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Immunotherapy directed against cancer-specific neoantigens derived from non-silent mutants is a promising individualized strategy for cancer treatment. Neoantigens shared across patients could be used as a public resource for developing T cell-based therapy. To identify potential public neoantigens for therapy in gastric cancer (GC), 74 GC patients were enrolled in this study. Combined with the TCGA cohort and other published studies, whole exome sequencing data from 942 GC patients were used to detect somatic mutations and predict neoantigens shared by GC patients. The mutations pattern between our study and the TCGA cohort is comparable, and C > T is the most common substitution. The number of neoantigens was significantly higher in older patients (age ≥60) compared to younger patients (age <60), both in this study and the TCGA cohort. Recurrent neoantigens were found in eight genes (TP53, PIK3CA, PGM5, ERBB3, C6, TRIM49C, OR4C16, and KRAS) in this study. The neoantigen-associated mutations PIK3CA (p.H1047R) and TP53 (p.R175H) are common across several cancer types, indicating their potential usage. Overall, our study illustrates a comprehensive genomic landscape of GC and provides the recurrent neoantigens to facilitate further immunotherapy. [ABSTRACT FROM AUTHOR]

Objectives. Percutaneous coronary intervention (PCI) is the mainstay treatment for coronary artery disease but complications such as in-stent restenosis and thrombosis remain problematic. Radiofrequency balloon angioplasty (RBA) can improve lumen dimension, fusing intimal tears, and artery dissection but is associated with higher restenosis rate. Methods. After establishing an atherosclerosis model based on endothelial abrasion and high cholesterol diet, forty-five rabbits were randomly divided into three groups: RBA (n=20), percutaneous transluminal angioplasty (PTA) (n=20), and control groups (n=5). The RBA and PTA groups were subdivided according to harvested time posttreatment, respectively (1 hour, 7 days, 14 days, and 28 days). Aorta segments were then isolated for hematoxylin and eosin staining, Masson trichrome staining, immunohistochemistry, and Western blot for TLR-4, NF-κB, MCP-1, and VCAM-1expression. Results. At 28 days, intimal area was significantly lower in the RBA group compared to the PTA and control groups, whilst luminal and medial area were comparable in the RBA and PTA group but higher and lower than the control group, respectively. Expression of TLR-4, NF-κB, MCP-1, and VCAM-1 showed no significant difference between RBA and PTA groups. Conclusions. RBA can depress the intimal hyperplasia and promote dilatation of the artery to greater extents than PTA at 28 days. However, this did not involve TLR-4 signaling pathway, which likely plays a negligible role in mediating restenosis. Reduction of intimal hyperplasia may be due to injury of ablation to the tunica media and inhibition of VSMC proliferation and migration. [ABSTRACT FROM AUTHOR]

Background. This study aims to identify the key genes and miRNAs in slow transit constipation (STC). Methods. MRNA and miRNA expression profiling were obtained. Differentially expressed genes (DEGs) and miRNAs were identified followed by the regulatory network construction. Functional annotation analysis and protein-protein interaction (PPI) network were conducted. The electronic validation was performed. Results. Hsa-miR-2116-3p, hsa-miR-3622a-5p, hsa-miR-424-5p, and hsa-miR-1273-3p covered most DEGs. HLA-DRB1, HLA-DRB5, C3, and ICAM were significantly involved in staphylococcus aureus infection. The PPI network generated several hub proteins including ZBTB16, FBN1, CCNF, and CDK1. Electronic validation of HLA-DRB1, PTGDR, MKI67, BIRC5, CCNF, and CDK1 was consistent with the RNA-sequencing analysis. Conclusion. Our study might be helpful in understanding the pathology of STC at the molecular level. [ABSTRACT FROM AUTHOR]

Displacement of the myotendinous junction (MTJ) obtained by ultrasound imaging is crucial to quantify the interactive length changes of muscles and tendons for understanding the mechanics and pathological conditions of the muscle-tendon unit during motion. However, the lack of a reliable automatic measurement method restricts its application in human motion analysis. This paper presents an automated measurement of MTJ displacement using prior knowledge on tendinous tissues and MTJ, precluding the influence of nontendinous components on the estimation of MTJ displacement. It is based on the perception of tendinous features from musculoskeletal ultrasound images using Radon transform and thresholding methods, with information about the symmetric measures obtained from phase congruency. The displacement of MTJ is achieved by tracking manually marked points on tendinous tissues with the Lucas-Kanade optical flow algorithm applied over the segmented MTJ region. The performance of this method was evaluated on ultrasound images of the gastrocnemius obtained from 10 healthy subjects (26.0±2.9 years of age). Waveform similarity between the manual and automatic measurements was assessed by calculating the overall similarity with the coefficient of multiple correlation (CMC). In vivo experiments demonstrated that MTJ tracking with the proposed method (CMC = 0.97±0.02) was more consistent with the manual measurements than existing optical flow tracking methods (CMC = 0.79±0.11). This study demonstrated that the proposed method was robust to the interference of nontendinous components, resulting in a more reliable measurement of MTJ displacement, which may facilitate further research and applications related to the architectural change of muscles and tendons. [ABSTRACT FROM AUTHOR]

Diabetic neuropathic pain (DNP), one of the early symptoms of diabetic neuropathy, relates to metabolic disorders induced by high blood glucose, neurotrophic vascular ischemia and hypoxia, and autoimmune factors. This study was aimed at exploring the effects of long noncoding RNA (lncRNA) BC168687 siRNA on DNP mediated by P2X7 receptor on SGCs in DRG of rats. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats, the expression levels of P2X7 mRNA and protein in the DRG, and nitric oxide (NO) in the serum were, respectively, detected in our study. Our experimental results showed that the level of BC168687 mRNA in DNP group was markedly higher than that of control group; the MWT and TWL of DNP + BC168687 si group were significantly increased, and the expression levels of P2X7 in DRG and the concentrations of NO in serum of DNP + BC168687 si group were decreased compared to those of the DNP group. In conclusion, lncRNA BC168687 may participate in the pathogenesis of DNP mediated by P2X7 receptor, which will provide a novel way for the study of the pathogenesis of diabetes mellitus complicated with neuropathic pain and its prevention and treatment. [ABSTRACT FROM AUTHOR]

CSCC is a systemic disease involving polygenic alteration and multiple steps, and HIF and VEGF are closely associated with tumorigenesis. Specimens surgically resected from 64 cases of CSCC and 22 cases of normal cervical tissue were selected randomly to detect the expression of HIF-2α and VEGF in CSCC for exploring their clinical significance; information regarding the age, lymph node metastasis, and FIGO staging were collected as well; expression of HIF-2α and VEGF was detected by qPCR and immunohistochemistry. We found that the expression of HIF-2α and VEGF mRNA in CSCC was significantly higher than that of normal cervical tissues and showed a positive correlation between them. The positive rates of HIF-2α and VEGF protein expression in CSCC and normal cervical tissues were 93.8% and 18.2%, respectively, with correlation between them. The expression of both HIF-2α and VEGF mRNA did not relate closely to age but the FIGO staging and lymph node metastasis. Compared with the counterpart control group, CSCC tissues with high FIGO staging and lymph node metastasis had a higher level of HIF-2α and VEGF mRNA expression. So, HIF-2α and VEGF were overexpressed in CSCC, which has a great clinical significance for its diagnosis. [ABSTRACT FROM AUTHOR]

This study aimed to understand the challenges that primary health care providers faced in the process of delivering mental healthcare and assess their attitudes towards patients with mental health problems. In-depth interviews were conducted among 42 primary health care providers in two counties of Guangxi province, China. All interviews were audio-recorded and analyzed thematically. Primary health care providers in both counties faced the same difficulties: lack of professional knowledge, fear of patients’ attack, more extra work, and less subsidies. However, most of primary health care providers (30/42) were still willing to do mental healthcare management. All the interviewees considered that communication skills with patients and their family members, proper attitude (without discrimination), and the professional knowledge of mental health are required. There are still several participants (15/42) who showed negative attitude toward mental disorders. Nearly all the respondents (39/42) emphasized the importance of increasing their income or subsidies by the government. This qualitative study provides insights into mental health services in rural communities of Guangxi and identified issues that could be considered in engaging primary health care providers in the management of mental disorders. [ABSTRACT FROM AUTHOR]

Recombinant proteins are primarily produced from cultures of mammalian, insect, and bacteria cells. In recent years, the development of deconstructed virus-based vectors has allowed plants to become a viable platform for recombinant protein production, with advantages in versatility, speed, cost, scalability, and safety over the current production paradigms. In this paper, we review the recent progress in the methodology of agroinfiltration, a solution to overcome the challenge of transgene delivery into plant cells for large-scale manufacturing of recombinant proteins. General gene delivery methodologies in plants are first summarized, followed by extensive discussion on the application and scalability of each agroinfiltration method. New development of a spray-based agroinfiltration and its application on field-grown plants is highlighted. The discussion of agroinfiltration vectors focuses on their applications for producing complex and heteromultimeric proteins and is updated with the development of bridge vectors. Progress on agroinfiltration in Nicotiana and non-Nicotiana plant hosts is subsequently showcased in context of their applications for producing high-value human biologics and low-cost and high-volume industrial enzymes. These new advancements in agroinfiltration greatly enhance the robustness and scalability of transgene delivery in plants, facilitating the adoption of plant transient expression systems for manufacturing recombinant proteins with a broad range of applications. [ABSTRACT FROM AUTHOR]