COVID-19 increases extracorporeal coagulation during hemodialysis associated with upregulation of vWF/FBLN5 signaling in patients with severe/critical symptoms.

BACKGROUND: COVID-19 has been shown to increase the risk of extracorporeal coagulation during hemodialysis in patients, but the underlying mechanism remains unclear. This study aimed to investigate the effect and mechanism of COVID-19 on the risk of extracorporeal coagulation in patients with chronic kidney disease undergoing hemodialysis. METHODS: A retrospective analysis of the extracorporeal coagulation status of 339 hemodialysis patients at our center before and after COVID-19 infection was performed, including subgroup analyses. Post-infection blood composition was analyzed by protein spectrometry and ELISA. RESULTS: Compared to the pre-COVID-19 infection period, COVID-19-induced extracorporeal coagulation predominantly occurred in patients with severe/critical symptoms. Further proteomic analysis demonstrated that in patients with severe/critical symptoms, the coagulation cascade reaction, platelet activation, inflammation, and oxidative stress-related pathways were significantly amplified compared to those in patients with no/mild symptoms. Notably, the vWF/FBLN5 pathway, which is associated with inflammation, vascular injury, and coagulation, was significantly upregulated. CONCLUSIONS: Patients with severe/critical COVID-19 symptoms are at a higher risk of extracorporeal coagulation during hemodialysis, which is associated with the upregulation of the vWF/FBLN5 signaling pathway. These findings highlight the importance of early anticoagulant therapy initiation in COVID-19 patients with severe/critical symptoms, particularly those undergoing hemodialysis. Additionally, vWF/FBLN5 upregulation may be a novel mechanism for virus-associated thrombosis/coagulation.

Pyroptosis and the tumor immune microenvironment: A new battlefield in ovarian cancer treatment.

Ovarian cancer is a less common tumor in women compared to cervical or breast cancer, however it is more malignant and has worse outcomes. Ovarian cancer patients still have a five-year survival rate < 50% despite advances in therapy. Due to recent developments in immune checkpoint inhibitors (ICIs), cancer immunotherapy has attracted increased interest. Pyroptosis is a highly inflammatory form of cell death, which is essential for bridging innate and adaptive immunity, and is involved in immune regulation within the tumor microenvironment (TME). Recent research has shown that pyroptosis can promote immunotherapy of ovarian cancer, including treatment with chimeric antigen receptor T-cells (CAR-T) or ICIs. Moreover, inflammasomes, various signaling pathways and lncRNAs can all affect pyroptosis in ovarian cancer. Here we discuss how pyroptosis affects the development and progression of ovarian cancer as well as the TME. We also provide a summary of small molecule drugs that could target pyroptotic cell death processes and may be useful in ovarian cancer therapy.

Effects of a death education based on narrative pedagogy in a palliative care course among Chinese nursing students.

Background: Death education has been confirmed to be an effective method to enhance nursing students' attitudes and coping abilities toward death. However, integrated Narrative Pedagogy into the death education to explore educational effectiveness is still limited. The study aimed to evaluate the effects of a death education based on Narrative Pedagogy in a palliative care course on the attitude toward death, coping with death, and attitude toward caring for the dying among undergraduate nursing students in China. Methods: The study was designed as a pre-post intervention study with a quasi-experimental design. All the participants received 6 class hours of death education which was designed in a palliative care course. The death education includes preparation, presentation, discussion, reflection, and practice of the narrative materials. Death Attitude Profile-Revised (DAP-R), Coping with Death Scale (CDS), and Frommelt Attitude Toward Care of the Dying-Form B (FATCOD-Form B) were used to measure outcomes. Results: Sixty undergraduate nursing students who consented. There were statistically significant increases in the mean score of neutral acceptance and approach acceptance in the DAP-R, CDS, and FATCOD-Form B before and after the intervention. Conclusion: This death education integrated Narrative Pedagogy which indicated to improve attitude toward death, competence to cope with death, and attitude toward the care of dying patients. The findings assist teachers in understanding the importance and urgency of death education, as well as providing a favorable approach to death education. However, the long-term effectiveness still needs to study in further.

Trends in metabolic indicators and microvascular complications in Chinese adults with newly diagnosed type 2 diabetes: A retrospective, single-centre study of twenty-years.

BACKGROUND: The purpose of this study is to assess metabolic indicators and trends in microvascular complications among Chinese adults with newly diagnosed type 2 diabetes during 2000-2020. METHODS: 3,907 patients were included and divided into three groups according to a time period of 7 years. This study analyzed trends in proportions of patients reached therapeutic targets of blood glucose, pressure and lipids, and trends in albuminuria, retinopathy, and peripheral neuropathy. RESULTS: In the past 20 years, the age of adults with newly diagnosed type 2 diabetes tended to be younger, and the proportion of female patients increased. There seemed no improvements in blood glucose and pressure. The rate of awareness and treatment on target of hypertension was less than 50%. There was a significant decrease in the prevalence of retinopathy, but no changes in nephropathy or peripheral neuropathy. Complications were more common for patients who were smoker, male, or with hypertension and obesity. CONCLUSIONS: Over the past two decades, there have been encouraging reductions in retinopathy in Chinese adults with newly diagnosed diabetes, but no significant change in albuminuria and peripheral neuropathy. It may be related to the low awareness of diabetes and insufficient controlled blood glucose, pressure and lipids on target.

FTO promotes the progression of cervical cancer by regulating the N6-methyladenosine modification of ZEB1 and Myc.

Cervical cancer is a malignant tumor of the cervix in women. However, the pathogenesis of cervical cancer has not been fully understood. N6-methyladenosine (m6A) is a kind of RNA modification that plays a critical role in cancer development. We aim to find out the possible m6A regulatory mechanism of the fat mass and obesity-associated protein (FTO) on the development of cervical cancer. The proliferative capacity of cervical cancer cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), colony formation and 5-ethynyl-20-deoxyuridine (EdU) staining. The migration and invasion of cervical cancer cells were determined by transwell assay. The function of FTO on tumor growth was evaluated by a xenograft model. We found that FTO was highly expressed in cervical cancer tissues and cell lines. FTO silencing suppressed the proliferation, migration, and invasion of cervical cancer cells. Mechanistically, FTO modulated the m6A modification of Zinc finger E-box binding homeobox 1 (ZEB1) and Myelocytomatosis oncogene (Myc). Furthermore, ZEB1 and Myc overexpression reverse the effect of FTO knockdown on the malignant behaviors of cervical cancer cells. FTO may be a novel therapeutic target for cervical cancer.

Rational targeting of autophagy in colorectal cancer therapy: From molecular interactions to pharmacological compounds.

The abnormal progression of tumors has been a problem for treatment of cancer and therapeutic should be directed towards targeting main mechanisms involved in tumorigenesis in tumors. The genomic mutations can result in changes in biological mechanisms in human cancers. Colorectal cancer is one of the most malignant tumors of gastrointestinal tract and its treatment has been faced some difficulties due to development of resistance in tumor cells and also, their malignant behavior. Hence, new therapeutic modalities for colorectal cancer are being investigated. Autophagy is a "self-digestion" mechanism that is responsible for homeostasis preserving in cells and its aberrant activation/inhibition can lead to tumorigenesis. The current review focuses on the role of autophagy mechanism in colorectal cancer. Autophagy may be associated with increase/decrease in progression of colorectal cancer due to mutual function of this molecular mechanism. Pro-survival autophagy inhibits apoptosis to increase proliferation and survival rate of colorectal tumor cells and it is also involved in cancer metastasis maybe due to EMT induction. In contrast, pro-death autophagy decreases growth and invasion of colorectal tumor cells. The status of autophagy (upregulation and down-regulation) is a determining factor for therapy response in colorectal tumor cells. Therefore, targeting autophagy can increase sensitivity of colorectal tumor cells to chemotherapy and radiotherapy. Interestingly, nanoparticles can be employed for targeting autophagy in cancer therapy and they can both induce/suppress autophagy in tumor cells. Furthermore, autophagy modulators can be embedded in nanostructures in improving tumor suppression and providing cancer immunotherapy.

Characteristics and occupational risk assessment of occupational silica-dust and noise exposure in ferrous metal foundries in Ningbo, China.

Introduction: To investigate the major existing occupational hazards and to assess the occupational health risks for ferrous metal foundries (FMFs) in Ningbo, China. Methods: Unified questionnaires were formulated to investigate the information on the basic situations, occupational hazards, and occupational health management for 193 FMFs in Ningbo. Furthermore, we used the semi-quantitative risk assessment model, which was developed by the International Council on Mining and Metals (ICMM), to assess occupational health risks for 59 of 193 the FMFs. Results: The casting process of FMFs in Ningbo was mainly divided into sand casting and investment casting, and silica-dust and noise were the major occupational hazards in both sand casting and investment casting foundries. Silica-dust mainly occurred in industries with such work as sand handling, modeling, falling sand, and sand cleaning, with the median of the permissible concentration-time weighted average (PC-TWA) was 0.80, 1.15, 3.52, 0.83 mg/m3, respectively. The noise mainly existed in industries with such work as sand handling, core making, falling sand, sand cleaning, cutting and grinding, and smelting with median of PC-TWA was 81.72 dB(A), 82.93 dB(A), 90.75 dB(A), 80.18 dB(A), 90.05 dB(A), 82.70 dB(A), respectively. In addition, the results of the ICMM assessment model indicated that 100 and 98.7% of the jobs exposed to silica-dust and noise in 59 FMFs have an "intolerable risk" level of risks of causing pneumoconiosis and noise deaf, respectively. Discussion: The hazard risk of silica-dust and noise is serious for FMFs in Ningbo. It is necessary to supervise enterprises to improve operating environmental conditions, accelerate the reduction of silica-dust and noise exposure risks, and promote the healthy and sustainable development of the foundry industry.

[Correlation Between Controlling Nutritional Status Scores and Amputation Risks in Patients with Diabetic Foot Ulcers].

Objective: To retrospectively analyze the clinical features and treatment outcomes of patients with diabetic foot ulcers (DFU), and to investigate the effect of controlling nutritional status (CONUT) scores on the amputation risks and hospital length-of-stay of DFU patients. Methods: A total of 357 DFU inpatients admitted to the Department of Endocrinology, PLA Strategic Support Force Characteristic Medical Center between January 1, 2016 and December 31, 2018 were enrolled and analyzed retrospectively. Based on their CONUT scores, the patients were divided into 3 groups, a normal nutritional status group consisting of patients with CONUT scores 0-1 ( n=100), a mild malnutrition group consisting of patients with CONUT scores 2-4 scores ( n=164), and a moderate-to-severe malnutrition group consisting of patients with CONUT scores≥5 ( n=93). According to whether they underwent amputation, patients were divided into an amputation group ( n=110) and a non-amputation group ( n=247). The clinical characteristics, amputation rate, and hospital length-of-stay were compared between groups with different CONUT scores. Logistic regression was conducted to analyze the independent risk factors of amputation. Results: The total amputation rate of DFU patients was 30.6%. Among all amputations, the major amputation (above-the-ankle amputation) rate was 1.8%, and the minor amputation rate was 98.2%. The amputation rate in patients with mild and moderate-to-severe malnutrition were 1.5 and 3.0 times higher than those in the normal nutritional status group, respectively. Logistic regression analysis showed that the moderate-to-severe nutritional status (5-12 scores), white blood cell, Wagner classification and ankle-brachial index were independent risk factors for amputation. Conclusion: CONUT score is closely associated with amputations in DFU patients. Improving the nutritional status of patients in the early stage could reduce the risk of amputation.

The Prognosis of Diabetic Foot Ulcer is Independent of age? A Comparative Analysis of the Characteristics of Patients with Diabetic Foot Ulcer in Different age Groups: A Cross-Sectional Study from China.

Background: With younger onset age of type 2 diabetes mellitus (T2DM), the incidence of diabetic foot ulcer (DFU) in young and middle-aged adults is also increasing. Elucidating the distinctive characteristics of DFU in different ages and exploring the influence of age on the prognosis of DFU are crucial to the improvement of DFU treatments. Methods: 684 patients hospitalized for DFU in the department of endocrinology were recruited and assigned into the young and middle-aged group (age <65 years old) and the elderly group (age ≥65 years old). Demographic data and clinical features were compared between two groups. Results: Compared with the elderly group, the young and middle-aged group had higher proportion of males (72.3% vs 49.6%, P < .01) and smokers (52.5% vs 35.8%, P < .01), shorter duration of diabetes mellitus (155 months vs 196 months, P < .01), higher levels of glycosylated hemoglobin (9.3% vs 8.7%, P < .01), lower ratio of ankle-brachial index <0.9 (25.8% vs 51.1%, P < .01) and higher levels of c-reactive protein and erythrocyte sedimentation rate (14 mg/L vs 10 mg/L, P < .05; 36 mm/h vs 30 mm/h, P < .05). The prevalence of diabetic peripheral neuropathy and Wagner Grade were similar in two groups. Of note, the prognosis was similar in different age groups, as there were no significant differences in the healing rate (59.7% vs 60.1%, P > .05), healing time (30 days vs 22 days, P > .05) and minor amputation rate (11.9% vs 8.7%, P > .05). Conclusions: We found that no evidence to suggest a better prognosis with younger DFU patients. Compared with elderly ones, young and middle-aged patients were characterized by a higher proportion of smoking, worse glycemic control, higher inflammatory biomarkers but less severe lower limb ischemia, indicating that smoking cessation, strict blood glucose control and early detection of infection were crucial for improving the prognosis of young and middle-aged diabetic DFU patients.

Blocking TIGIT/CD155 signalling reverses CD8+ T cell exhaustion and enhances the antitumor activity in cervical cancer.

OBJECTIVE: TIGIT/CD155 has attracted widespread attention as a new immune checkpoint and a potential target for cancer immunotherapy. In our study, we evaluated the role of TIGIT/CD155 checkpoints in the progression of cervical cancer. METHODS: The expression of CD155 and TIGIT in cervical cancer tissues was detected using flow cytometry, immunohistochemistry (IHC) and gene expression profiling. In vivo and in vitro experiments have proven that blocking TIGIT/CD155 restores the ability of CD8+ T cells to produce cytokines. Changes in the NF-κB and ERK pathways were detected using western blotting (WB) after blocking TIGIT/CD155 signalling. RESULTS: TIGIT expression was elevated in patients with cervical cancer. High TIGIT expression in CD8+ T lymphocytes from patients with cervical cancer promotes the exhaustion of CD8+ T lymphocytes. In addition, CD155 is expressed at high levels in cervical cancer tissues and is negatively correlated with the level of infiltrating CD8+ T cells. We found that TIGIT, upon binding to CD155 and being phosphorylated, inhibited NF-κB and ERK activation by recruiting SHIP-1, resulting in the downregulation of cytokine production. Blocking TIGIT in activated CD8+ T cells attenuates the inhibitory effect of SHIP-1 on CD8+ T cells and enhances the activation of NF-κB and ERK. In vivo and in vitro experiments have proven that blocking TIGIT/CD155 restores the ability of CD8+ T cells to produce cytokines. Injecting the blocking antibody TIGIT in vivo inhibits tumour growth and enhances CD8+ T lymphocyte function. Treatment with a combination of TIGIT and PD-1 inhibitors further increases the efficacy of the TIGIT blocking antibody. CONCLUSIONS: Our research shows that TIGIT/CD155 is a potential therapeutic target for cervical cancer.

Exploring midwifery students' experiences of professional identity development during clinical placement: A qualitative study.

BACKGROUND: Healthy China 2030 has proposed to strengthen the investment in midwifery education to prepare more qualified midwives to address the shortage of midwifery workforce in China. The formation of a strong professional identity has been demonstrated to be a vital enabler for successfully transitioning from university to work. As midwifery is a practice-based profession, clinical placement is a key period for midwifery students' professional identity development, where they can be part of the profession and exposed to professional behaviour and interaction in the real world. However, it has not yet been explored in terms of the professional identity development of midwifery students in China during clinical placement. AIM: To gain insight into the professional identity development experiences of midwifery students in China during clinical placement. DESIGN: A qualitative study using a descriptive phenomenological approach. METHODS: Semi-structured interviews were conducted with fourteen final-year midwifery students who were undertaking clinical placement in four public hospitals in central China between March 2021 and May 2021. The transcribed data were analyzed following the Colaizzi's phenomenological analysis method. RESULTS: A total of one category, two theme clusters and seven themes emerged. The overarching category "conflicting experiences of professional identity development" was identified from the interaction of two theme clusters, "positive experiences motivating professional identity development" and "negative experiences impeding professional identity development". Four themes including "feeling the sense of accomplishment for facilitating smooth births", "developing professional competence", "positive role models of clinical mentors", and "cooperative inter-professional relationships" fell into the theme cluster of "positive experiences motivating professional identity development"; while the other three themes including "high-intensity working state", "emotional instability of birthing women", and "feeling insufficient in professional competence" fell into the theme cluster of "negative experiences impeding professional identity development". CONCLUSIONS: The conflicting experiences of professional identity development among midwifery students might lead to the emergence of confusion and further decrease their retention intention in the profession. Thus, intervention strategies should be adopted to promote midwifery students' professional identity development during clinical placement, so as to prepare confident and motivated midwives to provide high-quality maternal care and address the shortage of midwifery workforce in China.

Human umbilical cord-derived mesenchymal stem cells alleviate insulin resistance in diet-induced obese mice via an interaction with splenocytes.

BACKGROUND: Previous research has demonstrated that the spleen plays an important role in mesenchymal stem cell (MSC)-mediated alleviation of acute inflammation, as MSC infusion increases the spleen-derived anti-inflammatory cytokine interleukin 10 (IL-10) levels. However, studies on splenic involvement in MSC-induced protection against chronic inflammatory diseases are limited. Obesity is characterized by chronic low-grade inflammation, a key driver of insulin resistance. This study aims to evaluate the effects of MSCs on obesity-related insulin resistance and explore the underlying mechanism, particularly regarding splenic involvement. METHODS: We induced obesity in mice by feeding them high-fat diets for 20 weeks. Human umbilical cord-derived MSCs (UC-MSCs) were systemically infused into the obese mice once per week for 6 weeks. Systemic glucose metabolic homeostasis and insulin sensitivity in epididymal adipose tissue (EAT) were evaluated. Then, we conducted in vivo blockade of IL-10 during UC-MSC infusion by intraperitoneally administrating an IL-10-neutralizing antibody twice per week. We also investigated the therapeutic effects of UC-MSCs on obese mice after removal of the spleen by splenectomy. RESULTS: UC-MSC infusions improved systemic metabolic homeostasis and alleviated insulin resistance in EAT but elicited no change in weight. Despite rare engraftment of UC-MSCs in EAT, UC-MSC infusions attenuated insulin resistance in EAT by polarizing macrophages into the M2 phenotype, coupled with elevated serum IL-10 levels. In vivo blockade of IL-10 blunted the effects of UC-MSCs on obese mice. Furthermore, UC-MSCs overwhelmingly homed to the spleen, and the ability of UC-MSCs to elevate serum IL-10 levels and alleviate insulin resistance was impaired in the absence of the spleen. Further in vivo and in vitro studies revealed that UC-MSCs promoted the capacity of regulatory T cells (Treg cells) to produce IL-10 in the spleen. CONCLUSIONS: Our results demonstrated that UC-MSCs elevated serum IL-10 levels and subsequently promoted macrophage polarization, leading to alleviation of insulin resistance in EAT. The underlying mechanism was that UC-MSCs improved the capacity of Treg cells to produce IL-10 in the spleen. Our findings indicated that the spleen played a critical role in amplifying MSC-mediated immunomodulatory effects, which may contribute to maximizing MSC efficacy in clinical applications in the future.

Construction and practice of a comprehensive nursing skills course with simulation in an RN-BSN program in China: a quasi-experimental study.

BACKGROUND: Simulation has been widely used in the teaching of pre-licensed nursing students and has shown positive results. However, there is limited evidence regarding the application of a comprehensive nursing course with simulation for Associated Degree in Nursing (ADN)-prepared nurses with different work experience times. Therefore, this study aimed to evaluate the satisfaction, self-confidence, and perceptions of scenario simulation among Chinese nurses in a comprehensive nursing skills course in an RN-BSN program. METHODS: A single-group post-test approach was used in the current study. Participants that completed a comprehensive nursing skills course with simulation in an RN-BSN program were enrolled. RESULTS: The mean satisfaction, self-confidence, educational practice, and simulation designs scores were rated highly. Self-confidence (p = 0.002), active learning (p = 0.020), collaboration (p = 0.030), support (p = 0.008), and problem-solving (p = 0.007) were significantly higher among students with more work experience compared to those with less experience. Then, four themes were analyzed: enthusiasm for learning, ability to experience different feelings during role-play, hybrid teaching format, and simulation fidelity. CONCLUSIONS: Results demonstrated that a comprehensive nursing skills course with simulation might improve Chinese ADN-prepared nurses' satisfaction and self-confidence in learning. Nurses with work experience gave a high rate to the scenario simulation, demonstrating that simulation can be widely applicable for students with different characteristics. Finally, the teaching strategy in the present study can be applied to more RN-BSN programs.

Cervical cancer-derived exosomal miR-663b promotes angiogenesis by inhibiting vinculin expression in vascular endothelial cells.

BACKGROUND: Angiogenesis provides essential nutrients and oxygen for tumor growth and has become the main mechanism of tumor invasion and metastasis. Exosomes are nanoscale membrane vesicles containing proteins, lipids, mRNA and microRNA (miRNA), which mediate intercellular communication and play an important role in tumor progression. Accumulated evidence indicates that tumor-derived exosomal miRNAs participate in the tumor microenvironment and promote angiogenesis. METHODS: Bioinformatic target prediction and dual luciferase reporter assays were performed to identify the binding site between miR-663b and the 3'-UTR of vinculin (VCL). VCL overexpression lentivirus and miR-663b overexpression/inhibition lentivirus were used to create a VCL overexpression model and miR-663b overexpression/inhibition model in-vitro. Immunohistochemistry (IHC) assays and western blot assays were used to detect protein expression. Exosome-cell cocultures, wound healing assays, tube formation assays and transwell assays were used to measure the migration and tube formation ability of vascular endothelial cells [human umbilical vein endothelial cells (HUVECs)]. siRNA targeted VCL was used to knockdown VCL. RESULTS: In the present study, we found that miR-663b was elevated in cervical cancer tissue and exosomes. miR-663b could bind the 3'-UTR of VCL and inhibit its expression. VCL is downregulated in cervical cancer, and decreased VCL has a negative correlation with a high level of miR-663b. Further studies demonstrated that exosomes secreted by cervical cancer cells can deliver miR-663b to HUVECs and inhibit the expression of VCL, thereby promoting angiogenesis and tumor growth. CONCLUSIONS: miR-663b derived from cancer cell exosomes acts as a driving factor for angiogenesis and a potential target of antiangiogenic therapy in cervical cancer. Our findings illustrated a new signaling pathway, including exosomes, miRNAs and target genes, which provides potential targets for antiangiogenic therapy.

The effects of flipped classroom characterized by situational and collaborative learning in a community nursing course: A quasi-experimental design.

BACKGROUND: Since traditional teaching could not help to develop competences, flipped classroom has caught the sight of researchers. Despite the uptake of flipped classroom in other disciplines, there is a dearth of evidence available about the use in nursing curricula. In addition, there is no consensus on how to best implement a flipped classroom. OBJECTIVE: This study aimed to (1) develop a flipped classroom underpinned by constructivism theory and (2) to verify its effectiveness. DESIGN: This study adopted a quasi-experimental design. SETTING AND PARTICIPANTS: This study was conducted in 2018 spring semester at a University in East China with 6th semester undergraduate nursing students in four parallel classes in Community Nursing Course. METHODS: A flipped classroom characterized by situational and collaborative learning was developed and carried out with two classes (intervention group, n = 98). In-class lectures was applied for the other two classes (control group, n = 90). Course examination score, experience (course experience questionnaire, CEQ), and students' appraisal were used to verify the effectiveness of flipped classroom. RESULTS: Compared to control group, the examination score was higher for intervention group. As for the four domains of CEQ, good teaching domain rating was lower, learning burden domain rating was higher for the intervention group. There was no statistical difference in classroom quality and harvest domains. More students in intervention group chose the course helped them in developing "critical thinking" and "self-cognition and evaluation" abilities. Satisfaction rating of groups was not statistically different. CONCLUSIONS: Flipped classroom was efficient in improving students' academic performance and promoting development of higher-level thinking abilities; however, it failed in improving students' satisfaction and course experience. These findings suggest that active learning strategies such as situational and collaborative learning of group problem solving and discussion should be integrated into nursing curriculum and refinement to flipped classroom are needed to create students' buy-in.

CD155 Promotes the Progression of Cervical Cancer Cells Through AKT/mTOR and NF-κB Pathways.

Expression of the immunoglobulin superfamily member CD155 was increased in a variety of human malignancies, but the role of CD155 in tumorigenesis and tumor development in cervical cancer has not been elucidated. In this study, immunohistochemistry and enzyme-linked immunosorbent assay analyses showed that CD155 expression gradually increases with the degree of cervical lesions. In vitro and in vivo, reducing the expression of CD155 inhibited cell proliferation, cell viability and tumor formation and arrested the cell cycle in G0/G1 phase. Antibody array-based profiling of protein phosphorylation revealed that CD155 knockdown can inhibited the AKT/mTOR/NF-κB pathway and activated autophagy and apoptosis; the opposite effects were observed upon CD155 has overexpression. We proved that there is an interaction between CD155 and AKT by immunoprecipitation. We further confirmed the mechanism between CD155 and AKT/mTOR/NF-κB through rescue experiments. AKT knockdown reversed the anti-apoptotic effects and activation of the AKT/mTOR/NF-κB pathway induced by CD155 overexpression. Our research demonstrated that CD155 can interact with AKT to form a complex, activates the AKT/mTOR/NF-κB pathway and inhibit autophagy and apoptosis. Thus, CD155 is a potential screening and therapeutic biomarker for cervical cancer.

KDM2A Targets PFKFB3 for Ubiquitylation to Inhibit the Proliferation and Angiogenesis of Multiple Myeloma Cells.

The lysine demethylase KDM2A (also known as JHDM1A or FBXL11) demethylates histone H3 at lysine K36 which lead to epigenetic regulation of cell proliferation and tumorigenesis. However, many biological processes are mediated by KDM2A independently by its histone demethylation activity. In the present study, we aimed to characterize the functional significance of KDM2A in multiple myeloma (MM) disease progression. Specifically, we defined that one of the key enzymes of glycolysis PFKFB3 (6-phosphofructo-2-kinase) is ubiquitylated by KDM2A which suppresses MM cell proliferation. Previous study showed that KDM2A and PFKFB3 promoted angiogenesis in various tumor cells. We further reveal that KDM2A targets PFKFB3 for ubiquitination and degradation to inhibit angiogenesis. Several angiogenic cytokines are also downregulated in MM. Clinically, MM patients with low KDM2A and high PFKFB3 levels have shown worse prognosis. These results reveal a novel function of KDM2A through ubiquitin ligase activity by targeting PFKFB3 to induce proliferation, glycolysis and angiogenesis in MM cells. The data provides a new potential mechanism and strategy for MM treatment.

An evaluation of mental health and emotion regulation experienced by undergraduate nursing students in China during the COVID-19 pandemic: A cross-sectional study.

The COVID-19 outbreak negatively impacted the mental health and emotions of many individuals. The study presented here explores the mental health and emotion regulation experienced by undergraduate nursing students in China during the pandemic. Potential risk factors related to negative mental health symptoms were identified in this study. An online cross-sectional study including 342 respondents was performed from March 6, 2020, to April 1, 2020, at a University in China. A Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Emotion Regulation Questionnaire (ERQ) were used to evaluate mental health and emotions. The statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 22. The prevalence of anxiety, depression, or comorbid anxiety and depression were 55.0%, 56.4%, and 31.6%, respectively. The mean score of cognitive reappraisal and expressive suppression was 29.36 ± 8.00 and 15.55 ± 5.14. Lower scores for cognitive reappraisal and higher scores for expressive suppression were susceptible to symptoms of anxiety, depression, or comorbid anxiety and depression. Issues with mental health occurred in nursing students during the COVID-19 pandemic. Findings from this study provide a better understanding of the association between mental health and emotion regulation, which will help direct psychological intervention that relieves these issues during the pandemic.

Effect of ketamine on mood dysfunction and spatial cognition deficits in PTSD mouse models via HCN1-BDNF signaling.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a debilitating mental disease with high morbidity and major social and economic relevance. No efficient treatment for PTSD has thus far been identified. Clinical research has shown that ketamine can rapidly alleviate symptoms in patients with chronic PTSD; however, its pharmacological mechanism has yet to be determined. METHODS: This study aimed to identify a model of single prolonged stress (SPS), which induced PTSD-like features in adult mice. Once the model was established, stress-related behavioral changes in the mouse model were evaluated after intraperitoneal injection of ketamine (10 mg/kg). Alterations in certain proteins (HCN1, BDNF, and PSD95) and synaptic ultrastructure in the prefrontal cortex (PFC) and hippocampus (HIP) were measured. RESULTS: The mice under the SPS model exhibited anxiety- and depression-like behaviors and induced spatial cognitive deficits, accompanied by elevated HCN1 protein expression in the PFC and HIP, reduced brain-derived neurotrophic factor (BDNF) and PSD95 proteins, and alterations in synaptic morphology. After ketamine administration, the SPS-treated mice restored their protein levels and synaptic ultrastructure in the PFC, and their PTSD-like behaviors improved. However, learning and memory in the SPS-treated mice did not improve in the water maze test, and no significant changes in protein level and synaptic ultrastructure in the HIP were shown. LIMITATIONS: The electrophysiological mechanism of the HCN1 ion channel after ketamine administration was not explored. CONCLUSION: Ketamine could generally improve SPS-induced mood dysfunction in mice but exerted no effect on the spatial cognitive function, which could be related to the alterations in synaptic morphology and function mediated by HCN1-related BDNF signaling in the PFC and HIP.