Mechanisms and challenges of nanocarriers as non-viral vectors of therapeutic genes for enhanced pulmonary delivery.

With the rapid development of biopharmaceuticals and the outbreak of COVID-19, the world has ushered in a frenzy to develop gene therapy. Therefore, therapeutic genes have received enormous attention. However, due to the extreme instability and low intracellular gene expression of naked genes, specific vectors are required. Viral vectors are widely used attributed to their high transfection efficiency. However, due to the safety concerns of viral vectors, nanotechnology-based non-viral vectors have attracted extensive investigation. Still, issues of low transfection efficiency and poor tissue targeting of non-viral vectors need to be addressed. Especially, pulmonary gene delivery has obvious advantages for the treatment of inherited lung diseases, lung cancer, and viral pneumonia, which can not only enhance lung targeting and but also reduce enzymatic degradation. For systemic diseases therapy, pulmonary gene delivery can enhance vaccine efficacy via inducing not only cellular, humoral immunity but also mucosal immunity. This review provides a comprehensive overview of nanocarriers as non-viral vectors of therapeutic genes for enhanced pulmonary delivery. First of all, the characteristics and therapeutic mechanism of DNA, mRNA, and siRNA are provided. Thereafter, the advantages and challenges of pulmonary gene delivery in exerting local and systemic effects are discussed. Then, the inhalation dosage forms for nanoparticle-based drug delivery systems are introduced. Moreover, a series of materials used as nanocarriers for pulmonary gene delivery are presented, and the endosomal escape mechanisms of nanocarriers based on different materials are explored. The application of various non-viral vectors for pulmonary gene delivery are summarized in detail, with the perspectives of nano-vectors for pulmonary gene delivery.

A Single Center Retrospective Study of the Impact of COVID-19 Infection on Immune-related Adverse Events in Cancer Patients Receiving Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) can cause a variety of immune-related adverse events (irAEs). The coronavirus disease 2019 (COVID-19) is associated with increased amounts of pro-inflammatory cytokines, which may affect the outcome of irAEs. Data are limited regarding the impact of COVID-19 on irAEs in ICI-treated cancer patients. Hence, in this study, we retrospectively analyzed ICI-treated adult patients with malignant solid tumors at a single institution between August 2020 and August 2021. Patients who had the most recent ICI treatment over 1-month before or after the positive COVID-19 test were excluded from the study. For the COVID-19 positive group, only the irAEs that developed after COVID-19 infection were considered as events. A total of 579 patients were included in our study, with 46 (7.9%) in the COVID-19 positive group and 533 (92.1%) in the COVID-19 negative group. The baseline characteristics of patients in the 2 groups were similar. With a median follow-up of 331 days (range: 21-2226), we noticed a nonsignificant higher incidence of all-grade irAEs in the COVID-19 positive group (30.4% vs. 19.9%, P =0.18). The incidence of grade 3 and 4 irAEs was significantly higher in the COVID-19 positive group (10.9% vs. 3.2%, P =0.02). Multivariate analysis confirmed the association between COVID-19 infection and increased risk of severe irAE development (odds ratio: 1.08, 95% confidence interval: 1.02-1.14, P =0.01). Our study suggested that COVID-19 may pose a risk of severe irAEs in cancer patients receiving ICIs. Close monitoring and possibly delaying ICI administration could be considered when cancer patients are infected with COVID-19.

Nursing ethics for prevention and control of major infectious disease outbreaks: Chinese expert consensus.

OBJECTIVES: Major infectious disease has become a serious threat to people's health worldwide. As the world's largest healthcare workforce and the core forces fighting against the epidemic, nurses are on the frontline of this battle. A number of ethical issues have given rise to numerous concerns that have largely affected nurses in different ways as they respond to the epidemic. In addition, excessive expectations from people can exert undue pressure, which can easily lead to burnout in nurses. METHODS: In this consensus, the expert panel method was used to develop and reach a consensus. The members involved in the formation of the consensus included an expert discussion panel and a consensus writing expert group, a methodologist, and four secretaries. After 16 rounds of online expert consultation and two rounds of expert panel meetings, the writing team analyzed and reviewed the 78 amendments suggested by the experts to develop a consensus on nursing ethics for prevention and control of major infectious disease outbreaks based on the ethical vision of life care. RESULTS: This expert consensus focuses on five essential domains: the responsibilities and rights of nurses, the nurse-patient relationship, the doctor-nurse relationship, and the relationship between society and nurses throughout the epidemic. CONCLUSIONS: We hope this consensus can help nurses better understand and respond to the ethical issues and challenges in public health emergencies, and raise reasonable public expectations of the roles and responsibilities of nurses in these situations.

Global Surface HCHO Distribution Derived from Satellite Observations with Neural Networks Technique

Formaldehyde (HCHO) is one of the most important carcinogenic air contaminants in outdoor air. However, the lack of monitoring of the global surface concentration of HCHO is currently hindering research on outdoor HCHO pollution. Traditional methods are either restricted to small areas or, for research on a global scale, too data-demanding. To alleviate this issue, we adopted neural networks to estimate the 2019 global surface HCHO concentration with confidence intervals, utilizing HCHO vertical column density data from TROPOMI, and in-situ data from HAPs (harmful air pollutants) monitoring networks and the ATom mission. Our results show that the global surface HCHO average concentration is 2.30 μg/m3. Furthermore, in terms of regions, the concentrations in the Amazon Basin, Northern China, South-east Asia, the Bay of Bengal, and Central and Western Africa are among the highest. The results from our study provide the first dataset on global surface HCHO concentration. In addition, the derived confidence intervals of surface HCHO concentration add an extra layer of confidence to our results. As a pioneering work in adopting confidence interval estimation to AI-driven atmospheric pollutant research and the first global HCHO surface distribution dataset, our paper paves the way for rigorous study of global ambient HCHO health risk and economic loss, thus providing a basis for pollution control policies worldwide.

Coronavirus Disease 2019-Related Stigma in China: A Descriptive Study.

Coronavirus disease 2019 (COVID-19) tremendously impacts the physical and mental health of humans worldwide. Consequently, studies on COVID-19 remain extensive. However, most of them were mainly focused on the pathological mechanisms and treatment methods from medical perspectives. Various reports have indicated that COVID-19 is closely related to stigma and discrimination, but little statistical information has been integrated quantitatively to describe the situation in China. Thus, this study investigated the COVID-19-related stigma of individuals. We collected the online survey data from 1,920 Chinese participants from October to December 2020. Findings showed that 306 (15.94%), 285 (14.84%), 265 (13.80%), and 100 (5.21%) participants endorsed stigma toward individuals in high-risk areas, recovered patients with COVID-19, families of recovered patients with COVID-19, and frontline healthcare providers, respectively. To understand the possible factors that could impact the COVID-19-related stigma, knowledge about COVID-19 was investigated. Generally, knowledge about COVID-19 was negatively associated with COVID-19-related stigma in general, while no significant relationship existed between the knowledge about COVID-19 and the COVID-19-related stigma in the groups who had held COVID-19-related stigma. Ultimately, individuals showed COVID-19-related stigma toward recovered patients and their families, individuals in high-risk areas, and frontline healthcare providers to some extent. The results of this study can provide reference to nations, governments, and organizations in addressing the stigma issues raised by the COVID-19 pandemic.

ICU outcomes and survival in patients with severe COVID-19 in the largest health care system in central Florida.

BACKGROUND: Observational studies have consistently described poor clinical outcomes and increased ICU mortality in patients with severe coronavirus disease 2019 (COVID-19) who require mechanical ventilation (MV). Our study describes the clinical characteristics and outcomes of patients with severe COVID-19 admitted to ICU in the largest health care system in the state of Florida, United States. METHODS: Retrospective cohort study of patients admitted to ICU due to severe COVID-19 in AdventHealth health system in Orlando, Florida from March 11th until May 18th, 2020. Patients were characterized based on demographics, baseline comorbidities, severity of illness, medical management including experimental therapies, laboratory markers and ventilator parameters. Major clinical outcomes analyzed at the end of the study period were: hospital and ICU length of stay, MV-related mortality and overall hospital mortality of ICU patients. RESULTS: Out of total of 1283 patients with COVID-19, 131 (10.2%) met criteria for ICU admission (median age: 61 years [interquartile range (IQR), 49.5-71.5]; 35.1% female). Common comorbidities were hypertension (84; 64.1%), and diabetes (54; 41.2%). Of the 131 ICU patients, 109 (83.2%) required MV and 9 (6.9%) received ECMO. Lower positive end expiratory pressure (PEEP) were observed in survivors [9.2 (7.7-10.4)] vs non-survivors [10 (9.1-12.9] p = 0.004]. Compared to non-survivors, survivors had a longer MV length of stay (LOS) [14 (IQR 8-22) vs 8.5 (IQR 5-10.8) p< 0.001], Hospital LOS [21 (IQR 13-31) vs 10 (7-1) p< 0.001] and ICU LOS [14 (IQR 7-24) vs 9.5 (IQR 6-11), p < 0.001]. The overall hospital mortality and MV-related mortality were 19.8% and 23.8% respectively. After exclusion of hospitalized patients, the hospital and MV-related mortality rates were 21.6% and 26.5% respectively. CONCLUSIONS: Our study demonstrates an important improvement in mortality of patients with severe COVID-19 who required ICU admission and MV in comparison to previous observational reports and emphasizes the importance of standard of care measures in the management of COVID-19.

Evaluation and Feedback for Telehealth From Patients and Physicians During the Early Stage of COVID-19 Pandemic Period.

Purpose Many health care providers adopted telehealth during the coronavirus disease 2019 (COVID-19) pandemic. This unprecedented transformation in medical practice posed challenges to both physicians and patients. However, little is known about the adaptation of attendings, residents, and patients to this new normal. Thus, a survey was sent out to investigate the feedback of both physicians and patients on telehealth.  Methods Surveys were administered via phone call to patients and electronic survey to physicians at an internal medicine resident clinic in one tertiary community hospital from April to June 2020. Demographic information and assessment of overall experience, satisfaction, and concerns of telehealth were collected. Statistical analyses were performed to compare feedback between patients and physicians. Results Fifty patients and 45 physicians participated in the study. Eighty-four percent of patients were first- or second-time users, and 50% of patients were older than 60 years. Eighty-four percent of patients were very or extremely satisfied with telehealth, while 72% wanted to continue telehealth in the future. Ninety-four percent of patients believed that their concerns were adequately addressed, but 14% experiencing technical issues. Physicians' feedback to telehealth was less positive than the patients'. More than 60% of physicians experienced technical issues, and nearly 60% of physicians were neutral or not satisfied with telehealth. Nearly 50% of physicians had difficulty transitioning to telehealth, while only 29% believed that their patients' complaints were adequately addressed. Most physicians had to schedule in-person visits after telehealth. Patients were more satisfied with telehealth than physicians (84% vs. 42%; p<0.001) and were more likely to believe that their concerns were properly addressed by telehealth (94% vs. 29%; p<0.001).  Conclusion This survey revealed that patients were more satisfied with telehealth than physicians. Further research with a larger sample should be considered to confirm this conclusion, and subjective studies are needed to determine the imbalance of satisfaction.