间充质干细胞治疗新型冠状病毒肺炎研究进展及相关临床试验难点

当前新型冠状病毒肆虐,全球确诊患者超过3 500万例,累计死亡患者超过50万例,对于突发疫情,临床尚缺乏有效特异性治疗,新型冠状病毒已成为危害人类健康、社会发展的主要公共卫生问题。间充质干细胞具有抗炎和免疫调节功能,可降低重症患者体内由冠状病毒引发的细胞因子风暴,改善患者肺部纤维化,促进损伤肺组织修复,有望降低新冠肺炎的死亡率。目前已开展多项间充质干细胞治疗新型冠状病毒肺炎临床试验,初步证实了间充质干细胞应用在新冠肺炎方面的安全及有效性。在间充质干细胞治疗新冠肺炎取得进展的同期,还应看到该疗法独有特点及疫情严峻形势对临床试验开和及评价带来的问题与挑战,包括临床试验方案设计、干细胞质量管理以及治疗中的伦理考量。只有对其加以重视,才能保证在严峻疫情下安全有效地开展间充质干细胞治疗新型冠状病毒肺炎的临床试验。     

Changes in physical activity and energy intake according to abdominal obesity in Korean adult men before and after COVID-19: Data from 2019 and 2020 Korea National Health and Nutrition Examination Survey (KNHANES)

[Purpose] This study aimed to investigate changes in physical activity and energy intake according to abdominal obesity in Korean adult men before and after COVID-19.[Methods] Using data from the 2019 and 2020 KNHANES, the physical activity level measured by the Global Physical Activity Questionnaire (GPAQ) the physical activity level by GPAQ, number of days of walking and strength training, aerobic exercise, and total energy, protein, fat, carbohydrate, dietary fiber, and sugar intake for a total of 2,799 participants were analyzed.[Results] There were no changes in energy intake during the pandemic. The number of days of weekly walking was higher (2019, p = 0.006; 2020, p = 0.012) and strength training was significantly higher (2019, p < 0.0001; 2020 p < 0.0001) in the non-abdominal obesity group than in the abdominal obesity group before and after COVID-19. Strength training at least once a week suppressed abdominal obesity (0.628 times in 2019, p < 0.0001; 0.605 times in 2020, p < 0.0001). In addition, even when the total energy intake and age were adjusted for, strength training influenced the suppression of abdominal obesity (0.634 times in 2019, p < 0.0001; 0.614 times in 2020, p < 0.0001).[Conclusion] Even with the change in the physical activity level, such as walking and aerobic exercise, due to the influence of social distancing measures, strength training influenced the suppression of abdominal obesity, regardless of the COVID-19 pandemic.     

COVID-19 Survivor Patients Carrying the Rs35705950 Risk Allele in MUC5B Have Higher Plasma Levels of Mucin 5B

Background: Genetic susceptibility to infectious diseases is partly due to the variation in the human genome, and COVID-19 is not the exception. This study aimed to identify whether risk alleles of known genes linked with emphysema (SERPINA1) and pulmonary fibrosis (MUC5B) are associated with severe COVID-19, and whether plasma mucin 5B differs according to patients’ outcomes. Materials and methods: We included 1258 Mexican subjects diagnosed with COVID-19. We genotyped rs2892474 and rs17580 of the SERPINA1 gene and rs35705950 of MUC5B. Based on the rs35705950 genotypes, mucin 5B plasma protein levels were quantified. Results: Homozygous for the risk alleles of the three polymorphisms were found in less than 5% of the study population, but no statistically significant difference in the genotype or allele association analysis. At the protein level, non-survivors carrying one or two copies of the risk allele rs35705950 in MUC5B (GT + TT) had lower levels of mucin 5B compared to the survivors (0.0 vs. 0.17 ng/mL, p = 0.0013). Conclusion: The polymorphisms rs28929474 and rs17580 of SERPINA1 and rs35705950 of MUC5B are not associated with the risk of severe COVID-19 in the Mexican population. COVID-19 survivor patients bearing one or two copies of the rs35705950 risk allele have higher plasma levels of mucin 5B.     

Association of disease severity and death outcome with vaccination status of admitted COVID-19 patients in delta period of SARS-COV-2 in mixed variety of vaccine background

To understand the effectual role of COVID-19 vaccination, we must analyze its effectiveness in dampening the disease severity and death outcome in patients who acquire infection and require hospitalization. The goal of this study was to see if there was an association between disease progression in admitted COVID-19 patients and their prior vaccination exposure. A prospective cohort study based on 1640 admitted COVID-19 patients were carried between June 2021 and October 2021. Depending on vaccination exposure they were divided into vaccinated (exposed) and unvaccinated (unexposed) groups, excluding partially vaccinated patients. Disease severity was assessed at admission on severity index scale. Disease progression to mortality or need of mechanical ventilation and survival were taken as outcome. Absolute difference with 95%CI and Risk Ratio were calculated using cross tabulation, Chi square test and multivariable logistic regression analysis. Among 1514 total analyzed cohort (median age, 53 years [IQR, 17,106]; 43.7% from 46 to 65 years of age group, 56.2% males,33.4% with no comorbid factor for disease progression) 369(24.4%) were vaccinated breakthrough cases and 1145(75.6%) were unvaccinated controls. 556(36.7%) progressed to death or mechanical ventilation, 958(63.3%) patients survived and were discharged home. Disease progression to death or mechanical ventilation was significantly associated with decreased likelihood of vaccination (24.9% among vaccinated breakthrough vs 40.5% unvaccinated controls, [Absolute difference ?15.6% 95%CI (?10.2% to ?20.6%); RR 0.615 95%CI (0.509, 0.744); p <.001]). This association was stronger for old age population and for increase time span between second dose of vaccine and onset of symptoms. There was no statistically significant difference among different types of vaccination and occurrence of outcome when compared to unvaccinated controls (RR 0.607(0.482, 0.763); 0.673(0.339, 1.33) and 0.623(0.441, 0.881) for Inactivated virus vaccine, mRNA and Adenovirus vector-based vaccine respectively. The patients who were fully vaccinated against SARS-COV-2 die or shift to mechanical ventilation less frequently than unvaccinated COVID-19 admitted patients.     

Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses

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Insight into the biological impact of COVID-19 and its vaccines on human health

COVID-19 (coronavirus disease-2019) is a contagious illness that has been declared a global epidemic by the World Health Organization (WHO). The coronavirus causes diseases ranging in severity from the common cold to severe respiratory diseases and death. Coronavirus primarily affects blood pressure by attaching to the angiotensin converting enzyme 2 (ACE 2) receptor. This virus has an impact on multiple organ systems, including the central nervous system, immune system, cardiovascular system, peripheral nervous system, gastrointestinal tract, endocrine system, urinary system, skin, and pregnancy. For the prevention of COVID-19, various vaccines such as viral-like particle vaccines, entire inactivated virus vaccines, viral vector vaccines, live attenuated virus vaccines, subunit vaccines, RNA vaccines, and DNA vaccines are now available. Some of the COVID-19 vaccines are reported to cause a variety of adverse effects that range from mild to severe in nature. SARS-CoV-2 replication is controlled by the RNA-Dependent RNA-Polymerase enzyme (RdRp). The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection. RdRp inhibitors, such as remdesivir (an anti-Ebola virus experimental drug) and favipiravir (an anti-influenza drug), inhibit RdRp and thus slow the progression of COVID-19 and associated clinical symptoms, as well as significantly shorten recovery time. Molnupiravir, an orally active RdRp inhibitor and noval broad spectrum antiviral agent, is an isopropyl pro-drug of EIDD-1931 for emergency use. Galidesivir's in vitro and in vivo activities are limited to RNA of human public health concern. Top seeds for antiviral treatments with high potential to combat the SARS-CoV-2 strain include guanosine derivatives (IDX-184), setrobuvir, and YAK. The goal of this review is to compile scattered information on available COVID-19 vaccines and other treatments for protecting the human body from their harmful effects and to provide options for making better choices in a timely manner.     

大粉瘤菌小亚基rDNA片段的克隆测序

对大粉瘤菌Lycogalaflavofuscum的19SrDNA片段进行了克隆测序,序列长度为1443bp。同时将之与多头绒泡菌的相应序列进行了比较,其序列同源性为58.16%。     

Cell death induced by Pteris semipinnata L. is associated with p53 and oxidant stress in gastric cancer cells

In this study, we demonstrated that Ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) had stronger cytotoxicity against MKN-45, a gastric cancer cell line bearing wild-type p53 than MKN-28, another gastric cancer cell line containing missense mutation in p53. The rapid increase of ROS level was involved in the mechanism of cytotoxicity. Classical features of apoptosis induced by 5F were observed in MKN-45 cells only or more significant in MKN-45 cells than MKN-28 cells. Translocation of Bax from cytosol to mitochondria, reduction of delta psi m and DNA fragmentation were induced by 5F in the p53-dependent manner. We conclude that the expression of Bax and its downstream molecules requires the presentation of a wild-type p53 in the cells treated by 5F.