Clinical significance of peripheral blood immune cells in patients with gastric cancer after surgery.

BACKGROUND: Gastric cancer is one of the most common malignant tumors worldwide, and surgical resection is one of the main ways to treat gastric cancer. However, the immune status of postoperative patients is crucial for prognosis and survival, and immune cells play an important role in this process. Therefore, it is helpful to understand the immune status of postoperative patients by evaluating the levels of peripheral blood immune cells, especially total T cells (CD3+), helper T cells (CD3+CD4+), and suppressor T cells (CD3+CD8+), and its relationship to survival. AIM: To analyzed the immune cells in peripheral blood of patients with gastric cancer after surgery, detect the levels of total T cells, helper T cells and suppressor T cells. METHODS: A total of 58 patients with gastric cancer who received surgical treatment were included in the retrospective study. Flow cytometry was used to detect the level of peripheral blood immune cells and analyze the correlation between total T cells, helper T cells and inhibitory T cells. To explore the relationship between these immune markers and patient survival. RESULTS: The results showed that the levels of total T cells, helper T cells, and suppressor T cells changed in patients after gastric cancer surgery. There was a significant positive correlation between total T cells, helper T cells and suppressor T cells (r = 0.35, P < 0.01; r = 0.56, P < 0.01). However, there was a negative correlation between helper T cells and suppressor T cells (r = -0.63, P < 0.01). Follow-up showed that the survival rate of patients in the high-level total T cell group was significantly higher than that in the low-level group (28.87 ± 24.98 months vs 18.42 ± 16.21 months). The survival curve shows that the curve of patients in the high-level group is shifted to the upper right, and that of the low-level group is shifted downward. There was no significant difference between the levels of helper T cells and suppressor T cells and patient survival time. CONCLUSION: By detecting peripheral blood immune cells with flow cytometry, we can initially evaluate the immune status of patients after gastric cancer surgery and initially explore its relationship with patient survival.

The combined detection of carcinoembryonic antigen, carcinogenic antigen 125, and carcinogenic antigen 19-9 in colorectal cancer patients.

BACKGROUND: Hepatic metastases are common and difficult to treat after colorectal cancer (CRC) surgery. The predictive value of carcinoembryonic antigen (CEA), cancer antigen (CA) 125 and CA19-9 combined tests for liver metastasis is unclear. AIM: To evaluate predictive value of combined tests for CEA, CA125, and CA19-9 levels in patients with liver metastases of CRC. METHODS: The retrospective study included patients with CRC alone (50 cases) and patients with CRC combined with liver metastases (50 cases) who were hospitalized between January 2021 and January 2023. Serum CEA, CA125 and CA19-9 levels were compared between the two groups, and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver metastasis. In addition, we performed receiver operating characteristic (ROC) curve analysis to assess its diagnostic accuracy. RESULTS: The results showed that the serum CEA, CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone group. Specifically, the average serum CEA level in the CRC with liver metastasis group was 162.03 ± 810.01 ng/mL, while that in the CRC alone group was 5.71 ± 9.76 ng/mL; the average serum CA125 levels were 43.47 ± 83.52 U/mL respectively. and 13.5 ± 19.68 U/mL; the average serum CA19-9 levels were 184.46 ± 473.13 U/mL and 26.55 ± 43.96 U/mL respectively. In addition, binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis (P < 0.05). ROC curve analysis results showed that the areas under the ROC curves of CEA, CA125 and CA19-9 were 0.607, 0.692 and 0.586. CONCLUSION: These results suggest that combined detection of these tumor markers may help early detection and intervention of CRC liver metastasis, thereby improving patient prognosis.

Disease progression subtypes of Parkinson's disease based on milestone events.

BACKGROUND: Parkinson's disease (PD) demonstrates considerable heterogeneity in the manifestation of clinical symptoms and disease progression. Recently, six clinical milestones have been proposed to evaluate disease severity in PD. However, the identification of PD progression subtypes based on these milestone events has not yet been performed. METHODS: Latent class analysis (LCA) was employed to identify subtypes of PD progression based on the timing of the first occurrence of six milestones within a 6-year follow-up period in Parkinson's Progression Markers Initiative (PPMI) database. RESULTS: The study cohort consisted of 354 early PD patients, of whom 42.9% experienced at least one milestone within six years. LCA identified two distinct subtypes of PD progression: slow progression (83%) and rapid progression (17%). The total number of milestones over six years was significantly higher in the rapid progression subtype compared to the slow progression subtype (median: 3.00 vs. 0.00, p < 0.001). At baseline, the rapid progression subtype, compared to the slow progression subtype, was characterized by an older age at onset and more severe motor and non-motor symptoms. On biomarkers, the rapid progression subtype demonstrated elevated CSF p-tau and serum NFL, but decreased mean striatal DAT uptake. Five clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, and RBD) were selected to construct the predictive model. The original predictive model achieved an AUC of 0.82. In internal validation using bootstrap resampling, the model achieved an AUC of 0.82, with a 95%CI ranging from 0.76 to 0.87. The model's performance was acceptable regarding both calibration and clinical utility. CONCLUSION: Approximately 17% of early PD patients exhibited the rapid progression subtype, characterized by the occurrence of more and earlier-onset milestones. The nomogram predictive model, incorporating five baseline clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, RBD), serves as a valuable tool for prognostic counseling and patient selection in PD clinical trials.

Efficient Anti-Icing of a Stable PFA Coating for Wind Power Turbine Blades.

Superhydrophobic coatings are increasingly recognized as a promising approach to enhancing power generation efficiency and prolonging the operational lifespan of wind turbines. In this research, a durable superhydrophobic perfluoroalkoxy alkane (PFA) coating was developed and specifically designed for spray application onto the surface of wind turbine blades. The PFA coating features a micronano hierarchical structure, exhibiting a high water contact angle of 167.0° and a low sliding angle of 1.7°. The optimal PFA coating exhibits stability and maintains a superhydrophobic performance during mechanical and chemical tests. The findings of this study establish a positive association between the surface energy of the coating and its effectiveness in anti-icing. The delayed icing time for the PFA-coated surface is 46.83 times longer than that of an uncoated surface, and the ice adhesion strength is only 1.875 kPa. Additionally, the PFA coating demonstrates remarkably high ice suppression efficiencies of 94.7 and 99.5% in anti-icing experiments at ambient temperatures of -6 and -10 °C, respectively. It is anticipated that this stable superhydrophobic PFA coating will be a candidate for anti-icing applications in wind turbine blades.

Two new cases with the UBQLN2 gene mutation in Han Chinese.

Variations in the UBQLN2 gene are associated with a group of diseases with X-linked dominant inheritance and clinical phenotypes of amyotrophic lateral sclerosis (ALS) and/or frontal temporal lobe dementia (FTD). Cases with UBQLN2 variations have been rarely reported worldwide. The reported cases exhibit strong clinical heterogeneity. Here, we report two adult-onset cases with UBQLN2 variations in Han Chinese. Whole exome sequencing revealed the hemizygous P506S (c.1516C > T) and the heterozygous P509S variation (c.1525C > T), both of which were located within the hotspot mutation region. The patient with the P506S variation was a 24-year-old male. The clinical feature was spastic paraplegia without lower motor neuron damage. The patient's mother was an asymptomatic heterozygote carrier with skewed X-chromosome inactivation. The patient with the P509S variation was a 63-year-old female. Clinical features included ALS and parkinsonism. 18F-fluorodopa PET-CT revealed presynaptic dopaminergic deficits in bilateral posterior putamen. These cases further highlight the clinical heterogeneity of UBQLN2 cases.

Single-shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad, durable and protective systemic and mucosal immunity in mice.

Current coronavirus disease 2019 vaccines face limitations including waning immunity, immune escape by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, limited cellular response, and poor mucosal immunity. We engineered a Clec9A-receptor binding domain (RBD) antibody construct that delivers the SARS-CoV-2 RBD to conventional type 1 dendritic cells. Compared with non-targeting approaches, single dose immunization in mice with Clec9A-RBD induced far higher RBD-specific antibody titers that were sustained for up to 21 months after vaccination. Uniquely, increasing neutralizing and antibody-dependent cytotoxicity activities across the sarbecovirus family was observed, suggesting antibody affinity maturation over time. Consistently and remarkably, RBD-specific follicular T helper cells and germinal center B cells persisted up to 12 months after immunization. Furthermore, Clec9A-RBD immunization induced a durable mono- and poly-functional T-helper 1-biased cellular response that was strongly cross-reactive against SARS-CoV-2 variants of concern, including Omicron subvariants, and with a robust CD8+ T cell signature. Uniquely, Clec9A-RBD single-shot systemic immunization effectively primed RBD-specific cellular and humoral immunity in lung and resulted in significant protection against homologous SARS-CoV-2 challenge as evidenced by limited body weight loss and approximately 2 log10 decrease in lung viral loads compared with non-immunized controls. Therefore, Clec9A-RBD immunization has the potential to trigger robust and sustained, systemic and mucosal protective immunity against rapidly evolving SARS-CoV2 variants.

Role of anticoagulation in non-ST-elevation myocardial infarction: a contemporary narrative review.

INTRODUCTION: Anticoagulants play a vital role as part of the antithrombotic therapy of myocardial infarction and are complementary to antiplatelet therapies. In the acute setting, the rationale for their use is to antagonize the ongoing clotting cascade including during percutaneous coronary intervention. Anticoagulation may be an important part of the longer-term antithrombotic strategy especially in patients who have other existing indications (e.g. atrial fibrillation) for their use. AREAS COVERED: In this narrative review, the authors provide a contemporary summary of the anticoagulation strategies of patients presenting with NSTEMI, both in terms of anticoagulation during the acute phase as well as suggested antithrombotic regimens for patients who require long-term anticoagulation for other indications. EXPERT OPINION: Patients presenting with non-ST-elevation myocardial infarction (NSTEMI) should be initiated on anticoagulation (e.g. heparin/low molecular weight heparin) for the initial hospitalization period for those medically managed or until percutaneous coronary intervention. Longer term management of NSTEMI for patients with an existing indication for long-term anticoagulation should comprise triple antithrombotic therapy of anticoagulant (preferably DOAC) with aspirin and clopidogrel for up to 1 month (typically 1 week or until hospital discharge), followed by DOAC plus clopidogrel for up to 1 year, and then DOAC monotherapy thereafter.

Dietary vitamin C and vitamin E with the risk of aortic aneurysm and dissection: A prospective population-based cohort study.

BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.

SIRT3 suppression resulting from the enhanced ß-catenin signaling drives glycolysis and promotes hypoxia-induced cell growth in hepatocellular carcinoma cells.

The precise mechanisms underlying the inhibitory effects of SIRT3, a mitochondrial sirtuin protein, on hepatocellular carcinoma (HCC) development, as well as its impact on mitochondrial respiration, remain poorly understood. We assessed sirtuins 3 (SIRT3) levels in HCC tissues and Huh7 cells cultured under hypoxic condition. We investigated the effects of SIRT3 on cell proliferation, glycolytic metabolism, mitochondrial respiration, mitophagy, and mitochondrial biogenesis in Huh7 cells. Besides, we explored the potential mechanisms regulating SIRT3 expression in hypoxically cultured Huh7 cells. Gradual reduction in SIRT3 expressions were observed in both adjacent tumor tissues and tumor tissues. Similarly, SIRT3 expressions were diminished in Huh7 cells cultured under hypoxic condition. Forced expression of SIRT3 attenuated the growth of hypoxically cultured Huh7 cells. SIRT3 overexpression led to a decrease in extracellular acidification rate while increasing oxygen consumption rate. SIRT3 downregulated the levels of hexokinase 2 and pyruvate kinase M2. Moreover, SIRT3 enhanced mitophagy signaling, as indicated by mtKeima, and upregulated key proteins involved in various mitophagic pathways while reducing intracellular reactive oxygen species levels. Furthermore, SIRT3 increased proxisome proliferator-activated receptor-gamma coactivator 1α levels and the amount of mitochondrial DNA in Huh7 cells. Notably, ß-catenin expressions were elevated in Huh7 cells cultured under hypoxic condition. Antagonists and agonists of ß-catenin respectively upregulated and downregulated SIRT3 expressions in hypoxically cultured Huh7 cells. The modulationsof glycolysis and mitochondrial respiration represent the primary mechanism through which SIRT3, suppressed by ß-catenin, inhibits HCC cell proliferation.

Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome.

BACKGROUND: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. METHODS: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. RESULTS: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. CONCLUSION: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

Association between daytime napping and incident arrhythmias: A prospective cohort study and mendelian randomization analysis.

BACKGROUND: Emerging evidence has linked daytime napping with the risk of cardiovascular events. Cardiac arrhythmias are considered an early clinical stage for cardiovascular diseases. However, whether napping frequency is associated with incident arrhythmias remains unknown. OBJECTIVE: This study aimed to prospectively investigate the association between napping frequency and cardiac arrhythmias. METHODS: Daytime napping frequency was self-reported in response to touchscreen questionnaires. The primary outcomes were incident arrhythmias including atrial fibrillation/flutter (AF/Af), ventricular arrhythmia, and bradyarrhythmia. Cox regression analysis was conducted on the basis of 491,117 participants free of cardiac arrhythmias from the UK Biobank. The 2-sample mendelian randomization (MR) and 1-sample MR were used to ensure a causal effect of genetically predicted daytime napping on the risk of arrhythmias. RESULTS: During a median follow-up of 11.91 years, 28,801 incident AF/Af cases, 4132 incident ventricular arrhythmias, and 11,616 incident bradyarrhythmias were documented. Compared with never/rarely napping, usually napping was significantly associated with higher risks of AF/Af (hazard ratio, 1.141; 95% CI, 1.083-1.203) and bradyarrhythmia (hazard ratio, 1.138; 95% CI, 1.049-1.235) but not ventricular arrhythmia after adjustment for various covariates. The 2-sample MR and 1-sample MR analysis showed that increased daytime napping frequency was likely to be a potential causal risk factor for AF/Af in FinnGen (odds ratio, 1.626; 95% CI, 1.061-2.943) and bradyarrhythmia in the UK Biobank (odds ratio, 1.005; 95% CI, 1.002-1.008). CONCLUSION: The results of this study add to the burgeoning evidence of an association between daytime napping frequency and an increased risk of cardiac arrhythmias including AF/Af, ventricular arrhythmia, and bradyarrhythmia.

Deep Learning Model and its Application for the Diagnosis of Exudative Pharyngitis.

OBJECTIVES: Telemedicine is firmly established in the healthcare landscape of many countries. Acute respiratory infections are the most common reason for telemedicine consultations. A throat examination is important for diagnosing bacterial pharyngitis, but this is challenging for doctors during a telemedicine consultation. A solution could be for patients to upload images of their throat to a web application. This study aimed to develop a deep learning model for the automated diagnosis of exudative pharyngitis. Thereafter, the model will be deployed online. METHODS: We used 343 throat images (139 with exudative pharyngitis and 204 without pharyngitis) in the study. ImageDataGenerator was used to augment the training data. The convolutional neural network models of MobileNetV3, ResNet50, and EfficientNetB0 were implemented to train the dataset, with hyperparameter tuning. RESULTS: All three models were trained successfully; with successive epochs, the loss and training loss decreased, and accuracy and training accuracy increased. The EfficientNetB0 model achieved the highest accuracy (95.5%), compared to MobileNetV3 (82.1%) and ResNet50 (88.1%). The EfficientNetB0 model also achieved high precision (1.00), recall (0.89) and F1-score (0.94). CONCLUSIONS: We trained a deep learning model based on EfficientNetB0 that can diagnose exudative pharyngitis. Our model was able to achieve the highest accuracy, at 95.5%, out of all previous studies that used machine learning for the diagnosis of exudative pharyngitis. We have deployed the model on a web application that can be used to augment the doctor's diagnosis of exudative pharyngitis.

Three­dimensional finite element analysis: Anatomical splint fixation for Colles fractures.

With the rapid development of digital research in clinical orthopedics, the efficacy and safety of splint fixation can be better evaluated through biomechanical analysis based on a three-dimensional (3D) finite element model. It is essential to address the current gap in understanding the biomechanical implications of anatomical splint fixation for Colles fractures. By employing advanced 3D finite element analysis, the present study aimed to provide a comprehensive evaluation, offering valuable insights that can contribute to enhancing the effectiveness of anatomical splint fixation in the clinical management of Colles fractures. The 3D finite element models of the forearm and hand were constructed using Mimics 15.0 according to data from computed tomography of a patient with a Colles fracture. After the validity of the model was verified, the corresponding material properties of the models were adjusted to simulate a Colles fracture. Subsequently, the reduction functions, such as radial inclination and ulnar deviation, of the simulated fracture were completed and the mechanical changes of the tissues surrounding the fracture were calculated. Anatomical splints were then placed on the surfaces of the 3D finite element models of Colles fractures at various positions to analyze the changes in the stress cloud diagram, such as for the soft tissue and anatomical splints. In the present study, the constructed 3D finite element models were accurate and valid. The maximum stress of the anatomical splints and soft tissues was 2.346 and 0.106 MPa in pronation, 1.780 and 0.069 MPa in median rotation and 3.045 and 0.057 MPa in supination, respectively. Splint stress reached the highest level in supination and soft tissue stress achieved the highest level in pronation. The peak of splint stress occurred during supination, which contrasts to the peak of soft tissue stress observed in pronation, suggesting splint fixation median rotation can effectively avoid compression of the local soft tissue.

Scurvy in a young man: a rare case report.

Scurvy, resulting from vitamin C deficiency, has nonspecific constitutional symptoms, including weakness, malaise, and fatigue. It is frequently misdiagnosed due to the lack of specific clinical manifestations. Although there are sporadic cases of scurvy currently reported in children, scurvy in young people is seldom encountered. Here, we report on a 25-year-old male patient without any underlying conditions who presented with severe pain and ecchymoses of both lower extremities. He was diagnosed with scurvy due to a long history of staying indoors and inadequate intake of fruits or vegetables.

Roxarsone biotransformation by a nitroreductase and an acetyltransferase in Pseudomonas chlororaphis, a bacterium isolated from soil.

Roxarsone (3-nitro-4-hydroxyphenylarsonic acid, Rox), a widely used organoarsenical feed additive, can enter soils and be further biotransformed into various arsenic species that pose human health and ecological risks. However, the pathway and molecular mechanism of Rox biotransformation by soil microbes are not well studied. Therefore, in this study, we isolated a Rox-transforming bacterium from manure-fertilized soil and identified it as Pseudomonas chlororaphis through morphological analysis and 16S rRNA gene sequencing. Pseudomonas chlororaphis was able to biotransform Rox to 3-amino-4-hydroxyphenylarsonic acid (3-AHPAA), N-acetyl-4-hydroxy-m-arsanilic acid (N-AHPAA), arsenate [As(V)], arsenite [As(III)], and dimethylarsenate [DMAs(V)]. The complete genome of Pseudomonas chlororaphis was sequenced. PcmdaB, encoding a nitroreductase, and PcnhoA, encoding an acetyltransferase, were identified in the genome of Pseudomonas chlororaphis. Expression of PcmdaB and PcnhoA in E. coli Rosetta was shown to confer Rox(III) and 3-AHPAA(III) resistance through Rox nitroreduction and 3-AHPAA acetylation, respectively. The PcMdaB and PcNhoA enzymes were further purified and functionally characterized in vitro. The kinetic data of both PcMdaB and PcNhoA were well fit to the Michaelis-Menten equation, and nitroreduction catalyzed by PcMdaB is the rate-limiting step for Rox transformation. Our results provide new insights into the environmental risk assessment and bioremediation of Rox(V)-contaminated soils.

Influenza A and B Viruses in Fine Aerosols of Exhaled Breath Samples from Patients in Tropical Singapore.

Influenza is a highly contagious respiratory illness that commonly causes outbreaks among human communities. Details about the exact nature of the droplets produced by human respiratory activities such as breathing, and their potential to carry and transmit influenza A and B viruses is still not fully understood. The objective of our study was to characterize and quantify influenza viral shedding in exhaled aerosols from natural patient breath, and to determine their viral infectivity among participants in a university cohort in tropical Singapore. Using the Gesundheit-II exhaled breath sampling apparatus, samples of exhaled breath of two aerosol size fractions ("coarse" > 5 µm and "fine" ≤ 5 µm) were collected and analyzed from 31 study participants, i.e., 24 with influenza A (including H1N1 and H3N2 subtypes) and 7 with influenza B (including Victoria and Yamagata lineages). Influenza viral copy number was quantified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Infectivity of influenza virus in the fine particle fraction was determined by culturing in Madin-Darby canine kidney cells. Exhaled influenza virus RNA generation rates ranged from 9 to 1.67 × 105 and 10 to 1.24 × 104 influenza virus RNA copies per minute for the fine and coarse aerosol fractions, respectively. Compared to the coarse aerosol fractions, influenza A and B viruses were detected more frequently in the fine aerosol fractions that harbored 12-fold higher viral loads. Culturable virus was recovered from the fine aerosol fractions from 9 of the 31 subjects (29%). These findings constitute additional evidence to reiterate the important role of fine aerosols in influenza transmission and provide a baseline range of influenza virus RNA generation rates.

Red Blood Cell-Derived Extracellular Vesicles Display Endogenous Antiviral Effects and Enhance the Efficacy of Antiviral Oligonucleotide Therapy.

The COVID-19 pandemic has resulted in a large number of fatalities and, at present, lacks a readily available curative treatment for patients. Here, we demonstrate that unmodified red blood cell-derived extracellular vesicles (RBCEVs) can inhibit SARS-CoV-2 infection in a phosphatidylserine (PS) dependent manner. Using T cell immunoglobulin mucin domain-1 (TIM-1) as an example, we demonstrate that PS receptors on cells can significantly increase the adsorption and infection of authentic and pseudotyped SARS-CoV-2 viruses. RBCEVs competitively inhibit this interaction and block TIM-1-mediated viral entry into cells. We further extend the therapeutic efficacy of this antiviral treatment by loading antisense oligonucleotides (ASOs) designed to target conserved regions of key SARS-CoV-2 genes into RBCEVs. We establish that ASO-loaded RBCEVs are efficiently taken up by cells in vitro and in vivo to suppress SARS-CoV-2 replication. Our findings indicate that this RBCEV-based SARS-CoV-2 therapeutic displays promise as a potential treatment capable of inhibiting SARS-CoV-2 entry and replication.

Serum albumin and risk of incident diabetes and diabetic microvascular complications in the UK Biobank cohort.

AIM: To examine the associations between serum albumin and the incidences of diabetes and diabetic microvascular complications in participants of the UK Biobank cohort. METHODS: There were 398,146 participants without diabetes and 30,952 patients with diabetes from the UK Biobank cohort included in this study. Multivariate-adjusted Cox proportional hazard models were used to analyze the association of albumin with the incidences of diabetes and diabetic microvascular complications. Mendelian randomization (MR) analysis was used to determine the genetic relationships between serum albumin and diabetes. RESULTS: After a median 12.90 years follow-up, 14,710 participants developed incident diabetes (58.83 ± 7.52 years, 56.10% male). After multivariate adjustment, serum albumin was inversely associated with incident diabetes: hazard ratio (HR) [95% confidence interval] per 10 g/l increase 0.88 [0.82;0.94]. MR analyses suggested a potential genetic influence of serum albumin on diabetes in both the UK Biobank and the FinnGen consortium: odds ratios (ORs) [95% confidence interval per 1 g/l increase 0.99 [0.98;1.00] and 0.78 [0.67;0.92], respectively. In patients with diabetes, higher serum albumin levels were significantly associated with lower risk for diabetic microvascular complications. Specifically, per 10 g/l increase in serum albumin, the HRs for diabetic nephropathy, ophthalmopathy, and neuropathy were 0.42 [0.30;0.58], 0.61 [0.52;0.72], and 0.67 [0.51;0.88], respectively. CONCLUSION: In this large prospective study, serum levels of albumin were inversely associated with the incidences of diabetes and diabetic microvascular complications. These findings underscore the importance of maintaining optimal nutrient status in reducing the risk of diabetes and its complications.

Identifying and Solving Gaps in Pre- and In-Hospital Acute Myocardial Infarction Care in Asia-Pacific Countries.

Acute myocardial infarction (AMI) is a major cause of morbidity and mortality in the Asia-Pacific region, and mortality rates differ between countries in the region. Systems of care have been shown to play a major role in determining AMI outcomes, and this review aims to highlight pre-hospital and in-hospital system deficiencies and suggest possible improvements to enhance quality of care, focusing on Korea, Japan, Singapore and Malaysia as representative countries. Time to first medical contact can be shortened by improving patient awareness of AMI symptoms and the need to activate emergency medical services (EMS), as well as by developing robust, well-coordinated and centralized EMS systems. Additionally, performing and transmitting pre-hospital electrocardiograms, algorithmically identifying patients with high risk AMI and developing hospital networks that appropriately divert such patients to percutaneous coronary intervention-capable hospitals have been shown to be beneficial. Within the hospital environment, developing and following clinical practice guidelines ensures that treatment plans can be standardised, whilst integrated care pathways can aid in coordinating care within the healthcare institution and can guide care even after discharge. Prescription of guideline directed medical therapy for secondary prevention and patient compliance to medications can be further optimised. Finally, the authors advocate for the establishment of more regional, national and international AMI registries for the formal collection of data to facilitate audit and clinical improvement.

The association between childhood adiposity in northeast China and anthropogenic heat flux: A new insight into the comprehensive impact of human activities.

Anthropogenic heat has been reported to have significant health impacts, but research on its association with childhood adiposity is still lacking. In this study, we matched the 2008-2012 average anthropogenic heat flux, as simulated by a grid estimation model using inventory methods, with questionnaire and measurement data of 49,938 children randomly recruited from seven cities in Northeast China in 2012. After adjusting for social demographic and behavioral factors, we used generalized linear mixed-effect models to assess the association between anthropogenic heat flux and adiposity among children. We also examined the effect modification of various social demographic and behavioral confounders. We found that each 10 W/m2 increase in total anthropogenic heat flux and that from the industry source was associated with an increase of 5.82% (95% CI = 0.84%-11.05%) and 6.62% (95% CI = 0.87%-12.70%) in the odds of childhood adiposity. Similarly, the excess rate of adiposity among children were 5.26% (95% CI = -1.33%-12.29%) and 8.51% (95% CI = 2.24%-15.17%) per 1 W/m2 increase in the anthropogenic heat flux from transportation and buildings, and was 7.94% (95% CI = 2.28%-13.91%) per 0.001 W/m2 increase in the anthropogenic heat flux from human metabolism. We also found generally greater effect estimates among female children and children who were exposed to passive smoking during pregnancy, born by caesarean section, non-breastfed/mixed-fed, or lived within 20 m adjacent to the main road. The potential deleterious effect of anthropogenic heat exposure on adiposity among children may make it a new but major threat to be targeted by future mitigation strategies.