The Relationship Between Physical Activity and Mobile Phone Addiction Among Adolescents and Young Adults: Systematic Review and Meta-analysis of Observational Studies.

BACKGROUND: Previous studies have reported a potential negative correlation between physical activity (PA) and mobile phone addiction (MPA) among adolescents and young adults. To date, the strength of this correlation has not been well characterized. OBJECTIVE: This review and meta-analysis aimed to synthesize available empirical studies to examine the correlations between PA and MPA among adolescents and young adults. We also explored several potential moderators, including time of data collection, country or region, and type of population, associated with the relationship between PA and MPA. METHODS: Four electronic databases (PubMed, Scopus, PsycINFO, and Web of Science) were searched from database inception to March 2022 to identify relevant studies. The pooled Pearson correlation coefficients and their corresponding 95% CIs for the relationship between PA and MPA were calculated using the inverse variance method. The methodological quality of the included cross-sectional studies was determined based on the Joanna Briggs Institute appraisal checklist. The study conformed to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-analyses) guidelines. RESULTS: In total, 892 relevant articles were identified, of which 22 were selected based on the inclusion and exclusion criteria. The final meta-analysis included 17 of the 22 studies. Results of random effects modeling revealed a moderate correlation between PA and MPA among adolescents and young adults (summary r=-0.243, P<.001). Sensitivity and publication bias analyses further demonstrated the robustness of our results. All the included studies were scored as high quality with a low risk of bias. Subgroup analysis further indicated that none of the hypothesized moderators (time of data collection, country or region, and type of population) significantly affected the relationship between PA and MPA, as confirmed by the mixed effects analysis. In addition, in the data collection subgroups, medium effect sizes were obtained for data collected before COVID-19 (r=-0.333, P<.001) and data collected during COVID-19 (r=-0.207, P<.001). In subgroup analyses for country or region, the correlation coefficient for China and other developing regions showed a similarly moderate effect size (r=-0.201, P<.001 and r= -0.217, P<.001, respectively). However, the effect sizes for developed regions were not significant (r=-0.446, P=.39). In a subgroup analysis based on the type of population, we found that the effect size for young adults was moderate (r=-0.250, P<.001). However, that of adolescents was not significant (r=-0.129, P=.24). CONCLUSIONS: Our results demonstrate a moderately negative relationship between PA and MPA among young adults. The strength of this relationship was not influenced by the time of data collection, country or region, or type of population.

Hematopoietic stem cell transplantation activity in China 2020-2021 during the SARS-CoV-2 pandemic: a report from the Chinese Blood and Marrow Transplantation Registry Group.

Between 2020 and 2021, 31,525 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) throughout mainland China. In this report, we describe the activity and current trends for HSCT in China during the SARS-CoV-2 pandemic. In 2020, a total of 13,415 cases of HSCT were reported from 166 transplant teams, and 75% (10,042 cases) were allogeneic HSCTs. In 2021, a total of 18,110 cases of HSCT were reported from 174 transplant teams, and 70% (12,744 cases) were allogeneic HSCTs. Haploidentical donor (HID) transplantation accounted for 63% (7977 cases) of allogeneic HSCTs in 2021. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (AML) (37%) and acute lymphoblastic leukemia (ALL) (23%), and the largest proportion of nonmalignant disease comprised aplastic anemia (AA) (13%). The PB stem cell source accounted for 41% of HIDs and 75% of MSDs. The BuCy-based regimen (57%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu-based regimen (28%) and TBI-based regimen (11%). This survey provides comprehensive information about the current activities and might benefit clinical physicians' decision planning for HSCT.

A novel heterologous receptor-binding domain dodecamer universal mRNA vaccine against SARS-CoV-2 variants.

There are currently approximately 4,000 mutations in the SARS-CoV-2 S protein gene and emerging SARS-CoV-2 variants continue to spread rapidly worldwide. Universal vaccines with high efficacy and safety urgently need to be developed to prevent SARS-CoV-2 variants pandemic. Here, we described a novel self-assembling universal mRNA vaccine containing a heterologous receptor-binding domain (HRBD)-based dodecamer (HRBDdodecamer) against SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.28.1), Delta (B.1.617.2) and Omicron (B.1.1.529). HRBD containing four heterologous RBD (Delta, Beta, Gamma, and Wild-type) can form a stable dodecameric conformation under T4 trimerization tag (Flodon, FD). The HRBDdodecamer -encoding mRNA was then encapsulated into the newly-constructed LNPs consisting of a novel ionizable lipid (4N4T). The obtained universal mRNA vaccine (4N4T-HRBDdodecamer) presented higher efficiency in mRNA transfection and expression than the approved ALC-0315 LNPs, initiating potent immune protection against the immune escape of SARS-CoV-2 caused by evolutionary mutation. These findings demonstrated the first evidence that structure-based antigen design and mRNA delivery carrier optimization may facilitate the development of effective universal mRNA vaccines to tackle SARS-CoV-2 variants pandemic.

Manganese-coordinated mRNA vaccines with enhanced mRNA expression and immunogenicity induce robust immune responses against SARS-CoV-2 variants.

It is urgent to develop more effective mRNA vaccines against the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants owing to the immune escape. Here, we constructed a novel mRNA delivery system [IC8/Mn lipid nanoparticles (IC8/Mn LNPs)]with high immunogenicity, via introducing a stimulator of interferon genes (STING) agonist [manganese (Mn)] based on a newly synthesized ionizable lipid (IC8). It was found that Mn can not only promote maturation of antigen-presenting cells via activating STING pathway but also improve mRNA expression by facilitating lysosomal escape for the first time. Subsequently, IC8/Mn LNPs loaded with mRNA encoding the Spike protein of SARS-CoV-2 Delta or Omicron variant (IC8/Mn@D or IC8/Mn@O) were prepared. Both mRNA vaccines induced substantial specific immunoglobulin G responses against Delta or Omicron. IC8/Mn@D displayed strong pseudovirus neutralization ability, T helper 1-biased immune responses, and good safety. It can be concluded that IC8/Mn LNPs have great potential for developing Mn-coordinated mRNA vaccines with robust immunogenicity and good safety.

Discovery of Novel Chinese Medicine Compounds Targeting 3CL Protease by Virtual Screening and Molecular Dynamics Simulation.

The transmission and infectivity of COVID-19 have caused a pandemic that has lasted for several years. This is due to the constantly changing variants and subvariants that have evolved rapidly from SARS-CoV-2. To discover drugs with therapeutic potential for COVID-19, we focused on the 3CL protease (3CLpro) of SARS-CoV-2, which has been proven to be an important target for COVID-19 infection. Computational prediction techniques are quick and accurate enough to facilitate the discovery of drugs against the 3CLpro of SARS-CoV-2. In this paper, we used both ligand-based virtual screening and structure-based virtual screening to screen the traditional Chinese medicine small molecules that have the potential to target the 3CLpro of SARS-CoV-2. MD simulations were used to confirm these results for future in vitro testing. MCCS was then used to calculate the normalized free energy of each ligand and the residue energy contribution. As a result, we found ZINC15676170, ZINC09033700, and ZINC12530139 to be the most promising antiviral therapies against the 3CLpro of SARS-CoV-2.

Impact Factors of COVID-19 Vaccination Hesitancy in patients after lung cancer surgery: an outpatients-based cross-sectional study (preprint)

Background The safety and efficacy of several vaccine candidates have been tested and found to be effective and safe against COVID-19. But, little is known about the actual level of people with lung cancer willing to accept a COVID-19 vaccine and the impact factors that affect acceptability. The survey aimed to determine the prevalence of vaccine hesitancy in lung cancer patients after surgery and characterize underlying factors contributing to reluctance.Methods An clinical survey was inducted from May 1, 2021, to August 20, 2021. Eligible participants were 18 years or older, were diagnosed with lung cancer, and received lung cancer surgery, including lobectomy, sublobectomy, and pneumonectomy. Data were collected on a self-administered questionnaire from 294 lung cancer patients after surgery.Results Among the final included 281 participants, 54.1% were female, and 93.6% were of Han ethnicity. 48.0% were in pathologic stage I, 36.3% in stage II, 10.3% in stage III, and 5.3% in stage IV. The vaccination hesitancy/refusal rate was 41.6%. In multivariable regression analysis, age over 60 years old, low educational level, duration of cancer (< 1 year), subjective health status, current cancer treatments use, presence of postoperative pain, and report of the items “ever hesitated or refused to get a vaccination,” “get negative information about getting the COVID-19 vaccine”, “worried about vaccine adverse reactions,” and “worried about the COVID vaccine interferes with cancer treatments” were independently associated with hesitant of the COVID-19 vaccine.Conclusions Vaccine hesitancy is common among lung cancer patients after surgery, related mainly to health status and concerns about side effects, worsens cancer prognosis, and interferes with cancer treatments. These results suggest that vaccination programs may need tailoring to specific populations’ hesitancy.

mRNA Vaccines Against SARS‐CoV‐2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids

SARS‐CoV‐2 variants are now still challenging all the approved vaccines, including mRNA vaccines. There is an urgent need to develop new generation mRNA vaccines with more powerful efficacy and better safety against SARS‐CoV‐2 variants. In this study, a new set of ionizable lipids named 4N4T are constructed and applied to form novel lipid nanoparticles called 4N4T‐LNPs. Leading 4N4T‐LNPs exhibit much higher mRNA translation efficiency than the approved SM‐102‐LNPs. To test the effectiveness of the novel delivery system, the DS mRNA encoding the full‐length S protein of the SARS‐CoV‐2 variant is synthesized and loaded in 4N4T‐LNPs. The obtained 4N4T‐DS mRNA vaccines successfully trigger robust and durable humoral immune responses against SARS‐CoV‐2 and its variants including Delta and Omicron. Importantly, the novel vaccines have higher RBD‐specific IgG titers and neutralizing antibody titers than SM‐102‐based DS mRNA vaccine. Besides, for the first time, the types of mRNA vaccine‐induced neutralizing antibodies are found to be influenced by the chemical structure of ionizable lipids. 4N4T‐DS mRNA vaccines also induce strong Th1‐skewed T cell responses and have good safety. This work provides a novel vehicle for mRNA delivery that is more effective than the approved LNPs and shows its application in vaccines against SARS‐CoV‐2 variants. In this study, mRNA vaccines against SARS‐CoV‐2 variants delivered by lipid nanoparticles based on 4N4T lipids are constructed, and successfully trigger robust and durable humoral immune responses against SARS‐CoV‐2 and its variants including Delta and Omicron. In addition, head‐to‐head comparison studies find that the novel 4N4T lipids have a higher mRNA delivery efficiency than SM‐102.

mRNA-based therapeutics: powerful and versatile tools to combat diseases.

The therapeutic use of messenger RNA (mRNA) has fueled great hope to combat a wide range of incurable diseases. Recent rapid advances in biotechnology and molecular medicine have enabled the production of almost any functional protein/peptide in the human body by introducing mRNA as a vaccine or therapeutic agent. This represents a rising precision medicine field with great promise for preventing and treating many intractable or genetic diseases. In addition, in vitro transcribed mRNA has achieved programmed production, which is more effective, faster in design and production, as well as more flexible and cost-effective than conventional approaches that may offer. Based on these extraordinary advantages, mRNA vaccines have the characteristics of the swiftest response to large-scale outbreaks of infectious diseases, such as the currently devastating pandemic COVID-19. It has always been the scientists' desire to improve the stability, immunogenicity, translation efficiency, and delivery system to achieve efficient and safe delivery of mRNA. Excitingly, these scientific dreams have gradually been realized with the rapid, amazing achievements of molecular biology, RNA technology, vaccinology, and nanotechnology. In this review, we comprehensively describe mRNA-based therapeutics, including their principles, manufacture, application, effects, and shortcomings. We also highlight the importance of mRNA optimization and delivery systems in successful mRNA therapeutics and discuss the key challenges and opportunities in developing these tools into powerful and versatile tools to combat many genetic, infectious, cancer, and other refractory diseases.

Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics.

Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative opportunistic pathogen that infects patients with cystic fibrosis, burn wounds, immunodeficiency, chronic obstructive pulmonary disorder (COPD), cancer, and severe infection requiring ventilation, such as COVID-19. P. aeruginosa is also a widely-used model bacterium for all biological areas. In addition to continued, intense efforts in understanding bacterial pathogenesis of P. aeruginosa including virulence factors (LPS, quorum sensing, two-component systems, 6 type secretion systems, outer membrane vesicles (OMVs), CRISPR-Cas and their regulation), rapid progress has been made in further studying host-pathogen interaction, particularly host immune networks involving autophagy, inflammasome, non-coding RNAs, cGAS, etc. Furthermore, numerous technologic advances, such as bioinformatics, metabolomics, scRNA-seq, nanoparticles, drug screening, and phage therapy, have been used to improve our understanding of P. aeruginosa pathogenesis and host defense. Nevertheless, much remains to be uncovered about interactions between P. aeruginosa and host immune responses, including mechanisms of drug resistance by known or unannotated bacterial virulence factors as well as mammalian cell signaling pathways. The widespread use of antibiotics and the slow development of effective antimicrobials present daunting challenges and necessitate new theoretical and practical platforms to screen and develop mechanism-tested novel drugs to treat intractable infections, especially those caused by multi-drug resistance strains. Benefited from has advancing in research tools and technology, dissecting this pathogen's feature has entered into molecular and mechanistic details as well as dynamic and holistic views. Herein, we comprehensively review the progress and discuss the current status of P. aeruginosa biophysical traits, behaviors, virulence factors, invasive regulators, and host defense patterns against its infection, which point out new directions for future investigation and add to the design of novel and/or alternative therapeutics to combat this clinically significant pathogen.

Endothelial Biomarkers in Patients Recovered from COVID-19 One Year after Hospital Discharge: A Cross-Sectional Study.

Background: COVID-19 is characterized by endothelial dysfunction and is presumed to have long-term cardiovascular sequelae. In this cross-sectional study, we aimed to explore the serum levels of endothelial biomarkers in patients who recovered from COVID-19 one year after hospital discharge. Methods: In this clinical follow-up study, 345 COVID-19 survivors from Huanggang, Hubei, and 119 age and gender-matched medical staff as healthy controls were enrolled. A standardized symptom questionnaire was performed, while electrocardiogram and Doppler ultrasound of lower extremities, routine blood tests, biochemical and immunological tests, serum soluble vascular cell adhesion molecule-1(VCAM-1), intercellular cell adhesion molecule-1(ICAM-1), P-selectin, and fractalkine were measured by enzyme-linked immunosorbent assays (ELISA). Results: At one year after discharge, 39% of recovers possessed post-COVID syndromes, while a few had abnormal electrocardiogram manifestations, and no deep vein thrombosis was detected in all screened survivors. There were no significant differences in circulatory inflammatory markers (leukocytes, neutrophils, lymphocytes, C-reactive protein and interleukin-6), alanine aminotransferase, estimated glomerular filtration rate, glucose, triglycerides, total cholesterol and D-dimer observed among healthy controls with previously mild or severe infected. Furthermore, serum levels of VCAM-1, ICAM-1, P-selectin, and fractalkine do not significantly differ between survivors and healthy controls. Conclusions: SARS-CoV-2 infection may not impose a higher risk of developing long-term cardiovascular events, even for those recovering from severe illness.

Analysis of online antenatal education class use via a mobile terminal app during the COVID-19 pandemic.

OBJECTIVE: To understand the use of online antenatal education classes accessed via the Mother and Child Health Handbook app during the COVID-19 pandemic in order to provide a basis and suggestions for optimizing Internet education during pregnancy under public health emergencies. METHODS: We compared and analyzed the use of online antenatal education classes via the Mother and Child Health Handbook app in Hangzhou in 2019 and 2020 (during the COVID-19 pandemic). RESULTS: Between January 1, 2019, and December 31, 2020, a total of 229,794 pregnant women created files and registered for the app, including 124,273 women in 2019 and 105,521 women in 2020. More pregnant women participated in online antenatal education learning (n = 36,379/34.5% vs. 29,226/23.5%, p = 0.000) in 2020 than in 2019. The proportion of pregnant women in the 18-34-year-old group who participated in online learning was higher than that in the advanced age group, and the difference was statistically significant (2019: 24.3% vs. 18.8%, p = 0.000) (2020: 35.7% vs. 27.4%, p = 0.000). More pregnant women accessed online antenatal education during early pregnancy (n = 13,463/37.0% vs. 9088/31.1%, p = 0.000) in 2020 than in 2019. Similar percentages of pregnant women participated in online antenatal education during mid-pregnancy (n = 15,426/52.8% vs. 19,269/53.0%, p = 0.639) in 2019 and 2020. Fewer pregnant women accessed online antenatal education during late pregnancy (n = 10,246/28.2% vs. 9476/32.4%, p = 0.000) in 2020 than in 2019. Fewer pregnant women choose to take 'Puerperal Health' courses in 2020 than in 2019 (early pregnancy: 36.20% vs. 42.79%, p = 0.000; mid-pregnancy: 41.65% vs. 48.19%, p = 0.000; late pregnancy: 55.31% vs. 58.41%, p = 0.000). Fewer pregnant women choose to take 'Psychological Adjustment' courses in 2020 than in 2019 (early pregnancy: 21.59% vs. 29.60%, p = 0.000; mid-pregnancy: 26.20% vs. 40.50%, p = 0.000; late pregnancy: 12.79% vs. 42.53%, p = 0.000). More pregnant women choose to study 'Nutrition and Exercise' in 2020 than in 2019 (early pregnancy: 44.48% vs. 25.95%, p = 0.000; mid-pregnancy: 47.77% vs. 40.75%, p = 0.000; late pregnancy: 55.94% vs. 42.99%, p = 0.000). "Pregnancy Care and Fetal Development" was the most selected course by pregnant women in early pregnancy (2019: 67.50%; 2020: 71.39%) and middle pregnancy (2019: 67.01%; 2020: 82.05%), and the proportion in 2020 was higher than it was in 2019. "Baby care" was the most selected course by pregnant women in late pregnancy, and the proportion in 2020 was higher than it was in 2019 (78.31% vs. 72.85%). CONCLUSION: During the COVID-19 pandemic, online antenatal education was well-used by pregnant women. More women participated in the online antenatal education modules during the COVID-19 pandemic than during 2019.The proportion of choosing different courses for pregnant women before and after the COVID-19 epidemic varied, and the learning course needs of pregnant women in different trimesters were different.

A Meta-Analysis of Accuracy and Sensitivity of CRISPR and Chest CT in COVID‑19 Diagnosis (preprint)

Objective: To clarify the accuracy of clusters of regularly spaced short palindrome repeats (CRISPR) technology and chest CT in the diagnosis of Corona Virus Disease2019(COVID-19). Methods: The term "Corona Virus Disease " "clustered regularly spaced short palindromic repeats" "CRISPR", "chest CT", "sensitivity and specificity" as the subject words or keywords were searched in databases such as Pubmed, Embase, Cochrane Library, Wiley and Scopus and Chinese academic databases (such as CNKI, Wanfang and Chongqing VIP data) for relevant literature on the use of CRISPR technology and chest CT for the diagnosis of COVID-19. Meta-analysis was performed after literature screening, quality assessment and data extraction . Results: A total of 418 articles were retrieved, and 17 articles were finally included. The results showed that the combined sensitivity of CRISPR technology for diagnosing new coronary pneumonia infection was 0.96 [95% CI (0.93, 0.98)], and the combined specificity was 1.00 [95% CI (0.92, 1.00)], the combined positive likelihood ratio is 458.69 [95%CI (11.51, 18280.8)], the combined negative likelihood ratio is 0.04 [95% CI (0.02, 0.07)], the area under the SROC curve is 0.99 [95%CI(0.97,0.99)]. The combined sensitivity of chest CT in diagnosing new coronary pneumonia infection was 0.94 [95%CI (0.83, 0.98)], combined specificity was 0.55 [95% CI (0.22, 0.83)], combined diagnostic odds ratio was 19.90 [95% CI (7.88, 50.25)], the combined positive likelihood ratio is 2.08 [95%CI (1.00, 4.32)], the combined negative likelihood ratio is 0.10 [95% CI (0.05, 0.23)], the area under the SROC curve is 0.91 [95% CI (0.88, 0.93)]. The Deek funnel chart indicates that there is no potential publication bias among the included studies (PCRISPR = 0.03, P chest CT = 0.55). Conclusion: CRISPR technology has a better ability to detect infections in patients with COVID-19, and is better than chest CT in disease diagnosis. CRISPR technology, especially non-SHERLOCK type and multi-target gene detection, can be used to diagnose COVID-19 with higher accuracy ,and can be used for large-scale population screening.

The Role of Collectivism-Individualism in Attitudes Toward Compliance and Psychological Responses During the COVID-19 Pandemic.

This study examined the role of individual differences in horizontal and vertical individualism and collectivism, trust and worries, and concerns about COVID-19 in predicting the attitudes toward compliance of health advice and psychological responses during the COVID-19 pandemic. Chinese university students (N=384, 324 female) completed measures of individualism and collectivism, trust, attitudes toward compliance, and psychological responses to the pandemic. Results showed that not only vertical collectivist orientation but also horizontal individualist orientation significantly predicted higher willingness to comply, whereas vertical individualist orientation significantly predicted lower willingness to comply. Vertical individualist and vertical collectivist orientations predicted higher psychological response in terms of distress, anxiety, and depression, while horizontal collectivistic orientation significantly predicted less psychological problems. Implications of the effect of individual-level cultural orientations on attitudes toward public health compliance and psychological well-being during global health crises are discussed.

Discovery and Nanosized Preparations of (S,R)-Tylophorine Malate as Novel anti-SARS-CoV-2 Agents.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has stimulated the search for effective drugs for its prevention and treatment. Natural products are an important source for new drug discovery. Here, we report that, NK007(S,R), a tylophorine malate, displays high antiviral activity against SARS-CoV-2 with an EC50 0.03 µM in vitro, which is substantially lower than that of remdesivir (EC50: 0.8 µM in vitro), the only authorized drug to date. The histopathological research revealed that NK007(S,R) (5 mg/kg/dose) displayed a protection effect in lung injury induced by SARS-CoV-2, which is better than remdesivir (25 mg/kg/dose). We also prepared two nanosized preparations of NK007(S,R), which also showed good efficacy (EC50: NP-NK007, 0.007 µM in vitro; LP-NK007, 0.014 µM in vitro). Our findings suggest that tylophora alkaloids, isolated from the traditional Chinese medicine Cynanchum komarovii AL, offer a new skeleton for the development of anticoronavirus drug candidate.

Traditional Chinese medicine for COVID-19 pandemic and emerging challenges: An online cross-sectional survey in China.

BACKGROUND: We aimed to investigate use of infection control behaviours, preventative and therapeutic interventions, and outcomes among respondents to an online survey during the COVID-19 pandemic in China. METHODS: The survey was designed by an international team, translated and adapted to simplified Chinese, including 132 kinds of traditional Chinese medicine (TCM) preparation recommended by guidelines. It was distributed and collected from February to May 2021, with data analysed by WPS spreadsheet and wjx.cn. Descriptive statistics were used to describe demographics and clinical characteristics, diagnosis, treatments, preventative behaviours and interventions, and their associated outcomes. RESULTS: The survey was accessed 503 times with 341 (67.8%) completions covering 23 provinces and four municipalities in China. Most (282/341, 82.7%) respondents reported no symptoms during the pandemic and the majority (290/341, 85.0%) reported having a SARS-CoV-2 PCR test at some point. Forty-five (13.2%) reported having a respiratory infection, among which 19 (42.2%) took one or more categories of modern medicine, e.g. painkillers, antibiotics; 16 (35.6%) used TCM interventions(s); while seven respondents combined TCM with modern medicine. All respondents reported using at least one behavioural or medical approach to prevention, with 22.3% taking TCM and 5.3% taking modern medicines. No respondents reported having a critical condition related to COVID-19. CONCLUSION: We found evidence of widespread use of infection control behaviours, modern medicines and TCM for treatment and prevention of COVID-19 and other respiratory symptoms. Larger scale studies are warranted, including a more representative sample exploring TCM preparations recommended in clinical guidelines.

The investigation of mRNA vaccines formulated in liposomes administrated in multiple routes against SARS-CoV-2.

COVID-19 pandemic has resulted in an unprecedented global public health crisis. It is obvious that SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Since obvious advantages including fast manufacturing speed, potent immunogenicity and good safety profile, six mRNA vaccines have been used to prevent SARS-CoV-2 infections in clinic with lipid nanoparticles (LNP) formulation via intramuscular injection. In this work, we first constructed RBD-encoding mRNA (RBD-mRNA) formulated in liposomes (LPX/RBD-mRNA) and investigated the influence of administration routes on the immunogenicity. LPX/RBD-mRNA can express RBD in vivo and successfully induced SARS-CoV-2 RBD specific antibodies in the vaccinated mice, which efficiently neutralized SARS-CoV-2 pseudotyped virus. Moreover, the administration routes were found to affect the virus neutralizing capacity of sera derived from the immunized mice and the types (Th1-type and Th2-type) of cellular immune responses. This study indicated that liposome-based RBD-mRNA vaccine with optimal administration route might be a potential candidate against SARS-CoV-2 infection with good efficacy and safety.

Chinese Herbal Medicine Used With or Without Conventional Western Therapy for COVID-19: An Evidence Review of Clinical Studies.

Objective: To present the evidence of the therapeutic effects and safety of Chinese herbal medicine (CHM) used with or without conventional western therapy for COVID-19. Methods: Clinical studies on the therapeutic effects and safety of CHM for COVID-19 were included. We summarized the general characteristics of included studies, evaluated methodological quality of randomized controlled trials (RCTs) using the Cochrane risk of bias tool, analyzed the use of CHM, used Revman 5.4 software to present the risk ratio (RR) or mean difference (MD) and their 95% confidence interval (CI) to estimate the therapeutic effects and safety of CHM. Results: A total of 58 clinical studies were identified including RCTs (17.24%, 10), non-randomized controlled trials (1.72%, 1), retrospective studies with a control group (18.97%, 11), case-series (20.69%, 12) and case-reports (41.38%, 24). No RCTs of high methodological quality were identified. The most frequently tested oral Chinese patent medicine, Chinese herbal medicine injection or prescribed herbal decoction were: Lianhua Qingwen granule/capsule, Xuebijing injection and Maxing Shigan Tang. In terms of aggravation rate, pooled analyses showed that there were statistical differences between the intervention group and the comparator group (RR 0.42, 95% CI 0.21 to 0.82, six RCTs; RR 0.38, 95% CI 0.23 to 0.64, five retrospective studies with a control group), that is, CHM plus conventional western therapy appeared better than conventional western therapy alone in reducing aggravation rate. In addition, compared with conventional western therapy, CHM plus conventional western therapy had potential advantages in increasing the recovery rate and shortening the duration of fever, cough and fatigue, improving the negative conversion rate of nucleic acid test, and increasing the improvement rate of chest CT manifestations and shortening the time from receiving the treatment to the beginning of chest CT manifestations improvement. For adverse events, pooled data showed that there were no statistical differences between the CHM and the control groups. Conclusion: Current low certainty evidence suggests that there maybe a tendency that CHM plus conventional western therapy is superior to conventional western therapy alone. The use of CHM did not increase the risk of adverse events.

COVID-19 Outbreak and Management Approach for Families with Children on Long-Term Kidney Replacement Therapy.

BACKGROUND AND OBJECTIVES: During the coronavirus disease 2019 outbreak, the treatment of families with children on long-term KRT is challenging. This study was conducted to identify the current difficulties, worries regarding the next 2 months, and mental distress experienced by families with children on long-term KRT during the coronavirus disease 2019 outbreak and to deliver possible management approaches to ensure uninterrupted treatment for children on long-term KRT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter online survey was conducted between February 10 and 15, 2020, among the families with children on long-term KRT from five major pediatric dialysis centers in mainland China. The primary caregivers of children currently on long-term KRT were eligible and included. Demographic information, severe acute respiratory syndrome coronavirus 2 infection status, current difficulties, and worries regarding the next 2 months were surveyed using a self-developed questionnaire. The Patient Health Questionnaire-9 and the General Anxiety Disorder Scale-7 were used to screen for depressive symptoms and anxiety, respectively. RESULTS: Among the children in the 220 families included in data analysis, 113 (51%) children were on dialysis, and the other 107 (49%) had kidney transplants. No families reported confirmed or suspected cases of coronavirus disease 2019. Overall, 135 (61%) and 173 (79%) caregivers reported having difficulties now and having worries regarding the next 2 months, respectively. Dialysis supply shortage (dialysis group) and hard to have blood tests (kidney transplantation group) were most commonly reported. A total of 29 (13%) caregivers had depressive symptoms, and 24 (11%) had anxiety. After the survey, we offered online and offline interventions to address their problems. At the time of the submission of this paper, no treatment interruption had been reported. CONCLUSIONS: The coronavirus disease 2019 outbreak has had physical, mental, logistical, and financial effects on families with children on long-term KRT.