Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in sleep in which the airways narrow or collapse during sleep, causing obstructive sleep apnea. The prevalence of OSAS continues to rise worldwide, particularly in middle-aged and elderly individuals. The mechanism of upper airway collapse is incompletely understood but is associated with several factors, including obesity, craniofacial changes, altered muscle function in the upper airway, pharyngeal neuropathy, and fluid shifts to the neck. The main characteristics of OSAS are recurrent pauses in respiration, which lead to intermittent hypoxia (IH) and hypercapnia, accompanied by blood oxygen desaturation and arousal during sleep, which sharply increases the risk of several diseases. This paper first briefly describes the epidemiology, incidence, and pathophysiological mechanisms of OSAS. Next, the alterations in relevant signaling pathways induced by IH are systematically reviewed and discussed. For example, IH can induce gut microbiota (GM) dysbiosis, impair the intestinal barrier, and alter intestinal metabolites. These mechanisms ultimately lead to secondary oxidative stress, systemic inflammation, and sympathetic activation. We then summarize the effects of IH on disease pathogenesis, including cardiocerebrovascular disorders, neurological disorders, metabolic diseases, cancer, reproductive disorders, and COVID-19. Finally, different therapeutic strategies for OSAS caused by different causes are proposed. Multidisciplinary approaches and shared decision-making are necessary for the successful treatment of OSAS in the future, but more randomized controlled trials are needed for further evaluation to define what treatments are best for specific OSAS patients.

Unequal impact of the COVID-19 pandemic on paediatric cancer care: a population-based cohort study in China.

BACKGROUND: The COVID-19 pandemic has had widespread adverse collateral effects on health care delivery for non-COVID-19 disease conditions. Paediatric oncology care is reliant on prompt testing and diagnosis and on timely and coordinated multimodal treatment, all of which have been impacted by the pandemic. This study aimed to quantify the initial and enduring effects of the COVID-19 pandemic on the utilization of paediatric cancer care and to examine whether the pandemic differentially impacted specific demographic groups. METHOD: We performed an interrupted time series analysis using negative binomial regression to estimate the change in the monthly admissions for paediatric cancer patients (Age 0-17) associated with the COVID-19 pandemic and subsequent lockdown policies. We obtained data from deidentified individual electronic medical records of paediatric cancer inpatients admitted between January 1, 2015 and May 31, 2021 to a tertiary hospital that provides general and specialized healthcare services to an estimated population of 8.4 million in Jining China. Relative risk (RR) estimates representing monthly admissions compared with expected admissions had the pandemic not occurred were derived. The number of inpatient admissions lost due to the pandemic were estimated. FINDINGS: The overall denominator for the paediatric population was 1 858 209 individuals in January 2015, which increased to 2 043 803 by May 2021. In total, there were 4 901 admissions for paediatric cancer during the study period, including 1 479 (30%) since February 2020 when the lockdown was implemented. A 33% reduction (95% CI: -43% to -22%) in admissions was observed in February 2020, with the largest relative reduction (-48%, 95% CI: -64% to -24%) among first-time admissions and admissions for patients from rural districts (-46%, 95% CI: -55% to -36%). Admissions quickly rebounded in March 2020 when many government-imposed mobility restrictions were lifted, and continued to resume gradually over time since April 2020, leading to a full recovery as of November 2020. However, the recovery for first-time admissions, and among female patients, younger patients (<5 years) and patients from rural districts was slower over time and incomplete (first-time admissions and rural patients) as of January 2021. INTERPRETATION: The COVID-19 pandemic has had substantial impact on the timely utilization of paediatric oncology services in China, particularly in the early stage of the first wave. Importantly, some population groups were disproportionately affected and the recovery of admissions among those subgroups has been slow and incomplete, warranting targeted approaches to address potentially exacerbated gender and socio-economic inequalities in access to healthcare resources.

One-Step Formation of Targeted Liposomes in a Versatile Microfluidic Mixing Device.

Targeted liposomes, as a promising carrier, have received tremendous attention in COVID-19 vaccines, molecular imaging, and cancer treatment, due to their enhanced cellular uptake and payload accumulation at target sites. However, the conventional methods for preparing targeted liposomes still suffer from limitations, including complex operation, time-consuming, and poor reproducibility. Herein, a facile and scalable strategy is developed for one-step construction of targeted liposomes using a versatile microfluidic mixing device (MMD). The engineered MMD provides an advanced synthesis platform for multifunctional liposome with high production rate and controllability. To validate the method, a programmed death-ligand 1 (PD-L1)-targeting aptamer modified indocyanine green (ICG)-liposome (Apt-ICG@Lip) is successfully constructed via the MMD. ICG and the PD-L1-targeting aptamer are used as model drug and targeting moiety, respectively. The Apt-ICG@Lip has high encapsulation efficiency (89.9 ± 1.4%) and small mean diameter (129.16 ± 5.48 nm). In vivo studies (PD-L1-expressing tumor models) show that Apt-ICG@Lip can realize PD-L1 targeted photoacoustic imaging, fluorescence imaging, and photothermal therapy. To verify the versatility of this approach, various targeted liposomes with different functions are further prepared and investigated. These experimental results demonstrate that this method is concise, efficient, and scalable to prepare multifunctional targeted liposomal nanoplatforms for molecular imaging and disease theranostics.

Repeat-Dose Toxicity of Candidate Omicron COVID-19 Vaccine in Sprague-Dawley Rats

Due to a large number of mutations in the spike protein and immune escape, the Omicron variant (B.1.1.529) has become a predominant variant of concern (VOC) strain. To prevent the disease, we developed a candidate inactivated vaccine (Omicron COVID-19 Vaccine (Vero Cell), Inactivated). To evaluate the safety of the vaccine, we tested the repeat-dose toxicity in Sprague-Dawley (SD) rats. The doses were administered randomly to three groups: physiological saline solution (control), aluminum adjuvant in PBS solution adjuvant (adjuvant group), and low-dose and high-dose omicron vaccines (vaccine group) for 6 weeks. The SD rats were allowed to recover for 4 weeks after withdrawal. We evaluated the physiological condition of the rats, including their ophthalmological condition, body weight, food intake, body temperature, blood biochemistry, urine, neutralizing antibody, inflammation at the injection site, and organs weight. In summary, no dose-dependent adverse toxicological changes were observed, and a recovery trend was obvious, which proved the preclinical safety of the candidate omicron vaccine and provided evidence for clinical trials in humans. [ FROM AUTHOR] Copyright of COVID is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Repeat-Dose Toxicity of Candidate Omicron COVID-19 Vaccine in Sprague-Dawley Rats

Due to a large number of mutations in the spike protein and immune escape, the Omicron variant (B.1.1.529) has become a predominant variant of concern (VOC) strain. To prevent the disease, we developed a candidate inactivated vaccine (Omicron COVID-19 Vaccine (Vero Cell), Inactivated). To evaluate the safety of the vaccine, we tested the repeat-dose toxicity in Sprague-Dawley (SD) rats. The doses were administered randomly to three groups: physiological saline solution (control), aluminum adjuvant in PBS solution adjuvant (adjuvant group), and low-dose and high-dose omicron vaccines (vaccine group) for 6 weeks. The SD rats were allowed to recover for 4 weeks after withdrawal. We evaluated the physiological condition of the rats, including their ophthalmological condition, body weight, food intake, body temperature, blood biochemistry, urine, neutralizing antibody, inflammation at the injection site, and organs weight. In summary, no dose-dependent adverse toxicological changes were observed, and a recovery trend was obvious, which proved the preclinical safety of the candidate omicron vaccine and provided evidence for clinical trials in humans.

Metabolic and Proteomic Profiles Associated with Immune Responses Induced by Different Inactivated SARS-CoV-2 Vaccine Candidates.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, the virus has been mutating continuously, resulting in the continuous emergence of variants and creating challenges for epidemic prevention and control. Here, we immunized mice with different vaccine candidates, revealing the immune, protein, and metabolomic changes that take place in vaccines composed of different variants. We found that the prototype strain and Delta- and Omicron-variant inactivated vaccine candidates could all induce a high level of neutralizing antibodies and cellular immunity responses in mice. Next, we found that the metabolic and protein profiles were changed, showing a positive association with immune responses, and the level of the change was distinct in different inactivated vaccines, indicating that amino acid variations could affect metabolomics and proteomics. Our findings reveal differences between vaccines at the metabolomic and proteomic levels. These insights provide a novel direction for the immune evaluation of vaccines and could be used to guide novel strategies for vaccine design.

Vaccination with Omicron Inactivated Vaccine in Pre-vaccinated Mice Protects against SARS-CoV-2 Prototype and Omicron Variants.

In response to the fast-waning immune response and the great threat of the Omicron variant of concern (VOC) to the public, we report the pilot-scale production of an inactivated Omicron vaccine candidate that induces high levels of neutralizing antibody titers to protect against the Omicron virus. Here, we demonstrate that the inactivated Omicron vaccine is safe and effective in recalling immune responses to the HB02, Omicron, and Delta viruses after one or two doses of BBIBP-CorV. In addition, the efficient productivity and good genetic stability of the manufactured inactivated vaccine is proved. These results support the further evaluation of the Omicron vaccine in a clinical trial.

Elevated D-dimer and Adverse In-hospital Outcomes in COVID-19 Patients and Synergism with Hyperglycemia.

Aim: One of the most common laboratory findings in COVID-19 patients has been observed to be hypercoagulability with elevated D-dimer levels. An activation of thrombosis may be generated by hyperglycemia. We aimed to explore the association between D-dimer and in-hospital outcomes, and evaluate the synergistic effect between elevated D-dimer and hyperglycemia on COVID-19 prognosis. Methods: A retrospective cohort study was undertaken with 2467 COVID-19 inpatients. D-dimer and fasting blood glucose (FBG) on admission and adverse in-hospital outcomes (events of death and aggravated severity) were collected. Cox proportional risk model was performed to assess the association of D-dimer and adverse in-hospital outcomes, and the combined effects of D-dimer and FBG. Results: Among these COVID-19 patients, 1100 (44.6%) patients had high D-dimer (≥0.50 mg/L). Patients with high D-dimer were older, with higher FBG (≥7.00 mmol/L), and had significantly higher adjusted risk of adverse in-hospital outcomes when comparing with those who with D-dimer<0.50 mg/L (hazard ratio, 2.73; 95% confidence interval, 1.46-5.11). Moreover, patients with high FBG and D-dimer levels had an increasing risk (hazard ratio, 5.72; 95% confidence interval: 2.65-12.34) than those with normal FBG and D-dimer. Conclusion: Risk of adverse in-hospital outcomes is higher among patients with high D-dimer levels. Additionally, this study found for the first time that elevated D-dimer and hyperglycemia had a synergistic effect on COVID-19 prognosis, and this risk was independent of diabetes history.

Immunogenicity Evaluating of the Multivalent COVID-19 Inactivated Vaccine against the SARS-CoV-2 Variants.

It has been reported that the novel coronavirus (COVID-19) has caused more than 286 million cases and 5.4 million deaths to date. Several strategies have been implemented globally, such as social distancing and the development of the vaccines. Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have appeared, such as Alpha, Beta, Gamma, Delta, and Omicron. With the rapid spread of the novel coronavirus and the rapidly changing mutants, the development of a broad-spectrum multivalent vaccine is considered to be the most effective way to defend against the constantly mutating virus. Here, we evaluated the immunogenicity of the multivalent COVID-19 inactivated vaccine. Mice were immunized by multivalent COVID-19 inactivated vaccine, and the neutralizing antibodies in serum were analyzed. The results show that HB02 + Delta + Omicron trivalent vaccine could provide broad spectrum protection against HB02, Beta, Delta, and Omicron virus. Additionally, the different multivalent COVID-19 inactivated vaccines could enhance cellular immunity. Together, our findings suggest that the multivalent COVID-19 inactivated vaccine can provide broad spectrum protection against HB02 and other virus variants in humoral and cellular immunity, providing new ideas for the development of a broad-spectrum COVID-19 vaccine.

Dynamic pyrolytic reaction mechanisms, pathways, and products of medical masks and infusion tubes.

Given the COVID-19 epidemic, the quantity of hazardous medical wastes has risen unprecedentedly. This study characterized and verified the pyrolysis mechanisms and volatiles products of medical mask belts (MB), mask faces (MF), and infusion tubes (IT) via thermogravimetric, infrared spectroscopy, thermogravimetric-Fourier transform infrared spectroscopy, and pyrolysis-gas chromatography/mass spectrometry analyses. Iso-conversional methods were employed to estimate activation energy, while the best-fit artificial neural network was adopted for the multi-objective optimization. MB and MF started their thermal weight losses at 375.8 °C and 414.7 °C, respectively, while IT started to degrade at 227.3 °C. The average activation energies were estimated at 171.77, 232.79, 105.14, and 205.76 kJ/mol for MB, MF, and the first and second IT stages, respectively. Nucleation growth for MF and MB and geometrical contraction for IT best described the pyrolysis behaviors. Their main gaseous products were classified, with a further proposal of their initial cracking mechanisms and secondary reaction pathways.

Patients with COVID-19 and HBV Coinfection are at Risk of Poor Prognosis.

INTRODUCTION: This study aimed to determine whether there is a difference in the risk of death/critical illness between different stages of hepatitis B virus (HBV) (resolved hepatitis B, HBeAg (-) chronic hepatitis B [CHB]/infection, HBeAg (+) CHB/infection, and HBV reactivation) coinfected with coronavirus disease 2019 (COVID-19); and if there is a difference, whether it is due to abnormal liver function and to what extent. METHODS: This cohort study included all COVID-19 inpatients of a single-center tertiary care academic hospital in Wuhan, Hubei, China, between February 4, 2020, and follow-up to April 14, 2020. A total of 2899 patients with COVID-19 were included as participants in this study, and they were divided into five groups based on hepatitis B infection status. Follow-up was conducted for mortality and ICU admission during hospitalization. RESULTS: The median follow-up time was 39 days (IQR, 30-50), with 66 deaths and 126 ICU admissions. After adjustment, compared with patients without CHB, the hazard ratio (HR) for ICU admission was 1.86 (95% CI: 1.05-3.31) for patients with HBeAg (+) CHB/infection. The HR for death was 3.19 (95% CI: 1.62-6.25) for patients with HBeAg (+) CHB/infection. The results for the mediating effect indicated that the total effect of HBeAg (+) CHB/infection on death/ICU stay was partially mediated by abnormal liver function, which accounted for 79.60% and 73.53%, respectively. CONCLUSION: Patients with COVID-19 coinfected with HBV at the HBeAg (+) CHB/infection stage have an increased risk of poor prognosis, and abnormal liver function partially mediates this increased risk of poor prognosis caused by the coinfection.

The association between BMI and metabolically unhealthy status with COVID-19 mortality: Based on 3019 inpatients from Wuhan, China.

BACKGROUND AND AIMS: Patients with multiple metabolic diseases are at high risk for the occurrence and death of COVID-19. Little is known about patients with underweight and metabolically healthy obesity. The aim of this study is to evaluate the impact of BMI and COVID-19 mortality in hospitalized patients, and also explore the association in different metabolically healthy (MHS) and unhealthy status (MUS). METHODS AND RESULTS: A retrospective cohort study based on 3019 inpatients from Wuhan was conducted. Included patients were classified into four groups according the BMI level (underweight, normal weight, overweight and obesity), and patients with at least one of the metabolic abnormalities (diabetes, hypertension, dyslipidemia) was defined as MUS. Multiple Cox model was used to calculate the hazard ratio (HR). Compared to patients with normal weight, the HRs of overweight and obesity for COVID-19 mortality were 1.91 (95%CI:1.02-3.58) and 2.54 (95%CI:1.22-5.25) respectively in total patients, and 2.58 (95%CI:1.16-5.75) and 3.89 (95%CI:1.62-9.32) respectively in the elderly. The HR of underweight for COVID-19 mortality was 4.58 (95%CI:1.56-13.48) in the elderly. For different metabolic statuses, both underweight, overweight and obesity had obviously negative association with COVID-19 mortality in total and elderly patients with MUS. However, no significance was found in non-elderly and patients with MHS. CONCLUSION: Not only overweight or obesity, but also underweight can be associated with COVID-9 mortality, especially in the elderly and in patients with MUS. More large-scale studies are needed for patients with underweight and metabolically healthy overweight or obesity.

Suspected SARS-CoV-2 infection with fever and coronary heart disease: A case report.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Suspected cases accounted for a large proportion in the early stage of the COVID-19 outbreak. The deviation of the nucleic acid test by throat swab (the current gold standard of COVID-19) caused by variation in sampling techniques and reagent kits and coupled with nonspecific clinical manifestations make confirmation of the suspected cases difficult. Proper management of the suspected cases of COVID-19 is crucial for disease control. CASE SUMMARY: A 65-year-old male presented with fever, lymphopenia, and chest computed tomography (CT) images similar to COVID-19 after percutaneous coronary intervention. The patient was diagnosed as having bacterial pneumonia with cardiogenic pulmonary edema instead of COVID-19. This was based on four negative results for throat swab detection of SARS-CoV-2 nucleic acid using reverse transcriptase-polymerase chain reaction assay and one negative result for serological antibody of SARS-CoV-2 with the serological assay. Additionally, the distribution of ground-glass opacities and thickened blood vessels from the CT images differed from COVID-19 features, which further supported the exclusion of COVID-19. CONCLUSION: Distinguishing COVID-19 patients from those with bacterial pneumonia with cardiogenic pulmonary edema can be difficult. Therefore, it requires serious identification.

Characterizing News Report of the Substandard Vaccine Case of Changchun Changsheng in China: A Text Mining Approach.

Background: The substandard vaccine case of that broke out in July 2018 in China triggered an outburst of news reports both domestically and aboard. Distilling the abundant textual information is helpful for a better understanding of the character during this public event. Methods: We collected the texts of 2211 news reports from 83 mainstream media outlets in China between 15 July and 25 August 2018, and used a structural topic model (STM) to identify the major topics and features that emerged. We also used dictionary-based sentiment analysis to uncover the sentiments expressed by the topics as well as their temporal variations. Results: The main topics of the news report fell into six major categories, including: (1) Media Investigation, (2) Response from the Top Authority, (3) Government Action, (4) Knowledge Dissemination, (5) Finance Related and (6) Commentary. The topic prevalence shifted during different stages of the events, illustrating the actions by the government. Sentiments generally spanned from negative to positive, but varied according to different topics. Conclusion: The characteristics of news reports on vaccines are shaped by various topics at different stages. The inner dynamics of the topic and its alterations are driven by the interaction between social sentiment and governmental intervention.

Impact of COVID-19 outbreak on the care of patients with inflammatory bowel disease: A comparison before and after the outbreak in South China.

BACKGROUND AND AIMS: Epidemics pose a great challenge to health care of patients. However, the impact of unprecedented situation of COVID-19 outbreak on health care of inflammatory bowel disease (IBD) patients in real-world setting has seldom been investigated. METHODS: We performed an observational study in a tertiary referral IBD center in China. The mode of health care and medication use was compared before and after COVID-19 outbreak. Electronic questionnaire surveys were performed among gastroenterologists and IBD patients to investigate the impact of COVID-19 outbreak on their attitudes towards telemedicine. RESULTS: COVID-19 outbreak resulted in substantial decrease of patients participating in standard face-to-face visit during 1 month post-outbreak (n = 51) than pre-outbreak (n = 249), whereas the participation in telemedicine was significantly higher than comparable period in 2019 (414 vs 93). During the 1 month after COVID-19 outbreak, 39 (39/56, 69.6%) patients had their infliximab infusion postponed with the mean delay of 3 weeks. The immunomodulator use was similar between pre-outbreak and post-outbreak. Six elective surgeries were postponed for a median of 43 days. In post-outbreak period, 193 (193/297, 64.98%) of the surveyed physicians have used telemedicine with an increase of 18.9% compared with 46.13% (137/292) in the pre-outbreak period (P < 0.001); 331 (331/505, 65.54%) of the surveyed IBD patients supported that the use of telemedicine should be increased in future health care. CONCLUSION: COVID-19 outbreak resulted in a great change in health-care access among IBD patients including decrease in standard face-to-face visit and delay of biologics use. There was an increased use and need of telemedicine after COVID-19 outbreak.

A chemical cocktail during the COVID-19 outbreak in Beijing, China: Insights from six-year aerosol particle composition measurements during the Chinese New Year holiday.

The rapidly spread coronavirus disease (COVID-19) has limited people's outdoor activities and hence caused substantial reductions in anthropogenic emissions around the world. However, the air quality in some megacities has not been improved as expected due to the complex responses of aerosol chemistry to the changes in precursors and meteorology. Here we demonstrate the responses of primary and secondary aerosol species to the changes in anthropogenic emissions during the COVID-19 outbreak in Beijing, China along with the Chinese New Year (CNY) holiday effects on air pollution by using six-year aerosol particle composition measurements. Our results showed large reductions in primary aerosol species associated with traffic, cooking and coal combustion emissions by 30-50% on average during the CNY, while the decreases in secondary aerosol species were much small (5-12%). These results point towards a future challenge in mitigating secondary air pollution because the reduced gaseous precursors may not suppress secondary aerosol formation efficiently under stagnant meteorological conditions. By analyzing the long-term measurements from 2012 to 2020, we found considerable increases in the ratios of nitrate to sulfate, secondary to primary OA, and sulfur and nitrogen oxidation capacity despite the overall decreasing trends in mass concentrations of most aerosol species, suggesting that the decreases in anthropogenic emissions have facilitated secondary formation processes during the last decade. Therefore, a better understanding of the mechanisms driving the chemical responses of secondary aerosol to the changes in anthropogenic emissions under complex meteorological environment is essential for future mitigation of air pollution in China.