Xuebijing injection inhibited neutrophil extracellular traps to reverse lung injury in sepsis mice via reducing Gasdermin D.

The mortality of sepsis and septic shock remains high worldwide. Neutrophil extracellular traps (NETs) release is a major cause of organ failure and mortality in sepsis. Targeting Gasdermin D (GSDMD) can restrain NETs formation, which is promising for sepsis management. However, no medicine is identified without severe safety concerns for this purpose. Xuebijing injection (XBJ) has been demonstrated to alleviate the clinical symptoms of COVID-19 and sepsis patients, but there are not enough animal studies to reveal its mechanisms in depth. Therefore, we wondered whether XBJ relieved pulmonary damage in sepsis by suppressing NETs formation and adopted a clinically relevant polymicrobial infection model to test this hypothesis. Firstly, XBJ effectively reversed lung injury caused by sepsis and restrained neutrophils recruitment to lung by down-regulating proinflammatory chemokines, such as CSF-3, CXCL-2, and CXCR-2. Strikingly, we found that XBJ significantly reduced the expressions of NETs component proteins, including citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). GSDMD contributes to the production of NETs in sepsis. Notably, XBJ exhibited a reduced effect on the expressions of GSDMD and its upstream regulators. Besides, we also revealed that XBJ reversed NETs formation by inhibiting the expressions of GSDMD-related genes. Collectively, we demonstrated XBJ protected against sepsis-induced lung injury by reversing GSDMD-related pathway to inhibit NETs formation.

Global incidence pattern and factors associated with common cutaneous reactions related to COVID-19 vaccination of 2.55 million participants in real-world settings: A systematic review and meta-analysis.

Background: Understanding the incidence pattern of cutaneous reactions is crucial for promoting COVID-19 vaccination. We aimed to report the global incidence pattern of, and factors associated with common cutaneous reactions related to COVID-19 vaccination in real-world settings. Methods: We searched five databases (PubMed, Web of Science, Embase, CNKI, and Wanfang) from inception to May 13, 2022, for studies reporting the incidence of common cutaneous reactions related to COVID-19 vaccines in real-world settings. The outcomes were the systematic skin reactions (rash and urticaria) and the local injection site reactions (pain, swelling, redness, and erythema). We conducted random-effects meta-analyses and explored associated factors using multi-step statistical analyses. Results: We included 35 studies and assessed 2 549 968 participants from 23 countries. The pooled incidence of overall systemic skin reactions was 3.8% (95% confidence interval (CI) = 2.4%-5.5%) with short duration (about one week). Specifically, the pooled incidence rates of rash and urticaria were 3.0% (95% CI = 2.1%-3.9%) and 1.1% (95% CI = 0.7%-1.5%), respectively. For overall local injection site reactions, the pooled incidence was 72.4% (95% CI = 65.7%-78.7%) with short duration (1 to 4.5 days). Except for local pain (72.2%, 95% CI = 65.3%-78.5%), other localized reactions had low incidence, including swelling (13.3%, 95% CI = 9.5%-17.7%), redness (11.5%, 95% CI = 5.7%-19.0%), and erythema (5.8%, 95% CI = 0.7%-15.4%). Geographically, different distribution patterns were observed for these reactions. Regarding associated factors, mRNA vaccines showed lower incidence of urticaria (P < 0.001). Asia population showed higher incidence of urticaria (P < 0.001). We observed lower incidence rates of overall local injection site reactions and pain among inactivated vaccines (P < 0.001). We found no significant difference among reactions between the first and the second dose of vaccines. Conclusions: We examined the global incidence pattern of common cutaneous reactions related to COVID-19 vaccination and found low incidence and short duration of systemic skin reactions and local injection site reactions (except for pain); discrepancies in these reactions were observed across different vaccine types. The cutaneous side effects related to COVID-19 vaccination do not seem to cause concern. Registration: PROSPERO: CRD42021258012.

Applying two behavioral theories to predict the willingness to receive COVID-19 vaccine booster in the elderly: A cross-sectional study.

BACKGROUND: The COVID-19 vaccination booster can effectively protect the elderly from infection while also lowering the risk of serious illness and death. However, barriers remain in willingness of the elderly to boost vaccination. OBJECTIVE: Using the protection motivation theory (PMT) and the theory of planned behavior (TPB), to study the factors that influence willingness of the elderly to get the COVID-19 vaccine booster. METHODS: The elderly who visited three randomly selected medical institutions in Nanjing's core urban region between March and April 2022 were chosen as study participants. A face-to-face survey was conducted using purposeful sampling and a self-designed questionnaire. The questionnaire contained sociodemographic characteristics, the elderly's willingness to obtain a COVID-19 vaccine booster, and psychosocial cognitive components based on the PMT and TPB. SmartPLS 3.0 was used to conduct structural equation modeling. RESULTS: 214 participants were included in the analysis. The combined model of the two behavioral theories explained the willingness to accept COVID-19 vaccine booster well with R2 of 0.490. Self-efficacy (ß = 0.315) was the strongest predictor of vaccine booster willingness. Subjective norms (ß = 0.160), perceived severity (ß = 0.157), and perceived vulnerability (ß = 0.159) also showed positive effects on vaccine booster willingness, while response cost (ß = -0.143) had a negative effect on the willingness. No significant association between attitudes, response efficacy and the willingness was discovered. CONCLUSION: The willingness of the elderly to receive the COVID-19 vaccine booster was affected by psychosocial cognitive factors. This study supports the applicability of the PMT and TPB models to interpret the willingness of the elderly in such areas.

Xuebijing injection inhibited neutrophil extracellular traps to reverse lung injury in sepsis mice via reducing Gasdermin D

The mortality of sepsis and septic shock remains high worldwide. Neutrophil extracellular traps (NETs) release is a major cause of organ failure and mortality in sepsis. Targeting Gasdermin D (GSDMD) can restrain NETs formation, which is promising for sepsis management. However, no medicine is identified without severe safety concerns for this purpose. Xuebijing injection (XBJ) has been demonstrated to alleviate the clinical symptoms of COVID-19 and sepsis patients, but there are not enough animal studies to reveal its mechanisms in depth. Therefore, we wondered whether XBJ relieved pulmonary damage in sepsis by suppressing NETs formation and adopted a clinically relevant polymicrobial infection model to test this hypothesis. Firstly, XBJ effectively reversed lung injury caused by sepsis and restrained neutrophils recruitment to lung by down-regulating proinflammatory chemokines, such as CSF-3, CXCL-2, and CXCR-2. Strikingly, we found that XBJ significantly reduced the expressions of NETs component proteins, including citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). GSDMD contributes to the production of NETs in sepsis. Notably, XBJ exhibited a reduced effect on the expressions of GSDMD and its upstream regulators. Besides, we also revealed that XBJ reversed NETs formation by inhibiting the expressions of GSDMD-related genes. Collectively, we demonstrated XBJ protected against sepsis-induced lung injury by reversing GSDMD-related pathway to inhibit NETs formation. Graphical

Behavioral Intention and Its Predictors toward COVID-19 Booster Vaccination among Chinese Parents: Applying Two Behavioral Theories.

The booster vaccination of COVID-19 is being implemented in most parts of the world. This study used behavioral psychology to investigate the predictors of parents' intentions regarding the COVID-19 booster vaccination for their children. This is a cross-sectional study with a self-designed questionnaire based on two behavioral theories-protective motivation theory (PMT) and theory of planned behavior (TPB). A stratified multi-stage sampling procedure was conducted in Nanjing, China, and multivariable regression analyses were applied to examine the parents' intentions. The intention rate was 87.3%. The response efficacy (ORa = 2.238, 95% CI: 1.360-3.682) and response cost (ORa = 0.484, 95% CI: 0.319-0.732) in the PMT, were significant psychological predictors of parents' intentions, and so were the attitude (ORa = 2.619, 95% CI: 1.480-4.636) and behavioral control (ORa = 3.743, 95% CI: 2.165-6.471) in the TPB. The findings of crucial independent predictors in the PMT and TPB constructs inform the evidence-based formulation and implementation of strategies for booster vaccination in children.

Behavioral Intention and Its Predictors toward COVID-19 Booster Vaccination among Chinese Parents: Applying Two Behavioral Theories

The booster vaccination of COVID-19 is being implemented in most parts of the world. This study used behavioral psychology to investigate the predictors of parents' intentions regarding the COVID-19 booster vaccination for their children. This is a cross-sectional study with a self-designed questionnaire based on two behavioral theories-protective motivation theory (PMT) and theory of planned behavior (TPB). A stratified multi-stage sampling procedure was conducted in Nanjing, China, and multivariable regression analyses were applied to examine the parents' intentions. The intention rate was 87.3%. The response efficacy (ORa = 2.238, 95% CI: 1.360–3.682) and response cost (ORa = 0.484, 95% CI: 0.319–0.732) in the PMT, were significant psychological predictors of parents' intentions, and so were the attitude (ORa = 2.619, 95% CI: 1.480–4.636) and behavioral control (ORa = 3.743, 95% CI: 2.165–6.471) in the TPB. The findings of crucial independent predictors in the PMT and TPB constructs inform the evidence-based formulation and implementation of strategies for booster vaccination in children.

Multiomics integration-based molecular characterizations of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly became a global health challenge, leading to unprecedented social and economic consequences. The mechanisms behind the pathogenesis of SARS-CoV-2 are both unique and complex. Omics-scale studies are emerging rapidly and offer a tremendous potential to unravel the puzzle of SARS-CoV-2 pathobiology, as well as moving forward with diagnostics, potential drug targets, risk stratification, therapeutic responses, vaccine development and therapeutic innovation. This review summarizes various aspects of understanding multiomics integration-based molecular characterizations of COVID-19, which to date include the integration of transcriptomics, proteomics, genomics, lipidomics, immunomics and metabolomics to explore virus targets and developing suitable therapeutic solutions through systems biology tools. Furthermore, this review also covers an abridgment of omics investigations related to disease pathogenesis and virulence, the role of host genetic variation and a broad array of immune and inflammatory phenotypes contributing to understanding COVID-19 traits. Insights into this review, which combines existing strategies and multiomics integration profiling, may help further advance our knowledge of COVID-19.

Determinants of physicians' online medical services uptake: a cross-sectional study applying social ecosystem theory.

OBJECTIVE: To investigate the determinants of willingness and practice of physicians' online medical services (OMS) uptake based on social ecosystem theory, so as to formulate OMS development strategies. DESIGN: Cross-sectional survey. SETTING: Research was conducted in two comprehensive hospitals and two community hospitals in Jiangsu, China, and the data were gathered from 1 June to 31 June 2020. PARTICIPANTS: With multistage sampling, 707 physicians were enrolled in this study. OUTCOME MEASURE: Descriptive statistics were reported for the basic characteristics. χ2 test, Mann-Whitney U test and Spearman's correlation analysis were used to perform univariate analysis. Linear regression and logistic regression were employed to examine the determinants of physicians' OMS uptake willingness and actual uptake, respectively. RESULTS: The mean score of the physicians' OMS uptake willingness was 17.33 (range 5-25), with an SD of 4.39, and 53.3% of them reported having conducted OMS. In the micro system, factors positively associated with willingness included holding administrative positions (b=1.03, p<0.05), OMS-related awareness (b=1.32, p<0.001) and OMS-related skills (b=4.88, p<0.001); the determinants of actual uptake included holding administrative positions (OR=2.89, 95% CI 1.59 to 5.28, p<0.01), OMS-related awareness (OR=1.90, 95% CI 1.22 to 2.96, p<0.01), OMS-related skills (OR=2.25, 95% CI 1.35 to 3.74, p<0.01) and working years (OR=2.44, 95% CI 1.66 to 3.59, p<0.001). In the meso system, the hospital's incentive mechanisms (b=0.78, p<0.05) were correlated with willingness; hospital advocated for OMS (OR=2.34, 95% CI 1.21 to 4.52, p<0.05), colleagues' experiences (OR=3.81, 95% CI 2.25 to 6.45, p<0.001) and patients' consultations (OR=2.93, 95% CI 2.02 to 4.25, p<0.001) were determinants of actual uptake. In the macro system, laws and policies were correlated with willingness (b=0.73, p<0.05) and actual uptake (OR=1.98, 95% CI 1.31 to 2.99, p<0.01); media orientation was also associated with willingness (b=0.74, p<0.05). CONCLUSION: Multiple determinants influence physicians' OMS application. Comprehensive OMS promotion strategies should be put forward from multidimensional perspectives including the micro, meso and macro levels.

COVID-19 Vaccination Acceptance Among Healthcare Workers and Non-healthcare Workers in China: A Survey.

Background: The coronavirus pneumonia is still spreading around the world. Much progress has been made in vaccine development, and vaccination will become an inevitable trend in the fight against this pandemic. However, the public acceptance of COVID-19 vaccination still remains uncertain. Methods: An anonymous questionnaire was used in Wen Juan Xing survey platform. All the respondents were divided into healthcare workers and non-healthcare workers. Multinomial logistic regression analyses were performed to identify the key sociodemographic, cognitive, and attitude associations among the samples of healthcare workers and non-healthcare workers. Results: A total of 2,580 respondents completed the questionnaire, including 1,329 healthcare workers and 1,251 non-healthcare workers. This study showed that 76.98% of healthcare workers accepted the COVID-19 vaccine, 18.28% workers were hesitant, and 4.74% workers were resistant. Among the non-healthcare workers, 56.19% workers received the COVID-19 vaccine, 37.57% workers were hesitant, and 6.24% workers were resistant. Among the healthcare workers, compared with vaccine recipients, vaccine-hesitant individuals were more likely to be female (AOR = 1.52, 95% CI: 1.12-2.07); vaccine-resistant individuals were more likely to live in the suburbs (AOR = 2.81, 95% CI: 1.44-3.99) with an income of 10,000 RMB or greater (AOR = 2.00, 95% CI: 1.03-3.90). Among the non-healthcare workers, vaccine-hesitant individuals were more likely to be female (AOR = 1.66, 95% CI: 1.31-2.11); vaccine-resistant individuals were also more likely to be female (AOR = 1.87, 95% CI: 1.16-3.02) and older than 65 years (AOR = 4.96, 95% CI: 1.40-7.62). There are great differences between healthcare workers and non-healthcare workers in their cognition and attitude toward vaccines. Conclusions: Our study shows that healthcare workers are more willing to be vaccinated than non-healthcare workers. Current vaccine safety issues continue to be a major factor affecting public acceptance, and to expand vaccine coverage in response to the COVID-19 pandemic, appropriate vaccination strategies and immunization programs are essential, especially for non-healthcare workers.

Exploring the impact of the COVID-19 epidemic on the medical emergency calls and calls for cardiovascular diseases in Hangzhou, China.

AIMS: We aimed to evaluate the impact of the COVID-19 epidemic on emergency and cardiovascular disease-related calls in Hangzhou, China. METHODS: We conducted a single-center retrospective study, collecting data on emergency calls to the Hangzhou Emergency Center (HEC) during the COVID-19 epidemic (January 20, 2020, to March 15, 2020). Data were compared with the same period in 2019. RESULTS: Compared to 2019, the number of emergency calls has dropped by 21.63%, ambulance calls by 29.02%, rescue calls by 22.57%, and cardiovascular disease-related emergency calls by 32.86%. The numbers of emergency, ambulance, and rescue calls in 2020 were significantly lower than in 2019. CONCLUSIONS: During the COVID-19 epidemic in Hangzhou, the numbers of emergency and cardiovascular disease-related calls have decreased significantly. These results point to a severe social problem that requires the attention of the medical community and the government.

Risk of Malnutrition Is Common in Patients with Coronavirus Disease 2019 (COVID-19) in Wuhan, China: A Cross-sectional Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has quickly spread across the world. However, the nutritional status of COVID-19 patients has not yet been extensively examined. OBJECTIVES: The aim of this study was to evaluate the nutritional status of COVID-19 patients and to identify factors independently associated with malnutrition risk. METHODS: In this single-center, cross-sectional study, we analyzed data from 760 hospitalized COVID-19 patients between 29 January 2020 and 15 March 2020. Based on the Nutrition Risk Screening (NRS) 2002 score, we divided patients into the normal nutrition group (NRS score <3) and the malnutrition risk group (NRS score ≥3). The associations of age, gender, symptoms, comorbidities, BMI, serum albumin and prealbumin concentrations, disease severity, activities of daily living (ADL) score, and clinical outcomes with malnutrition risk were analyzed. Multivariable logistic regression analysis was used to identify independent factors associated with malnutrition risk. RESULTS: Of patients with COVID-19, 82.6% were at risk of malnutrition. There were statistical differences in the age, incidence of fever, BMI, serum albumin and prealbumin concentrations, ADL score, and disease severity between the 2 groups. Multivariable logistic regression analysis revealed that age ≥65 y (vs. <65 y; OR: 5.40; P < 0.001), serum albumin <35 g/L (vs. ≥35 g/L; OR: 3.61; P < 0.001), serum prealbumin <150 mg/L (vs. ≥150 mg/L; OR: 2.88; P = 0.042), critical cases (vs. moderate cases; OR: 4.46; P < 0.001), ADL score 41-60 (vs. ADL score 100; OR: 4.50; P = 0.012), and ADL score ≤40 (vs. ADL score 100; OR: 9.49; P < 0.001) were significantly associated with the risk of malnutrition in COVID-19 patients. CONCLUSIONS: This study showed that prevalence of malnutrition risk was high in COVID-19 patients. Older age, low serum albumin and prealbumin concentrations, ADL score <60, and disease severity were independent factors associated with malnutrition risk.

Laboratory diagnosis of COVID-19 in China: A review of challenging cases and analysis.

Since the initial emergence of coronavirus disease 2019 (COVID-19) in Wuhan, Hubei province, China, a rapid spread of the disease occurred around the world, rising to become an international global health concern at pandemic level. In the face of this medical challenge threatening humans, the development of rapid and accurate methods for early screening and diagnosis of COVID-19 became crucial to containing the emerging public health threat, and prevent further spread within the population. Despite the large number of COVID-19 confirmed cases in China, some problematic cases with inconsistent laboratory testing results, were reported. Specifically, a high false-negative rate of 41% on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by real-time reverse transcription-polymerase chain reaction (qRT-PCR) assays was observed in China. Although serological testing has been applied worldwide as a complementary method to help identify SARS-CoV-2, several limitations on its use have been reported in China. Therefore, the use of both qRT-PCR and serological testing in the diagnosis of COVID-19 in China and elsewhere, presented considerable challenges, but when used in combination, can be valuable tools in the fight against COVID-19. In this review, we give an overview of the advantages and disadvantages of different molecular techniques for SARS-CoV-2 detection that are currently used in several labs, including qRT-PCR, gene sequencing, loop-mediated isothermal amplification (LAMP), nucleic acid mass spectrometry (MS), and gene editing technique based on clustered regularly interspaced short palindromic repeats (CRISPR/Cas13) system. Then we mainly review and analyze some causes of false-negative qRT-PCR results, and how to resolve some of the diagnostic dilemma.

Effect of COVID-19 outbreak on the treatment time of patients with acute ST-segment elevation myocardial infarction.

OBJECTIVE: To explore the effect of COVID-19 outbreak on the treatment time of patients with ST-segment elevation myocardial infarction (STEMI) in Hangzhou, China. METHODS: We retrospectively reviewed the data of STEMI patients admitted to the Hangzhou Chest Pain Center (CPC) during a COVID-19 epidemic period in 2020 (24 cases) and the same period in 2019 (29 cases). General characteristics of the patients were recorded, analyzed, and compared. Moreover, we compared the groups for the time from symptom onset to the first medical contact (SO-to-FMC), time from first medical contact to balloon expansion (FMC-to-B), time from hospital door entry to first balloon expansion (D-to-B), and catheter room activation time. The groups were also compared for postoperative cardiac color Doppler ultrasonographic left ventricular ejection fraction (LVEF),the incidence of major adverse cardiovascular and cerebrovascular events (MACCE),Kaplan-Meier survival curves during the 28 days after the operation. RESULTS: The times of SO-to-FMC, D-to-B, and catheter room activation in the 2020 group were significantly longer than those in the 2019 group (P < 0.05). The cumulative mortality after the surgery in the 2020 group was significantly higher than the 2019 group (P < 0.05). CONCLUSION: The pre-hospital and in-hospital treatment times of STEMI patients during the COVID-19 epidemic were longer than those before the epidemic. Cumulative mortality was showed in Kaplan-Meier survival curves after the surgery in the 2020 group was significantly different higher than the 2019 group during the 28 days.The diagnosis and treatment process of STEMI patients during an epidemic should be optimized to improve their prognosis.

From SARS to COVID-19: What we have learned about children infected with COVID-19.

INTRODUCTION: Coronaviruses, both SARS-CoV and SARS-CoV-2, first appeared in China. They have certain biological, epidemiological and pathological similarities. To date, research has shown that their genes exhibit 79% of identical sequences and the receptor-binding domain structure is also very similar. There has been extensive research performed on SARS; however, the understanding of the pathophysiological impact of coronavirus disease 2019 (COVID-19) is still limited. METHODS: This review drew upon the lessons learnt from SARS, in terms of epidemiology, clinical characteristics and pathogenesis, to further understand the features of COVID-19. RESULTS: By comparing these two diseases, it found that COVID-19 has quicker and wider transmission, obvious family agglomeration, and higher morbidity and mortality. Newborns, asymptomatic children and normal chest imaging cases emerged in COVID-19 literature. Children starting with gastrointestinal symptoms may progress to severe conditions and newborns whose mothers are infected with COVID-19 could have severe complications. The laboratory test data showed that the percentage of neutrophils and the level of LDH is higher, and the number of CD4+ and CD8+T-cells is decreased in children's COVID-19 cases. CONCLUSION: Based on these early observations, as pediatricians, this review put forward some thoughts on children's COVID-19 and gave some recommendations to contain the disease.