INTRODUCTION: In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus emerged and caused a worldwide pandemic, leading to measures being imposed by many countries to reduce its transmission. Singapore implemented the 'circuit breaker', which restricted all movements except for access to necessities and healthcare services. We aimed to investigate the impact of lockdown measures on the pattern of trauma and its effects. METHODS: An observational, retrospective, single-centre descriptive study was conducted using the trauma registry in Singapore General Hospital. It included patients above 18 years old who presented to the emergency department with trauma and were subsequently admitted. Patients admitted from 1 February 2020 to 31 July 2020 and those admitted during the same timeframe in 2019 were studied. Subgroup analyses were performed for patients aged ≥65 years and those <65 years. RESULTS: A total of 1,037 patients were included for analysis. A 17.6% increase in trauma presentations was seen from 2019 to 2020. Patients aged ≥65 years accounted for the rise in admissions. The predominant mechanism of injury was falls at home for older patients and vehicular accidents in patients <65 years. There were no significant differences in injury severity score, intensive care/high-dependency unit admission rates, length of stay, mortality rate, and subsequent need for inpatient rehabilitation. CONCLUSION Our study provided information on differences in trauma presentations before and during the COVID-19 pandemic. Further studies are required to better inform on additional precautionary measures needed to reduce trauma and improve safety during future lockdowns and pandemics.
Humans ; COVID-19/prevention & control* ; Aged ; Retrospective Studies ; Singapore/epidemiology* ; Male ; Female ; Wounds and Injuries/epidemiology* ; Aged, 80 and over ; Middle Aged ; SARS-CoV-2 ; Hospitalization/statistics & numerical data* ; Adult ; Emergency Service, Hospital/statistics & numerical data* ; Registries ; Accidental Falls/statistics & numerical data* ; Pandemics ; Patient Admission/statistics & numerical data* ; Length of Stay ; Accidents, Traffic/statistics & numerical data*

Objective To investigate the expression of Follistatin-like 3(FSTL3)protein in lung adenocarcinoma(LUAD)tissue and its association with clinical pathological indicators and prognosis.Methods A total of 268 LUAD patients who underwent radical resection of lung cancer were collected,and the expression of FSTL3 protein in LUAD and paired paracancerous normal tissues was detected using immunohistochemistry.The clinical pathological indicators and overall survival(OS)rate were compared among patients with different levels of FSTL3 expression.Cox regression model was used to analyze the influencing factors of postoperative OS in LUAD patients.Results The high expression rate of FSTL3 protein in LUAD tissue(55.97％)was significantly higher than that in paracancerous tissues(33.21％)(x2=28.098,P＜0.001).The expression level of FSTL3 protein showed significant differences among LUAD patients with different degrees of differentiation,lymph node metastasis,distant metastasis,and TNM stage(all P＜0.05).The OS rate of patients with high FSTL3 protein expression was significantly lower than that of patients with low expression(x2=4.706,P=0.030).Cox regression analysis indicated that lymph node metastasis,distant metastasis,TNM stages Ⅲ,and high expression of FSTL3 were independent risk factors affecting postoperative OS in LUAD patients(all P＜0.05).Conclusion The expression of FSTL3 protein significantly increased in LUAD tissue,and it was associated with tumor differentiation,lymph node metastasis,distant metastasis,and TNM stage.High expression of FSTL3 was an independent risk factor affecting the postoperative prognosis of LUAD patients.FSTL3 protein has the potential to become a biomarker for early diagnosis and prognostic prediction of LUAD.

This study aims to investigate the role and specific mechanisms of HO1 in mitigating lung inflammation after RSV infection.An RSV-infected mouse model was established,and lung tissues were collected for RNA-seq and differential gene expression analysis.HE staining and BALF cell counting were used to observe inflammation in the mouse lung tissues.Changes in HO1 expression were detected through immunohistochemistry,Western blotting,and qRT-PCR;inflammatory cytokine levels were assessed using qRT-PCR.HEMIN target proteins were predicted and analyzed by underwent GO and KEGG enrichment test;ROS levels in alveolar epithelial cells were measured using flow cytometry and immunofluorescence.Lysosomal changes were observed using transmission electron microscopy.The results demonstrated that HO1 expression was upregulated in the lung tissues of RSV-infected mice.Inducing HO1 expression alleviated lung tissue pathology,and lowered inflammatory cytokines IL-6 and TNF-α levels.RSV infection promoted ROS release and accumulation in lung epithelial cells,leading to an increase in autolysosomes.The induction of HO1 expression facilitated ROS clearance and reduced the number of autolysosomes.Therefore,the protective effect of HO 1 against oxidative stress reduces intracellular ROS generation,maintains organelle homeostasis,and reducing inflammatory cytokine IL-6,IL-8 and CXCL-10 levels.

Helicobacter pylori(Hp)is a common Gram-negative bacillus causing gastrointestinal infec-tions.It mainly exists on the surface of gastric epithelial cells and in mucus and is associated with gastric ulcers,gastric cancer,and gastric mucosa-associated lymphomas.Studies have shown that Hp can induce or exacerbate certain extragastric diseases and is associated with the occurrence of coronavirus disease 2019.It is hypothesized that Hp may be indirectly or directly involved in the occurrence and development of diseases by stimulating the production of inflammatory cytokines or inducing cross-immune reactions.In addition,Hp can enter Candida to release toxins continuously and play a role in escaping the recognition of the host immune system and the bacteri-cidal effect of drugs.This article reviews the research progress in Hp-associated extragastric diseases in recent years,aiming to draw the attention of clinical workers to Hp-associated extragastric diseases and enrich the knowledge about Hp infection for formulating countermeasures to avoid the aggravation or triggering of other disea-ses by Hp.

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Mice ; Animals ; Spiral Ganglion/physiology* ; Cochlea/physiology* ; Neurons

INTRODUCTION: The burden of frequent attenders (FAs) of emergency departments (EDs) on healthcare resources is underestimated when single-centre analyses do not account for utilisation of multiple EDs by FAs. We aimed to quantify the extent of multiple ED use by FAs and to characterise FAs. METHODS: We reviewed nationwide ED attendance in Singapore data from 1 January 2006 to 31 December 2018 (13 years). FAs were defined as patients with ≥4 ED visits in any calendar year. Single ED FAs and multiple ED FAs were patients who attended a single ED exclusively and ≥2 distinct EDs within the year, respectively. Mixed ED FAs were patients who attended a mix of a single ED and multiple EDs in different calendar years. We compared the characteristics of FAs using multivariable logistic regression. RESULTS: We identified 200,130 (6.3%) FAs who contributed to1,865,704 visits (19.6%) and 2,959,935 (93.7%) non-FAs who contributed to 7,671,097 visits (80.4%). After missing data were excluded, the study population consisted of 199,283 unique FAs. Nationwide-linked data identified an additional 15.5% FAs and 29.7% FA visits, in addition to data from single centres. Multiple ED FAs and mixed ED FAs were associated with male sex, younger age, Malay or Indian ethnicity, multiple comorbidities, median triage class of higher severity, and a higher frequency of ED use. CONCLUSION A nationwide approach is needed to quantify the national FA burden. The multiple comorbidities and higher frequency of ED use associated with FAs who visited multiple EDs and mixed EDs, compared to those who visited a single ED, suggested a higher level of ED burden in these subgroups of patients. The distinct characteristics and needs of each FA subgroup should be considered in future healthcare interventions to reduce FA burden.
Comorbidity ; Emergency Service, Hospital ; Ethnicity ; Humans ; Logistic Models ; Male ; Retrospective Studies ; Triage

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

INTRODUCTION: Early reperfusion of ST-segment elevation myocardial infarction (STEMI) results in better outcomes. Interventions that have resulted in shorter door-to-balloon (DTB) time include prehospital cardiovascular laboratory activation and prehospital electrocardiogram (ECG) transmission, which are only available for patients who arrive via emergency ambulances. We assessed the impact of mode of transport on DTB time in a single tertiary institution and evaluated the factors that affected various components of DTB time. METHODS: We conducted a retrospective cohort study using registry data of patients diagnosed with STEMI in the emergency department (ED) who underwent primary percutaneous coronary intervention. We compared patients who arrived by emergency ambulances with those who came via their own transport. The primary study end point was DTB, defined as the earliest time a patient arrived in the ED to balloon inflation. As deidentified data was used, ethics review was waived. RESULTS: A total of 321 patients were included for analysis after excluding 7 with missing data. The mean age was 61.4±11.4 years old with 49 (15.3%) females. Ninety-nine (30.8%) patients arrived by emergency ambulance. The median DTB time was shorter for patients arriving by ambulance versus own transport (52min, interquartile range [IQR] 45-61 vs 67min, IQR 59-74; CONCLUSION Arrival via emergency ambulance was associated with a decreased DTB for STEMI patients compared to arriving via own transport. There is a need for public education to increase the usage of emergency ambulances for suspected heart attacks to improve outcomes.
Aged ; Ambulances ; Angioplasty, Balloon, Coronary ; Female ; Humans ; Middle Aged ; Percutaneous Coronary Intervention ; Retrospective Studies ; Time Factors

Atrial fibrillation (AF) is one of the most common arrhythmias, associated with high morbidity, mortality, and healthcare costs, and it places a significant burden on both individuals and society. Anti-arrhythmic drugs are the most commonly used strategy for treating AF. However, drug therapy faces challenges because of its limited efficacy and potential side effects. Catheter ablation is widely used as an alternative treatment for AF. Nevertheless, because the mechanism of AF is not fully understood, the recurrence rate after ablation remains high. In addition, the outcomes of ablation can vary significantly between medical institutions and patients, especially for persistent AF. Therefore, the issue of which ablation strategy is optimal is still far from settled. Computational modeling has the advantages of repeatable operation, low cost, freedom from risk, and complete control, and is a useful tool for not only predicting the results of different ablation strategies on the same model but also finding optimal personalized ablation targets for clinical reference and even guidance. This review summarizes three-dimensional computational modeling simulations of catheter ablation for AF, from the early-stage attempts such as Maze III or circumferential pulmonary vein isolation to the latest advances based on personalized substrate-guided ablation. Finally, we summarize current developments and challenges and provide our perspectives and suggestions for future directions.