Overexpression of TRIM44 mediates the NF-κB pathway to promote the progression of ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is the second most commonly seen cancer in the US, and patients with OC are commonly diagnosed in the advanced stage. Research into the molecular mechanisms and potential therapeutic targets of OC is becoming increasingly urgent. In our study, we worked to discover the role of TRIM44 in OC development. OBJECTIVE: This study explored whether the overexpression of TRIM44 mediates the NF-kB pathway to promote the progression of OC. METHODS: A TRIM44 overexpression model was constructed in SKOV3 cells, and the proliferation ability of the cells was detected using the CCK-8 assay. The migration healing ability of cells was detected using cell scratch assay. Cell migration and invasion were detected using Transwell nesting. TUNEL was applied to detect apoptosis, and ELISA and western blot were used to detect the expression of NF-κB signaling pathway proteins. The pathological changes of the tumor tissues were observed using HE staining in a mouse ovarian cancer xenograft model. Immunofluorescence double staining, RT-PCR, and western blot were used to determine the expression of relevant factors in tumour tissues. RESULTS: TRIM44 overexpression promoted the proliferation, migration, and invasion of SKOV3 cells in vitro and inhibited apoptosis while enhancing the growth of tumours in vivo. TRIM44 regulated the NF-κB signaling pathway. CONCLUSIONS: TRIM44 overexpression can regulate the NF-κB signaling pathway to promote the progression of OC, and TRIM44 may be a potential therapeutic target for OC.

Chlorin e6 and BLZ945 Based Self-Assembly for Photodynamic Immunotherapy through Immunogenic Tumor Induction and Tumor Associated Macrophage Depletion.

Immunotherapeutic effect is restricted by the non-immunogenic tumor phenotype and immunosuppression behaviors of tumor associated macrophages (TAMs). In this work, a drug self-assembly (designated as CeBLZ) is fabricated based on chlorin e6 (Ce6) and BLZ945 to activate photodynamic immunotherapy through tumor immunogenic induction and tumor associated macrophage depletion. It is found that Ce6 tends to assemble with BLZ945 without any drug excipients, which can enhance the cellular uptake, tumor penetration and blood circulation behaviors. The robust photodynamic therapy effect of CeBLZ efficiently suppresses the primary tumor growth and also triggers immunogenic cell death to reverse the non-immunogenic tumor phenotype. Moreover, CeBLZ can deplete TAMs in tumor tissues to reverse the immunosuppression microenvironment, activating abscopal effect for distant tumor inhibition. In vitro and in vivo results confirm the superior anti-tumor effect of CeBLZ with negligible side effect, which might promote the development of sophisticated drug combinations for systematic tumor management. This article is protected by copyright. All rights reserved.

Linear optimal transport subspaces for point set classification.

Learning from point sets is an essential component in many computer vision and machine learning applications. Native, unordered, and permutation invariant set structure space is challenging to model, particularly for point set classification under spatial deformations. Here we propose a framework for classifying point sets experiencing certain types of spatial deformations, with a particular emphasis on datasets featuring affine deformations. Our approach employs the Linear Optimal Transport (LOT) transform to obtain a linear embedding of set-structured data. Utilizing the mathematical properties of the LOT transform, we demonstrate its capacity to accommodate variations in point sets by constructing a convex data space, effectively simplifying point set classification problems. Our method, which employs a nearest-subspace algorithm in the LOT space, demonstrates label efficiency, non-iterative behavior, and requires no hyper-parameter tuning. It achieves competitive accuracies compared to state-of-the-art methods across various point set classification tasks. Furthermore, our approach exhibits robustness in out-of-distribution scenarios where training and test distributions vary in terms of deformation magnitudes.

The Bacterial and Fungal Compositions in the Rhizosphere of Asarum heterotropoides Fr. Schmidt var. mandshuricum (Maxim.) Kitag. in a Typical Planting Region.

Asarum is a traditional Chinese medicinal plant, and its dried roots are commonly used as medicinal materials. Research into the traits of the bacteria and fungus in the Asarum rhizosphere and how they relate to the potency of medicinal plants is important. During four cropping years and collecting months, we used ITS rRNA gene amplicon and sequencing to assess the population, diversity, and predominant kinds of bacteria and fungus in the rhizosphere of Asarum. HPLC was used to determine the three bioactive ingredients, namely asarinin, aristolochic acid I, and volatile oil. The mainly secondary metabolites of Asarum, relationships between microbial communities, soil physicochemical parameters, and possible influences on microbial communities owing to various cropping years and collecting months were all statistically examined. The cropping years and collecting months affected the abundance and diversity of rhizosphere bacteria and fungi, but the cropping year had a significant impact on the structures and compositions of the bacterial communities. The rhizosphere microorganisms were influenced by both the soil physicochemical properties and enzyme activities. Additionally, this study revealed that Trichoderma was positively correlated with the three bioactive ingredients of Asarum, while Tausonia showed entirely opposite results. Gibberella and Leptosphaeria demonstrated a significantly negative correlation with asarinin and violate oil, but they were weakly correlated with the aristolochic acid I content. This study revealed variations in the Asarum rhizosphere microorganism population, diversity, and dominant types across four cropping years and collecting months. The relationship between Asarum secondary metabolites, the soil physicochemical properties, enzyme activities, and rhizosphere microorganisms was discussed. Our results will guide the exploration of the soil characteristics and rhizosphere microorganisms' structures by regulating the microbial community to enhance Asarum quality.

Bilateral Pattern Electroretinogram Abnormalities in Patients with Herpes Zoster Keratitis and Conjunctivitis.

INTRODUCTION: Herpes zoster ophthalmicus (HZO) results from the reactivation of varicella zoster virus (VZV) in the ophthalmic branch of the trigeminal nerve. The inflammation caused by VZV involves multiple tissues in the eyes. Our goal is to evaluate pattern electroretinogram (PERG) changes and their relationship with corneal sub-basal nerve changes in patients with HZO. METHODS: Twenty-two patients with herpes zoster keratitis or conjunctivitis and 20 healthy volunteers were recruited for this cross-sectional study. A PERG test was performed on both eyes of HZO patients and one eye of the healthy controls. In vivo confocal microscopy (IVCM) was also performed on both eyes of the HZO patients to detect corneal nerve damage. RESULTS: Our results showed changes in the PERG parameters in both eyes of HZO patients compared to the healthy controls. Affected eyes showed delayed N95 peak time and decreased P50 and N95 amplitude compared to the unaffected eyes (p < 0.05, respectively). Both affected and unaffected eyes in HZO patients showed delayed P50 peak time and decreased N95 amplitude (p < 0.05, respectively) compared to controls. In HZO patients, no significant differences in each PERG parameter were found between eyes with and without corneal lesions or between eyes with and without increased Langham's cells in the corneal epithelial sub-basal layer. The IVCM images showed decreased total nerve length and number at the sub-basal layer of the epithelial cornea in affected eyes compared to unaffected eyes (p < 0.05). No significant correlation was found between total nerve length and PERG changes. CONCLUSIONS: Our results showed that VZV-affected eyes without central cornea involvement displayed reduced N95 amplitude and prolonged P50 peak time in bilateral eyes compared to the healthy controls. Larger studies are needed to further explore the effect of HZO on the electrophysiological response of the eye and the posterior segment.

Optical controlled and nuclear targeted CECR2 competitor to downregulate CSF-1 for metastatic breast cancer immunotherapy.

The crosstalk between breast cancer cells and tumor associated macrophages (TAMs) greatly contributes to tumor progression and immunosuppression. In this work, cat eye syndrome chromosome region candidate 2 (CECR2) is identified to overexpress in breast cancer patients, which can recognize v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) and activate nuclear factor κB (NF-κB) to release colony stimulating factor-1 (CSF-1). Pharmacological inhibition of CECR2 by the bromodomain competitor (Bromosporine, Bro) can downregulate CSF-1 to inhibit M2 type TAMs. To amplify the immunotherapeutic effect, a chimeric peptide-based and optical controlled CECR2 competitor (designated as N-PB) is constructed to enhance the nuclear targeted delivery of Bro and initiate an immunogenic cell death (ICD). In vivo results indicate a favorable breast cancer targeting ability and primary tumor suppression effect of N-PB under optical irradiation. Importantly, N-PB downregulates CSF-1 by competitive inhibition of CECR2 and NF-κB(RelA) interactions, thus inhibiting immunosuppressive M2-like TAMs while improving the antitumorigenic M1-like phenotype. Ultimately, the systemic anti-tumor immunity is activated to suppress the metastatic breast cancer in an optical controlled manner. This study provides a promising therapeutic target and reliable strategy for metastatic breast cancer treatment by interrupting immunosuppressive crosstalk between tumor cells and macrophages.

End-to-End Signal Classification in Signed Cumulative Distribution Transform Space.

This paper presents a new end-to-end signal classification method using the signed cumulative distribution transform (SCDT). We adopt a transport generative model to define the classification problem. We then make use of mathematical properties of the SCDT to render the problem easier in transform domain, and solve for the class of an unknown sample using a nearest local subspace (NLS) search algorithm in SCDT domain. Experiments show that the proposed method provides high accuracy classification results while being computationally cheap, data efficient, and robust to out-of-distribution samples with respect to the existing end-to-end classification methods. The implementation of the proposed method in Python language is integrated as a part of the software package PyTransKit.

Multi-omics subgroups associated with glycaemic deterioration in type 2 diabetes: an IMI-RHAPSODY Study.

Introduction: Type 2 diabetes (T2D) onset, progression and outcomes differ substantially between individuals. Multi-omics analyses may allow a deeper understanding of these differences and ultimately facilitate personalised treatments. Here, in an unsupervised "bottom-up" approach, we attempt to group T2D patients based solely on -omics data generated from plasma. Methods: Circulating plasma lipidomic and proteomic data from two independent clinical cohorts, Hoorn Diabetes Care System (DCS) and Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS), were analysed using Similarity Network Fusion. The resulting patient network was analysed with Logistic and Cox regression modelling to explore relationships between plasma -omic profiles and clinical characteristics. Results: From a total of 1,134 subjects in the two cohorts, levels of 180 circulating plasma lipids and 1195 proteins were used to separate patients into two subgroups. These differed in terms of glycaemic deterioration (Hazard Ratio=0.56;0.73), insulin sensitivity and secretion (C-peptide, p=3.7e-11;2.5e-06, DCS and GoDARTS, respectively; Homeostatic model assessment 2 (HOMA2)-B; -IR; -S, p=0.0008;4.2e-11;1.1e-09, only in DCS). The main molecular signatures separating the two groups included triacylglycerols, sphingomyelin, testican-1 and interleukin 18 receptor. Conclusions: Using an unsupervised network-based fusion method on plasma lipidomics and proteomics data from two independent cohorts, we were able to identify two subgroups of T2D patients differing in terms of disease severity. The molecular signatures identified within these subgroups provide insights into disease mechanisms and possibly new prognostic markers for T2D.

Tumor Homing Chimeric Peptide Rhomboids to Improve Photodynamic Performance by Inhibiting Therapy-Upregulated Cyclooxygenase-2.

Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP-Mel) are fabricated to improve photodynamic performance by inhibiting PDT-upregulated cyclooxygenase-2 (COX-2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic-K(PpIX)CGNKRTR), which can encapsulate the COX-2 inhibitor of meloxicam. The well dispersed NP-Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP-Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL-6 and TNF-α expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP-Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance.

Genes in Axonal Regeneration.

This review explores the molecular and genetic underpinnings of axonal regeneration and functional recovery post-nerve injury, emphasizing its significance in reversing neurological deficits. It presents a systematic exploration of the roles of various genes in axonal regrowth across peripheral and central nerve injuries. Initially, it highlights genes and gene families critical for axonal growth and guidance, delving into their roles in regeneration. It then examines the regenerative microenvironment, focusing on the role of glial cells in neural repair through dedifferentiation, proliferation, and migration. The concept of "traumatic microenvironments" within the central nervous system (CNS) and peripheral nervous system (PNS) is discussed, noting their impact on regenerative capacities and their importance in therapeutic strategy development. Additionally, the review delves into axonal transport mechanisms essential for accurate growth and reinnervation, integrating insights from proteomics, genome-wide screenings, and gene editing advancements. Conclusively, it synthesizes these insights to offer a comprehensive understanding of axonal regeneration's molecular orchestration, aiming to inform effective nerve injury therapies and contribute to regenerative neuroscience.

Chemotherapy-Enabled Colorectal Cancer Immunotherapy of Self-Delivery Nano-PROTACs by Inhibiting Tumor Glycolysis and Avoiding Adaptive Immune Resistance.

The chemo-regulation abilities of chemotherapeutic medications are appealing to address the low immunogenicity, immunosuppressive lactate microenvironment, and adaptive immune resistance of colorectal cancer. In this work, the proteolysis targeting chimera (PROTAC) of BRD4 (dBET57) is found to downregulate colorectal cancer glycolysis through the transcription inhibition of c-Myc, which also inhibits the expression of programmed death ligand 1 (PD-L1) to reverse immune evasion and avoid adaptive immune resistance. Based on this, self-delivery nano-PROTACs (designated as DdLD NPs) are further fabricated by the self-assembly of doxorubicin (DOX) and dBET57 with the assistance of DSPE-PEG2000. DdLD NPs can improve the stability, intracellular delivery, and tumor targeting accumulation of DOX and dBET57. Meanwhile, the chemotherapeutic effect of DdLD NPs can efficiently destroy colorectal cancer cells to trigger a robust immunogenic cell death (ICD). More importantly, the chemo-regulation effects of DdLD NPs can inhibit colorectal cancer glycolysis to reduce the lactate production, and downregulate the PD-L1 expression through BRD4 degradation. Taking advantages of the chemotherapy and chemo-regulation ability, DdLD NPs systemically activated the antitumor immunity to suppress the primary and metastatic colorectal cancer progression without inducing any systemic side effects. Such self-delivery nano-PROTACs may provide a new insight for chemotherapy-enabled tumor immunotherapy.

Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

Clinical manifestation and long-term follow-up of presumed ocular tuberculosis in China.

Background: This study aimed to report the clinical manifestations of presumed ocular tuberculosis (OTB) and the treatment response after anti-tuberculosis therapy (ATT) in a Chinese population. Methods: Clinical data, including general characteristics, ocular lesions, visual acuity at baseline, and final follow-up of patients with presumed OTB from 2006 to 2022 in two eye clinics in China, were retrospectively analyzed. Results: The study included 84 eyes of 52 patients. The following ocular manifestations were observed: anterior uveitis (4.8%), posterior uveitis (34.5%), panuveitis (11.9%), retinal vasculitis (40.5%) and optic neuropathy (8.3%). After ATT, the vision improved by varying degrees in 48 eyes (57.1%), remained stable in 34 eyes (40.5%) and decreased in 2 eyes (2.4%). Conclusions: OTB is likely to be misdiagnosed as other infectious uveitis and optic neuropathy. Clinical features must be interpreted in conjunction with topical and general laboratory findings and in collaboration with other subspecialties to make a final diagnosis.

The Effect of Post-Activation Potentiation Enhancement Alone or in Combination with Caffeine on Anaerobic Performance in Boxers: A Double-Blind, Randomized Crossover Study.

Post-activation performance enhancement (PAPE) is a physiological phenomenon that refers to an acute excitation of the neuromuscular system following intense exercise that ends in enhanced physical performance in a subsequent bout of exercise. The scientific literature has primarily examined the effectiveness of PAPE alone or combined with caffeine (CAF) intake in all-out tests lasting ≤10 s, as the effect of PAPE is transitory. The aim of the present study was to determine the effect of a protocol to induce PAPE alone or in combination with caffeine intake on the 30 s Wingate Anaerobic Test in highly trained boxers. Twenty-five male and highly trained boxers (mean age: 20 ± 1 years) participated in a double-blind, randomized crossover study consisting of three different experimental conditions: (i) control (CON), with no substance intake and no PAPE protocol before the Wingate Anaerobic Test; (ii) PAPE + PLA, involving the intake of a placebo 60 min before and a PAPE protocol comprising a 10 s cycling sprint overloaded with 8.5% of the participants' body weight 10 min before the Wingate Anaerobic Test; and (iii) PAPE + CAF, involving the intake of 3 mg/kg of caffeine 60 min before and the same PAPE protocol used in the (ii) protocol before the Wingate Anaerobic Test. In all conditions, the participants performed the 30 s version of the Wingate Anaerobic Test with a load equivalent to 7.5% of their body weight, while the cycle ergometer setting was replicated. Immediately following the Wingate test, heart rate (HR), the rating of perceived exertion (RPE), and blood lactate concentration (Bla) were measured. In comparison to CON, PAPE + PLA enhanced mean power (p = 0.024; Effect size [ES] = 0.37) and total work (p = 0.022; ES = 0.38) during the Wingate test, accompanied by an increase in post-test blood lactate concentration (p < 0.01; ES = 0.83). In comparison to CON, PAPE + CAF enhanced mean power (p = 0.001; ES = 0.57), peak power (p = 0.013; ES = 0.57), total work (p = 0.001; ES = 0.53), post-test blood lactate concentration (p < 0.001; ES = 1.43) and participants' subjective perception of power (p = 0.041). There were no differences in any variable between PAPE + PLA and PAPE + CAF. In summary, a PAPE protocol that involves a 10 s all-out sprint 10 min before the Wingate Anaerobic Test was effective in enhancing Wingate mean power in highly trained boxers. The addition of 3 mg/kg of caffeine to the PAPE protocol produced an effect on mean power of a higher magnitude than PAPE alone, and it enhanced peak power along with participants' subjective perception of power. From a practical point of view, PAPE before exercise seems to be an effective approach for increasing Wingate performance in highly trained boxers, while the addition of caffeine can increase some benefits, especially peak power.

Internet addiction and depressive and anxious symptoms among Chinese rural left-behind adolescents: Mediating roles of resilience and friendship quality.

BACKGROUND: Rural left-behind adolescents are more vulnerable to Internet addiction and depressive and anxious symptoms due to the lack of family support and parental supervision. This study was the first to investigate the longitudinal relationships between Internet addiction and depressive and anxious symptoms and to examine the mediating roles of resilience and friendship quality in rural left-behind adolescents. METHODS: Included in this study, which was from a longitudinal study conducted five times over 2 years, were 1001 rural left-behind adolescents. The internationally used scales for depressive and anxious symptoms, Internet addiction, resilience and friendship quality were administered. A structural equation model was used for analysis. RESULTS: The prevalence of Internet addiction, depressive and anxious symptoms among rural left-behind adolescents were 17.7%, 35.8% and 27.6%, respectively. Internet addiction predicted the later depressive and anxious symptoms (ß = 0.200, 95% confidence interval [CI]: 0.116-0.274 and ß = 0.263, 95% CI: 0.188-0.330). Resilience acted as an independent mediator in the relationships between Internet addiction and depressive and anxious symptoms (ß = 0.037 and 0.034, P < 0.01). Resilience and friendship quality played a chain-mediating role on the longitudinal relationships between Internet addiction and depressive and anxious symptoms (ß = 0.011 and 0.010, P < 0.001). The mediating effects accounted for 24.0% and 16.7% of the total effects, respectively. CONCLUSION: Resilience and friendship quality play an independent or chain-mediating role in longitudinal relationships between Internet addiction and depressive and anxious symptoms. The findings inform targeted intervention strategies to improve the mental health of left-behind adolescents.

Intestinal Electrical Stimulation Synchronized With Intestinal Slow Wave Ameliorates Glucagon-Induced Hyperglycemia in Rats.

BACKGROUND: Synchronized intestinal electrical stimulation (SIES), in which intestinal electrical stimulation (IES) is delivered in synchronization with the intrinsic slow wave of small intestine, was previously reported to be more potent in accelerating small intestine transit than IES delivered at fixed frequency and phase. We hypothesized that SIES is more potent in suppressing postprandial blood glucose by enhancing the release of glucagon-like peptide-1 (GLP-1) and insulin. MATERIALS AND METHODS: Rats underwent long-term implant of two pairs of electrodes at the duodenum for IES and SIES, respectively. Acute hyperglycemia was induced with glucagon, and the oral glucose tolerance test was performed on separate days with IES, SIES, or sham (no stimulation). RESULTS: 1. Glucagon reduced the percentage of normal slow wave in sham (70.9% ± 4.1%) from (84.9% ± 2.6%, p = 0.006) of control, which was ameliorated by SIES (82.5% ± 3.3%, p = 0.031). 2. IES and SIES reduced glucagon-induced increase of blood glucose (192 mg/dl) at 30 minutes by 17% and 20%, respectively. SIES showed a further inhibitory effect at 60 minutes (147 vs 171 mg/dl, p = 0.003, vs sham). 3. Compared with sham (139 pg/ml), GLP-1 at 30 minutes was increased in both IES (158 pg/ml) and SIES (169 pg/ml). GLP-1 level was still high at 60 minutes in rats with SIES. 4. At 30 minutes, the plasma insulin level was increased by 18.8 µIU/ml with SIES, which was significantly higher than that with sham (7.1 µIU/ml, p < 0.001) and IES (13.2 µIU/ml, p = 0.041). CONCLUSION: SIES is more effective than IES in reducing glucagon-induced acute hyperglycemia by enhancing the release of GLP-1 and insulin.

Recent Progress in Phage-Based Nanoplatforms for Tumor Therapy.

Nanodrug delivery systems have demonstrated a great potential for tumor therapy with the development of nanotechnology. Nonetheless, traditional drug delivery systems are faced with issues such as complex synthetic procedures, low reproducibility, nonspecific distribution, impenetrability of biological barrier, systemic toxicity, etc. In recent years, phage-based nanoplatforms have attracted increasing attention in tumor treatment for their regular structure, fantastic carrying property, high transduction efficiency and biosafety. Notably, therapeutic or targeting peptides can be expressed on the surface of the phages through phage display technology, enabling the phage vectors to possess multifunctions. As a result, the drug delivery efficiency on tumor will be vastly improved, thereby enhancing the therapeutic efficacy while reducing the side effects on normal tissues. Moreover, phages can overcome the hindrance of biofilm barrier to elicit antitumor effects, which exhibit great advantages compared with traditional synthetic drug delivery systems. Herein, this review not only summarizes the structure and biology of the phages, but also presents their potential as prominent nanoplatforms against tumor in different pathways to inspire the development of effective nanomedicine.

Autonomic and cytokine mechanisms of acute electroacupuncture in a rodent model of functional dyspepsia.

BACKGROUND: Cytokines have been presumed to play an important role in the pathophysiology of functional dyspepsia (FD). Electroacupuncture (EA) has been used for FD treatment; however, its mechanisms remain largely unknown. This study aimed to (1) compare the plasma levels of cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-10, in "FD" rats with normal control rats; (2) investigate whether EA, using chronically implanted electrodes, could inhibit the release of these cytokines; and (3) explore the correlation of cytokine levels with plasma norepinephrine (NE) levels and gastric emptying (GE). METHODS: A rodent model of FD was established via neonatal treatment with intragastric iodoacetamide. After 8 weeks, the rats were implanted with electrodes at acupoint ST36 for EA. The plasma levels of cytokines and NE were measured using enzyme-linked immunosorbent assay. We explored the correlations of cytokine levels with NE levels and GE. KEY RESULTS: (i) "FD" rats demonstrated increased levels of TNF-α, IL-1ß, and IL-6 (p < 0.05 each) compared with the control rats. (ii) EA significantly decreased the plasma levels of TNF-α, IL-1ß, and IL-6 in "FD" rats (p < 0.05 each) compared with sham EA. (iii) The plasma levels of NE were positively correlated with those of IL-6 (r = 0.86, p < 0.05) and IL-1ß (r = 0.81, p < 0.05), whereas NE levels and GE were negatively correlated with IL-10 levels (r = -0.870, p < 0.05 and r = -0.791, p < 0.05, respectively). CONCLUSIONS: EA inhibits the release of proinflammatory cytokines probably via the suppression of sympathetic activity in "FD" rats.

Appropriate time for ejection fraction reassessment after revascularization in patients with left ventricular dysfunction for risk stratification of sudden cardiac death.

BACKGROUND: Appropriate time for ejection fraction (EF) reassessment after revascularization in patients with left ventricular dysfunction has not been investigated comprehensively, although 3 months after revascularization is recommended to stratify the risk of sudden cardiac death (SCD). HYPOTHESIS: EF reassessed within different timeframe after revascularization may have incosistent contribution for risk stratification of SCD. METHODS: Patients who had EF ≤ 40% before revascularization and had EF reassessment at least once during follow-up were included. The role of early (<3 months) versus late (3-12 months) EF measurements in prediction of all-cause mortality and SCD were compared. RESULTS: A total of 1589 patients were identified. EF reassessed <3 months was lower than EF reassessed within 3-12 months (42.1 ± 9.7% vs. 45.8 ± 10.8%; p < .01). Among 1069 patients who had EF reassessed <3 months, EF ≤ 35% was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.22-2.29; p < .01), but had no association with the risk of SCD (HR, 1.44; 95% CI, 0.84-2.48; p = .18). By contrast, among 595 patients who had EF reassessed within 3-12 months, EF ≤ 35% was associated with higher risks of both all-cause death (HR, 1.81; 95% CI, 1.06-3.10; p = .03) and SCD (HR, 2.71; 95% CI, 1.31-5.61; p < .01). The relative contribution of SCD to all-cause death was higher in patients with EF ≤ 35% than patients with EF > 35% when EF was reassessed within 3-12 months (p = .04). However, when EF was reassessed <3 months, the mode of death was similar in patients with EF ≤ 35% versus >35% (p = .85). CONCLUSIONS: 3 to 12 months after revascularization may be appropriate for cardiac function reassessment and SCD risk stratification.