Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT04288102). METHODS: A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs). FINDINGS: Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups. INTERPRETATION: Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period. FUNDING: The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6).

Socialized Farmland Operation - An Institutional Interpretation of Farmland Scale Management

Farmland scale management is an important approach for developing countries to ensure food security in the face of the COVID-19 pandemic. At present, the realization of farmland scale management through the path of farmland use rights trading encounters obstacles in practice;moreover, the new model of farmland scale management has rarely been systematically discussed. Considering the farmland trusteeship practice implemented in Shandong Province of China as the research case, this study discusses the essence and realization premise of the new farmland scale management model represented by farmland trusteeship based on case analysis. The conclusions are as follows. (1) The high cost generated from farmland scale management is the main obstacle to realize this model. (2) The process of realizing farmland scale management through farmland trusteeship is actually the process of meeting the requirements of the socialization of farmland use, the socialization of the farmland management process, and the socialization of farmland output. Thus, in the context of the existence of a large number of small and scattered farmers in China, the socialized farmland operation is the essence of farmland scale management. (3) Effective collective action is the premise of realizing socialized farmland operation. Undeniably, a lot more systematic explorations are further demanded to strengthen the irrigation management and infrastructures, promote and ensure stable village leadership, and comprehensively improve the ability of rural collective action to ensure the further strengthening of socialized farmland operation so as to realize stable farmland scale management, which will be pursued in the future.

Stochastic Lag Time Parameterization for Markov State Models of Protein Dynamics.

Markov state models (MSMs) play a key role in studying protein conformational dynamics. A sliding count window with a fixed lag time is widely used to sample sub-trajectories for transition counting and MSM construction. However, sub-trajectories sampled with a fixed lag time may not perform well under different selections of lag time, which requires strong prior practice and leads to less robust estimation. To alleviate it, we propose a novel stochastic method from a Poisson process to generate perturbative lag time for sub-trajectory sampling and utilize it to construct a Markov chain. Comprehensive evaluations on the double-well system, WW domain, BPTI, and RBD-ACE2 complex of SARS-CoV-2 reveal that our algorithm significantly increases the robustness and power of a constructed MSM without disturbing the Markovian properties. Furthermore, the superiority of our algorithm is amplified for slow dynamic modes in complex biological processes.

Commodity Information Collection and System Construction of e-Commerce Platform Based on Network Data

In order to quickly and accurately collect the massive commodities and corresponding transaction data of large-scale e-commerce platforms, and improve the ability of data analysis and mining, this paper proposes a platform commodity information collection system based on splash technology. The system prerenders the javascript code in the product page, combined with the Scrapy crawler framework, to realize a system that quickly and effectively collects product data from different platforms, and uses “mobile phone” as the retrieval keyword to verify the designed system, respectively. The experimental results show that the system can effectively collect up to 60,000 comments and 6,000 system requests. Conclusion. The platform commodity information collection system based on splash technology has certain application value and promotion for the commodity data collection of different platforms of e-commerce.

Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects.

VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE). A total of 86 healthy subjects were enrolled in the studies. VV116 tablets or placebo were administered per protocol requirements. Blood samples were collected at the scheduled time points for pharmacokinetic analysis. 116-N1, the metabolite of VV116, was detected in plasma and calculated for the PK parameters. In SAD, AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25-800 mg. T1/2 was within 4.80-6.95 h. In MAD, the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116. In FE, the standard meal had no effect on Cmax and AUC of VV116. No serious adverse event occurred in the studies, and no subject withdrew from the studies due to adverse events. Thus, VV116 exhibited satisfactory safety and tolerability in healthy subjects, which supports the continued investigation of VV116 in patients with COVID-19.

A qualitative study of the first batch of medical assistance team's first-hand experience in supporting the nursing homes in Wuhan against COVID-19.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has global impact, Wuhan in Hubei province is a high-risk area. And the older people in nursing homes are the most susceptible group to COVID-19. The aim of this study was to describe the practice and experience of the first-line medical team, to provide insights of coping with COVID-19 in China. METHOD: This qualitative study used a descriptive phenomenological design to describe the experience of medical staff supported the nursing homes in Wuhan fighting against COVID-19. Unstructured interviews via online video were conducted with seven medical staffs who supported the nursing homes in Wuhan. Data were analyzed using content analysis in five main themes: for nursing homes, we interviewed the difficulties faced at the most difficult time, services for the older people, and prevention and management strategies, for the medical staff, the psychological experience were interviewed, and the implications for public health emergencies were also reported. CONCLUSIONS: It is imperative that effective preventive and response measures be implemented to face the outbreak of COVID-19 and meet the care needs of older people in the context of COVID-19. IMPLICATIONS: Findings will inform managers of some reasonable instructional strategies for implementing effective infection management. Nursing homes need to provide targeted services to help alleviating their bad psychology for residents.

Potential effects of SARS-CoV-2 on the gastrointestinal tract and liver.

COVID-19 is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early reported symptoms include fever, cough, and respiratory symptoms. There were few reports of digestive symptoms. However, with COVID-19 spreading worldwide, symptoms such as vomiting, diarrhoea, and abdominal pain have gained increasing attention. Research has found that angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, is strongly expressed in the gastrointestinal tract and liver. Whether theoretically or clinically, many studies have suggested a close connection between COVID-19 and the digestive system. In this review, we summarize the digestive symptoms reported in existing research, discuss the impact of SARS-CoV-2 on the gastrointestinal tract and liver, and determine the possible mechanisms and aetiology, such as cytokine storm. In-depth exploration of the relationship between COVID-19 and the digestive system is urgently needed.

Professional Identity of Chinese Medical Students During the COVID-19 Pandemic (preprint)

Background: Although professional identity is a strong predictor of career choice, only a few studies report on career attitudes of medical students during a public health emergency. This study investigates the changes in medical students’ professional identity and career attitude during the COVID-19 pandemic, evaluates their mental health and social support system under stress, and explores the relationship between their career attitude and other factors. Method: An online survey of 6226 Chinese medical students was conducted to collect information on demographics, professional identity, and career attitudes. The collected data were assessed using the Patient Health Questionnaire, the Generalized Anxiety Disorder Scale, and the Social Support Rating Scale. Results: The results revealed that most participants had their professional identity strengthened, did not change their career attitude, and preferred to participate in the frontline during the COVID-19 pandemic. Low social support, depressive symptoms, male gender, and senior year residency were factors that affected career attitude negatively. Conclusions: After the outbreak of the pandemic, it was necessary to carry out diversified professional identity research to support medical students, especially those with low social support and depressive symptoms.

Factors associated with a SARS-CoV-2 recurrence after hospital discharge among patients with COVID-19: systematic review and meta-analysis.

BACKGROUND: The proportion of recurrences after discharge among patients with coronavirus disease 2019 (COVID-19) was reported to be between 9.1% and 31.0%. Little is known about this issue, however, so we performed a meta-analysis to summarize the demographical, clinical, and laboratorial characteristics of non-recurrence and recurrence groups. METHODS: Comprehensive searches were conducted using eight electronic databases. Data regarding the demographic, clinical, and laboratorial characteristics of both recurrence and non-recurrence groups were extracted, and quantitative and qualitative analyses were conducted. RESULTS: Ten studies involving 2071 COVID-19 cases were included in this analysis. The proportion of recurrence cases involving patients with COVID-19 was 17.65% (between 12.38% and 25.16%) while older patients were more likely to experience recurrence (weighted mean difference (WMD)=1.67, range between 0.08 and 3.26). The time from discharge to recurrence was 13.38 d (between 12.08 and 14.69 d). Patients were categorized as having moderate severity (odds ratio (OR)=2.69, range between 1.30 and 5.58), while those with clinical symptoms including cough (OR=5.52, range between 3.18 and 9.60), sputum production (OR=5.10, range between 2.60 and 9.97), headache (OR=3.57, range between 1.36 and 9.35), and dizziness (OR=3.17, range between 1.12 and 8.96) were more likely to be associated with recurrence. Patients presenting with bilateral pulmonary infiltration and decreased leucocyte, platelet, and CD4+ T counts were at risk of COVID-19 recurrence (OR=1.71, range between 1.07 and 2.75; WMD=-1.06, range between -1.55 and -0.57, WMD=-40.39, range between -80.20 and -0.48, and WMD=-55.26, range between -105.92 and -4.60, respectively). CONCLUSIONS: The main factors associated with the recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after hospital discharge were older age, moderate severity, bilateral pulmonary infiltration, laboratory findings including decreased leucocytes, platelets, and CD4+ T counts, and clinical symptoms including cough, sputum production, headache, and dizziness. These factors can be considered warning indicators for the recurrence of SARS-CoV-2 and might help the development of specific management strategies.

Mental Health Problems and Related Factors in Chinese University Students During the COVID-19 Pandemic (preprint)

Background: The coronavirus disease-2019 (COVID-19) pandemic is a serious threat to global public health, including a wide range of metal health problems. Current research focuses mainly on mental health status and related factors among Chinese university students during the COVID-19 pandemic.Methods: Data from 11133 participants was obtained through an online survey of university students in mainland China. Depressive and anxiety symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9), and the 7-item Generalized Anxiety Disorder Scale (GAD-7), respectively.Results: In total, 37.0% of the subjects were experiencing depressive symptoms, 24.9% anxiety symptoms, 20.9% comorbid depressive and anxiety symptoms, and 7.3% suicidal ideation. Multivariable logistic regression analysis revealed an increased presence of mental health problems in female students, graduate students, and those with personal COVID-19 exposure. Living with family and awareness of COVID-19 were protective factors against depressive and anxiety symptoms. In addition, male, depressive and anxiety symptoms were risk factors for suicidal ideation. Living with family, graduate students, prevention and control measures and projections of COVID-19 trends were protective factors against suicidal ideation.Conclusions: The findings underlined that the mental health of university students should be monitored, and provided important information for healthcare planning during the COVID-19 pandemic.

Mental Health Problems and Related Factors in Chinese University Students During the COVID-19 Pandemic (preprint)

Background: The coronavirus disease-2019 (COVID-19) pandemic is a serious threat to global public health, including a wide range of metal health problems. Current research focuses mainly on mental health status and related factors among Chinese university students during the COVID-19 pandemic.Methods: Data from 11133 participants was obtained through an online survey of university students in mainland China. Depressive and anxiety symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9), and the 7-item Generalized Anxiety Disorder Scale (GAD-7), respectively.Results: In total, 37.0% of the subjects were experiencing depressive symptoms, 24.9% anxiety symptoms, 20.9% comorbid depressive and anxiety symptoms, and 7.3% suicidal ideation. Multivariable logistic regression analysis revealed an increased presence of mental health problems in female students, graduate students, and those with personal COVID-19 exposure. Living with family and awareness of COVID-19 were protective factors against depressive and anxiety symptoms. In addition, male, depressive and anxiety symptoms were risk factors for suicidal ideation. Living with family, graduate students, prevention and control measures and projections of COVID-19 trends were protective factors against suicidal ideation.Conclusions: The findings underlined that the mental health of university students should be monitored, and provided important information for healthcare planning during the COVID-19 pandemic.