N1 and LNC Reveal the Differential Electrophysiological Signatures of Functional and Hedonic Images Processing.

In the process of creative sentence or phrase utilization, novel and appropriate evaluations cause the different brain responses observed in event-related potentials: the N400 reflects the novelty evaluation, whereas a late negative component marks appropriate processing. Do we have similar brain reactions in image perception when we rapidly browse pictures of objects with different novelty, functional/appropriate, and hedonic value? To explore this question, participants were presented with four novel object images with high or low functional and hedonic properties, as well as the ordinary product images, with the instruction to attentively observe and understand each image. We found a clear dissociation between processing of novelty and functional value: novelty objects produced negative deflections in the N2-N400 time window relative to the ordinary object images, whereas images with high functional value elicited a larger N2 and late negative waves (LNC) resembling the late component found for the appropriate phrases. Object images with high hedonic value, however, were associated with earlier aesthetic preference reflected in smaller N1 amplitudes, but failed to elicit a LNC effect. We therefore conclude that the processing of novelty, functional, and hedonic value are dissociation, and the perception of hedonic value is earlier (N1) than the novelty processing (N400) and the verification of functional value (LNC).

Ultrafast dynamics of exciton-polariton fluids at non-zero momenta.

In this study, we have explored the ultrafast formation and decay dynamics of exciton-polariton fluids at non-zero momenta, non-resonantly excited by a small-spot femtosecond pump pulse in a ZnO microcavity. Using the femtosecond angle-resolved spectroscopic imaging technique, multidimensional dynamics in both the energy and momentum degrees of freedom have been obtained. Two distinct regions with different decay rate in the energy dimension and various decay-channels in the momentum dimension can be well-resolved. Theoretical simulations based on the generalized Gross-Pitaevskii equation can reach a qualitative agreement with the experimental observations, demonstrating the significance of the initial potential barrier induced by the pump pulse during the decay process. The finding of our study can provide additional insights into the fundamental understanding of exciton-polariton condensates, enabling further advancements for controlling the fluids and practical applications.

Local dynamics and failure of inhomogeneous polymer networks.

Inhomogeneous crosslinked polymers are powerful platforms for materials design, because they can be synthesized from materials that provide complimentary properties to the resulting gel. For example, a membrane with both glassy and rubbery domains will be mechanically robust while enabling transport. The dynamics, and mechanical and failure properties of rubbery/glassy conetworks are only beginning to be studied, and there is likely to be strong heterogeneities in the dynamics and mechanical response. In this study, we use coarse-grained molecular dynamics simulations to generate microphase separated rubbery/glassy polymer networks with a bicontinuous morphology via in silico crosslinking. We study the effect of phase boundary on the local mobility gradient, and our simulation results reveal an asymmetric shift in the local mobility gradient across the interface that extends deeper into the phase with a lower Tg when the system temperature is between the glass transition temperatures of the two phases. Moreover, by employing a model that allows bond breaking, we examine the microscopic mechanism for failure in these networks as a function of the molecular weight of polymer strands between crosslinks and the number fraction of the glassy domain. Under uniaxial extension, we find that the stress is initially larger in the glassy domain. As the deformation proceeds, the segmental dynamics of the two phases homogenize, and subsequently bond breaking begins.

The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis.

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.

The efficacy of electroacupuncture for cervical nerve edema and movement disorder caused by the brachial plexus injury: a case report.

The brachial plexus injury (BPI) is one of the most severe types of peripheral nerve injuries, often caused by upper limb traction injury. In clinic, the surgery is widely used to treat the BPI. However, surgery may need to be performed multiple times at different stages, which carries risks and brings heavy economic burden. In non-surgical treatment, splinting, local injection of corticosteroids, and oral corticosteroids can achieve significant short-term benefits, but they are prone to recurrence and may cause complications of mechanical or chemical nerve damage. In this report, we present a case of a 46-year-old female patient with BPI. The patient had difficulty in raising, flexing and extending of the left upper limb, and accompanied with the soreness and pain of neck and shoulder. After 3 months of EA treatment, a significant reduction in the inner diameter of the left C5 to C7 root at the outlet of brachial plexus nerve was detected by musculoskeletal ultrasound, and the soreness and pain in the left neck and shoulder were significantly reduced. The soreness and pain in the left neck and shoulder did not recur for 2 years. Case summary: The patient is a 46-year-old female with BPI. She experienced difficult in lifting, flexing and extending of the left upper limb, which accompanied by soreness and pain in the left neck and shoulder. After 3 months of EA treatment, the patient's pain and limb's movement disorder was improved. After 2 years of follow-up, the patient's left neck and shoulder showed no further pain. Conclusion: EA has shown satisfied efficacy in BPI, improving limb restrictions and relieving pain in patients for at least 2 years.

Efficacy and safety of transcutaneous auricular vagus nerve stimulation (ta-VNS) in the treatment of tinnitus: protocol for an updated systematic review and meta-analysis.

INTRODUCTION: With an increasing incidence and significant effects on patients, tinnitus has become a major disease burden. There is a dearth of therapies with established efficacy for tinnitus. Transcutaneous auricular vagus nerve stimulation (ta-VNS) is being investigated as a potential therapy for tinnitus, but the current body of evidence remains inconclusive due to conflicting results across different studies. As a result, this protocol aims to synthesise and update the evidence to clarify whether ta-VNS is effective and safe for alleviating tinnitus. METHODS AND ANALYSIS: To identify relevant randomised controlled trials (RCTs), seven representative bibliographical databases will be searched from their inception to December 2023: PubMed, Embase (via OVID), Cochrane Library, Chinese National Knowledge Infrastructure, Wangfang Database, Chinese BioMedical Literature Database, and Chongqing VIP Chinese Science and Technology Periodical Database. Publications in English or Chinese will be considered for inclusion. RCTs comparing ta-VNS with active treatments, no intervention, waitlist control or sham ta-VNS in adult patients with subjective tinnitus will be included. Studies on objective tinnitus will be excluded. Primary outcome is tinnitus symptom severity measured by validated scales. With all eligible trials included, when applicable, quantitative analysis via meta-analyses will be performed using RevMan V.5.4.1 software. Otherwise, a qualitative analysis will be conducted. The methodological quality of the included RCTs will be assessed using the Risk of Bias 2.0 tool. Sensitivity analyses, subgroup analysis and publication bias evaluation will also be performed. The Grading of Recommendations, Assessment, Development, and Evaluation approach will be used to grade the certainty of the evidence. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review, as no primary data will be collected. The results will be reported and disseminated through publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022351917.

Perceived stress and brain connectivity in subthreshold depression: Insights from eyes-closed and eyes-open states.

Perceived stress is an acknowledged risk factor for subthreshold depression (StD), and fluctuations in perceived stress are thought to disrupt the harmony of brain networks essential for emotional and cognitive functioning. This study aimed to elucidate the relationship between eye-open (EO) and eye-closed (EC) states, perceived stress, and StD. We recruited 27 individuals with StD and 33 healthy controls, collecting resting state fMRI data under both EC and EO conditions. We combined intrinsic connectivity and seed-based functional connectivity analyses to construct the functional network and explore differences between EC and EO conditions. Graph theory analysis revealed weakened connectivity strength in the right superior frontal gyrus (SFG) and right median cingulate and paracingulate gyrus (MCC) among participants with StD, suggesting an important role for these regions in the stress-related emotions dysregulation. Notably, altered SFG connectivity was observed to significantly relate to perceived stress levels in StD, and the SFG connection emerges as a neural mediator potentially influencing the relationship between perceived stress and StD. These findings highlight the role of SFG and MCC in perceived stress and suggest that understanding EC and EO states in relation to these regions is important in the neurobiological framework of StD. This may offer valuable perspectives for early prevention and intervention strategies in mental health disorders.

Natural Product Quercetin-3-methyl ether Promotes Colorectal Cancer Cell Apoptosis by Downregulating Intracellular Polyamine Signaling.

Dysregulation of cellular metabolism is a key marker of cancer, and it is suggested that metabolism should be considered as a targeted weakness of colorectal cancer. Increased polyamine metabolism is a common metabolic change in tumors. Thus, targeting polyamine metabolism for anticancer therapy, particularly polyamine blockade therapy, has gradually become a hot topic. Quercetin-3-methyl ether is a natural compound existed in various plants with diverse biological activities like antioxidant and antiaging. Here, we reported that Quercetin-3-methyl ether inhibits colorectal cancer cell viability, and promotes apoptosis in a dose-dependent and time-dependent manner. Intriguingly, the polyamine levels, including spermidine and spermine, in colorectal cancer cells were reduced upon treatment of Quercetin-3-methyl ether. This is likely resulted from the downregulation of SMOX, a key enzyme in polyamine metabolism that catalyzes the oxidation of spermine to spermidine. These findings suggest Quercetin-3-methyl ether decreases cellular polyamine level by suppressing SMOX expression, thereby inducing colorectal cancer cell apoptosis. Our results also reveal a correlation between the anti-tumor activity of Quercetin-3-methyl ether and the polyamine metabolism modulation, which may provide new insights into a better understanding of the pharmacological activity of Quercetin-3-methyl ether and how it reprograms cellular polyamine metabolism.

Treating adolescent pseudomyopia and elevated intraocular pressure using chiropractic and moxibustion: A CARE-compliant case report.

RATIONALE: This case report aims to provide clinical evidence on the effectiveness of integrating chiropractic and moxibustion techniques for treating pseudomyopia accompanied by elevated intraocular pressure resulting from cervical spine issues because the application of complementary medicine modalities for managing such vision disorders currently lacks adequate investigations. PATIENT CONCERNS: A 6-year-old patient presented with blurred vision, intermittent ocular discomfort, and upper cervical discomfort. DIAGNOSES: Spine-related increased intraocular pressure and pseudomyopia. INTERVENTIONS: The patient received integrative treatment of chiropractic and walnut-shell moxibustion 3 times a week for a total of 10 treatment sessions. OUTCOMES: The patient exhibited progressive improvements in visual acuity and reductions in intraocular pressure over the treatment period, with unaided vision exceeding 2 lines of improvement in visual acuity charts and normalized intraocular pressure after 10 treatment sessions. These therapeutic effects were sustained at 3-month follow-up. LESSONS: The integrative use of chiropractic and walnut-shell moxibustion demonstrates considerable potential in alleviating symptoms of pseudomyopia, reducing intraocular pressure, and restoring visual function in spine-related pseudomyopia cases.

Application of functional near-infrared spectroscopy (fNIRS) in tinnitus research: contemporary insights and perspectives.

Tinnitus, characterized by phantom sound perception, is a highly disruptive condition lacking clearly effective treatments. Its complex neural mechanisms are not fully elucidated. Functional near-infrared spectroscopy (fNIRS) is a promising neuroimaging tool well-suited for assessing tinnitus due to its quietness, portability, and ability to directly measure cortical hemodynamic responses. This study timely summarizes the recent applications of fNIRS in investigating tinnitus pathology, correlating neuroimaging biomarkers with symptom severity, and evaluating treatment efficacy. Further studies with larger samples are warranted to reproduce existing findings. Thus, fNIRS appears to be a promising tool in tinnitus research. Addressing technical limitations, optimizing control groups, advancing data analysis, integrating standardized, and individualized experimental protocols can facilitate the extended and robust utilization of fNIRS in tinnitus research.

Professor FU Wenbin's experience of "acupuncture-moxibustion-consolidation" holistic idea in treatment of laryngeal herpes zoster with vocal cord paralysis. / 符文彬教授整合思维"一针二灸三巩固"模式治疗喉带状疱疹伴声带麻痹的临床经验.

This paper introduces professor FU Wenbin's clinical experience in the treatment of laryngeal herpes zoster with vocal cord paralysis, using the holistic mode of treatment, in which, acupuncture, moxibustion and consolidation regimens are integrated. Regarding the core pathogenesis of the disease, the invaded exogenous toxic heat is transformed into fire that flows to the throat. Soothing liver and releasing heat is the general principle of treatment, guiding the entire process of treatment. For acupuncture regimen, the filiform needling is used and the acupoint prescription is composed of Baihui (GV 20), Yintang (GV 24+), Lianquan (CV 23), the four-gate points (bilateral Hegu [LI 4] and Taichong [LR 3]), the group points for conducting qi back to the primary (Zhongwan [CV 12], Xiawan [CV 10], Qihai [CV 6] and Guanyuan [CV 4]), as well as bilateral Fengchi (GB 20), Wangu (GB 12) and Yifeng (TE 17). Besides, the pricking technique is delivered to the posterior wall of the pharynx for soothing the liver, regulating the spirit, reducing the heat and benefiting the throat. For the moxibustion regimen, moxibustion is applied to Fengchi (GB 20), Feishu (BL 13), the four-flower points (bilateral Geshu [BL 17] and Danshu [BL 19]), Shenshu (BL 23) and Mingmen (GV 4), which nourishes the spleen and stomach and reduces the heat pathogen through the heating action of moxibustion specially. In the stage of consolidation, the bloodletting and cupping technique is used at Xinshu (BL 15), Ganshu (BL 18) and Jianjing (GB 21) to eliminate the liver stagnation and the intradermal needling is delivered to sustain the needling stimulation and consolidate the therapeutic effect.

Towards provably efficient quantum algorithms for large-scale machine-learning models.

Large machine learning models are revolutionary technologies of artificial intelligence whose bottlenecks include huge computational expenses, power, and time used both in the pre-training and fine-tuning process. In this work, we show that fault-tolerant quantum computing could possibly provide provably efficient resolutions for generic (stochastic) gradient descent algorithms, scaling as [Formula: see text], where n is the size of the models and T is the number of iterations in the training, as long as the models are both sufficiently dissipative and sparse, with small learning rates. Based on earlier efficient quantum algorithms for dissipative differential equations, we find and prove that similar algorithms work for (stochastic) gradient descent, the primary algorithm for machine learning. In practice, we benchmark instances of large machine learning models from 7 million to 103 million parameters. We find that, in the context of sparse training, a quantum enhancement is possible at the early stage of learning after model pruning, motivating a sparse parameter download and re-upload scheme. Our work shows solidly that fault-tolerant quantum algorithms could potentially contribute to most state-of-the-art, large-scale machine-learning problems.

Research progress on the treatment of perimenopausal insomnia with Chaihu Jia Longgu Muli decoction based on brain-intestine-bacteria axis: A review.

With the progress and rapid societal development, women are confronted with multifaceted pressures in their lives, encompassing familial and other domains. Furthermore, during the perimenopausal phase, endocrine equilibrium is disrupted, leading to the emergence of psychological and physiological health challenges. Insomnia is a prevalent symptom among perimenopausal individuals. The brain-gut-bacteria axis assumes a pivotal role in the prevention, diagnosis, and management of perimenopausal insomnia. Chaihu Jia Longgu Muli decoction is a commonly prescribed remedy for addressing perimenopopausal insomnia. Consequently, this paper aims to investigate the interplay between the brain-gut-bacteria axis, intestinal microbiota, and the pathogenesis of perimenopausal insomnia. The study focuses on examining the regulatory effects of Chaihu Jia Longgu Muli decoction on the nervous system, intestinal microbiota, and the hypothalamus-pituitary-adrenal axis. Additionally, it explores the mechanisms underlying Hujia Longgu Muli decoction in mitigating perimenopausal insomnia.

Role of SARS­CoV­2 nucleocapsid protein in affecting immune cells and insights on its molecular mechanisms.

The present study aimed to explore the immune regulatory function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein and related mechanisms. In a series of protein activity experiments, SARS-CoV-2 N protein promoted proliferation of three immune cell lines: mouse Raw264.7, human Jurkat and human Raji in a dose-dependent manner. A total of 10 µg/ml N protein could significantly change cell cycle progression of the aforementioned three immune cell lines and could promote quick entry of Raw264.7 cells into G2/M phase from S phase to achieve rapid growth. Additionally, the N protein could also stimulate Raw264.7 cells to secrete a number of proinflammatory factors such as TNF-α, IL-6 and IL-10. RNA sequencing analysis indicated that the N protein changed the expression of certain genes involved in immune-related functions and four important signaling pathways, including JAK-STAT, TNF, NF-κB and MAPK signaling pathways, which suggested that the N protein may not only regulate the expression of genes involved in the process of resisting viral infection in macrophages of the immune system, but also change cellular signal processing.

The chemical profiling of Salvia plebeia during different growth periods and the biosynthesis of its main flavonoids ingredients.

Salvia plebeia (Lamiaceae) is a valuable medicinal plant widely distributed across Asia and Oceania. However, the composition and accumulation patterns of its active ingredients in different organs during the growth and their biosynthetic mechanism remain unknown. Therefore, we conducted metabolite profiling, transcriptomic analysis, and biological functional verification to explore the distribution, accumulation, and biosynthesis mechanisms of flavonoids in S. plebeia. We identified 70 metabolites including 46 flavonoids, 16 phenolic acids, seven terpenoids, and one organic acid, of which 21 were previously unreported in S. plebeia. Combining metabolomic-transcriptomic analysis and biological functional verification, we identified the key genes involved in biosynthesis of its main active ingredients, hispidulin and homoplantaginin, including SpPAL, SpC4H, Sp4CL2, Sp4CL5, SpCHS1, SpCHI, SpFNS, SpF6H1, SpF6OMT1, SpF6OMT2, SpUGT1, SpUGT2, and SpUGT3. Using the identified genes, we reconstructed the hispidulin and homoplantaginin biosynthesis pathways in Escherichia coli, and obtained a yield of 5.33 and 3.86 mg/L for hispidulin and homoplantaginin, respectively. Our findings provide valuable insights into the changes in chemical components in different organs of S. plebeia during different growth and harvest stages and establishes a foundation for identifying and synthesizing its active components.

Targeted inhibition of eIF5Ahpu suppresses tumor growth and polarization of M2-like tumor-associated macrophages in oral cancer.

Eukaryotic initiation factor 5A2 (eIF5A2) is overexpressed in many types of cancer, and spermidine-mediated eIF5A hypusination (eIF5Ahpu) appears to be essential to most of eIF5A's biological functions, including its important role in regulating cancer cell proliferation, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties as well as immune cell functions. Here we investigated the role of eIF5Ahpu in the growth of oral squamous cell carcinoma cells (OSCCs) and OSCC-induced polarization of M2-like tumor-associated macrophages (TAMs). TCGA dataset analysis revealed an overall upregulation in the mRNA expression of eIF5A2 and several key enzymes involved in polyamine (PA) metabolism in HNSCC, which was confirmed by Western blot and IHC studies. Blocking eIF5Ahpu by GC-7 but not the upstream key enzyme activities of PA metabolism, remarkably inhibited cell proliferation and the expression of EMT- and CSC-related genes in OSCC cells. In addition, blocking eIF5Ahpu robustly inhibited OSCC-induced M2-like TAM polarization in vitro. More Importantly, blocking eIF5Ahpu dramatically retarded tumor growth and infiltration/polarization of M2-like TAM in a syngeneic orthotopic murine tongue SCC model. Thus, eIF5Ahpu plays dual functions in regulating tumor cell growth and polarization of M2-TAMs in OSCC.

Semi-supervised OCT lesion segmentation via transformation-consistent with uncertainty and self-deep supervision.

Optical coherence tomography (OCT) is a non-invasive, high-resolution ocular imaging technique with important implications for the diagnosis and management of retinal diseases. Automatic segmentation of lesions in OCT images is critical for assessing disease progression and treatment outcomes. However, existing methods for lesion segmentation require numerous pixel-wise annotations, which are difficult and time-consuming to obtain. To address this challenge, we propose a novel framework for semi-supervised OCT lesion segmentation, termed transformation-consistent with uncertainty and self-deep supervision (TCUS). To address the issue of lesion area blurring in OCT images and unreliable predictions from the teacher network for unlabeled images, an uncertainty-guided transformation-consistent strategy is proposed. Transformation-consistent is used to enhance the unsupervised regularization effect. The student network gradually learns from meaningful and reliable targets by utilizing the uncertainty information from the teacher network, to alleviate the performance degradation caused by potential errors in the teacher network's prediction results. Additionally, self-deep supervision is used to acquire multi-scale information from labeled and unlabeled OCT images, enabling accurate segmentation of lesions of various sizes and shapes. Self-deep supervision significantly improves the accuracy of lesion segmentation in terms of the Dice coefficient. Experimental results on two OCT datasets demonstrate that the proposed TCUS outperforms state-of-the-art semi-supervised segmentation methods.

FDCT: Fusion-Guided Dual-View Consistency Training for semi-supervised tissue segmentation on MRI.

Accurate tissue segmentation on MRI is important for physicians to make diagnosis and treatment for patients. However, most of the models are only designed for single-task tissue segmentation, and tend to lack generality to other MRI tissue segmentation tasks. Not only that, the acquisition of labels is time-consuming and laborious, which remains a challenge to be solved. In this study, we propose the universal Fusion-Guided Dual-View Consistency Training(FDCT) for semi-supervised tissue segmentation on MRI. It can obtain accurate and robust tissue segmentation for multiple tasks, and alleviates the problem of insufficient labeled data. Especially, for building bidirectional consistency, we feed dual-view images into a single-encoder dual-decoder structure to obtain view-level predictions, then put them into a fusion module to generate image-level pseudo-label. Moreover, to improve boundary segmentation quality, we propose the Soft-label Boundary Optimization Module(SBOM). We have conducted extensive experiments on three MRI datasets to evaluate the effectiveness of our method. Experimental results demonstrate that our method outperforms the state-of-the-art semi-supervised medical image segmentation methods.

The upregulation of peripheral blood polyamine metabolites spermidine and spermine in children with hand, foot, mouth disease is related to enterovirus 71 capsid protein VP1, but not VP4.

Background: Hand, foot, and mouth disease (HFMD) is a common viral childhood illness caused most commonly by enterovirus 71 (EV71) and coxsackievirus A16. The pathogenesis of EV71 has been extensively studied, and the regulation of the host immune response is suspected to aggravate the serious complications induced by EV71. Our previous research showed that EV71 infection significantly increased the release of circulating interleukin (IL)-6, IL-10, IL-13, and IL-27. Notably, these cytokines are related to the EV71 infection risk and clinical stage. Polyamines are compounds that are ubiquitous in mammalian cells and play a key role in various cellular processes. Several studies have shown that targeting polyamine metabolic pathways can reduce infections caused by viruses. However, the significance of polyamine metabolism in EV71 infection remains largely unknown. Methods: Serum samples from 82 children with HFMD and 70 healthy volunteers (HVs) were collected to determine the polyamine metabolites spermidine (SPD) and spermine (SPM), and IL-6 levels. In addition, peripheral blood mononuclear cells (PBMCs) were treated with EV71 viral protein 1 (VP1) and EV71 VP4, and the cells and supernatant were then collected to analyze the expression of polyamine metabolism-related enzymes by western blot. The data were analyzed using GraphPad Prism 7.0 software (USA). Results: The serum polyamine metabolites SPD and SPM were elevated in the HFMD patients, especially in the EV71-infected children. Further, a positive correlation was found between serum SPD and IL-6 levels in the EV71-infected children. We also found that the upregulation of peripheral blood polyamine metabolites in the EV71-infected HFMD children was related to EV71 capsid protein VP1, but not VP4. VP1 may promote the expression of polyamine metabolism-related enzymes and promote the production of polyamine metabolites, thereby upregulating the SPD/nuclear factor kappa B/IL-6 signaling pathway. However, VP4 has the opposite effect in this process. Conclusions: Our results suggest that EV71 capsid protein may regulate the polyamine metabolic pathways of infected cells in a variety of ways. This study provides insights into the mechanism of EV71 infection and polyamine metabolism and has good reference value for the development of EV71 vaccine.

Development and internal validation of a prediction model to evaluate the risk of severe hemorrhage following mini-percutaneous nephrolithotomy.

PURPOSE: To develop a new prediction model for assessing the severe hemorrhage events in post mini-percutaneous nephrolithotomy (mini-PCNL) patients and internally validate it, thus to guide decision making in clinical practice. METHODS: The patients who underwent mini-PCNL were retrospectively reviewed. Potential risk factors were included as prediction variables for multivariate logistic regression analysis to identify independent risk factors, and prediction model was constructed. The predictive ability of the model was evaluated using the Concordance index (C-index) and Brier score. Bootstrapping resampling technique was used to perform internal validation. The related packages in R were used to generate the web application based on the prediction model. RESULTS: Multiple-tract was the strongest predictor of severe hemorrhage following mini-PCNL. Other risk factors were none or mild hydronephrosis, congenital anomalies of urinary system, urinary tract infection, operation time and stone peak Hounsfield unit. A prediction model was constructed to assess the probability of severe hemorrhage after mini-PCNL. The C-index and Brier score were 0.731 and 0.093, respectively after correcting for optimism, which signified the excellent discrimination and calibration. CONCLUSION: A new prediction model was developed to estimate risk of severe hemorrhage after mini-PCNL. It had been internally validated with good discrimination and calibration. The prediction model might be beneficial for endourologists in surgical decision-making and risk aversion.