Myeloproliferative neoplasm with eosinophilia and coexisting BCR::ABL1 and PDGFRB rearrangement: favorable and rapid response to imatinib.

Here, we present a rare case of myeloproliferative neoplasms (MPN) with eosinophilia harboring both BCR::ABL1 and PDGFRB rearrangements, posing a classification dilemma. The patient exhibited clinical and laboratory features suggestive of chronic myeloid leukemia (CML) and myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK), highlighting the diagnostic challenges associated with overlapping phenotypes. Despite the complexity, imatinib treatment swiftly achieved deep molecular remission, underscoring the therapeutic efficacy of tyrosine kinase inhibitors in such scenarios. Furthermore, the rapid attainment of deep remission by this patient in response to imatinib closely resembles that observed in MLN-TK patients with PDGFRB rearrangements. Further research is warranted to elucidate the underlying mechanisms driving the coexistence of multiple oncogenic rearrangements in MPNs and to optimize therapeutic strategies for these complex cases.

An integrative review on the maternal health literacy among maternal and child workers.

AIMS: This study aim to capture the most comprehensive evidence-based dimensions of maternal health literacy, including summarizing the definitions, theoretical frameworks, measuring instruments, and the association between maternal health literacy and health behaviours. BACKGROUND: Maternal health literacy has been recognized as an important approach to achieving high-quality maternal and child health; however, little is known about maternal health literacy comprehensively and scientifically. EVALUATION: An integrative review retrieved articles from 11 databases, following the methodology of Whittemore and Knafl. Inductive content analysis and narrative synthesis were conducted, guided by the aim of this review. KEY ISSUES: A total of 5580 articles were retrieved and 23 articles were finally identified. Existing definitions and theoretical frameworks took less consideration of maternal applicability and failed to summarize maternal health literacy from a dynamic and systematic perspective. Measurement instruments were set up with many items that make it difficult to quickly screen for poor maternal health literacy. Most articles proved the association between maternal health literacy and health behaviours through correlation analysis or regression analysis but less explored the influence pathways between them. CONCLUSION: The definition and theoretical framework need to focus on maternal applicability and explain the process of individual mothers acquiring and understanding health knowledge and skills from a dynamic and systematic perspective. A rapid instrument for maternal health literacy should be developed and high-quality empirical research was conducted to understand the associated mechanisms between maternal health literacy and health behaviours. IMPLICATIONS FOR NURSING MANAGEMENT: It is necessary to strengthen maternal and child health education of primary health care nurses and enhance their ability to help perinatal women use maternal and child health information effectively.

[Effect of Xiaoyao San on OVX combined with CUS anxiety and depression model rats based on hippocampal microglia M1 polarization].

To investigate the anti-anxiety and anti-depression effect and mechanism of Xiaoyao San on rats with ovariectomy(OVX) combined with chronic unpredictable stress(CUS) model. The model of perimenopausal depression was established by OVX and CUS; the level of anxiety and depression was evaluated by open field test; the levels of interleukin-1ß(IL-1ß) and interleukin-6(IL-6) mRNA in rat hippocampus were detected by Real-time qPCR; double staining immunofluorescence was used to detect the expression of ionized calcium binding adaptor molecule-1(Iba-1) and inducible nitric oxide synthase(iNOS) in microglia of rat dentate gyrus(DG); Western blot was used to detect the protein expression of Iba-1 and iNOS of microglia in DG region of rat hippocampus. The results showed that in the model group, the number of horizontal movement, the number of vertical movement and central residence time were significantly reduced, and the grooming time was significantly prolonged(P<0.05 or P<0.01); the levels of IL-1ß and IL-6 in hippocampus increased significantly(P<0.05); the number of positive cells with co-expression of Iba-1/iNOS of microglia cells in DG region of hippocampus increased; the expression levels of Iba-1 and iNOS protein in hippocampus were significantly increased(P<0.01), suggesting that microglia in DG region of hippocampus was activated and polarized toward M1 type in rats with stress. The high dose group of Xiaoyao San significantly increased the number of horizontal movement, vertical movement and central residence time of model rats(P<0.05 or P<0.01), and significantly down-regulated the levels of inflammatory factors IL-1ß and IL-6(P<0.05). Meanwhile, it reversed the activation and quantity change of microglia in hippocampus. Although the Xiaoyao San low dose group had no significant effect on the behavioral indicators in the open field test and the levels of IL-1ß and IL-6, they all showed a trend of improvement. Low dose Xiaoyao San significantly decreased iNOS protein level(P<0.05), and high dose Xiaoyao San significantly down-regulated the protein expression of Iba-1 and iNOS in hippocampus microglia(P<0.05 or P<0.01). In conclusion, Xiaoyao San can improve anxiety and depression-like behavior in OVX combined with CUS model rats, and its mechanism is related to its anti-inflammatory effect by inhibiting M1 polarization of hippocampal microglia.

Quantitative analysis of 3-OHB[a]P and (+)-anti-BPDE as biomarkers of B[a]P exposure in rats.

The aim of this study was to develop an analytical method for the determination the levels of metabolites of benzo[a]pyrene (B[a]P), 3-hydroxybenzo(a)pyrene (3-OHB[a]P) and (+)-anti-benzo(a)pyrene diol-epoxide [(+)-anti-BPDE, combined with DNA to form adducts], in rat blood and tissues exposed to B[a]P exposure by high-performance liquid chromatography with fluorescence detection (HPLC/FD), and to investigate the usefulness of 3-OHB[a]P and (+)-anti-BPDE as markers of intragastrical exposure to B[a]P in rats. The levels of 3-OH-B[a]P and B[a]P-tetrol I-1 released after acid hydrolysis of (+)-anti-BPDE in the samples were measured by HPLC/FD. The calibration curves were linear (r(2) > 0.9904), and the lower limit of quantification ranged from 0.34 to 0.45 ng/mL for 3-OHB[a]P and from 0.43 to 0.58 ng/mL for (+)-anti-BPDE. The intra- and inter-day stability assay data suggested that the method is accurate and precise. The recoveries of 3-OHB[a]P and (+)-anti-BPDE were in the ranges of 73.6 ± 5.0 to 116.5 ± 6.3% and 73.3 ± 8.5 to 141.2 ± 13.8%, respectively. A positive correlation was found between the concentration of intragastrical B[a]P and the concentrations of 3-OH-B[a]P and (+)-anti-BPDE in the blood and in most of the tissues studied, except for the brain and kidney, which showed no correlation between B[a]P and 3-OHB[a]P and between B[a]P and (+)-anti-BPDE, respectively. A sensitive, reliable and rapid HPLC/FD was developed and validated for analysis of 3-OHB[a]P and (+)-anti-BPDE in rat blood and tissues. There was a positive correlation between the concentration of 3-OHB[a]P or (+)-anti-BPDE in the blood and the concentration of 3-OHB[a]P or (+)-anti-BPDE in the most other tissues examined. The concentration of 3-OHB[a]P or (+)-anti-BPDE in the blood could be used as an indicator of the concentration of 3-OHB[a]P or (+)-anti-BPDE in the other tissues in response to B[a]P exposure. These results demonstrate that 3-OHB[a]P and (+)-anti-BPDE are potential biomarkers of B[a]P exposure, which would also be useful to assess the carcinogenic risks from B[a]P exposure.

Advances in nanobubbles for cancer theranostics: Delivery, imaging and therapy.

Maximizing treatment efficacy and forecasting patient prognosis in cancer necessitates the strategic use of targeted therapy, coupled with the prompt precise detection of malignant tumors. Theutilizationof gaseous systems as an adaptable platform for creating nanobubbles (NBs) has garnered significant attention as theranostics, which involve combining contrast chemicals typically used for imaging with pharmaceuticals to diagnose and treattumorssynergistically in apersonalizedmanner for each patient. This review specifically examines the utilization of oxygen NBsplatforms as a theranostic weapon in the field of oncology. We thoroughly examine the key factors that impact the effectiveness of NBs preparations and the consequences of these treatment methods. This review extensively examines recent advancements in composition schemes, advanced developments in pre-clinical phases, and other groundbreaking inventions in the area of NBs. Moreover, this review offers a thorough examination of the optimistic future possibilities, addressing prospective methods for improvement and incorporation into widely accepted therapeutic practices. As we explore the ever-changing field of cancer theranostics, the incorporation of oxygen NBs appears as a promising development, providing new opportunities for precision medicine and marking a revolutionary age in cancer research and therapy.

Is the expression of different discrete emotions related to time? Evidence from online Chinese reviews using sentiment analysis and human behavior dynamics.

Objectives: The online behavior of online users has taken on complex and diverse characteristics, and posting product reviews on e-commerce platforms is no exception. In fact, reviews contain rich and multi-dimensional discrete emotional information, and whether there is a relationship between the expression of these different discrete emotions and the time interval between product purchase and review posting as well as their related characteristics are the issues that this study needs to analyze and solve in depth. Methods: Based on the OCC model (named after three proposers) of psychological emotional cognitive evaluation theory as the basis for emotion classification, the study used the massive amounts of Chinese reviews of mobile phones on the Chinese e-commerce platform Jingdong Mall as the research object, applied supervised machine learning methods to classify discrete emotions, and constructed a large corpus containing satisfaction, disappointment, admiration, reproach, love, and hate; then the study delved into the distribution and behavioral dynamics characteristics of consumers' comments containing the different discrete emotions at different "purchase-comment" time intervals. Results: The results showed that the first peak of the distribution curves of the six discrete emotions at different "purchase-comment" time intervals occurs on the first day after purchase and then decreases gradually but at different rates. The three curves for satisfaction, love, and hate emotions also show a second peak on the eleventh day, which is more similar to the bimodal distribution, implying that the corresponding product reviews are more objective. In addition, the distribution of reviews containing the six discrete emotions at different "purchase-comment" time intervals follows a power-law distribution and has the temporal characteristics of human behavioral dynamics, that is, "strong paroxysms and weak memory". However, the reviews containing the admiration and reproach emotions were most intensively written by consumers after the purchase, indicating that the service provided by the seller, logistics, and e-commerce platform stimulates more consumers to give quick responses and detailed reviews. Conclusion: This study is not only of great significance for exploring the internal mechanisms of consumer discrete emotional expression but also provides important decision-making references for potential consumer purchasing decisions, product updates for developers, marketing strategy formulation for marketing teams, and service improvement for sellers, logistics companies, and e-commerce platforms.

Poly[di-methyl-ammonium [(µ2-benzene-1,2-di-carboxyl-ato-κ(2) O (1):O (3))[µ2-3-(pyri-din-4-yl)-1H-pyrazol-1-ido-κ(2) N (1):N (3)]cuprate(II)]].

In the title complex, {(C2H8N)[Cu(C8H4O4)(C8H6N3)]} n , there are two Cu(II) cations (each located on a centre of inversion), one benzene-1,2-di-carboxyl-ate dianion, one 3-(pyridin-4-yl)-1H-pyrazol-1-ide anion and one di-methyl-ammonium cation in the asymmetric unit. The di-methyl-ammonium cation was highly disordered and was treated with the SQUEEZE routine in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148-155]; the crystallographic data takes into account the presence of the cation. Each Cu(II) cation exhibits a square-planar coordination geometry. A benzene-1,2-di-carboxyl-ate dianion bridges two Cu(II) cations, building a linear chain along [001]. The chains are connected by 3-(pyridin-4-yl)-1H-pyrazol-1-ide anions, constructing a layer parallel to (101). The layers are assembled into a three-dimensional supra-molecular network through C-H⋯π inter-actions.

Dissociable effects of transcranial direct current stimulation (tDCS) on early and later stages of visual motion perceptual learning.

Transcranial direct current stimulation (tDCS) has the potential to benefit visual perceptual learning (VPL). However, previous studies investigated the effect of tDCS on VPL within early sessions, and the influence of tDCS on learning effects at later stages (plateau level) is unclear. Here, participants completed 9 days of training on coherent motion direction identification to reach a plateau (stage 1) and then continued training for 3 days (stage 2). The coherent thresholds were measured before training, after stage 1 and after stage 2. In the first group, anodal tDCS was applied when participants trained over a period of 12 days (stage 1 + stage 2). In the second group, participants completed a 9-day training period without any stimulation to reach a plateau (stage 1); after that, participants completed a 3-day training period while anodal tDCS was administered (stage 2). The third group was treated the same as the second group except that anodal tDCS was replaced by sham tDCS. The results showed that anodal tDCS did not improve posttest performance after the plateau was reached. The comparison of learning curves between the first and third groups showed that anodal tDCS decreased the threshold at the early stage, but it did not improve the plateau level. For the second and third groups, anodal tDCS did not further enhance the plateau level after a continued 3-day training period. These results suggest that anodal tDCS boosts VLP during the early period of training sessions, but it fails to facilitate later learning effects. This study contributed to a deep understanding of the dissociable tDCS effects at distinct temporal stages, which may be due to the dynamic change in brain regions during the time course of VPL.

Self-assembly and emulsification of poly{[styrene-alt-maleic acid]-co-[styrene-alt-(N-3,4-dihydroxyphenylethyl-maleamic acid)]}.

Self-assembled polymeric micelles can be used as efficient particulate emulsifiers. To explore the relationship between the structure and the oil-water interfacial behavior of the micelle emulsifiers, a new type of amphiphilic random copolymer, poly{(styrene-alt-maleic acid)-co-[styrene-alt-(N-3,4-dihydroxyphenylethyl-maleamic acid)]} (SMA-Dopa), was synthesized, self-assembled into micelles, and used as emulsifiers. SMA-Dopa was synthesized via an aminolysis reaction between dopamine and commercial alternating copolymer poly(styrene-alt-maleic anhydride) (SMA). Dopamine moiety facilitated the self-assembly of the SMA-Dopa in selective-solvent into stable micelles, and increased the adsorption of the SMA-Dopa at the oil-water interface. Additionally, the structural transition of the self-assembled SMA-Dopa52 micelles in response to pH and salinity changes were confirmed by means of TEM, AFM, DLS, aqueous electrophoresis techniques, potentiometric titration, and pyrene fluorescence probe methods. Micelles shrunk with increasing salinity, and flocculation of the shrunken primary micelles occurred at salt concentration exceeding 0.1 M. The micelles swelled with increasing pH, and the disassociation of the SMA-Dopa52 micelles occurred at pH above approximately 6.5. The structure of the micelles plays a crucial role in the oil-water interfacial performance. Micelles with various structures were used as emulsifiers to adsorb at the styrene-water and toluene-water interfaces. The emulsifying characteristics demonstrated that self-assembled SMA-Dopa52 micelles with moderately swollen structure (at 2 < pH < 6) combine the advantages of the solid particulate emulsifiers and polymeric surfactants, possessing excellent emulsifying efficiency and good emulsion stability. Moreover, the emulsifying performance of the SMA-Dopa52 micelles could be enhanced by the addition of salt.

The relationship between transthoracic echocardiography and mortality in adult patients with multiple organ dysfunction syndrome: analysis of the MIMIC-III database.

Background: For patients with multiple organ dysfunction syndrome (MODS), timely assessment of the condition and real-time adjustment of the treatment plan are of critical importance. To this end, transthoracic echocardiography (TTE) is widely used in clinical practice, but whether TTE can improve the short-term prognosis of MODS patients is currently unclear. Methods: We extracted data of patients from the Medical Information Mart for Intensive Care III (MIMIC-III) database and included cases according to inclusion and exclusion criteria. The primary endpoint was the mortality within 28 days after admission to the intensive care unit (ICU), and multi-variate regression analysis was conducted to infer the risk factors associated death within 28 days after ICU admission. Double robust analysis was conducted to investigate the correlation between TTE and the endpoint. A gradient-boosted model (GBM) was constructed to calculate the propensity score (PS) of patients received TTE, so as to reduce the difference of variates between these two groups. Results: A total of 13,844 MODS cases were included and were divided into a TTE group and a non-TTE group. There were 5,022 cases (36.28%) in the TTE group, 2,416 (48.10%) of whom were female; and 8,822 (63.72%) in the non-TTE group, 4,129 of whom (46.80%) were female. The covariates that contributed significantly to PS included chronic heart failure (CHF), creatine kinase (CK), troponin, partial pressure of oxygen (PO2), and sequential organ failure assessment (SOFA) scores. Double robust analysis showed that within 28 days after ICU admission, the TTE group had lower risk of death when compared with the non-TTE group. The adjusted odds ratio (OR) value of TTE for 28 days death was 0.73 [95% confidence interval (CI): 0.65-0.82; P<0.001]. The other 3 models had similar results, suggesting that conduct TTE for patients with MODS in ICU was associated with lower risk of 28 days mortality. Conclusions: TTE can reduce the mortality of MODS patients in the ICU.

Long-term prediction of sea surface chlorophyll-a concentration based on the combination of spatio-temporal features.

Harmful algal blooms (HABs) events have a serious impact on marine fisheries and marine management. They occur globally with high frequency and are characterized by a long duration and difficult governance. HABs incidents have occurred in the South China Sea (SCS), and the frequency of occurrence has been on the rise in recent decades. Predicting the long-term chlorophyll-a (Chl-a) concentration has the potential to facilitate long-term monitoring and early warning of HABs events. Currently, long-term predictions of ocean circulation and temperature are common, while long-term predictions of marine biochemistry are still in their infancy. Traditional Chl-a prediction methods have problems, such as low accuracy and the inability to carry out long-term predictions. This research improved the CNN-LSTM model by combining spatio-temporal features to predict Chl-a concentrations. This model can extract both the temporal and spatial features of Chl-a, expand the dataset, and improve the prediction accuracy and training speed. The predictions were made using a Chl-a dataset for the Reed Tablemount in the SCS. The time series of Chl-a used was the satellite data of NASA's official website from January 2002 to June 2020. The results indicate that the predictions of the CNN-LSTM model are better than those of the LSTM and SARIMA models. The five-year long-term rolling prediction of Chl-a was carried out, and the three-year Pearson correlation coefficient reached 0.5. The novelty of this study is the realization of a three-year long-term prediction of Chl-a concentrations. The Mann-Kendall trend test method and the least square method were used to fit the straight line to detect the trend of the five-year predicted value and the true value, respectively. The results indicated that the prediction value and true value of the sea surface Chl-a from 2015 to 2020 both exhibited an overall upward trend. In addition, the prediction performance of the model in large-scale prediction is better than that in small-scale prediction.

Inhibition of cell proliferation by Tas of foamy viruses through cell cycle arrest or apoptosis underlines the different mechanisms of virus-host interactions.

Foamy viruses belong to the Spumaretrovirinae subfamily member of the Retroviridae family and produce nonpathogenic infection to hosts in the natural conditions. However, infections of foamy viruses can dramatically cause severe cytopathic effects in vitro. To date, the exact molecular mechanism has remained unclear which implied the tremendous importance of virus-host cell immune reactions. In this study, we found that the transactivator Tas in two foamy viruses isolated from Old World Monkey (OWM) induced obvious inhibition of cell proliferation via the upregulation of Foxo3a expression. It was mediated by the generation of ROS and the initiation of ER stress, and ultimately, the mitochondrial apoptosis pathway was triggered. Notably, PFV Tas contributed to the accumulation of G0/G1 phase cycle arrest induced by the activation of the p53 signaling pathway and the nuclear transportation of HDAC4 via upregulating PPM1E expression. Together, these results demonstrated the different survival strategies by which foamy virus can hijack host cell cytokines and regulate virus-host cell interactions.

The effect of damaged skin barrier induced by subclinical irritation on the sequential irritant contact dermatitis.

Skin damage caused by a single specific stimulus has been extensively studied. However, many additional mild skin irritants are experienced every day before obvious irritant contact dermatitis (ICD) appears. The effect that these previously experienced mild irritations have on the incidence and severity of sequential ICD remains undefined. The purpose of this work was to explore whether the effects of skin barrier damage induced by either the open patch test with 1% sodium lauryl sulfate (SLS), tape stripping test (TAP) (10×), or irradiation with 0.75 median erythemal dose UVB (MED) will affect the severity of sequential irritant dermatitis induced by a 0.5% SLS occlusive patch test (PT). Nine treatments were applied to nine different locations of the ventral forearm of each subject at random. The nine treatment types were as follows: open patch test with 1% SLS; 10× TAP; UVB irradiation with 0.75 MED; open patch test with 1% SLS + PT with 0.5% SLS (SLSPT); 10× TAP + PT with 0.5% SLS (TAPPT); UVB irradiation with 0.75 MED + PT with 0.5% SLS (UVPT); PT with distilled water (DISPT); PT with 0.5% SLS (PT); and the CONTROL (no treatment). After 5 days of subclinical irritation, the PT was applied on day 6. Transepidermal water loss (TEWL), capacitance (CAP), and skin color (a*) were measured at baseline and on days 6, 7, and 8. After the PT, indices of irritancy of PT, UVPT, SLSPT, and TAPPT were 60, 80, 87 and 100%, respectively. The index of irritancy of TAPPT and SLSPT were significantly higher than that of PT (p < 0.05). Clinical scores of SLSPT and TAPPT were also significantly higher than PT (p < 0.05). After 5 days of irritation, TEWL of SLS, TAP, SLSPT, and TAPPT were increased significantly compared to that of baseline. After the PT, D-value of TEWL between day 8 and day 6 ((≥6-8)TEWL) of SLSPT and TAPPT were greater than that of PT, and D-value of TEWL between day 8 and day 7 ((≥7-8)TEWL) of SLSPT and TAPPT were less than that of PT values. After the PT, a* values of SLSPT, TAPPT and PT all increased. The D-value of a* between day 8 and day 6 ((≥6-8)a*) of SLSPT and TAPPT were significantly greater than that of PT. After the PT, D-value of CAP between day 8 and day 6 ((≥6-8)CAP) of SLSPT was significantly different as compared to PT. The open patch test with 1% SLS and 10× TAP destroys the skin barrier and is able to significantly increase the irritancy and severity of sequential ICD by 0.5% SLS PT, and therefore influences the recovery speed of inflammation. The open patch test with 1% SLS, 10× TAP, and UVB irradiation with 0.75 MED affects the skin barrier to different degrees. TEWL is a sensitive biophysical parameter that can reflect mild damage to the skin barrier induced by subclinical irritation.

Cutaneous and sensory effects of two types of sanitary pads with different surfaces in the Shanghai, Chinese population.

BACKGROUND: Regional differences in practices, ethnicity, and climate may influence the skin compatibility of sanitary pads. Although several clinical trials have been performed in North America, Mexico, Western Europe, Eastern Europe, and Africa, there is no clinical study reported for Asia. OBJECTIVE: The purpose of this study was to examine the skin compatibility of two types of modern sanitary pads in Chinese women along with a dermatological assessment and their satisfaction and preference. MATERIALS AND METHODS: The self-feeling and safety of a new sanitary pad with a non-woven top specially-shaped surface sheet was tested and compared with a conventional sanitary pad with a perforated film top sheet. The subjects studied were 22 Chinese women (age: 20-50 years) with a history of mild and occasional sanitary pad dermatitis residing in Shanghai. One subject wished to discontinue the trial for personal reasons, thus 21 subjects completed the trial. These subjects were randomly assigned to two types of sanitary pads, and used one type during their next menstrual period, and another type during their following menstrual period. After each menstrual period, a dermatologist examined the objective and subjective skin symptoms and determined a score. The subjects were asked to rate their level of satisfaction with respect to overall usability, softness, stickiness, dryness, and absorbency, and to choose which pad they had preferred. RESULTS: No adverse effect was observed for either type of pad. Edema, erythema, burning, and stinging were not obvious symptoms for either type of pad. For itching, 30-65% of the subjects scored slight or mild for both types of pads. A comprehensive evaluation showed that several symptoms were observed on both type of pads at slight and mild levels, but minimal and insignificant differences were found between them. The majority of subjects were highly satisfied with both types, but preferred the new sanitary pad with a non-woven specially-shaped surface top sheet for its softness and absorbency. CONCLUSION: Our results indicate that both types of sanitary pads were tolerated well by Chinese women, thereby providing an important extension of earlier studies.

The Pathogenesis Mechanism, Structure Properties, Potential Drugs and Therapeutic Nanoparticles against the Small Oligomers of Amyloid-ß.

Alzheimer's Disease (AD) is a devastating neurodegenerative disease that affects millions of people in the world. The abnormal aggregation of amyloid ß protein (Aß) is regarded as the key event in AD onset. Meanwhile, the Aß oligomers are believed to be the most toxic species of Aß. Recent studies show that the Aß dimers, which are the smallest form of Aß oligomers, also have the neurotoxicity in the absence of other oligomers in physiological conditions. In this review, we focus on the pathogenesis, structure and potential therapeutic molecules against small Aß oligomers, as well as the nanoparticles (NPs) in the treatment of AD. In this review, we firstly focus on the pathogenic mechanism of Aß oligomers, especially the Aß dimers. The toxicity of Aß dimer or oligomers, which attributes to the interactions with various receptors and the disruption of membrane or intracellular environments, were introduced. Then the structure properties of Aß dimers and oligomers are summarized. Although some structural information such as the secondary structure content is characterized by experimental technologies, detailed structures are still absent. Following that, the small molecules targeting Aß dimers or oligomers are collected; nevertheless, all of these ligands have failed to come into the market due to the rising controversy of the Aß-related "amyloid cascade hypothesis". At last, the recent progress about the nanoparticles as the potential drugs or the drug delivery for the Aß oligomers are present.

Synergistic Inhibition of Renal Fibrosis by Nintedanib and Gefitinib in a Murine Model of Obstructive Nephropathy.

BACKGROUND: Our recent studies demonstrated that both nintedanib, an FDA-approved quadruple kinase inhibitor, and gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, protect against obstructive kidney disease. It remains unknown whether they have a synergistic effect. METHODS: In this study, we investigated the effect of combined administration of nintedanib and gefitinib on renal fibrosis in a murine model of renal fibrosis induced by unilateral ureteral obstruction (UUO). RESULTS: Combined treatment with nintedanib and gefitinib after UUO resulted in a greater antifibrotic effect compared with their individual application. Mechanistically, administration of nintedanib blocked UUO-induced phosphorylation of multiple kinase receptors associated renal fibrosis, including platelet-derived growth factor receptors, fibroblast growth factor receptors, vascular endothelial growth factor receptors, and Src family kinase, while gefitinib inhibited EGFR phosphorylation. Their combination also exhibited a more pronounced effect in reducing expression of tissue inhibitors of metalloproteinase-2 (TIMP-2), increasing expression of matrix metalloproteinase-2 (MMP-2), and suppressing renal proinflammatory cytokine expression and macrophage infiltration in the injured kidney. Furthermore, simultaneous administration of nintedanib and gefitinib was more potent in inhibiting UUO-induced renal phosphorylation of signal transducer and activator of transcription-3 (STAT3), nuclear factor-κB, and Smad-3 compared with monotherapy. In cultured renal interstitial fibroblasts, cotreatment with these 2 inhibitors also had synergistic effects in abrogating transforming growth factor ß1-induced activation of renal fibroblasts and phosphorylation of Akt, STAT3, and Smad3. CONCLUSIONS: Combined application of nintedanib and gefitinib has a synergistic antifibrotic effect in the kidney and may hold translational potential for the treatment of chronic kidney disease.

Ellagic acid-induced hypercoagulable state in animals: a potentially useful animal hypercoagulable model for evaluation of anticoagulants.

OBJECTIVE: To establish and evaluate a hypercoagulable animal model for the assessment of anticoagulants. METHODS: Forty mice, thirty-two rats, and twenty-four rabbits were randomly and equally divided into control group (saline) and three ellagic acid (EA)-treated groups (low, middle, and high doses). In the mice, bleeding time (BT) was estimated with tail transaction, and clotting time (CT) with template method. Prothrombin time (PT) and the activated partial thromboplastin time (APTT) in rats and rabbits were measured by means of Quick's one-stage assay and modified APTT assay respectively. In addition, thrombin activity was estimated in rats with PT assay using a hemagglutination analyzer. The circulating platelet aggregates were detected in rabbits through platelet counting and presented as the circulating platelet aggregate ratio (CPAR). RESULTS: EA shortened BT and CT in mice, PT and APTT in rats, and increased thrombin activity and CPAR, all in a dose-dependent manner. EA also brought reduction of PT and APTT in rabbits in dose- and time-dependent manners. CONCLUSION: EA could induce hypercoagulable state through activating coagulation system and platelets in mice, rats, and rabbits.

Associations of oxytocin with metabolic parameters in obese women of childbearing age.

INTRODUCTION: The aim of this study was to compare plasma oxytocin levels in obese women of childbearing age with non-obese women of childbearing age, and to investigate the relationship between plasma oxytocin levels and metabolic parameters (including blood glucose, insulin resistance, blood lipid, and blood pressure). MATERIAL AND METHODS: A total of 151 obese women of childbearing age and 160 non-obese women of childbearing age were enrolled in this study. Plasma oxytocin levels were measured by electrochemiluminescence immunoassays. Height, body weight, body mass index (BMI), fasting blood glucose (FBG), fasting insulin (FI), homeostasis model assessment for insulin resistance (HOMA-IR), total triglycerides (TG), total cholesterol (TC), low-density lipoprotein-C (LDL-C), high-density lipoprotein-C (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured in all subjects. Quantile regression analysis was used to analyse the associations of plasma oxytocin levels with FBG, FI, HOMA-IR, TG, TC, LDL-C, HDL-C, SBP, and DBP. RESULTS: In obese women of childbearing age, plasma oxytocin levels were lower compared with non-obese controls. After adjusting for age, quantile regression analysis showed that the plasma oxytocin levels were inversely associated with HOMA-IR at the quantile level between 0.27 and 0.79 (i.e. the HOMA-IR level of 2.11 and 3.07, respectively), the plasma oxytocin levels were inversely associated with TC after the quantile level of 0.21 (i.e. the TC level of 3.78 ), and the plasma oxytocin levels were inversely associated with LDL-C at all quantile levels of LDL-C. In addition, the plasma oxytocin levels showed a positive association with HDL-C at all quantile levels of HDL-C. No significant associations were found between the plasma oxytocin levels and FBG, FI, TG, SBP, and DBP. CONCLUSIONS: Oxytocin deficiency was common in obese women of childbearing age. Oxytocin showed negative correlation with HOMA-IR, TC, and LDL-C, while it showed positive association with HDL-C. Our findings suggest that oxytocin played an important role in inhibiting metabolic disorders associated with obesity in women of childbearing age.

Functional characterization of the Wrab17 gene in the interaction process between wheat and Puccinia triticina.

In the interaction between wheat and Puccinia triticina, wheat resists the invasion of P. triticina by producing hypersensitive reaction-programmed cell death (HR-PCD). To better understand the mechanism of wheat resistance to P. triticina, it is important to identify the defensive genes involved in wheat resistance to leaf rust. This paper systematically presented the role of Wrab17 in the HR-PCD process in wheat after infection by P. triticina. The subcellular location analysis is performed using the full length of Wrab17 coding sequences and Wrab17 is found to be localized in cell nucleus and cytoplasm. Quantitative RT-PCR (RT-qPCR) and western blot analysis showed that expression of Wrab17 at both mRNA and protein levels increased by P. triticina infection, indicating that the Wrab17 gene participated in the interaction between wheat and P. triticina. Wrab17 knockdown plants were generated by RNA-mediated gene silencing technology (RNA interference, RNAi) and confirmed by southern blot. Further analysis with P. triticina inoculation found that knockdown of Wrab17 exhibited decreased HR expansion area in incompatible combination (L10×260) and significant higher sensitivity to the compatible pathogen P. triticina race 165. In all, this work reports that Wrab17 is a new defensive gene playing a role in wheat resistance to leaf rust.

[Epidemiological survey on clonorchiasis and awareness of prevention and control knowledge in Xinfeng County of Jiangxi Province].

OBJECTIVE: To understand the epidemic status of clonorchiasis and awareness of prevention and control knowledge in Xinfeng County of Jiangxi Province, so as to provide the evidences for control measures. METHODS: The baseline survey was carried out with a clue in vestigation of raw-fish eating behavior in potential endemic areas in 2016.The residents were examined by stool tests. The metacercariae of Clonorchis sinensis in fish, the rediae and cercariae in freshwater mollusk were detected. The feces samples of cats, dogs and pigs were collected and examined by sedimentation technique. Meanwhile, the epidemic factors, health knowledge and behavior were also surveyed. RESULTS: The residents in 26 villages had the habit of eating raw freshwater fish, and 19.51% of the respondents had this habit. The average infection rates of the population, Parafossarulus striatulus, freshwater fishes and reservoir hosts were 21.56%, 0, 8.24% and 2.27%, respectively. The infection rate of the population increased with age. There was a significant positive correlation between the behavior and the infection rate of the population (r = 0.88, P < 0.01). Only 11.46% of the respondents knew that eating raw-fish might cause C. sinensis infection, and 5.28% of them knew that C. sinensis was harmful to health. CONCLUSIONS: Twenty-six villages in five townships were endemic areas of clonorchiasis in Xinfeng County. The permanent solution of prevention and control of clonorchiasis is to strengthen the health education and change the habit of raw-fish eating gradually.