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Previous studies have shown that the ATP-P2X4 receptor signaling pathway mediates the activation of the Nod-like receptor family protein 3 (NLRP3) inflammasome. The NLRP3 inflammasome may promote renal interstitial inflammation in diabetic nephropathy. As inflammation also plays an important role in the pathogenesis of Parkinson’s disease, we hypothesized that the ATP-P2X4 receptor signaling pathway may activate the NLRP3 inflammasome in Parkinson’s disease. A male rat model of Parkinson’s disease was induced by stereotactic injection of 6-hydroxydopamine into the pars compacta of the substantia nigra. The P2X4 receptor and the NLRP3 inflammasome (interleukin-1β and interleukin-18) were activated. Intracerebroventricular injection of the selective P2X4 receptor antagonist 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one (5-BDBD) or knockdown of P2X4 receptor expression by siRNA inhibited the activation of the NLRP3 inflammasome and alleviated dopaminergic neurodegeneration and neuroinflammation. Our results suggest that the ATP-P2X4 receptor signaling pathway mediates NLRP3 inflammasome activation, dopaminergic neurodegeneration, and dopamine levels. These findings reveal a novel role of the ATP-P2X4 axis in the molecular mechanisms underlying Parkinson’s disease, thus providing a new target for treatment. This study was approved by the Animal Ethics Committee of Qingdao University, China, on March 5, 2015 (approval No. QYFYWZLL 26119).

Abstract Background Sepsis is a potentially fatal systemic inflammatory response syndrome (SIRS) that threatens millions of lives worldwide. Echinococcus granulosus antigen B (EgAgB) is a protein released by the larvae of the tapeworm. This protein has been shown to play an important role in modulating host immune response. In this study we expressed EgAgB as soluble recombinant protein in E. coli (rEgAgB) and explored its protective effect on sepsis. Methods The sepsis model was established by cecal ligation and puncture (CLP) procedure in BALB/c mice. The therapeutic effect of rEgAgB on sepsis was performed by interperitoneally injecting 5 µg rEgAgB in mice with CLP-induced sepsis and observing the 72 h survival rate after onset of sepsis. The proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-6] and regulatory cytokines [IL-10, transforming growth factor beta (TGF-β)] were measured in sera, and the histopathological change was observed in livers, kidneys, and lungs of septic mice treated with rEgAgB compared with untreated mice. The effect of rEgAgB on the macrophage polarization was performed in vitro by incubating rEgAgB with peritoneal macrophages. The levels of TLR2 and MyD88 were measured in these tissues to determine the involvement of TLR-2/MyD88 in the sepsis-induced inflammatory signaling pathway. Results In vivo, we observed that treatment with rEgAgB significantly increased the survival rate of mice with CLP-induced sepsis up to 72 h while all mice without treatment died within the same period. The increased survival was associated with reduced pathological damage in key organs such as liver, lung, and kidneys. It was supported by the reduced proinflammatory cytokine levels and increased regulatory cytokine expression in peripheral blood and key organ tissues. Further study identified that treatment with rEgAgB promoted macrophage polarization from classically activated macrophage (M1) to regulatory M2-like macrophage via inhibiting TLR2/MyD88 signal pathway. Conclusions The therapeutic effects of rEgAgB on mice with sepsis was observed in a mice model that was associated with reduced inflammatory responses and increased regulatory responses, possibly through inducing polarization of macrophages from proinflammatory M1 to regulatory M2 phenotype through inhibiting TLR2/MyD88 inflammatory pathway. Graphical Abstract

Urinary cell-free DNA (UcfDNA) is gaining recognition as an important biomarker for diagnosing bladder cancer. UcfDNA contains tumor derived DNA sequences, making it a viable candidate for non-invasive early detection, diagnosis, and surveillance of bladder cancer. The quantification and qualification of UcfDNA have demonstrated high sensitivity and specificity in the molecular characterization of bladder cancer. However, precise analysis of UcfDNA for clinical bladder cancer diagnosis remains challenging. This review summarizes the history of UcfDNA discovery, its biological properties, and the quantitative and qualitative evaluations of UcfDNA for its clinical significance and utility in bladder cancer patients, emphasizing the critical role of UcfDNA in bladder cancer diagnosis. Emerging bioactive technologies and materials currently offer promising tools for multiple UcfDNA analysis, aiming to achieve more precise and efficient capture of UcfDNA, thereby significantly enhancing diagnostic accuracy. This review also highlights breakthroughs in detection technologies and substrates with the potential to revolutionize bladder cancer diagnosis in clinic.

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSVA) and B (HRSVB) of HRSV. Next, the Pyrococcus furiosus Argonaute (PfAgo) protein utilizes small 5’-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/μL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSVA and HRSVB infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings.

Pancreatic cancer is a highly malignant tumor known for its extremely low survival rate. The combination of genetic disorders within pancreatic cells and the tumor microenvironment contributes to the emergence and progression of this devastating disease. Extensive research has shed light on the nature of the microenvironmental cells surrounding the pancreatic cancer, including peripheral nerves and immune cells. Peripheral nerves release neuropeptides that directly target pancreatic cancer cells in a paracrine manner, while immune cells play a crucial role in eliminating cancer cells that have not evaded the immune response. Recent studies have revealed the intricate interplay between the nervous and immune systems in homeostatic condition as well as in cancer development. In this review, we aim to summarize the function of nerves in pancreatic cancer, emphasizing the significance to investigate the neural-immune crosstalk during the advancement of this malignant cancer.

Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury. This study aimed to decipher the dynamics of systemic immune responses, initiated by spinal cord injury. The spinal cord in mice was completely transected at T8. Changes in the in vivo inflammatory response, between the acute and subacute stages, were observed. A rapid decrease in C-reactive protein levels, circulating leukocytes and lymphocytes, spleen-derived CD4+ interferon-γ+ T-helper cells, and inflammatory cytokines, and a marked increase in neutrophils, monocytes, and CD4+CD25+FOXP3+ regulatory T-cells were observed during the acute phase. These systemic immune alterations were gradually restored to basal levels during the sub-acute phase. During the acute phase of spinal cord injury, systemic immune cells and factors showed significant inhibition; however, this inhibition was transient, and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase. All experiments were performed in accordance with the institutional animal care guidelines, approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital, China (approval No. 2019AE01040) on June 25, 2019.

Abstract Background This study aims to provide a systematic compilation of existing measures of self-efficacy developed specifically for use in cancer patients and provide descriptions and comparative evaluations of the characteristics, psychometric properties and performance parameters. Method A systematic electronic database search was conducted in PubMed, Ovid (PsyINFO), EBSCO, Elsevier, Scopus to identify self-efficacy assessment tools for cancer patients, between January 1977 to February 2018. The characteristics of target population, instrument, development process and psychometric properties were summarized. All included instruments were subsequently appraised using a psychometric quality assessment tool based on previous publications. Validity of the quality assessment was reviewed and confirmed by five experts. Results Fifteen cancer-related self-efficacy instruments were identified. Among them, (40.0%) 6/15 were task-specific, focusing on cancer-related health issues such as fatigue, communication, rehabilitation, exercise, and narcotic pain killer usage. Six instruments were disease-specific for breast cancer, lung cancer, or advanced cancer. Weaknesses of the development processes included the singularity of instrument construction methods, and non-transparent selection of the final items. The main limitation seen in the validation processes was that some important properties of instruments (e.g. test-retest reliability, criterion validity, responsiveness, interpretability, feasibility, and acceptability) were not evaluated. Conclusions This review summarizes the limitations and strengths of current self-efficacy instruments for cancer patient. The information reported here can assist clinicians and researchers in the selection of the appropriate instrument. Finally, it points out the need for reporting validation statistics to facilitate the use of these instruments.

Objectives: To examine Chinese nurses' practice of reading and understanding scientific literature and elucidate the motivating and deterring factors. Methods: This is a cross-sectional study conducted between March and June 2015. A random sample of 853 full-time registered nurses from three tertiary and two secondary hospitals in China filled out a set of self-administered questionnaires, including literature habit questionnaire(41 items), the situational motivation scale and the socio-demographic and professional characteristics questionnaire(15 items). Results: Significant majority (89.2%) of the respondents reported perception of barriers to keeping up to date with literature. The language barrier was the most prominent, followed by poor presentation and readability of articles. Using simpler language when writing articles, improving ones' foreign language proficiency and getting education or training on nursing research were raised as the top facilitators. Additionally, reading and understanding literature was significantly associated with the nurses' educational background, motivation, genders and work settings. Conclusions: The survey of the current status of literature education among Chinese nurses suggests that providing protected time, training for critical thinking, and incentive mechanisms will help improve nurses' engagement in literature and create a culture of academic inquiry.

Objective: The platelet-to-lymphocyte ratio (PLR) is a new marker of atherosclerotic inflammation and has been identified as a predictive factor in cardiovascular diseases, but its significance in patients with acute ischaemic stroke (AIS) who have undergone intravenous thrombolysis (IVT) is still unknown.Methods: Consecutive patients who were treated with IVT using recombinant tissue plasminogen activator (rtPA) for AIS were included from May 2012 to August 2018. The PLR was calculated according to platelet and lymphocyte counts within 24 h after thrombolysis therapy. Functional outcomes were assessed by the modified Rankin Scale (mRS) at 3 months after thrombolysis. Stroke severity was assessed by National Institutes of Health Stroke Scale (NIHSS) scores. The primary endpoint was an unfavorable outcome (mRS > 2), and the secondary endpoint was death at 3 months.Results: A total of 286 patients were included in the study. The median age was 69.5 (59.0–80.0) years, and 59.1% of patients were men. A total of 120 (42.0%) patients had an unfavorable outcome, and 38 (13.2%) died. Patients with an unfavorable outcome had significantly higher PLR values compared with those with a favorable outcome [172.5 (105.3–239.0) vs. 139 (97.0–194.5), P = 0.008], and the PLR values of the patients who died at 3 months were higher than those of the surviving patients [189.5 (127.5–289.0) vs. 142.0 (98.0–215.5), P = 0.006]. After adjustment for other variables, the PLR was independently associated with the two endpoints: unfavorable outcome (OR 2.220, 95% CI 1.245–3.957, P = 0.007) and death (OR 2.825, 95% CI 1.050–7.601, P = 0.040) at 3 months after thrombolysis. In addition, PLR was correlated with the NIHSS score (R = 0.230, P < 0.001).Conclusions: Higher PLR levels were independently associated with an unfavorable outcome and death at 3 months in AIS patients treated with IVT.

The aims of this article are to investigate the effects of Th22 and Th17 cells and plasma cytokines in patients with nonalcoholic fatty liver disease (NAFLD) and to examine the correlation between Th22 and Th17 cells levels and disease progression. Blood samples from 70 patients with NAFLD and 26 healthy controls (HCs) were collected. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were performed. ELISA revealed interleukin (IL)-22 plasma level in FibroScan subgroup patients was 2.2-fold higher than that in the HCs ( P

Since the early 1980s, the one-child policy has been implemented nationwide in China. A special group called the "only-child-lost family" (OCL family) has emerged and has become a social phenomenon that cannot be ignored. We report latent profiles of posttraumatic growth and their relation to differences in resilience among OCL people in China.A total of 222 OCL people were investigated using the Posttraumatic Growth Inventory and the Connor-Davidson Resilience Scale. Latent profile analysis was applied to explore PTG latent profiles. Multinomial logistic regression was used to analyze the socio-demographic variables in each latent profile and the association between profile membership and resilience.Three latent profiles were identified and labeled the "high appreciation-power group" (30.6%), the "general moderate growth group" (47.7%) and the "low growth and extreme possibility group" (21.7%). Compared to those in the high appreciation-power group, individuals with monthly income >2000 ($312) were less likely to be in the general moderate growth group (OR = 0.13, P