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Please see manuscript PDF for full abstract with equations.We consider the following semiclassical generalized quasilinear Schr\"{o}dinger equation\begin{equation*}-\varepsilon^2\text{div} (g^2(v)\nabla v)+\varepsilon^2g(v)g'(v)|\nabla v|^2+V(x)v=f(v), \quad x\in \mathbb{R}^{N},\end{equation*} where $V\in C^1(\mathbb{R}^N)$ is bounded and $f$ is odd in $v$ and satisfies a monotonicity condition. We establish the existence of multiple localized solutions concentrating at the set of critical points of $V$.

Objective To evaluate the effect and safety of acupuncture for the treatment of irritable bowel syndrome (IBS) through comparisons with those of polyethylene glycol (PEG) 4000 and pinaverium bromide. Patients and Methods This multicenter randomized controlled trial was conducted at 7 hospitals in China and enrolled participants who met the Rome III diagnostic criteria for IBS between May 3, 2015, and June 29, 2018. Participants were first stratified into constipation-predominant or diarrhea-predominant IBS group. Participants in each group were randomly assigned in a 2:1 ratio to receive acupuncture (18 sessions) or PEG 4000 (20 g/d, for IBS-C)/pinaverium bromide (150 mg/d, for IBS-D) over a 6-week period, followed by a 12-week follow-up. The primary outcome was change in total IBS-Symptom Severity Score from baseline to week 6. Results Of 531 patients with IBS who were randomized, 519 (344 in the acupuncture group and 175 in the PEG 4000/ pinaverium bromide group) were included in the full analysis set. From baseline to 6 weeks, the total IBS-Symptom Severity Score decreased by 123.51 (95% CI, 116.61 to 130.42) in the acupuncture group and 94.73 (95% CI, 85.03 to 104.43) in the PEG 4000/pinaverium bromide group. The between-group difference was 28.78 (95% CI, 16.84 to 40.72; P Conclusion Acupuncture may be more effective than PEG 4000 or pinaverium bromide for the treatment of IBS, with effects lasting up to 12 weeks. Trial Registration Chinese Clinical Trials Register, ChiCTR-IOR-15006259.

Introduction: Diabetic nephropathy (DN) is the leading cause of kidney failure worldwide. To explore the pathogenesis and effective biological target of DN is beneficial to seeking novel treatment strategies. Objective: This study aimed to investigate the role of the lncRNA Dlx6os1/SOX6/EZH2 axis in DN progression. Methods: PAS staining was performed to evaluate extracellular matrix accumulation; ELISA was carried out to assess the levels of urine microalbumin and blood glucose concentration; RT-qPCR was carried out to detect the levels of lncRNA Dlx6os1, TNF-α, IL-1β, IL-6, SOX6, and EZH2. Western blot was performed to assess the levels of Col-IV, FN, TGF-β1, and SOX6 proteins. RIP assay was carried out to verify the interaction between lncRNA Dlx6os1 and EZH2. ChIP-qPCR was conducted to verify the interaction between EZH2 and SOX6 promoter. Results: Our results illustrated that lncRNA Dlx6os1 was highly expressed in DN mice and HG-induced SV40 MES13 cells. LncRNA Dlx6os1 knockdown inhibited HG-induced SV40 MES13 cell proliferation, fibrosis, and inflammatory cytokine release. LncRNA Dlx6os1 inhibited SOX6 expression by recruiting EZH2 in HG-SV40 MES13 cells, and SOX6 mediated the effects of lncRNA Dlx6os1 on proliferation, fibrosis, and inflammatory factor release of HG-induced SV40 MES13 cells. Conclusion: LncRNA Dlx6os1 accelerates the progression of DN by epigenetically repressing SOX6 via recruiting EZH2.

Distribution of SARS-CoV-2 virus and pathological features of multiple organs in COVID-19 patients remains unclear, which interferes with the improvement of COVID-19 diagnosis and treatment. In this article, we summarize the pathological findings obtained from systematic autopsy (37 cases) and percutaneous multiple organ biopsy (“minimally invasive autopsy”, 54 cases). These findings should shed light on better understanding of the progression of COVID-19 infection and the means of more effective intervention.

With the rapid development of high-throughput sequencing technology and computer science, the amount of large omics data has increased exponentially, the advantages of multi-omics analysis have gradually emerged, and the application of artificial intelligence has become more and more extensive. In this review, we introduce the application progress of multi-omics data analysis and artificial intelligence in the medical field in recent years, and also show the cases and advantages of their combined application. Finally, we briefly explain the current challenges of multi-omics analysis and artificial intelligence in order to provide new research ideas for the medical industry and to promote the development and application of precision medicine.随着高通量测序技术和计算机科学的飞速发展,组学数据量指数倍增长,多组学分析优势逐渐显现,人工智能应用也愈加广泛。本文介绍了近年来多组学数据分析和人工智能各自在医学领域的应用进展,同时也介绍了两者相结合应用的案例以及优势,最后简单阐述多组学分析和人工智能在现阶段面临的挑战,旨在为医学行业提供新的研究思路,助推精准医学发展应用。.

To explore the bidirectional regulation of acupuncture based on a subgroup analysis of multicenter randomized controlled trial of acupuncture withA total of 519 patients were included in the analysis, including 137 patients with constipation type irritable bowel syndrome (IBS-C) (92 cases in the acupuncture group and 45 cases in the polyethylene glycol [PEG] group), and 382 patients with diarrhea type irritable bowel syndrome (IBS-D) (252 cases in the acupuncture group and 130 cases in the pinaverium group). The patients in the acupuncture group were given acupuncture at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) once every other day, 3 times a week. The patients in the PEG group received polyethylene glycol 4000 powder orally, and the pinaverium group received pinaverium bromide tablets orally. All were treated for 6 weeks. The IBS symptom severity score (IBS-SSS) was assessed at baseline, treatment period (2, 4, 6 weeks of treatment) and 12 weeks of follow-up, and the IBS quality of life (IBS-QOL) score was evaluated at the baseline period, 6 weeks of treatment and 12 weeks of follow-up.The total IBS-SSS scores of the two groups of IBS-C patients at 2, 4, 6 weeks of treatment and follow-up of 12 weeks were lower than those in the baseline period (Acupuncture with

To compare the curative effect on diarrhea-predominant irritable bowel syndrome (IBS-D) between acupuncture for regulatingA total of 231 patients with IBS-D were randomized into an acupuncture group (154 cases) and a western medication group (77 cases) at the ratio of 2 to 1. In the acupuncture group, acupuncture was applied to acupoint regimen for regulatingAfter treatment and in follow-up, the total scores of IBS-SSS in the patients of the two groups were all reduced as compared with those before treatment (Acupuncture for regulating

We consider the following quasilinear Schrodinger equation \begin{document} $ - \Delta u + V(x)u - \Delta ({u^2})u = q(x)g(u),\;\;\;\;x \in {\mathbb{R}^N}, $ \end{document} where \begin{document}$N≥ 1$\end{document} , \begin{document}$0 , \begin{document}$g∈ C(\mathbb{R}^+, \mathbb{R})$\end{document} and \begin{document}$g(u)/u^3 \to 1$\end{document} , as \begin{document}$u \to ∞.$\end{document} We establish the existence of a positive solution to this problem by using the method developed in Szulkin and Weth [ 27 , 28 ].

We consider the following equation $$\begin{aligned} -\Delta u+u=Q_n(x)|u|^{p-2}u, \quad x\in {\mathbb {R}}^{N}, \end{aligned}$$ where $$Q_n$$ are concrete bounded functions whose self-focusing core $$\text{ supp }\, Q_n^+$$ shrinks to a finite set of points as $$n\rightarrow \infty $$ . We investigate the limiting profile of concentration for the ground state solutions and construct localized bound state solutions of concentration type.

In this article we study the following quasilinear Schrodinger equation \begin{document}$-Δ u+V(x)u-Δ(u^{2})u=g(u), x∈ \mathbb{R}^{N},$ \end{document} where \begin{document}$ V(x)$\end{document} tends to some limit \begin{document}$V_{∞}>0 $\end{document} as \begin{document}$|x|\to∞ $\end{document} and \begin{document}$g∈ C(\mathbb{R},\mathbb{R}) $\end{document} . We prove the existence of positive solutions by using the Nehari manifold.

Background: Apatinib is an oral small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Some clinical trials have demonstrated that apatinib is efficacious against advanced nonsquamous NSCLC. Objective: This study aimed to probe efficacy and safety of apatinib plus docetaxel, as the second or above line treatment, in advanced nonsquamous NSCLC. Design: Multicenter, prospective, single arm study. Setting: Three teaching hospitals centers in the Sichuan. Participants: Fourteen patients with stage IVA/B nonsquamous NSCLC had previously received at least 1 platinum-based chemotherapy regimen. Intervention: Patients who were enrolled between November 2016 and January 2018 were given docetaxel (75 mg/m2, i.v., d1) plus oral apatinib (250 mg/d), 4 weeks as one cycle, until disease progression or intolerance to adverse events (AE). Main outcome measures: The primary endpoint was progression-free survival (PFS). The secondary endpoints comprised objective response rate (ORR), disease control rate (DCR), overall survival (OS), and AE incidence rate. Results: All patients carried adenocarcinoma by pathological type. The median follow-up duration was 9.76 months. Out of 14 cases, 12 were evaluable, showing ORR of 33.33%, DCR of 66.67%, DCR of 50% in cases with brain metastasis, median PFS of 2.92 months (95% CI: 1.38–4.48), and 6-month OS of 80%. Primary AEs encompassed: leukopenia in 7 cases (58.33%), hand-foot skin reaction in 5 cases (41.67%), and diarrhea in 4 cases (33.33%). Among them, grade 3 AEs were: leukopenia in 4 cases (33.33%), and hand-foot skin reaction in 1 case (8.33%). No grade 4/5 AEs were reported. Univariate and multivariate analysis were conducted respectively for PFS and OS. These factors encompassed: gender, age, gene mutations, clinical stage, ECOG scores, quantity of metastatic foci, brain metastasis, and hand-foot skin reaction. Results demonstrated zero risk factors for PFS or OS. Conclusion: Apatinib plus docetaxel, as the second or above line treatment, is effective and safe against advanced nonsquamous NSCLC, with good tolerance profile. Trial registration: NCT03416231.

We are concerned with the following Schrodinger–Poisson systems $$\begin{aligned} \left\{ \begin{array}{l@{\quad }l} -\Delta u+u+K(x)\phi (x)u=q(x)f(u), &{}\quad x\in {\mathbb {R}}^3, \\ -\Delta \phi =K(x)u^2, &{} \quad x\in {\mathbb {R}}^3, \end{array} \right. \end{aligned}$$ where f is asymptotically cubic, $$\lim _{|x|\rightarrow \infty }K(x)=0$$ and $$\lim _{|x|\rightarrow \infty }q(x)=q_{\infty }>0$$ . We establish the existence of bound state solutions to this problem by using the method developed in Szulkin and Weth [20, 21].

Gene editing technologies are used to specifically edit the target sequence. With the development of zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), regular clustering of short palindrome repeats (CRISPR) and single base editing (BE) techniques, gene editing technologies not only provide powerful tools for gene functional studies, but also offer new therapeutic strategies in biomedical research. Gene editing has demonstrated broad application prospects in the gene therapy field, as well as in the construction of animal and cell models, drug target screening and gene functional research. In this review, we summarize several typical gene editing technologies, their characteristics and applications in gene therapy and discusses their opportunities and challenges in gene therapy, thereby providing critical insights and references on the clinical application of gene editing technologies.

Krüppel-like factors (KLFs) regulate diverse physiological processes such as the differentiation and development of red blood cells. However, it remains unclear whether KLFs exhibit synergistic regulatory effects. Transcriptomic data from our previous study showed that KLF1 and KLF9 expression was significantly higher in differentiated red blood cells than in hematopoietic stem cells. In the present study, we manipulated KLF1 and KLP9 gene expression by overexpressing or knocking down KLF1 and KLF9 in K562 cells and revealed a positive correlation between the expression of KLF1 and KLF9; their co-expression can significantly promote erythroid differentiation and specifically enhance β-globin gene expression. Further, we analyzed the transcriptome data of K562 cells with altered KLF1/KLF9 levels and found that KLF1 and KLF9 synergistically regulated erythroid differentiation through the PI3K-Akt and FoxO signaling pathways. KLF1 and KLF9 may exert this synergistic effect through FOS, TF, and IL8 in K562 cells. We have provided evidence that KLF1 and KLF9 play a synergistic role in regulating erythroid differentiation.

With the development of the omic technologies, the acquisition approaches of various biological data on different levels and types are becoming more mature. As a large amount of data will be produced in the process of diagnosis and treatment of diseases, it is necessary to utilize the artificial intelligence such as machine learning to analyze complex, multi-dimensional and multi-scale data and to construct clinical decision support tools. It will provide a method to figure out rapid and effective programs in diagnosis and treatment. In this process, the choice of artificial intelligence seems to be particularly important, such as machine learning. The article reviews the type and algorithm of machine learning used in clinical decision support, such as support vector machines, logistic regression, clustering algorithms, Bagging, random forests and deep learning. The application of machine learning and other methods in clinical decision support has been summarized and classified. The advantages and disadvantages of machine learning are elaborated. It will provide a reference for the selection between machine learning and other artificial intelligence methods in clinical decision support.

We consider the following quasilinear Schrödinger equation [Formula: see text] where [Formula: see text], [Formula: see text], and [Formula: see text] satisfies a weaker growth condition than the Ambrosetti–Rabinowitz type condition in Byeon and Wang [Standing waves with a critical frequency for nonlinear Schrödinger equations, Arch. Ration. Mech. Anal. 165(4) (2002) 295–316; Standing waves with a critical frequency for nonlinear Schrödinger equations, II, Calc. Var. 18(2) (2003) 207–219]. We obtain the existence of the localized bound state solutions concentrating at an isolated component of the local minimum of [Formula: see text] and whose amplitude goes to 0 as [Formula: see text].

In this paper we are concerned with the quasilinear Schrödinger equation −Δu + V(x)u − Δ(u2)u = q(x)|u|p−2u, x ∈ ℝN, where N ≥ 3, 4 < p < 4N/(N − 2), and V(x) and q(x) go to some positive limits V∞ and q∞ respectively as |x| → ∞. Under a weak one-sided asymptotic estimate for V(x) and q(x) at infinity, we obtain the existence of a ground state solution.

Long noncoding RNAs (lncRNAs) are a class of non-protein coding transcripts exceeding 200 nucleotides in length. Accumulating evidence achieved by several sophisticated techniques such as chromatin conformation capture and RNA-seq has led to new questions concerning correlations between lncRNAs and chromatin structures. Many studies have revealed that lncRNAs exert great influences on gene expression through regulating chromatin 3D structures. In addition, lncRNAs play a crucial role in tumorigenesis and therefore hold great promises in disease diagnosis and prognosis. Here, we mainly focus on introducing how lncRNAs regulate gene expression by modulating nuclear architecture and discussing clinical values of lncRNAs in oncotherapy.

Liquid biopsy is an emerging and promising detection tool for cancer, with the benefit of being non-invasive and convenient. It analyzes tumor-derived information in the blood or other body fluids including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA) and exosomes. Nowadays, with the expansion of liquid biopsy research contents and the development of capture and detection technologies, liquid biopsy is increasingly utilized in clinical applications, promoting the development of tumor precision medicine. Here, we mainly focus on reviewing the objects and technologies about liquid biopsy, as well as its applications, development and challenges in clinical practices.

Aims Ischemia reperfusion (I/R) injury is an inevitable event arising during the cardiovascular diseases development and the process of potent surgical treatments. microRNAs (miRNAs) are critical regulators of multiple cell processes including I/R injury. The present study aims to quantify miRNA alterations and regulated genes upon hypoxia-reoxygenation (H/R) injury in a rat heart failure model comparing with normal cardiomyocytes. Main methods Chronic heart failure was established by injecting doxorubicin (2 mg/kg/week) for 6 weeks, then H/R was performed on primary cultured cardiomyocytes isolated from normal and failed heart. Cellular injury was evaluated by detecting LDH release levels, cell variability and apoptotic rate. Dysregulated miRNAs in control, hypoxia preconditioning (HPC) and morphine preconditioning (MPC) groups under two conditions were quantified by microarray analysis. Fas protein expression was analyzed using Western Blotting analysis. Key findings Chronic heart failure was confirmed with lower ejection fraction (EF), and significant cellular injury. HPC could reverse the injury induced by H/R in normal heart rather than failed heart, otherwise, MPC significantly attenuated cellular injury dose dependently in both conditions. There was 12 miRNAs significantly altered after doxorubicin injection, 7 downregulated and 5 upregulated. miR-133b-5p, miR-6216, miR-664-1-5p and let7e-5p were differentially expressed after HPC and MPC treatments. The direct interaction between miR-133b-5p and target gene Fas were established. The Fas protein expression was manipulated by MPC not HPC affording protective effect against H/R injury. Significance We investigated that miR-133b-5p might play a particularly important role in the cardioprotective effect of MPC by regulating the target gene Fas.

With the development and improvement of high-throughput sequencing technologies, the acquisition and processing approaches of various biological omics data on different levels are becoming more mature. Despite several new disease-associated factors have been discovered based on single omics data analysis, identification of disease targets by integrative analysis of multi-omics data is still growing. Since life is a complex regulatory system in which the regulation of gene mutations, epigenetic alterations, abnormal gene expression as well as anomalous variations in signal pathway are related with the occurrence and development of diseases, it is obvious that finding therapeutic factors using single omics data analysis has its limitation. Systematical studies of clinical and pathological mechanisms and identification of optimal therapeutic targets through integrative analysis of multi-omics data from different levels and resources have become an important research direction of precision medicine, which would provide innovative perspectives on disease study and new theoretical basis for early diagnosis, personalized treatment and medicine guide. In this review, we introduce new technologies and research progresses in screening therapeutic targets using systematic omics such as genomics, transcriptomics and epigenomics, and also discusse new strategies and advantages of integrative analysis among them.

Melanoma is a malignant cutaneous cancer of high metastasis and lethal rates. Epithelial-mesenchymal transition (EMT) plays an important role in the embryonic developmental process that is often activated during tumorigenesis and metastasis. In this study, we integrated of mRNA and miRNA transcriptome sequencing data of melanocyte and melanoma cell lines to identify genes involved in the process of tumor EMT in the first place, and uncovered 11 miRNAs including miR-130a-3p, miR-130b-3p, miR-125a-5p, miR-30a-3p, miR-195-5p, miR-345-5p, miR-509-3-5p, miR-374a-5p, miR-509-5p, miR-148a-3p and miR-330-3p, negatively related with EMT genes using the Mirsystem software. Bioinformatics analysis with target genes of these miRNAs revealed two networks closely related with cellular development and cell-to-cell interactions, as well as multiple signaling pathways participating in EMT. Validation of the 11 miRNAs with molecular biology experiments demonstrated that four miRNAs regulated oncogenes in melanomas, including miR-195-5p, miR-130a-3p, miR-509-5p, and miR-509-3-5p. Our study integrates two kinds of omics data to screen for EMT-related miRNAs, providing a new research idea in the precision genomics of cancer research.

e21213Background: There is no effective treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) who experienced progression with one or two lines of chemotherapy. Apatinib,...