Analysis of onset-to-door time and its influencing factors in Chinese patients with acute ischemic stroke during the 2020 COVID-19 epidemic: a preliminary, prospective, multicenter study.

BACKGROUND: Pre-hospital delay in China is a serious issue with unclear relevant reasons, seriously impeding the adoption of appropriate measures. Herein, we analyzed the onset-to-door time (ODT) in Chinese patients with acute ischemic stroke (AIS) and its influencing factors. METHODS: We prospectively recruited 3,459 patients with AIS from nine representative tertiary general hospitals in China between January and June 2022. Patients were divided into ODT ≤ 3 h and ODT > 3 h groups. Following single-factor analysis, binary logistic regression analysis was performed to evaluate the risk factors leading to pre-hospital delay. RESULTS: In total, 763 (21.83%) patients arrived at the hospital within 3 h of onset. After adjusting for confounding factors, the risk factors for ODT were residence in rural areas (odds ratio [OR]: 1.478, 95% credibility interval [CI]: 1.024-2.146) and hospital transfer (OR: 7.479, 95% CI: 2.548-32.337). The protective factors for ODT were location of onset ≤ 20 km from the first-visit hospital (OR: 0.355, 95% CI: 0.236-0.530), transportation by emergency medical services (OR: 0.346, 95% CI: 0.216-0.555), history of atrial fibrillation (OR: 0.375, 95% CI: 0.207-0.679), moderate stroke (OR: 0.644, 95% CI: 0.462-0.901), and severe stroke (OR: 0.506, 95% CI: 0.285-0.908). CONCLUSIONS: Most patients with AIS fail to reach a hospital within the critical 3-h window. The following measures are recommended to reduce pre-hospital delays: reasonable distribution of hospitals accessible to nearby residents, minimizing interhospital transfer, paying attention to patients with mild stroke, and encouraging patients to use ambulance services. Pre-hospital delays for patients can be reduced by implementing these measures, ultimately improving the timeliness of treatment and enhancing patient prognosis. This study was carried out amid the COVID-19 pandemic, which presented challenges and constraints.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

Total Infectome Characterization of Respiratory Infections during the 2022-23 COVID-19 Outbreak in China Revealed Extensive Coinfections with Links to SARS-CoV-2 Status, Age, and Disease Severity.

Between 7 December 2022 and 28 February 2023, China experienced a new wave of COVID-19 that swept across the entire country and resulted in an increasing amount of respiratory infections and hospitalizations. The purpose of this study is to reveal the intensity and composition of coinfecting microbial agents. In total, 196 inpatients were recruited from The Third People's Hospital of Shenzhen, and 169 respiratory and 73 blood samples were collected for metagenomic next-generation sequencing. The total "Infectome" was characterized and compared across different groups defined by the SARS-CoV-2 detection status, age groups, and severity of disease. Our results revealed a total of 22 species of pathogenic microbes (4 viruses, 13 bacteria, and 5 fungi), and more were discovered in the respiratory tract than in blood. The diversity of the total infectome was highly distinguished between respiratory and blood samples, and it was generally higher in patients that were SARS-CoV-2-positive, older in age, and with more severe disease. At the individual pathogen level, HSV-1 seemed to be the major contributor to these differences observed in the overall comparisons. Collectively, this study reveals the highly complex respiratory infectome and high-intensity coinfection in patients admitted to the hospital during the period of the 2023 COVID-19 pandemic in China.

[Relationship Between Hearing Loss and Cognitive Function in Elderly Chinese People: A Study Based on Propensity Score Matching]. / åŸºäºŽå€¾å‘å¾—åˆ†åŒ¹é æŽ¢è®¨ä¸­å›½è€å¹´äººå¬åŠ›æŸå¤±ä¸Žè®¤çŸ¥åŠŸèƒ½ä¹‹é—´çš„å ³ç³».

Objective: To explore the relationship between hearing loss and cognitive function in the elderly population through propensity score matching method. Methods: We analyzed the data of 7605 participants aged 60 and above who were included in the 2018 China Health and Retirement Longitudinal Study (CHARLS). The non-substitutable 1∶1 nearest neighbor matching method without caliper value was used for propensity score matching and G-computation was used to estimate the average treatment effect (ATE) of hearing loss on all dimensions of cognitive function. Results: Before matching, there were 3626 (47.68%) women, with 1409 (18.53%) of whom suffering from hearing loss and 3031 (39.86%) of whom suffering from cognitive impairment. After matching, 1409 subjects were included in the hearing loss group and 1409, in the normal hearing group, with both groups sharing similar distribution of basic demographic characteristics. The results for the average treatment effect of the population indicated that the cognitive function scores of the hearing loss group were lower than those of the normal hearing group, with the overall cognitive function being 0.593 points lower (95% confidence intervel [CI]: －0.916-－0.257, P<0.001), orientation being 0.183 points lower (95% CI: －0.302-－0.055, P=0.004), immediate memory being 0.150 points lower (95% CI: －0.218-－0.085, P<0.001), and language skills being 0.178 points lower (95% CI: －0.303-－0.058, P=0.006). The prevalence of cognitive impairment of the hearing loss group was 4.2% higher than that of the normal hearing group (95% CI: 0.007-0.077, P=0.020). Conclusion: Hearing loss adversely affects the orientation, memory, and language skills of the elderly population and forms a potential risk factor for cognitive impairment in the elderly population.

Intravascular ultrasonography assisted carotid artery stenting for treatment of carotid stenosis: Two case reports.

BACKGROUND: Digital subtraction angiography (DSA), the gold standard of cerebrovascular disease diagnosis, is limited in its diagnostic ability to evaluate arterial diameter. Intravascular ultrasonography (IVUS) has advantages in assessing stenosis and plaque nature and improves the evaluation and effectiveness of carotid artery stenting (CAS). CASE SUMMARY: Case 1: A 65-year-old man presented with a five-year history of bilateral lower limb weakness due to stroke. Physical examination showed decreased strength (5-/5) in both lower limbs. Carotid artery ultrasound, magnetic resonance angiography, and computed tomography angiography (CTA) showed a right proximal internal carotid artery (ICA) stenosis (70%-99%), acute cerebral infarction, and severe right ICA stenosis, respectively. We performed IVUS-assisted CAS to measure the stenosis and detected a low-risk plaque at the site of stenosis prior to stent implantation. Post-stent balloon dilatation was performed and postoperative IVUS demonstrated successful expansion and adherence. CTA six months postoperatively showed no significant increase in in-stent stenosis. Case 2: A 36-year-old man was admitted with a right common carotid artery (CCA) dissection detected by ultrasound. Physical examination showed no positive neurological signs. Carotid ultrasound and CTA showed lumen dilation in the proximal CCA with an intima-like structure and bulging in the proximal segment of the right CCA with strip-like low-density shadow (dissection or carotid web). IVUS-assisted DSA confirmed right CCA dissection. CAS was performed and intraoperative IVUS suggested a large residual false lumen. Post-stent balloon dilatation was performed reducing the false lumen. DSA three months postoperatively indicated good stent expansion with mild stenosis. CONCLUSION: IVUS aids decision-making during CAS by accurately assessing carotid artery wall lesions and plaque nature preoperatively, dissection and stenosis morphology intraoperatively, and visualizing and confirming CAS postoperatively.

[Comparative Analysis of Influencing Factors of Health Service Utilization Among Urban and Rural Residents in Tibet].

Objective: To examine the differences and commonalities of factors influencing the utilization of health services among urban and rural residents in Tibet and to identify vulnerable populations in the utilization of health services, thereby providing references for the formulation of local health policies and the allocation of health resources. Methods: Using the Tibetan area data from the Sixth National Health Service Survey, we conducted statistical analysis of the health service utilization status of 8 297 residents of agro-pastoral areas and 2 179 residents of urban areas with χ 2 test and logistic regression model. Results: The two-week outpatient visit rates of residents in agro-pastoral areas and that of the urban residents were 65.3% and 57.1%, respectively, and the one-year hospitalization rates were 8.3% and 8.9%, respectively. The influencing factors of two-week outpatient visits for rural and pastoral residents included urban and rural health insurance coverage, Three Guarantees in One coverage, distance to medical facilities, chronic disease status, physical examination, family doctor contract status, employment status, and health status self-assessment. The influencing factors of two-week outpatient visit for urban residents included chronic disease status, urban and rural medical insurance coverage, health status self-assessment, health records, and physical examination. The factors influencing hospitalization for agro-pastoral residents were sex, age, marital status, urban and rural medical insurance coverage, Three Guarantees in One coverage, critical illness insurance, health self-assessment, mobility, health records, physical examination, and chronic disease status. The factors influencing the hospitalization of urban residents were sex, marital status, health status self-assessment, health records, urban employee medical insurance coverage, and chronic disease status. The factors influencing the hospitalization of urban residents were sex, marital status, health status self-assessment, health records, urban employee medical insurance coverage, and chronic disease status. Conclusion: The urban and rural residents in Tibet have relatively poor health and their awareness of seeking early medical help after they fall ill is relatively weak. The health institutions concerned should dedicate more attention to the vulnerable populations who have difficulty accessing health services, focus on the commonly shared influencing factors of health service utilization among urban and rural residents, take into account the differences, rationally allocate health resources, and improve the effective utilization rate of health services among residents in Tibet.

Metagenomic analysis of individual mosquitos reveals the ecology of insect viruses.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Using a meta-transcriptomic approach, we analysed the virome of 2,438 individual mosquitos (79 species), spanning ~4000 km along latitudes and longitudes in China. From these data we identified 393 core viral species associated with mosquitos, including seven (putative) arbovirus species. We identified potential species and geographic hotspots of viral richness and arbovirus occurrence, and demonstrated that host phylogeny had a strong impact on the composition of individual mosquito viromes. Our data revealed a large number of viruses shared among mosquito species or genera, expanding our knowledge of host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, possibly facilitated by long-distance mosquito migrations. Together, our results greatly expand the known mosquito virome, linked the viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the ecology of viruses of insect vectors.

Near-Infrared Afterglow ONOO--Triggered Nanoparticles for Real-Time Monitoring and Treatment of Early Ischemic Stroke.

Early detection and drug intervention with the appropriate timing and dosage are the main clinical challenges for ischemic stroke (IS) treatment. The conventional therapeutic agents relay fluorescent signals, which require real-time external light excitation, thereby leading to inevitable autofluorescence and poor tissue penetration. Herein, we report endogenous peroxynitrite (ONOO-)-activated BDP-4/Cur-CL NPs that release NIR afterglow signals (λmax 697 nm) for real-time monitoring of the progression of ischemia reperfusion (I/R) brain injury while releasing curcumin for the safe treatment of IS. The BDP-4/Cur-CL NPs exhibited bright NIR afterglow luminescence (maximum 732-fold increase), superb sensitivity (LOD = 82.67 nM), high energy-transfer efficiency (94.6%), deep tissue penetration (20 mm), outstanding antiapoptosis, and anti-inflammatory effects. The activated NIR afterglow signal obtained in mice with middle cerebral artery occlusion (MCAO) showed three functions: (i) the BDP-4/Cur-CL NPs are rapidly activated by endogenous ONOO-, instantly illuminating the lesion area, distinguishing I/R damage from normal areas, which can be successfully used for endogenous ONOO- detection in the early stage of IS; (ii) real-time reporting of in situ generation and dynamic fluctuations of endogenous ONOO- levels in the lesion area, which is of great value in monitoring the evolutionary mechanisms of IS; and (iii) dynamic monitoring of the release of curcumin drug for safe treatment. Indeed, the released curcumin effectively decreased apoptosis, enhanced survival, alleviated neuroinflammation, reduced brain tissue loss, and improved the cognition of MCAO stroke mice. This work is the first example of afterglow luminescence for early diagnosis, real-time reporting, drug tracing, and treatment for IS.

[Effect of the Interaction Between Overweight/Obesity and Dyslipidemia on the Risk of Hypertension in Tibetan Population Living in Tibet].

Objective: To explore the possible interaction between overweight/obesity and dyslipidemia and to provide some evidence for the interaction of the risk of hypertension with overweight/obesity and dyslipidemia. Methods: By using multi-stage stratified cluster random sampling method, the subjects of the study were randomly selected from Naqu city, Shannan city, and Ali prefecture, Tibet. A total of 4047 Tibetans with complete data were included. Investigators obtained relevant information on the subjects through questionnaire surveys, measured their height, body mass index, and blood pressure, and collected fasting venous blood samples. The multivariate logistic regression model was used to analyze the independent effects of overweight/obesity and dyslipidemia and hypertension. Stratified analysis and an additive interaction model were used to evaluate the effect of two-factor interaction on the risk of hypertension. Results: The overall prevalence of hypertension, overweight/obesity, and dyslipidemia among Tibetans living in Tibet was 29.3%, 46.2%, and 40.9%, respectively. Overweight/obesity (odds ratio [ OR]=2.151) and dyslipidemia ( OR=1.240) were risk factors of hypertension. Evaluation results of the effect of additive interaction showed significant additive interaction of overweight/obesity and dyslipidemia on hypertension ( P=0.028), with the synergy index ( SI) being 1.318. Conclusion: Overweight/obesity and dyslipidemia are risk factors for having hypertension and there is an additive interaction between dyslipidemia and overweight/obesity.

Glycogen Branching Enzyme with a Novel Chain Transfer Mode Derived from Corallococcus sp. Strain EGB and Its Potential Applications.

Dietary starch with an increased content of resistant starch (RS) has the potential to reduce the prevalence of diabetes, obesity, and cardiovascular diseases. Here, an efficient glycogen branching enzyme, CcGBE, from Corallococcus sp. strain EGB was identified, and its relevant properties, including potential application in the preparation of modified starch, were evaluated. The purified CcGBE exhibited a maximal specific activity of approximately 20,000 U/mg using cassava starch as the optimal substrate. The content of α-1,6-glucosidic bonds in CcGBE-modified cassava starch increased from 2.9 to 13.2%. Meanwhile, both the average chain length (CL) of CcGBE-modified starch and the blue value of the color complex formed by starch and iodine initially increased and then decreased, indicating that a new CL transfer mode was reported. Perforated small starch granules were released after CcGBE treatment, and a time-dependent decrease in the retrogradation enthalpy (ΔHr) of cassava starch indicated that CcGBE inhibited the long-term retrogradation of starch. Moreover, the RS content and cold water solubility (CWS) of CcGBE-modified starch increased from 3.3 to 12.8% and from 23.1 to 93.8%, respectively. These findings indicate the application potential of CcGBE for the preparation of modified starch with increased RS and CWS.

Acute air embolism caused by autotransfusion during percutaneous atrial septal defect closure: A case report.

Atrial septal defect is a common congenital heart disease in adults and it is often asymptomatic. Percutaneous device closure is gaining popularity, but percutaneous repair of atrial septal defect leading to left atrial rupture and subsequent autotransfusion under high pressure leading to air embolism has not been reported yet.

Novel nanofibrous membrane-supporting stem cell sheets for plasmid delivery and cell activation to accelerate wound healing.

The integration of biomaterials with cells for high overall performances is vitally important in tissue engineering, as scaffold-free cell sheet lacks enough mechanical performance and cell viability while cell-free scaffold possesses limited biological functions. In this study, we propose a new strategy to strengthen cell sheets and enhance cell activity for accelerating wound healing based on a novel sandwich structure of cell sheet-plasmid@membrane-cell sheet (CpMC). Specifically, the CpMC contains two adipose-derived stem cell (ADSC) sheets on outer surfaces and an electrospun gelatin/chitosan nanofibrous membrane (NFM) encapsulating vascular endothelial growth factor (VEGF) plasmids in between. The physicochemical properties of NFM including swelling, stiffness, strength, elasticity, and biodegradation can be tailored by simply adjusting the ratio between gelatin and chitosan to be 7:3 which is optimal for most effectively supporting ADSCs adhesion and proliferation. The swelling/biodegradation of NFM mediates the sustained release of encapsulated VEGF plasmids into adjacent ADSCs, and NFM assists VEGF plasmids to promote the differentiation of ADSCs into endothelial, epidermal, and fibroblast cells, in support of the neoangiogenesis and regeneration of cutaneous tissues within 2 weeks. The proposed membrane-supporting cell sheet strategy provides a new route to tissue engineering, and the developed CpMC demonstrates a high potential for clinical translation.

Effect of ventilation strategy during cardiopulmonary bypass on postoperative pulmonary complications after cardiac surgery: a randomized clinical trial.

BACKGROUND: To determine whether maintaining ventilation during cardiopulmonary bypass (CPB) with a different fraction of inspired oxygen (FiO2) had an impact on the occurrence of postoperative pulmonary complications (PPCs). METHODS: A total of 413 adult patients undergoing elective cardiac surgery with CPB were randomly assigned into three groups: 138 in the NoV group (received no mechanical ventilation during CPB), 138 in the LOV group (received a tidal volume (VT) of 3-4 ml/kg of ideal body weight with the respiratory rate of 10-12 bpm, and the positive end-expiratory pressure of 5-8 cmH2O during CPB; the FiO2 was 30%), and 137 in the HOV group (received the same ventilation parameters settings as the LOV group while the FiO2 was 80%). RESULTS: The primary outcomes were the incidence and severity of PPCs during hospitalization. The composite incidence of PPCs did not significantly differ between the NoV (63%), LOV (49%) and HOV (57%) groups (P = 0.069). And there was also no difference regarding the incidence of PPCs between the non-ventilation (NoV) and ventilation (the combination of LOV and HOV) groups. The LOV group was observed a lower proportion of moderate and severe pulmonary complications (grade ≥ 3) than the NoV group (23.1% vs. 44.2%, P = 0.001). CONCLUSION: Maintaining ventilation during CPB did not reduce the incidence of PPCs in patients undergoing cardiac surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800015261. Prospectively registered 19 March 2018. http://www.chictr.org.cn/showproj.aspx?proj=25982.

Ventilation strategies with different inhaled Oxygen conceNTration during CardioPulmonary Bypass in cardiac surgery (VONTCPB): study protocol for a randomized controlled trial.

BACKGROUND: There is no consensus on the ventilation management during cardiopulmonary bypass (CPB), and the anesthesiologists or the surgeons usually ventilate the lungs with different ventilation strategies or keep them static. Better outcomes are more likely to occur when the ventilation is administered during CPB according to the existing literatures. However, the use of high fraction of inspired oxygen (FiO2) is debatable in cardiac surgery. And the potential effects of strategies combining low tidal volume (VT) ventilation with different FiO2 during CPB on postoperative pulmonary complications (PPCs) are unclear. DESIGN: The VONTCPB trial is a single-center, prospective, double-blinded, randomized, controlled trial. We are going to recruit total 420 elective cardiac surgery patients with median sternotomy under CPB, who will be equally randomized into three different ventilation strategy groups: NoV, LOV and HOV. (1) The NoV group receives no mechanical ventilation during CPB; (2) the LOV group receives a low VT of 3-4 ml/kg of ideal body weight (IBW) with the respiratory rate (RR) of 10-12 acts/min, and the positive end-expiratory pressure (PEEP) of 5-8 cmH2O during CPB; the FiO2 is 30%; (3) the HOV group receives a low VT of 3-4 ml/kg of IBW with the RR of 10-12 acts/min, and the PEEP of 5-8 cmH2O during CPB; the FiO2 is 80%. The primary endpoints are the incidence of the composite of PPCs and the PPCs score. The secondary endpoints refer to the incidence of the oxygenation index (PaO2/FiO2 ratio) < 300 mmHg at three time points (the moment arriving in the ICU, 6 and 12 h after arrival in the ICU), the surgical incision healing grade, the intubation time, the stay of ICU, the length of hospital stay, and mortality at 30 days after the surgery. DISCUSSION: The VONTCPB trial is the first study to assess the effects of strategies combining low tidal volume (VT) ventilation with different FiO2 during CPB on patients' outcomes. TRIAL REGISTRATION: ChiCTR1800015261 . Registered on 20 March 2018.

Synthesis of A B C-ring subunit of C-nor-D-homo-steroidal alkaloids: towards the total synthesis of cyclopamine.

A practical approach to the synthesis of the A, B and C-ring subunit of cyclopamine has been developed. This synthetic tactic highlights the utility of mandelate acetal-mediated resolution of the fused ring ketone (±)-4 and IBX-mediated oxidation cascades from 12 to 9. The availability of advanced intermediates from enantiomerically pure (+)-4 and 2 could provide efficient access to biologically active and structurally diverse C-nor-D-homo-steroidal alkaloids such as cyclopamine.