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"Peng, Qianwen"
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A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants
The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.
Here the authors report the isolation and structural and biological characterization of a humanized angiotensin-converting enzyme 2 (ACE2)-blocking antibody, which exterts potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages both in vitro and in hACE2 mouse model.
Journal Article
Cancer cell-expressed BTNL2 facilitates tumour immune escape via engagement with IL-17A-producing γδ T cells
Therapeutic blockade of the immune checkpoint proteins programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has transformed cancer treatment. However, the overall response rate to these treatments is low, suggesting that immune checkpoint activation is not the only mechanism leading to dysfunctional anti-tumour immunity. Here we show that butyrophilin-like protein 2 (BTNL2) is a potent suppressor of the anti-tumour immune response. Antibody-mediated blockade of BTNL2 attenuates tumour progression in multiple in vivo murine tumour models, resulting in prolonged survival of tumour-bearing mice. Mechanistically, BTNL2 interacts with local γδ T cell populations to promote IL-17A production in the tumour microenvironment. Inhibition of BTNL2 reduces the number of tumour-infiltrating IL-17A-producing γδ T cells and myeloid-derived suppressor cells, while facilitating cytotoxic CD8
+
T cell accumulation. Furthermore, we find high BTNL2 expression in several human tumour samples from highly prevalent cancer types, which negatively correlates with overall patient survival. Thus, our results suggest that BTNL2 is a negative regulator of anti-tumour immunity and a potential target for cancer immunotherapy.
Cancer cells producing ligands for the immune checkpoint molecules PD-1 and CTLA-4 is an important mechanism of tumour immune resistance. Here authors show that BTNL2 expression on cancer cells generates a dysfunctional tumour immune microenvironment via promoting IL-17A-producing γδ T cells.
Journal Article
Professional identity and sense of coherence affect the between compassion fatigue and work engagement among Chinese hospital nurses
Background
With the continuous improvement of people’s health needs, the public’s requirements for medical care are also getting higher and higher. Work engagement is a positive psychological state related to the work. It is very important to maintain nurses’ work engagement, however, due to many factors, the level of nurses’ work engagement is not high and nursing managers should identify the influencing factors of work engagement, and take positive measures to fully improve nurses’ work engagement.
Objectives
To explore the influence of compassion fatigue, professional identity and sense of coherence on nurses’ work engagement.
Methods
From January 2022 to June 2022, convenience sampling was used to select clinical nurses from 9 tertiary hospitals in Henan Province of China as the research objects for a questionnaire survey. Statistical methods included descriptive statistical analysis, Pearson correlation analysis and the PROCESS Macro Model 4 and 7 in regression analysis.
Results
The results showed that compassion fatigue was significantly negatively correlated with sense of coherence, professional identity and work engagement (
P
<0.01), professional identity was significantly positively correlated with sense of coherence and work engagement (
P
<0.01), and there was a significant positive correlation between sense of coherence and work engagement (
P
<0.01). Professional identity played a partial mediating role between compassion fatigue and work engagement, accounting for 46.40% of the total effect; meanwhile, sense of coherence moderated the effect of compassion fatigue on professional identity and formed a moderated mediation model.
Conclusions
Compassion fatigue has a negative predictive effect on nurses’ work engagement. Professional identity and sense of coherence further explained the relationship of compassion fatigue on compassion fatigue and work engagement through mediating and moderating effects.
Journal Article
TAGAP instructs Th17 differentiation by bridging Dectin activation to EPHB2 signaling in innate antifungal response
The
TAGAP
gene locus has been linked to several infectious diseases or autoimmune diseases, including candidemia and multiple sclerosis. While previous studies have described a role of TAGAP in T cells, much less is known about its function in other cell types. Here we report that TAGAP is required for Dectin-induced anti-fungal signaling and proinflammatory cytokine production in myeloid cells. Following stimulation with Dectin ligands, TAGAP is phosphorylated by EPHB2 at tyrosine 310, which bridges proximal Dectin-induced EPHB2 activity to downstream CARD9-mediated signaling pathways. During
Candida albicans
infection, mice lacking TAGAP mount defective immune responses, impaired Th17 cell differentiation, and higher fungal burden. Similarly, in experimental autoimmune encephalomyelitis model of multiple sclerosis, TAGAP deficient mice develop significantly attenuated disease. In summary, we report that TAGAP plays an important role in linking Dectin-induced signaling to the promotion of effective T helper cell immune responses, during both anti-fungal host defense and autoimmunity.
TAGAP gene variants are linked to human autoimmunity. Here the authors identify TAGAP as a Dectin-1 and EphB2-binding protein mediating antifungal innate immune signaling and cytokine production, and demonstrate TAGAP in non-T cells promotes Th17 response in mouse models of infection and autoimmunity.
Journal Article
Inpatient case characteristics of SGLT2 inhibitor-associated diabetic ketoacidosis: a retrospective study
ObjectivesDiabetic ketoacidosis (DKA) is a serious complication in patients treated with sodium-glucose co-transporter 2 inhibitors (SGLT2i). The aim of this study was to investigate the relationship between SGLT2i and the risk of DKA, and to identify high-risk groups and characteristics that should be emphasised.MethodsA retrospective case series study was conducted to collect medical records of inpatients diagnosed with DKA and using SGLT2i before the onset of the disease from September 2022 to September 2023 in a tertiary hospital in Shanghai. Cases that met the inclusion criteria were retrieved through the electronic medical record system. Information was collected to compare the risk of DKA in patients with different characteristics.ResultsA total of 21 patients (12 men and 9 women) met the criteria for SGLT2i-associated DKA. The mean diabetes duration was 10.4 years, with 47.6% (10/21) of patients diagnosed with euglycaemic DKA. The drug treatment regimen most commonly used was the combination of SGLT2i and metformin, representing 52.4% (11/21) of cases. The most common clinical symptoms were nausea, vomiting, abdominal pain and malaise. Common predisposing factors were acute infections, acute pancreatitis (predominantly hyperlipidaemic type), dietary inappropriateness, acute cardiovascular and cerebrovascular events and surgery. 71.4% of patients (15/21) had multiple risk factors.ConclusionThe use of SGLT2i in diabetic patients is associated with an increased risk of DKA, particularly in the presence of predisposing factors such as infection. Furthermore, long diabetes duration, decreased pancreatic β-cell function and the combined use of metformin may also contribute to the risk of DKA in patients treated with SGLT2i. The findings of this study provide valuable insights for better identification and management of DKA risks associated with SGLT2i in clinical practice.
Journal Article
The mediating effects of coping style and resilience on the relationship between parenting style and academic procrastination among Chinese undergraduate nursing students: a cross-sectional study
Background
How to kindle the learning enthusiasm of nursing students and reduce the incidence of academic procrastination is an important factor in reducing student attrition and improving the quality of nursing education.
Objectives
To investigate the mediating role of coping style and resilience on the association between parenting styles and academic procrastination among nursing undergraduates.
Methods
A cross-sectional study of 683 nursing undergraduates was conducted in China from March to May 2022. Parenting styles, coping style, resilience, and academic procrastination were measured using questionnaires. Descriptive analysis, Pearson’s correlation analysis and Hayes' PROCESS Macro in SPSS 25.0 were used to test the model.
Results
Positive parenting style had a significantly direct effect on academic procrastination and through three significantly indirect pathways: (1) through positive coping style (B = − 0.048, 95% CI: − 0.074 to − 0.025), accounting for 14.71% of the total effect; (2) through negative coping style (B = − 0.044, 95% CI: − 0.071 to − 0.021), accounting for 13.64% of the total effect; and (3) through resilience (B = − 0.074, 95% CI: − 0.107 to − 0.044), accounting for 22.82% of the total effect. Moreover, negative parenting style had a significantly direct effect on academic procrastination and through two significantly indirect pathways: (1) through negative coping style (B = 0.056, 95% CI: 0.032 to 0.086), accounting for 21.73% of the total effect, and (2) through resilience (B = 0.028, 95% CI: 0.004 to 0.055), accounting for 10.93% of the total effect.
Conclusions
Intervention measures to reduce the academic procrastination of nursing undergraduates should include the evaluations of coping styles and resilience of nursing students and cultivation strategies to promote their positive coping styles and resilience.
Journal Article
The association between perfectionism and academic procrastination among undergraduate nursing students: The role of self‐efficacy and resilience
This study aimed to investigate the associations between perfectionism and undergraduate nursing students' academic procrastination, the mediating effects of self-efficacy and the moderating role of resilience.
A cross-sectional survey.
The survey was conducted from March to May 2022 with a sample of 587 undergraduate nursing students in two undergraduate universities in China. A descriptive statistical approach, Pearson's correlation analysis and the Hayes' PROCESS Macro model 4 and 14 were used to analyse the available data.
Adaptive perfectionism and maladaptive perfectionism negatively and positively predicted academic procrastination in nursing undergraduates, respectively. Self-efficacy played a partially mediating role in the association between adaptive perfectionism and academic procrastination. Furthermore, resilience played a moderating role in the association between adaptive perfectionism and academic procrastination.
Maladaptive perfectionism and low levels of resilience and self-efficacy may increase the risk of academic procrastination among nursing undergraduates. Nursing educators can take measures to decrease the risk of academic procrastination among nursing undergraduate students by guiding them to cultivate adaptive perfectionism tendencies and improve their self-efficacy and resilience.
The findings of this study can be used to develop targeted coping and prevention measures for nursing educators to reduce the incidence of academic procrastination among nursing undergraduates.
Five hundred eighty-seven undergraduate nursing students from two undergraduate universities participated in the study and responded to questions on perfectionism and academic procrastination, etc.
Journal Article
A meta‐analysis on the relationship between posttraumatic growth and resilience in people with breast cancer
Aim To quantitatively synthesize the correlation between posttraumatic growth and resilience among breast cancer patients and explore the potential moderators affecting the relation. Design A meta‐analysis of cross‐sectional studies. Methods This meta‐analysis followed the Preferred Reporting Items for Systematic Review and Meta‐Analyses 2020 guidelines. This meta‐analysis was carried out by searching Chinese and English databases of China National Knowledge Infrastructure, WANFANG DATA, Chongqing VIP Information Co., Ltd., PubMed, Embase, Web of Science, and PsycINFO from inception to February 25, 2022. Pooled Pearson's correlation coefficients between posttraumatic growth and resilience was calculated by the Stata software (version 17.0) using the random effects model. Results Seventeen studies including 4156 breast cancer patients were identified. A high positive correlation was found between posttraumatic growth and resilience (r = 0.448, 95% CI: 0.370–0.519, p < 0.001), and region and publication type significantly moderated the relation.
Journal Article
Cardiologists vs Endocrinologists in Glycemic Control for Coronary Artery Disease Patients with Type 2 Diabetes: A Cross-Sectional Study
The comorbidity of coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) presents significant challenges in clinical management, particularly regarding glycemic control. The clinical management of CAD complicated by T2DM requires coordinated glycemic control, as poor management can exacerbate cardiovascular risks and increase morbidity and mortality. While endocrinologists traditionally manage diabetes, cardiologists are increasingly involved due to the cardiovascular risks associated with poor glycemic control. This study explores the current practices of glycemic management by cardiologists and endocrinologists in patients with CAD and T2DM, focusing on treatment intensification in a Chinese hospital setting.
This cross-sectional study included 1,074 hospitalized patients with both CAD and T2DM, admitted to the Cardiology Department of Ruijin Hospital between January 2021 and December 2023. Data were retrospectively collected from electronic medical records, including demographic information, clinical characteristics, and treatment interventions. Patients were stratified by year, and differences in treatment strategies between cardiologists and endocrinologists were analyzed. Glycemic control was assessed using HbA1c levels, with treatment intensification defined by any adjustment in antidiabetic therapy and consideration for comprehensive cardiovascular risk factors.
Endocrinologists were significantly more likely to initiate treatment intensification, especially in cases of severe hyperglycemia (HbA1c ≥9.0%), while cardiologists' role in glycemic management was limited, with a preference for outpatient endocrinology referrals over in-hospital adjustments. Despite improvements in glycemic control, the percentage of patients achieving comprehensive cardiovascular risk management targets remained low.
This study underscored the distinct yet complementary roles of cardiologists and endocrinologists in managing glycemic control among patients with CAD and T2DM, noting endocrinologists' more active involvement in treatment intensification. Future integrated care models should harness the unique expertise of both specialties to optimize patient outcomes, better address glycemic control needs, and enhance overall cardiovascular risk management in this high-risk patient population.
Journal Article