynamic threshold method and the optical scanning image reconstruction (t = 1.005, P = 0.325 > 0.05). As per the Bland-Altman plot, the results were evenly distributed within the region of ± 1.96 standard deviations of the mean, with no increasing or decreasing trends and good consistency. Conclusion: In this study, we designed a computer-aided root segmentation system based on a personalized dynamic threshold algorithm to automatically segment the roots of isolated teeth in CBCT images with a voxel size of 0.3 mm. We found that the RSA calculated using this approach was highly accurate, and a voxel of 0.3 mm in size could accurately display the surface area data in CBCT images. Overall, our findings in this study provide a foundation for future work on accurate automatic segmentation of tooth roots in full-mouth CBCT images and the computation of RSA. [ABSTRACT FROM AUTHOR]

Introduction: Relapse remained the major obstacle to improving the prognosis of children with acute lymphoblastic leukemia (ALL). This study aimed to investigate the changing patterns of Ig/TCR gene rearrangements between diagnosis and relapse and the clinical relevance and to explore the mechanism of leukemic relapse. Methods: Clonal Ig/TCR gene rearrangements were screened by multiplex PCR amplification in 85 paired diagnostic and relapse bone marrow (BM) samples from children with ALL. The new rearrangements presented at relapse were quantitatively assessed by the RQ‐PCR approach targeting the patient‐specific junctional region sequence in 19 diagnostic samples. The relapse clones were further back‐traced to diagnostic and follow‐up BM samples from 12 patients. Results: Comparison of Ig/TCR gene rearrangements between diagnosis and relapse showed that 40 (57.1%) B‐ALL and 5 (33.3%) T‐ALL patients exhibited a change from diagnosis to relapse, and 25 (35.7%) B‐ALL patients acquired new rearrangements at relapse. The new relapse rearrangements were present in 15 of the 19 (78.9%) diagnostic samples as shown by RQ‐PCR, with a median level of 5.26 × 10−2. The levels of minor rearrangements correlated with B immunophenotype, WBC counts, age at diagnosis, and recurrence time. Furthermore, back‐tracing rearrangements in 12 patients identified three patterns of relapse clone dynamics, which suggested the recurrence mechanisms not only through clonal selection of pre‐existing subclones but also through an ongoing clonal evolution during remission and relapse. Conclusion: Backtracking Ig/TCR gene rearrangements in relapse clones of pediatric ALL revealed complex patterns of clonal selection and evolution for leukemic relapse. [ABSTRACT FROM AUTHOR]

Background: Lung cancer, especially non‐small cell lung cancer (NSCLC), is one of the leading causes of cancer‐related deaths worldwide. Vincristine (VCR) is a chemotherapeutic agent for lung cancers; however, its effectiveness is limited by side effects and the development of drug resistance. Patchouli alcohol (PA), from Pogostemon cablin extract, is known to possess anti‐inflammatory and anticancer properties. In this study, we investigated the role of PA in inducing reactive oxygen species (ROS)‐mediated DNA damage in A549 and VCR‐resistant A549/V16 NSCLC cells. Methods: The anticancer potential of PA was studied using the MTT assay, colony formation, flow cytometry analysis, western blotting, DCFDA staining, immunofluorescence staining, and TUNEL assay techniques. Results: The intracellular ROS levels were enhanced in PA‐treated cells, activating the CHK1 and CHK2 signaling pathways. PA further inhibited proliferation and colony‐forming abilities and induced cell cycle arrest at the G0/G1 phase by regulating p53/p21 and CDK2/cyclin E1 expression. Moreover, PA increased the percentage of cells in the subG1 phase and induced apoptosis by activating the Bax/caspase‐9/caspase‐3 intrinsic pathway. In addition, drug resistance (p‐glycoprotein) and cancer stem cell (CD44 and CD133) markers were downregulated after PA treatment. Furthermore, combining PA and cisplatin exhibited synergistic inhibitory activity in A549 and A549/V16 cells. Conclusions: PA induced ROS‐mediated DNA damage, triggered cell cycle arrest and apoptosis, attenuated drug resistance and cancer stem cell phenotypes, and synergistically inhibited proliferation in combination with cisplatin. These findings suggest that PA has the potential to be used for the treatment of NSCLC with or without VCR resistance. [ABSTRACT FROM AUTHOR]

Rosa roxburghii Tratt is a traditional Chinese plant that has been used to treat different inflammatory diseases. The purpose of this study was to investigate the mechanism of action of Rosa roxburghii Tratt extract (RRTE) against ulcerative colitis (UC) using network pharmacology and experimental validation. HPLC-Q/Orbitrap MS was used to rapidly identify the substances contained in RRTE after extracting the active components from the fruit. Then, network pharmacology combined with molecular docking was used to explore the critical target and potential mechanism of RRTE against UC using the active ingredients in RRTE as the research object. Data are presented in a visual manner. Finally, the pharmacological effects of RRTE in alleviating UC were further verified using a DSS-induced UC model of NCM460. The results showed that 25 components in RRTE were identified. A total of 250 targets of the active components and 5376 targets associated with UC were collected. Furthermore, a systematic analysis of the Protein–Protein Interaction (PPI) networks suggests that epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and serine/threonine kinase 1 (AKT1) are critical targets for RRTE in the treatment of UC. A comprehensive regulatory network analysis showed that RRTE alleviated UC through the EGFR-mediated PI3K/Akt pathway, and molecular docking showed that active components could strongly bind to EGFR, PIK3R1, and AKT1. In addition, RRTE alleviated dextran sulfate sodium salt (DSS)-induced cell injury and significantly decreased the protein expression levels of EGFR, PIK3R1, and p-AKT in NCM460 cells in vitro. Furthermore, RRTE significantly regulated the expression of the apoptosis-related proteins Apoptotic protease-activating factor 1 (Apaf1), cleaved caspase-3, B-cell lymphoma-2 (Bcl2), and Bcl2 associated X protein (Bax). In conclusion, the components of RRTE are complex, and RRTE can relieve UC through the EGFR-mediated PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

Introduction: AML patients with KMT2A‐MLLT3 and other 11q23 abnormalities belong to the intermediate and high‐risk level groups, respectively. Whether the poor prognostic value of Ecotropic Viral Integration site‐1 (EVI1) overexpression suits either the subtypes of KMT2A‐MLLT3 or Non‐KMT2A‐MLLT3 AML patients (intermediate and high risk group) needs to be further investigated. Methods: We retrospectively analyzed the clinical characteristics of 166 KMT2A‐r and KMT2A‐PTD AML patients. Results: For the Non‐KMT2A‐MLLT3 group, patients in the EVI1‐high subgroup had shorter OS and DFS and higher CIR than those in the EVI1‐low subgroup (p =.027, p =.018, and p =.020, respectively). Additionally, both KMT2A‐MLLT3 and Non‐KMT2A‐MLLT3 patients who received chemotherapy alone had poorer prognosis than patients who also received allogeneic hematopoietic stem cell transplant (allo‐HSCT) regardless of their EVI1 expression level (all p <.001). For transplanted patients with KMT2A‐MLLT3 or Non‐KMT2A‐MLLT3 rearrangement, the EVI1‐high subgroup had worse prognosis than the EVI1‐low subgroup (all p <.05). The 2‐year CIR of the KMT2A‐MLLT3 and Non‐KMT2A‐MLLT3 groups with high EVI1 expression was high (52% and 49.6%, respectively). However, for patients with low EVI1 expression, the 2‐year CIR of transplanted patients with KMT2A‐MLLT3 and Non‐KMT2A‐MLLT3 was relatively low. Conclusions: Our study showed that for the Non‐KMT2A‐MLLT3 group, the EVI1‐high group had shorter OS and DFS than the EVI1‐low group. High EVI1 expression showed an adverse effect in AML with KMT2A rearrangement in different risk stratification subtypes. For the EVI1‐high patients with non‐KMT2A‐MLLT3 rearrangement, other novel regimens towards relapse should be taken into consideration. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to investigate key long noncoding RNAs (lncRNAs) involved in competitive endogenous RNA (ceRNA) network associated with laryngeal squamous cell carcinoma (LSCC). Materials and Methods: Three mRNA datasets, two miRNA datasets, and one lncRNA dataset of LSCC were downloaded from GEO database. Following the identification of differentially expressed mRNAs (DEmRNAs), (microRNAs) miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) in LSCC compared with adjacent tissues, functional enrichment of DEmRNAs was performed. Then, construction of the ceRNA (DElncRNA‐DEmiRNA‐DEmRNA) regulatory network and functional analyses of all DEmRNAs in ceRNA regulatory network were conducted. Quantitative real‐time polymerase chain reactions (qRT‐PCR) were used to detect the expression levels of selected DEmRNAs, DEmiRNAs, and DElncRNAs. Results: A total of 3449 DEmRNAs, 40 DEmiRNAs, and 100 DElncRNAs were identified in LSCC. The ceRNA networks, which contained 132 DElncRNA‐DEmiRNA pairs and 287 DEmiRNA‐DEmRNA pairs, involving 44 lncRNAs, 3 miRNAs, and 271 mRNAs, were obtained. DEmRNAs in ceRNA regulatory networks were significantly enriched in pathways in cancer, prostate cancer, and aldosterone‐regulated sodium reabsorption. Except for HCG22 and hsa‐miR‐1246, expressions of the others in the qRT‐PCR results played the same pattern with that in our integrated analysis, generally. Conclusions: We concluded that HCG22/EGOT‐hsa‐miR‐1275‐FAM107A and HCG22/EGOT‐hsa‐miR‐1246‐Glycerol‐3‐phosphate dehydrogenase 1 like interaction pairs may play a central role in LSCC. [ABSTRACT FROM AUTHOR]

Recently, ciquitins A and B isolated from the powdered and defatted airdried aerial parts of Leucophyllum ambiguum were reported as a mixture of conformers in a solution at room temperature. Considering the existence of a hemiacetal hydroxyl fragment in the ciquitins A and B, they are more likely to exist in the form of epimer rather than the mixture of conformers. To confirm this hypothesis, the NMR calculations of two epimers at C-9 (1-a and 1-b) were performed and the results matched well with experimental NMR data of mixtures (1). Moreover, a brief discussion on the reason for this hypothesis was also presented. [ABSTRACT FROM AUTHOR]

Background: The KODEX-EPD system is a novel, dielectric three-dimensional mapping system. We aim to illustrate the feasibility, safety, and outcomes of ablation using the KODEX-EPD system.Methods: A total of 272 patients with supraventricular arrhythmias were enrolled and underwent catheter ablation using the KODEX-EPD system from October 2020 to July 2021. The feasibility, safety, and ablation outcomes were analyzed.Results: Of the enrolled patients, 15 (5.4%) had atrial tachycardia (AT), 88 (31.4%) had atrioventricular reentrant tachycardia (AVRT), 141 (50.4%) had atrioventricular nodal reentrant tachycardia (AVNRT), 34 (12.1%) had atrial fibrillation (AF), and 9 (3.2%) had atrial flutter (AFL). All AF patients included were first-do-pulmonary vein isolation (PVI); there were 26 paroxysmal AF and 8 persistent AF. All patients achieved immediate success of ablation. The mean follow-up duration was 11.8 ± 2.4 months. One patient (1.1%) in the AVRT subgroup and two patients (1.4%) in the AVNRT subgroup experienced recurrence. When considering a three-month blanking time, the estimated freedom of AF at one-year post-ablation with and without AADs was 75.7% and 70.4%, respectively. The Kaplan-Meier analysis showed no significant difference in the overall AF recurrence (log-rank; P = 0.931) or AAD-free AF recurrence (log-rank; P = 0.841) between RFCA and cryoablation. One patient had mild pulmonary embolism. None of the patients died or had a cerebrovascular event in the periprocedural period.Conclusions: This retrospective, two-center study demonstrated that catheter ablation of supraventricular arrhythmias using the KODEX-EPD system is feasible, safe, and effective. Trial registration Retrospectively registered. [ABSTRACT FROM AUTHOR]

Ten compounds (1–10) including four new compounds (1–4) and six known compounds (5–10) were isolated from Solanum nigrum. Their structures were elucidated on the basis of spectroscopic data, gauge-including atomic orbital (GIAO) calculation of NMR data, DP4+ probability analysis and comparison of their experimental and calculated electronic circular dichroism (ECD) spectral data. All the isolated compounds were tested for their neuroprotective activities against H2O2-induced damage in SH-SY5Y cells. Among them, compounds 1, 5 and 7 displayed moderate neuroprotective effects. [ABSTRACT FROM AUTHOR]

Background: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm. A few LCH patients had Macrophage activation syndrome-hemophagocytic lymphohistiocytosis (MAS-HLH), a life-threatening, hyper-inflammatory syndrome. We retrospectively described the clinical-biological characteristics of a series of 28 pediatric LCH patients with MAS-HLH in a single center. We further analyzed the difference in treatment outcomes between second-line chemotherapy (cytarabine and cladribine) and targeted therapy (dabrafenib) for BRAF-V600E-positive patients.Results: LCH patients with MAS-HLH were aged < 2 years, harbored high frequencies of risk organ, skin, or lymph nodes involvement, and most of them carried BRAF-V600E mutation in lesions (88.0%) or plasma (90.5%). Patients were firstly treated with the initial induction first-line therapy (vindesine-steroid combination), and most of them (26/28) failed to control the active MAS-HLH after one six-week course of induction treatment. Then they were shifted to second-line chemotherapy or targeted therapy dabrafenib. BRAF-V600E-mutant patients treated with dabrafenib had prompt resolution of MAS-HLH signs and symptoms with less toxicity than second-line chemotherapy. Moreover, the progression-free survival (PFS) rate for patients given dabrafenib was much higher than those treated with chemotherapy (4 year-PFS: 75% vs. 14.6%, P = 0.034).Conclusions: LCH patients with MAS-HLH harbored specific clinical-biology characteristics compared to the multisystem LCH without MAS-HLH. The BRAF inhibitor dabrafenib provides a promising treatment option for LCH with MAS-HLH. [ABSTRACT FROM AUTHOR]

Background: Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective haematopoiesis and immune deregulation. Emerging evidence has shown the effect of bone marrow (BM) endothelial progenitor cells (EPCs) in regulating haematopoiesis and immune balance. However, the number and functions of BM EPCs in patients with different stages of MDS remain largely unknown.Methods: Patients with MDS (N = 30), de novo acute myeloid leukaemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. MDS patients were divided into lower-risk MDS (N = 15) and higher-risk MDS (N = 15) groups according to the dichotomization of the Revised International Prognostic Scoring System. Flow cytometry was performed to analyse the number of BM EPCs. Tube formation and migration assays were performed to evaluate the functions of BM EPCs. In order to assess the gene expression profiles of BM EPCs, RNA sequencing (RNA-seq) were performed. BM EPC supporting abilities of haematopoietic stem cells (HSCs), leukaemia cells and T cells were assessed by in vitro coculture experiments.Results: Increased but dysfunctional BM EPCs were found in MDS patients compared with HDs, especially in patients with higher-risk MDS. RNA-seq indicated the progressive change and differences of haematopoiesis- and immune-related pathways and genes in MDS BM EPCs. In vitro coculture experiments verified that BM EPCs from HDs, lower-risk MDS, and higher-risk MDS to AML exhibited a progressively decreased ability to support HSCs, manifested as elevated apoptosis rates and intracellular reactive oxygen species (ROS) levels and decreased colony-forming unit plating efficiencies of HSCs. Moreover, BM EPCs from higher-risk MDS patients demonstrated an increased ability to support leukaemia cells, characterized by increased proliferation, leukaemia colony-forming unit plating efficiencies, decreased apoptosis rates and apoptosis-related genes. Furthermore, BM EPCs induced T cell differentiation towards more immune-tolerant cells in higher-risk MDS patients in vitro. In addition, the levels of intracellular ROS and the apoptosis ratios were increased in BM EPCs from MDS patients, especially in higher-risk MDS patients, which may be therapeutic candidates for MDS patients.Conclusion: Our results suggest that dysfunctional BM EPCs are involved in MDS patients, which indicates that improving haematopoiesis supporting ability and immuneregulation ability of BM EPCs may represent a promising therapeutic approach for MDS patients. [ABSTRACT FROM AUTHOR]

Background: Recent evidence of genetics and metabonomics indicated a potential role of apolipoprotein M (ApoM) in the pathogenesis of Alzheimer's disease (AD). Here, we aimed to investigate the association between plasma ApoM with AD. Methods: A multicenter, cross-sectional study recruited patients with AD (n = 67), age- and sex-matched cognitively normal (CN) controls (n = 73). After the data collection of demographic characteristics, lifestyle risk factors, and medical history, we examined and compared the plasma levels of ApoM, tau phosphorylated at threonine 217 (p-tau217) and neurofilament light (NfL). Multivariate logistic regression analysis was applied to determine the association of plasma ApoM with the presence of AD. The correlation analysis was used to explore the correlations between plasma ApoM with cognitive function [Mini–Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)], activities of daily living (ADL), and the representative blood-based biomarkers (plasma p-tau217 and NfL). Receiver operating characteristic (ROC) analysis and Delong's test were used to determine the diagnostic power of plasma ApoM. Results: Plasma ApoM and its derived indicators (ratios of ApoM/TC, ApoM/TG, ApoM/HDL-C, and ApoM/LDL-C) were significantly higher in AD group than those in CN group (each p < 0.0001). After adjusted for the risk factors of AD, the plasma ApoM and its derived indicators were significantly associated with the presence of AD, respectively. ApoM (OR = 1.058, 95% CI: 1.027–1.090, p < 0.0001), ApoM/TC ratio (OR = 1.239, 95% CI: 1.120–1.372, p < 0.0001), ApoM/TG ratio (OR = 1.064, 95% CI: 1.035–1.095, p < 0.0001), ApoM/HDL-C ratio (OR = 1.069, 95% CI: 1.037–1.102, p < 0.0001), and ApoM/LDL-C ratio (OR = 1.064, 95% CI:1.023–1.106, p = 0.002). In total participants, plasma ApoM was significantly positively correlated with plasma p-tau217, plasma NfL, and ADL (each p < 0.0001) and significantly negatively correlated with MMSE and MoCA (each p < 0.0001), respectively. In further subgroup analyses, these associations remained in different APOE ϵ 4 status participants and sex subgroups. ApoM/TC ratio (ΔAUC = 0.056, p = 0.044) and ApoM/TG ratio (ΔAUC = 0.097, p = 0.011) had a statistically remarkably larger AUC than ApoM, respectively. The independent addition of ApoM and its derived indicators to the basic model [combining age, sex, APOE ϵ 4, and body mass index (BMI)] led to the significant improvement in diagnostic power, respectively (each p < 0.05). Conclusion: All the findings preliminarily uncovered the association between plasma ApoM and AD and provided more evidence of the potential of ApoM as a candidate biomarker of AD. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy (DR) has become a leading cause of global blindness as a microvascular complication of diabetes. Regular screening of diabetic retinopathy is strongly recommended for people with diabetes so that timely treatment can be provided to reduce the incidence of visual impairment. However, DR screening is not well carried out due to lack of eye care facilities, especially in the rural areas of China. Artificial intelligence (AI) based DR screening has emerged as a novel strategy and show promising diagnostic performance in sensitivity and specificity, relieving the pressure of the shortage of facilities and ophthalmologists because of its quick and accurate diagnosis. In this study, we estimated the cost-effectiveness of AI screening for DR in rural China based on Markov model, providing evidence for extending use of AI screening for DR.Methods: We estimated the cost-effectiveness of AI screening and compared it with ophthalmologist screening in which fundus images are evaluated by ophthalmologists. We developed a Markov model-based hybrid decision tree to analyze the costs, effectiveness and incremental cost-effectiveness ratio (ICER) of AI screening strategies relative to no screening strategies and ophthalmologist screening strategies (dominated) over 35 years (mean life expectancy of diabetes patients in rural China). The analysis was conducted from the health system perspective (included direct medical costs) and societal perspective (included medical and nonmedical costs). Effectiveness was analyzed with quality-adjusted life years (QALYs). The robustness of results was estimated by performing one-way sensitivity analysis and probabilistic analysis.Results: From the health system perspective, AI screening and ophthalmologist screening had incremental costs of $180.19 and $215.05 but more quality-adjusted life years (QALYs) compared with no screening. AI screening had an ICER of $1,107.63. From the societal perspective which considers all direct and indirect costs, AI screening had an ICER of $10,347.12 compared with no screening, below the cost-effective threshold (1-3 times per capita GDP of Chinese in 2019).Conclusions: Our analysis demonstrates that AI-based screening is more cost-effective compared with conventional ophthalmologist screening and holds great promise to be an alternative approach for DR screening in the rural area of China. [ABSTRACT FROM AUTHOR]

Background: Increasing studies have focused on the predictive value of high estimated glomerular filtration rate (eGFR) on cardiovascular diseases and mortality; however, the association between high eGFR with cognitive function is still not established. Thus, this study aimed to determine the co-relationship between high eGFR and cognitive performance in the hypertensive population. Methods: We conducted a baseline cross-sectional study using data from the China H-type Hypertension Registry study. Mini-Mental State Examination (MMSE) assessment was performed to evaluate the cognitive function scale, and serum creatinine was collected to estimate eGFR level. Different MMSE cutoff values were applied in participants with the various educational background to define dementia: <24 in participants with secondary school and above education setting, <20 in those with primary school, and <17 in illiterate participants. Results: A total of 9,527 hypertensive adults with mean age 63.7 ± 9.8 years and 67% female gender were analyzed. The eGFR cutoff value of 71.52 ml/min/1.73 m2 was found after adjusting for potential covariates in a threshold effect analysis. The MMSE increased significantly with the increment of eGFR (β, 0.27; 95% CI: 0.12–0.41) in participants with eGFR < 71.52 ml/min/1.73 m2 and decreased (β, −0.28; 95% CI: −0.39 to −0.17) in participants with eGFR ≥ 71.52 ml/min/1.73 m2. Individuals with eGFR ≥ 85 ml/min/1.73 m2 have an elevated risk of cognitive impairment than those with eGFR of 65–75 ml/min/1.73 m2. Subgroup analysis showed that a greater reduction degree of MMSE was observed in female individuals and those who had body mass index (BMI) ≥ 24 kg/m2 among participants with eGFR ≥ 71.52 ml/min/1.73 m2. Conclusion: Our findings observed an inverted U-shaped relationship between eGFR and cognitive function. Both the low and high levels of eGFR were independently associated with worse cognitive assessment in the hypertensive population. [ABSTRACT FROM AUTHOR]

Eighteen novel 3/5(3,5)-(di)nitropaeonol hydrazone derivatives were prepared, and their structures well characterized by 1H NMR, HRMS, and mp. Due to the steric hindrance, the substituents on the C = N double bond of all hydrazine compounds (except E/Z = 4/1 for IV-1g, IV-1l, IV-2b, and E/Z = 3/2 for IV-1n, IV-3a) adopted E configuration. Among all compounds, four compounds 2, 4, IV-1j, and IV-1n exhibited potent nematicidal activity than their precursor paeonol, especially 5-nitropaeonol (2) and 3,5-dinitropaeonol (4) displayed the most potent nematicidal activity Heterodera glycines in vivo with LC50 values of 32.3307 and 36.7074 mg/L, respectively. [ABSTRACT FROM AUTHOR]

Chemical investigations of the 75% EtOH extract from the fruits of Crataegus pinnatifida led to the isolation of three undescribed naturally occurring sesquineolignans with two 8-O-4'-type neolignan moieties, cratapinnatifidas A-C (1–3). Their chemical structures were elucidated by the comprehensive spectroscopic analyses (HRESIMS, 1D and 2D-NMR). In the bioactivity assay, their cytotoxic activities against two human hepatoma cell lines (HepG2 and Hep3B) were evaluated and no significant activity was seen with IC50 values ranging from 12.5 to 50.0 μM. [ABSTRACT FROM AUTHOR]

One new terpenylated coumarin ailanthuscoumarin was isolated from the root barks of Ailanthus altissima (Mill.) Swingle. The high oxidation of the compound led to the difficulty of structure elucidation by 2D-NMR spectra. Its structure was determined with the aid of computer-assisted structure elucidation (CASE) expert systems and Gauge-independent atomic orbital (GIAO) NMR calculations. The absolute configuration of ailanthuscoumarin was determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. The anti-hepatoma activity of ailanthuscoumarin against two human hepatoma cells (Hep3B, HepG2) was also reported. [ABSTRACT FROM AUTHOR]

Three new compounds, crotalariapallins A-C (1-3), were isolated from the 95% EtOH extract of the seeds of Crotalaria pallida. Their structures were established based on extensive spectroscopic methods, including HRESIMS, UV, 1D and 2D NMR. All compounds were evaluated for their inhibitory activities to tyrosinase. These compounds showed different degrees of inhibitory activities, among them, compound 3 exhibited the strongest inhibition activity (IC50 = 0.42 mM). [ABSTRACT FROM AUTHOR]

Coronavirus disease (COVID-19) is a new infectious disease associated with high mortality, and traditional Chinese medicine decoctions (TCMDs) have been widely used for the treatment of patients with COVID-19 in China; however, the impact of these decoctions on severe and critical COVID-19-related mortality has not been evaluated. Therefore, we aimed to address this gap. In this retrospective cohort study, we included inpatients diagnosed with severe/critical COVID-19 at the Tongren Hospital of Wuhan University and grouped them depending on the recipience of TCMDs (TCMD and non-TCMD groups). We conducted a propensity score-matched analysis to adjust the imbalanced variables and treatments and used logistic regression methods to explore the risk factors associated with in-hospital death. Among 282 patients with COVID-19 who were discharged or died, 186 patients (66.0%) received TCMD treatment (TCMD cohort) and 96 (34.0%) did not (non-TCMD cohort). After propensity score matching at a 1:1 ratio, 94 TCMD users were matched to 94 non-users, and there were no significant differences in baseline clinical variables between the two groups of patients. The all-cause mortality was significantly lower in the TCMD group than in the non-TCMD group, and this trend remained valid even after matching (21.3% [20/94] vs. 39.4% [37/94]). Multivariable logistic regression model showed that disease severity (odds ratio: 0.010; 95% CI: 0.003, 0.037; P ¡ 0.001) was associated with increased odds of death and that TCMD treatment significantly decreased the odds of in-hospital death (odds ratio: 0.115; 95% CI: 0.035, 0.383; P ¡ 0.001), which was related to the duration of TCMD treatment. Our findings show that TCMD treatment may reduce the mortality in patients with severe/critical COVID-19. [ABSTRACT FROM AUTHOR]

Previous work has shown that the lignans from the twigs and leaves of Archidendron clypearia (Jack) I.C.N. possess anti-β-amyloid aggregation activity. Here we report a new dilignan, archidendronin A (1), along with one known sesquilignan (2). Their structures were determined by extensive spectroscopic methods, including UV, HRESIMS, 1 D and 2 D NMR data. The inhibitory activity on Aβ1-42 aggregation was screened by ThT assay with curcumin as the positive control, and compounds 1 and 2 showed inhibition rate of 60.0% and 64.4% at 20 μM, respectively. [ABSTRACT FROM AUTHOR]

Background: Bile duct invasion is a relatively rare event and is not well characterised in hepatocellular carcinoma (HCC). It remains very difficult to diagnose HCC with bile duct tumour thrombus (BDTT) before surgery. Increasing evidence has revealed that inflammation plays a critical role in tumorigenesis. This study aimed to develop nomograms based on systemic and hepatic inflammation markers to predict microscopic BDTT (micro-BDTT) before surgery in HCC.Methods: A total of 723 HCC patients who underwent hepatectomy as initial therapy between January 2012 and June 2020 were included in the study. Logistic regression analysis was used to identify independent risk factors for micro-BDTT. The nomograms were constructed using significant predictors, including α-fetoprotein (AFP), alkaline phosphatase (ALP), direct bilirubin (DB), prognostic nutritional index (PNI), and γ-glutamyl transferase (γ-GT)/alanine aminotransferase (ALT). The prediction accuracies of the nomograms were evaluated using the area under the receiver operating characteristic (ROC) curve.Results: AFP, ALP, DB, PNI, and γ-GT/ALT were independent risk factors for predicting micro-BDTT (P = 0.036, P = 0.004, P = 0.013, P = 0.012, and P = 0.006, respectively), which were assembled into the nomograms. The area under the ROC curve of the nomograms combining PNI and γ-GT/ALT for predicting micro-BDTT was 0.804 (95% confidence interval [CI]: 0.730-0.878). The sensitivity and specificity values when used in predicting micro-BDTT before surgery were 0.739 (95% CI: 0.612-0.866) and 0.781 (95% CI: 0.750-0.813), respectively.Conclusions: The nomogram based on combining systemic and hepatic inflammation markers is suitable for predicting micro-BDTT before surgery in HCC patients, leading to a rational therapeutic choice for HCC. [ABSTRACT FROM AUTHOR]

Four new alkaloids (1-4) and one known alkaloid were isolated from the stems of Picrasma quassioides. The structures of these isolated compounds were elucidated by spectroscopic analyses, a combination of computer-assisted structure elucidation software (ACD/Structure Elucidator) and gauge-including atomic orbital (GIAO) calculation of 1 D NMR data. All compounds were evaluated for their cytotoxic activities against hepatocellular carcinoma HepG2 and Hep3B cells. However, they did not show obvious inhibitory activities. [ABSTRACT FROM AUTHOR]

Two new benzoic acid derivatives (1–2), together with four known compounds (3–6) have been isolated from the n-BuOH soluble fraction of ethanolic extract from Ailanthus altissima. The gross structures of the new compounds were deduced by detailed spectroscopic analysis including HRESIMS and 1D/2D NMR spectroscopy. The stereochemistry of 1 was determined by modified Mosher's method. All compounds were evaluated for their neuroprotective effects against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells and none of them displayed obvious neuroprotective activities. [ABSTRACT FROM AUTHOR]

Background: Well-designed retrospective studies (RSs) and small-sample prospective studies (PSs) evaluating the efficacy of interventions have received much attention. This study was designed to evaluate the differences between well-designed RSs and small-sample randomized controlled trials based on the efficacy of laparoscopic distal gastrectomy (LDG) and open distal gastrectomy (ODG) for advanced gastric cancer (GC).Methods: The clinicopathological data of 1360 patients with GC who underwent DG were analysed. After propensity score matching (1:1), 380 cases (ODG = 190, LDG = 190) were finally selected in a RS. Meanwhile, data from 120 patients (ODG = 60, LDG = 60) who enrolled in a PS were analysed.Results: In the PS, the LDG group had less intraoperative blood loss, shorter time to first flatus, and shorter time to fluid diet than the ODG group. In the RS, the LDG group had less intraoperative blood loss, and a shorter postoperative hospital stay than the ODG group. In the PS, the 3-year overall survival (OS) rate was 83.3% in the LDG group and 83.2% in the ODG group (p = 0.877). In the RS, the 3-year OS rate was 68.7% in the LDG group and 66.6% in the ODG group (p = 0.752). No significant interactions were observed between the two groups and any of the variables examined, either in the PS or RS. The recurrence patterns were similar in the two groups. Furthermore, Cox regression analysis showed that surgical method (LDG/ODG) was not a prognostic factor affecting OS or DFS, either prospectively or retrospectively.Conclusions: The oncologic efficacy of laparoscopic and open distal gastrectomy for advanced GC is comparable. Well-designed RSs can be similar to small sample of PSs in assessing long-term oncologic outcomes of surgical interventions, but the short-term outcomes obtained should be treated with caution. [ABSTRACT FROM AUTHOR]

Background: Paroxysmal kinesigenic dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline-rich transmembrane protein 2 have been identified as the major pathogenic factor.Objectives: We analyzed 600 paroxysmal kinesigenic dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of paroxysmal kinesigenic dyskinesia in China and to provide new thoughts on diagnosis and therapy.Methods: The China Paroxysmal Dyskinesia Collaborative Group was composed of departments of neurology from 22 hospitals. Clinical manifestations and proline-rich transmembrane protein 2 screening results were recorded using unified paroxysmal kinesigenic dyskinesia registration forms. Genotype-phenotype correlation analyses were conducted in patients with and without proline-rich transmembrane protein 2 mutations. High-knee exercises were applied in partial patients as a new diagnostic test to induce attacks.Results: Kinesigenic triggers, male predilection, dystonic attacks, aura, complicated forms of paroxysmal kinesigenic dyskinesia, clustering in patients with family history, and dramatic responses to antiepileptic treatment were the prominent features in this multicenter study. Clinical analysis showed that proline-rich transmembrane protein 2 mutation carriers were prone to present at a younger age and have longer attack duration, bilateral limb involvement, choreic attacks, a complicated form of paroxysmal kinesigenic dyskinesia, family history, and more forms of dyskinesia. The new high-knee-exercise test efficiently induced attacks and could assist in diagnosis.Conclusions: We propose recommendations regarding diagnostic criteria for paroxysmal kinesigenic dyskinesia based on this large clinical study of paroxysmal kinesigenic dyskinesia. The findings offered some new insights into the diagnosis and treatment of paroxysmal kinesigenic dyskinesia and might help in building standardized paroxysmal kinesigenic dyskinesia clinical evaluations and therapies. © 2020 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

For acute myeloid leukemia (AML) with nucleophosmin 1 mutation (NPM1m), multiparameter flow cytometry (FCM) and real-time quantitative polymerase chain reaction (RQ-PCR) are used to monitor minimal residual disease (MRD). However, the results of the two methods are sometimes inconsistent. This study was designed to analyze how to address the discordant results of FCM and RQ-PCR in AML patients undergoing chemotherapy, especially when positive FCM (FCM+) and negative NPM1m (NPM1m-) results are detected in the same sample. Our study included 93 AML patients with NPM1m positive (NPM1m+) who received chemotherapy but did not undergo hematopoietic stem cell transplantation. We monitored NPM1m and leukemia-associated immunophenotypes (LAIPs) by RQ-PCR and FCM, respectively, to assess MRD after each chemotherapy course. After each course of chemotherapy, all patients were classified into four groups based on the results of FCM and RQ-PCR: both negative (group 1, FCM-NPM1m-), single positive (group 2, FCM-NPM1m+; group 3, FCM+NPM1m-), or both positive (group 4, FCM+NPM1m+). The results showed that there was not a significant difference in the 2-year cumulative incidence of relapse (CIR) after each course of chemotherapy between group 2 and group 3. Furthermore, patients in groups 2 and 3 had a lower 2-year CIR than those in group 4 and a significantly higher 2-year CIR than those in group 1 after the first two courses. The patients in group 4 had a significantly higher 2-year CIR than those in group 1 after the first two courses. These results suggested that in the MRD monitoring process of AML patients, when the results of FCM and RQ-PCR are inconsistent (especially when FCM is positive and NPM1m is negative), these single-positive results still have predictive significance for relapse. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of Croton crassifolius roots afforded five sesquiterpenes (1–5), including two new sesquiterpenes 6S-hydroxy-cyperenoic acid (1) and crassifterpenoid A (5), together with three known compounds (2–4). The structures of the new compounds were determined by comprehensive spectroscopic methods, and their absolute configurations were determined by quantum chemical ECD calculation. Crassifterpenoid A (5) is the first germacrane-type sesquiterpene isolated from C. crassifolius, which enriched the diversity of chemical constituents in Croton crassifolius. In addition, the cytotoxicities of all compounds against human liver cancer lines HepG2 and Hep3B were determined, but none showed significant activity. [ABSTRACT FROM AUTHOR]

Objective: To assess significant liver fibrosis by multiparametric ultrasomics data using machine learning.Materials and Methods: This prospective study consisted of 144 patients with chronic hepatitis B. Ultrasomics-high-throughput quantitative data from ultrasound imaging of liver fibrosis-were generated using conventional radiomics, original radiofrequency (ORF) and contrast-enhanced micro-flow (CEMF) features. Three categories of features were explored using pairwise correlation and hierarchical clustering. Features were selected using diagnostic tests for fibrosis, activity and steatosis stage, with the histopathological results as the reference. The fibrosis staging performance of ultrasomics models with combinations of the selected features was evaluated with machine-learning algorithms by calculating the area under the receiver-operator characteristic curve (AUC).Results: ORF and CEMF features had better predictive power than conventional radiomics for liver fibrosis stage (both p < 0.01). CEMF features exhibited the highest diagnostic value for activity stage (both p < 0.05), and ORF had the best diagnostic value for steatosis stage (both p < 0.01). The machine-learning classifiers of adaptive boosting, random forest and support vector machine were found to be optimal algorithms with better (all mean AUCs = 0.85) and more stable performance (coefficient of variation = 0.01-0.02) for fibrosis staging than decision tree, logistic regression and neural network (mean AUC = 0.61-0.72, CV = 0.07-0.08). The multiparametric ultrasomics model achieved much better performance (mean AUC values of 0.78-0.85) than the features from a single modality in discriminating significant fibrosis (≥ F2).Conclusion: Machine-learning-based analysis of multiparametric ultrasomics can help improve the discrimination of significant fibrosis compared with mono or dual modalities.Key Points: • Multiparametric ultrasomics has achieved much better performance in the discrimination of significant fibrosis (≥ F2) than the single modality of conventional radiomics, original radiofrequency and contrast-enhanced micro-flow. • Adaptive boosting, random forest and support vector machine are the optimal algorithms for machine learning. [ABSTRACT FROM AUTHOR]

Investigation on bioactive chemical constituents of safflower led to the isolation of 10 compounds from the aqueous extract, including a new alkaloid (1), a new glucopyranoside (2), and 8 known compounds (3-10). The structures of two new compounds were elucidated on the basis of extensive spectral analyses, including 1D, 2D-NMR and HRESIMS. Biological research on the isolates indicated that compounds 3, 4 and 9 remarkably inhibited tyrosinase with IC50 at 0.11, 0.20 and 0.11 mM, respectively, compared with the positive control arbutin (0.26 mM). To investigate the interaction between enzyme and isolated compounds, an in silico docking study was carried out. The research provided valuable experience for phytochemistry and biological investigation on safflower. [ABSTRACT FROM AUTHOR]

Two new tetralone derivatives, named cyclopalosides A (1) and B (2), were isolated from the leaves of Cyclocarya paliurus by column chromatography on silica gel, reversed-phase C18 silica gel and preparative HPLC. Their chemical structures were established on the basis of extensive analyses of spectroscopic data. Their structural characteristic is tetralone glycoside with a caffeoyl unit. The antioxidant activities of compound 1 were evaluated by using hydroxyl, superoxide anion, and DPPH radical scavenging assay. [ABSTRACT FROM AUTHOR]

Aims and objectives: To compare and evaluate the reliability, validity, feasibility, clinical utility, and nurses’ preference of the Premature Infant Pain Profile‐Revised, the Neonatal Pain, Agitation, and Sedation Scale, and the Neonatal Infant Acute Pain Assessment Scale used for procedural pain in ventilated neonates. Background: Procedural pain is a common phenomenon but is undermanaged and underassessed in hospitalised neonates. Information for clinician selecting pain measurements to improve neonatal care and outcomes is still limited. Design: A prospective observational study was used. Methods: A total of 1,080 pain assessments were made at 90 neonates by two nurses independently, using three scales viewing three phases of videotaped painful (arterial blood sampling) and nonpainful procedures (diaper change). Internal consistency, inter‐rater reliability, discriminant validity, concurrent validity and convergent validity of scales were analysed. Feasibility, clinical utility and nurses’ preference of scales were also investigated. Results: All three scales showed excellent inter‐rater coefficients (from 0.991–0.992) and good internal consistency (0.733 for the Premature Infant Pain Profile‐Revised, 0.837 for the Neonatal Pain, Agitation, and Sedation Scale and 0.836 for the Neonatal Infant Acute Pain Assessment Scale, respectively). Scores of painful and nonpainful procedures on the three scales changed significantly across the phases. There was a strong correlation between the three scales with adequate limits of agreement. The mean scores of the Neonatal Pain, Agitation, and Sedation Scale for feasibility and utility were significantly higher than those of the Neonatal Infant Acute Pain Assessment Scale, but not significantly higher than those of the Premature Infant Pain Profile‐Revised. The Neonatal Pain, Agitation, and Sedation Scale was mostly preferred by 55.9% of the nurses, followed by the Neonatal Infant Acute Pain Assessment Scale (23.5%) and the Premature Infant Pain Profile‐Revised (20.6%). Conclusions: The three scales are all reliable and valid, but the Neonatal Pain, Agitation, and Sedation Scale and the Neonatal Infant Acute Pain Assessment Scale perform better in reliability. The Neonatal Pain, Agitation, and Sedation Scale appears to be a better choice for frontier nurses to assess procedural pain in ventilated neonates based on its good feasibility, utility and nurses’ preference. Relevance to clinical practice: Choosing a valid, reliable, feasible and practical measurement is the key step for better management of procedural pain for ventilated newborns. Using the right and suitable tool is helpful to accurately identify pain, ultimately improve the neonatal care and outcomes. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the barks of Juglans mandshurica Maxim led to the isolation, purification, and identification of one new lignan named Juglansol A (1), along with nine known compounds (2-10). Their structures were determined by the results of UV, IR, CD, HRESIMS, 1D, and 2D NMR spectroscopic analysis. Compounds 1-10 were evaluated for their cytotoxicities against A549, HepG2, Hep3B, Bcap-37, and MCF-7 cell lines. The results showed that compound 2 possessed stronger cytotoxicities against the tested tumor cell lines compared with positive control 5-fluorouracil. [ABSTRACT FROM AUTHOR]

Background: Our previous study demonstrated a close relationship between NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). HES1 is a well-known target gene of NOTCH signaling pathway. The purpose of the present study was to further explore the molecular mechanism of HES1 in SACC.Methods: Comparative transcriptome analyses by RNA-Sequencing (RNA-Seq) were employed to reveal NOTCH1 downstream gene in SACC cells. Immunohistochemical staining was used to detect the expression of HES1 in clinical samples. After HES1-siRNA transfected into SACC LM cells, the cell proliferation and cell apoptosis were tested by suitable methods; animal model was established to detect the change of growth ability of tumor. Transwell and wound healing assays were used to evaluate cell metastasis and invasion.Results: We found that HES1 was strongly linked to NOTCH signaling pathway in SACC cells. The immunohistochemical results implied the high expression of HES1 in cancerous tissues. The growth of SACC LM cells transfected with HES1-siRNAs was significantly suppressed in vitro and tumorigenicity in vivo by inducing cell apoptosis. After HES1 expression was silenced, the SACC LM cell metastasis and invasion ability was suppressed.Conclusions: The results of this study demonstrate that HES1 is a specific downstream gene of NOTCH1 and that it contributes to SACC proliferation, apoptosis and metastasis. Our findings serve as evidence indicating that HES1 may be useful as a clinical target in the treatment of SACC. [ABSTRACT FROM AUTHOR]

Single-nucleotide polymorphisms (SNPs) of cytotoxic T lymphocyte antigen-4 (CTLA-4) are important risk factors associated with autoimmune diseases and malignancies. This study explored the association of CTLA-4SNPs with the development of myeloma and evaluated the outcome of patients receiving bortezomib-based regimens in relation to CTLA-4SNPs. Peripheral blood samples from 86 patients with multiple myeloma (MM) and 154 healthy controls were obtained to investigate CTLA4 polymorphisms. Five SNP genotypes of CTLA-4, namely, -1772 (rs733618), -1661 (rs4553808), -318 (rs5742909), CT60 (rs3087243), and +49 (rs231775), were evaluated through TaqMan SNP genotyping assays (Applied Biosystems). Some of the CTLA-4 polymorphisms displayed frequencies that vary among ethnic groups. Kaplan-Meier analysis revealed that patients with rs733618 GG showed a significantly lower disease-free survival (0 vs. 57.4%, P = 0.020) and overall survival (46.3 vs. 83.3%, P = 0.026) than those with GA+AA following bortezomib-based therapy. Multivariate analyses showed that rs733618 GG was a risk factor for OS (HR = 0.012; 95% CI = 0.001-0.199; P = 0.002). The incidence of nonhematologic grade 3/4 adverse events significantly increased in the rs4553808 GG+GA group compared with that in the AA group (P = 0.036). CTLA-4 rs733618 GG reduced the progression-free survival and the overall survival of patients with MM who received bortezomib-based therapy. Information regarding CTLA-4 polymorphisms and haplotypes may be used to improve MM therapy. Future studies must determine the precise effect of CTLA-4 polymorphisms and haplotypes on MM therapy outcomes by using different cohorts with a large number of subjects. [ABSTRACT FROM AUTHOR]

A new meroterpenoid, tomentodione E (1), along with four known ones (2-5) were isolated from the leaves of Rhodomyrtus tomentosa. Their structures were elucidated based on extensive spectroscopic data as well as computational methods. Compound 1 represents the first example of meroterpenoid possessing a sec-pentyl syncarpic acid motif coupled with a caryophyllene. Compounds 1-4 were evaluated for their in vitro antiviral activity against respiratory syncytial virus (RSV) with cytopathic effect (CPE) reduction assay, and 2 showed potent in vitro anti-RSV effect. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), the most common type of liver cancer, has high morbidity and mortality rates, and its prognosis is poor. The treatment options of HCC are limited by the lack of effective chemotherapy. Therefore, looking for effective drugs with little toxicity is very urgent. The aim of this study was to search for small molecule targeting on liver cancer fromJuglans mandshurica, which has been used to treat cancers for a long time in China. Under the guide of anti-hepatoma activity, a new coumarin (1), together with eight reported analogs (2‒9), was isolated from the 75% EtOH extract. The structures of these compounds were determined by 1D and 2D NMR experiments. The absolute configuration of1was established by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Thein vitrocytotoxicity experiments on two liver cancer cell lines (HepG2 and Hep3B) showed that compounds2and5had moderate antitumor activities on both cell lines. And further studies of antitumor mechanisms by the observation of morphological changes and Western blot analyses exhibited that induction of apoptosis might be a possible way that inhibited cell growth. [ABSTRACT FROM PUBLISHER]

In our ongoing search for bioactive constituents, a new sesquiterpene polyol ester, named triptersinine U (1), together with five known triterpenes (2–6) and seven sesquiterpene pyridine alkaloids (7–13), were isolated from the roots ofTripterygium wilfordiiHook. f. Their chemical structures were elucidated using extensive spectroscopic analyses, including 1D and 2D NMR, and HRESIMS, as well as comparison with previously reported data. Cytotoxic activities of all compounds1–13were evaluated against six human tumor cell lines (HepG2, Hep3B, Bcap37, U251, MCF-7 and A549) using the MTTin vitroassay. The results showed that triterpenes exhibited moderate cytotoxic activities toward the tested cell lines. [ABSTRACT FROM PUBLISHER]

Two new polyketides, aspergchromones A (1) and B (2), together with five known compounds, secalonic acid D (3), noreugenin (4), (3S)-5-hydroxymellein (5), (4S)-6-hydroxyisosclerone (6), and (-)-regiolone (7), were isolated from the ethyl acetate extract of marine sponge-derived fungusAspergillussp. SCSIO XWS03F03. Their structures were elucidated by means of spectroscopic techniques (1D and 2D NMR, MS, UV, and IR). The absolute configurations of the new compounds were established by ECD calculations. Compound3showed moderate antimicrobial activity. [ABSTRACT FROM PUBLISHER]

Twenty-four gramine derivatives were synthesized and evaluated on MT1and 5-HT1Areceptorsin vitro. Among them, seven derivatives (7,8,16,19,20,21,and24)exhibited higher agonisting activities on MT1or 5-HT1Areceptors. Compared with gramine, derivatives7,8,16,19,20,21,and24displayed 1.6–3.5-fold increase in agonistic rates on 5-HT1Areceptor. Particularly, derivatives7,19,and21exhibited significant agonistic activities on MT1and 5-HT1Areceptors with EC50values of 0.51, 0.39, 0.50 mΜ and 0.28, 0.46, 0.23 mΜ, respectively. The preliminary structure–activity relationships of gramine derivatives were summarized for further investigation on MT1and 5-HT1Areceptors as new potential agonists. [ABSTRACT FROM PUBLISHER]

Three new ecdysteroid glycosides (1–3) and one new ecdysteroid (4), were isolated from the roots ofSerratula chinensis. Their structures were established on the basis of extensive spectroscopic analysis and chemical methods. [ABSTRACT FROM PUBLISHER]

Background:Measles is one of the most highly contagious diseases which have not been eliminated in China. This study aimed to investigate the epidemiological characteristics of measles in Bozhou city, China between 2005 and 2015 and provide scientific basis for the prevention, control and elimination of measles. Methods:Cases of measles derived from the China Information System for Disease Prevention and Control, and demographic data were obtained from the Public Security Bureau of Bozhou city. Results:Among the 2934 cases, the average annual incidence of measles was 45.934 (per 1,000,000 persons) and no death occurred. The incidence of males was higher than females (Z = 10.794,p < 0.05). Scattered children accounted for 63.2% (1854/2934) in occupation distributing. In terms of immunization history of cases, 57.5% had 0 doses, 15.0% had one dose, 7.5% had two doses and others were uncertain. Conclusions:Our study has investigated the epidemiological characteristics of measles in Bozhou City. To eventually eliminate measles in Bozhou city, improving measles vaccination coverage and quality of routine immunization services were important. [ABSTRACT FROM PUBLISHER]