Advances in wastewater-based epidemiology in 2021

Wastewater-based epidemiology (WBE) is a powerful and cost-effective tool for investigating chemicals consumption/pathogens infection and health status of populations, and is rapidly evolving as COVID-19 continues to ravage the world. This paper reviews the significant developments and breakthroughs of WBE in 2021 including collection, pretreatment and analysis of sewage samples, materials stability, correction factors calculation and uncertainty analysis, implementation cases and so on, based on the research findings published in international top academic journals or the most influential achievements. It provides reference for clarifying the development of WBE and promoting the research and application of WBE.

Patients without Increased Lymphocyte Counts and Decreased CT Scores During the Early 2nd Week of Illness Onset may Develop to Severe COVID-19.

BACKGROUND: Lymphopenia and high CT score is associated with COVID-19 severity. Herein we describe the change pattern in lymphocyte count and CT score during hospitalization and explore a possible association with the severity of COVID-19. METHODS: In this retrospective study, 13 non-severe COVID-19 patients diagnosed at admission were enrolled. One patient progressed to severe disease. Change patterns in lymphocyte counts and CT scores of all patients were analyzed. RESULTS: Lymphocyte count increased gradually from day 5 post-illness onset (day 5 vs. day 15, p = 0.001). Lymphocyte count of the severe patient fluctuated at low levels throughout the 15-day period. Chest CT scores of non-severe patients increased significantly during the first 5 days of illness onset, but decreased gradually beginning day 9 (illness onset vs. day 5, p = 0.002, day 9 vs. day 15, p = 0.015). In the severe patient, CT score continued to increase over the 11 days post-illness onset period. CONCLUSIONS: Non-severe COVID-19 patients had significantly increased lymphocyte counts and decreased CT scores beginning day 5 and day 9 of illness onset, respectively. The patients without increased lymphocyte counts and decreased CT scores during the early 2nd week of illness onset may develop to severe COVID-19.

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).

Machine Learning-Based Scoring System for Early Prognosis Evaluation of Patients with Coronavirus Disease 2019

Background The global spread of coronavirus disease 2019 (COVID-19) continues to threaten human health security, exerting considerable pressure on healthcare systems worldwide. While prognostic models for COVID-19 hospitalized or intensive care patients are currently available, prognostic models developed for large cohorts of thousands of individuals are still lacking. Methods Between February 4 and April 16, 2020, we enrolled 3,974 patients admitted with COVID-19 disease in the Wuhan Huo-Shen-Shan Hospital and the Maternal and Child Hospital, Hubei Province, China. (1) Screening of key prognostic factors: A univariate Cox regression analysis was performed on 2,649 patients in the training set, and factors affecting prognosis were initially screened. Subsequently, a random survival forest model was established through machine analysis to further screen for factors that are important for prognosis. Finally, multivariate Cox regression analysis was used to determine the synergy among various factors related to prognosis. (2) Establishment of a scoring system: The nomogram algorithm established a COVID-19 patient death risk assessment scoring system for the nine selected key prognostic factors, calculated the C index, drew calibration curves and drew training set patient survival curves. (3) Verification of the scoring system: The scoring system assessed 1,325 patients in the test set, splitting them into high- and low-risk groups, calculated the C-index, and drew calibration and survival curves. Results The cross-sectional study found that age, clinical classification, sex, pulmonary insufficiency, hypoproteinemia, and four other factors (underlying diseases: blood diseases, malignant tumor;complications: digestive tract bleeding, heart dysfunction) have important significance for the prognosis of the enrolled patients with COVID-19. Herein, we report the discovery of the effects of hypoproteinemia and hematological diseases on the prognosis of COVID-19. Meanwhile, the scoring system established here can effectively evaluate objective scores for the early prognoses of patients with COVID-19 and can divide them into high- and low-risk groups (using a scoring threshold of 117.77, a score below which is considered low risk). The efficacy of the system was better than that of clinical classification using the current COVID-19 guidelines (C indexes, 0.95 vs. 0.89). Conclusions Age, clinical typing, sex, pulmonary insufficiency, hypoproteinemia, and four other factors were important for COVID-19 survival. Compared with general statistical methods, this method can quickly and accurately screen out the relevant factors affecting prognosis, provide an order of importance, and establish a scoring system based on the nomogram model, which is of great clinical significance.

Tight junction protein occludin is an internalization factor for SARS-CoV-2 infection and mediates virus cell-to-cell transmission.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads efficiently by spike-mediated, direct cell-to-cell transmission. However, the underlying mechanism is poorly understood. Herein, we demonstrate that the tight junction protein occludin (OCLN) is critical to this process. SARS-CoV-2 infection alters OCLN distribution and expression and causes syncytium formation that leads to viral spread. OCLN knockdown fails to alter SARS-CoV-2 binding but significantly lowers internalization, syncytium formation, and transmission. OCLN overexpression also has no effect on virus binding but enhances virus internalization, cell-to-cell transmission, and replication. OCLN directly interacts with the SARS-CoV-2 spike, and the endosomal entry pathway is involved in OCLN-mediated cell-to-cell fusion rather than in the cell surface entry pathway. All SARS-CoV-2 strains tested (prototypic, alpha, beta, gamma, delta, kappa, and omicron) are dependent on OCLN for cell-to-cell transmission, although the extent of syncytium formation differs between strains. We conclude that SARS-CoV-2 utilizes OCLN as an internalization factor for cell-to-cell transmission.

Exploration of the Shared Molecular Mechanisms between COVID-19 and Neurodegenerative Diseases through Bioinformatic Analysis

The COVID-19 pandemic has caused millions of deaths and remains a major public health burden worldwide. Previous studies found that a large number of COVID-19 patients and survivors developed neurological symptoms and might be at high risk of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). We aimed to explore the shared pathways between COVID-19, AD, and PD by using bioinformatic analysis to reveal potential mechanisms, which may explain the neurological symptoms and degeneration of brain that occur in COVID-19 patients, and to provide early intervention. In this study, gene expression datasets of the frontal cortex were employed to detect common differentially expressed genes (DEGs) of COVID-19, AD, and PD. A total of 52 common DEGs were then examined using functional annotation, protein–protein interaction (PPI) construction, candidate drug identification, and regulatory network analysis. We found that the involvement of the synaptic vesicle cycle and down-regulation of synapses were shared by these three diseases, suggesting that synaptic dysfunction might contribute to the onset and progress of neurodegenerative diseases caused by COVID-19. Five hub genes and one key module were obtained from the PPI network. Moreover, 5 drugs and 42 transcription factors (TFs) were also identified on the datasets. In conclusion, the results of our study provide new insights and directions for follow-up studies of the relationship between COVID-19 and neurodegenerative diseases. The hub genes and potential drugs we identified may provide promising treatment strategies to prevent COVID-19 patients from developing these disorders.

An integrated strategy to identify COVID-19 causal genes and characteristics represented by LRRC37A2.

Genome-wide association study (GWAS) could identify host genetic factors associated with coronavirus disease 2019 (COVID-19). The genes or functional DNA elements through which genetic factors affect COVID-19 remain uncharted. The expression quantitative trait locus (eQTL) provides a path to assess the correlation between genetic variations and gene expression. Here, we firstly annotated GWAS data to describe genetic effects, obtaining genome-wide mapped genes. Subsequently, the genetic mechanisms and characteristics of COVID-19 were investigated by an integrated strategy that included three GWAS-eQTL analysis approaches. It was found that 20 genes were significantly associated with immunity and neurological disorders, including prior and novel genes such as OAS3 and LRRC37A2. The findings were then replicated in single-cell datasets to explore the cell-specific expression of causal genes. Furthermore, associations between COVID-19 and neurological disorders were assessed as a causal relationship. Finally, the effects of causal protein-coding genes of COVID-19 were discussed using cell experiments. The results revealed some novel COVID-19-related genes to emphasize disease characteristics, offering a broader insight into the genetic architecture underlying the pathophysiology of COVID-19.

Bat-Origin Swine Acute Diarrhea Syndrome Coronavirus Is Lethal to Neonatal Mice.

Bats are reservoirs for diverse coronaviruses, including swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV has been reported to have broad cell tropism and inherent potential to cross host species barriers for dissemination. We rescued synthetic wild-type SADS-CoV using one-step assembly of a viral cDNA clone by homologous recombination in yeast. Furthermore, we characterized SADS-CoV replication in vitro and in neonatal mice. We found that SADS-CoV caused severe watery diarrhea, weight loss, and a 100% fatality rate in 7- and 14-day-old mice after intracerebral infection. We also detected SADS-CoV-specific N protein in the brain, lungs, spleen, and intestines of infected mice. Furthermore, SADS-CoV infection triggers excessive cytokine expression that encompasses a broad array of proinflammatory mediators, including interleukin 1ß (IL-1ß), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), C-X-C motif chemokine ligand 10 (CXCL10), interferon beta (IFN-ß), IFN-γ, and IFN-λ3. This study highlights the importance of identifying neonatal mice as a model for developing vaccines or antiviral drugs against SADS-CoV infection. IMPORTANCE SADS-CoV is the documented spillover of a bat coronavirus that causes severe disease in pigs. Pigs are in frequent contact with both humans and other animals and theoretically possess a greater chance, compared to many other species, of promoting cross-species viral transmission. SADS-CoV has been reported to have broad cell tropism and inherent potential to cross host species barriers for dissemination. Animal models are an essential feature of the vaccine design toolkit. Compared with neonatal piglets, the mouse is small, making it an economical choice for animal models for SADS-CoV vaccine design. This study showed the pathology of neonatal mice infected with SADS-CoV, which should be very useful for vaccine and antiviral studies.

Exploration of the Shared Molecular Mechanisms between COVID-19 and Neurodegenerative Diseases through Bioinformatic Analysis.

The COVID-19 pandemic has caused millions of deaths and remains a major public health burden worldwide. Previous studies found that a large number of COVID-19 patients and survivors developed neurological symptoms and might be at high risk of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). We aimed to explore the shared pathways between COVID-19, AD, and PD by using bioinformatic analysis to reveal potential mechanisms, which may explain the neurological symptoms and degeneration of brain that occur in COVID-19 patients, and to provide early intervention. In this study, gene expression datasets of the frontal cortex were employed to detect common differentially expressed genes (DEGs) of COVID-19, AD, and PD. A total of 52 common DEGs were then examined using functional annotation, protein-protein interaction (PPI) construction, candidate drug identification, and regulatory network analysis. We found that the involvement of the synaptic vesicle cycle and down-regulation of synapses were shared by these three diseases, suggesting that synaptic dysfunction might contribute to the onset and progress of neurodegenerative diseases caused by COVID-19. Five hub genes and one key module were obtained from the PPI network. Moreover, 5 drugs and 42 transcription factors (TFs) were also identified on the datasets. In conclusion, the results of our study provide new insights and directions for follow-up studies of the relationship between COVID-19 and neurodegenerative diseases. The hub genes and potential drugs we identified may provide promising treatment strategies to prevent COVID-19 patients from developing these disorders.

Long non-coding RNAs in virus-related cancers.

Some viral infections lead to tumourigenesis explained by a variety of underlying molecular mechanisms. Long non-coding RNAs (lncRNAs) have the potential to be added to this list due to their diverse mechanisms in biological functions and disease processes via gene alternation, transcriptional regulation, protein modification, microRNA sponging and interaction with RNA/DNA/proteins. In this review, we summarise the dysregulation and mechanism of lncRNAs in virus-related cancers focussing on Hepatitis B virus, Epstein-Barr virus, Human Papillomavirus. We will also discuss the potential implications of lncRNAs in COVID-19.

Effect of Methylprednisolone on Mortality and Clinical Courses in Patients with Severe COVID-19: A Propensity Score Matching Analysis

Background Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19. Methods This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants' epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors. Results Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% vs. 1.65%, P < 0.001), which was maintained after propensity score matching (13.98% vs. 5.38%, P = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242;95% confidence interval [CI], 0.802 to 34.246;P = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327;95% CI, 1.702 to 6.501;P < 0.001), lower lymphocyte count (OR, 0.076;95% CI, 0.012 to 0.461;P = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008;95% CI, 1.003 to 1.013;P = 0.002), and anticoagulation therapy (OR, 11.187;95% CI, 2.459 to 50.900;P = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (β Value 0.081;95% CI, −1.012 to 3.657;P = 0.265) or discharge (β Value 0.114;95% CI, −0.723 to 6.408;P = 0.117). d-dimer (β Value, 0.144;95% CI, 0.012 to 0.817;P = 0.044), LDH (β Value 0.260;95% CI, 0.010 to 0.034;P < 0.001), and antiviral therapy (β Value 0.220;95% CI, 1.373 to 6.263;P = 0.002) were associated with a longer length from admission to viral clearance. The lymphocyte count (β Value −0.206;95% CI, −6.248 to −1.197;P = 0.004), LDH (β Value 0.231;95% CI, 0.012 to 0.048;P = 0.001), antiviral therapy (β Value 0.143;95% CI, 0.058 to 7.497;P = 0.047), and antibacterial therapy (β Value 0.152;95% CI, 0.133 to 8.154;P = 0.043) were associated with a longer hospitalization duration from admission to discharge. Further stratified analysis revealed that the low daily dose group (≤60 mg/d) and the low total dose group (≤200 mg) had shorter duration from admission to viral clearance (Z=−2.362, P = 0.018;Z=−2.010, P = 0.044) and a shorter hospital stay (Z=−2.735, P = 0.006;Z=−3.858, P < 0.001). Conclusions In patients with severe COVID-19, methylprednisolone is safe and does not prolong the duration from admission to viral clearance or discharge. Low-dose, short-term methylprednisolone treatment may be more beneficial in shortening the disease course.

Effect of Methylprednisolone on Mortality and Clinical Courses in Patients with Severe COVID-19: A Propensity Score Matching Analysis.

Background: Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19. Methods: This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants' epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors. Results: Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% vs. 1.65%, P < 0.001), which was maintained after propensity score matching (13.98% vs. 5.38%, P = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242; 95% confidence interval [CI], 0.802 to 34.246; P = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327; 95% CI, 1.702 to 6.501; P < 0.001), lower lymphocyte count (OR, 0.076; 95% CI, 0.012 to 0.461; P = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008; 95% CI, 1.003 to 1.013; P = 0.002), and anticoagulation therapy (OR, 11.187; 95% CI, 2.459 to 50.900; P = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (ß Value 0.081; 95% CI, -1.012 to 3.657; P = 0.265) or discharge (ß Value 0.114; 95% CI, -0.723 to 6.408; P = 0.117). d-dimer (ß Value, 0.144; 95% CI, 0.012 to 0.817; P = 0.044), LDH (ß Value 0.260; 95% CI, 0.010 to 0.034; P < 0.001), and antiviral therapy (ß Value 0.220; 95% CI, 1.373 to 6.263; P = 0.002) were associated with a longer length from admission to viral clearance. The lymphocyte count (ß Value -0.206; 95% CI, -6.248 to -1.197; P = 0.004), LDH (ß Value 0.231; 95% CI, 0.012 to 0.048; P = 0.001), antiviral therapy (ß Value 0.143; 95% CI, 0.058 to 7.497; P = 0.047), and antibacterial therapy (ß Value 0.152; 95% CI, 0.133 to 8.154; P = 0.043) were associated with a longer hospitalization duration from admission to discharge. Further stratified analysis revealed that the low daily dose group (≤60 mg/d) and the low total dose group (≤200 mg) had shorter duration from admission to viral clearance (Z=-2.362, P = 0.018; Z=-2.010, P = 0.044) and a shorter hospital stay (Z=-2.735, P = 0.006; Z=-3.858, P < 0.001). Conclusions: In patients with severe COVID-19, methylprednisolone is safe and does not prolong the duration from admission to viral clearance or discharge. Low-dose, short-term methylprednisolone treatment may be more beneficial in shortening the disease course.

Global research trends in the COVID-19 and digestive disease: A review of visualization and bibliometric study.

BACKGROUND: The rapid spread of coronavirus disease 2019 (COVID-19) has attracted worldwide attention. There were also reported gastrointestinal symptoms in patients with COVID-19. This work aims to analyze the global research trends in COVID-19 and digestive disease. METHODS: The related papers on COVID-19 and digestive disease were identified with Pubmed and web of science core collection on September 3, 2021. Bibliometric visualization was conducted through VOSviewer and CiteSpace. RESULTS: The analytic research was based on original articles and reviews. There were 997 articles found, with citations ranging from 0 to 878. These articles were distributed among 86 countries and 355 journals. The USA mainly contributed (288 articles), where 3 of the top 10 institutions were located. Followed by China (215 articles) and Italy (160 articles). The highest level of scientific collaboration has been formed between the USA to China. The World Journal of Gastroenterology (39 papers) published the most significant number of articles. Concerning the research topic, the colon/small bowel had the largest number of articles, followed by the liver and pancreaticobiliary. "Liver injury," "inflammatory bowel disease," "management," and "endoscopy" were the hotspot keywords. The largest cluster of liver transplantation had offered hints regarding research frontiers. CONCLUSION: The analytic results showed that the liver, especially liver transplantation, and inflammatory bowel disease were the 2 most influential research topics in COVID-19 and digestive disease.

Global research trends in the COVID-19 and digestive disease: A review of visualization and bibliometric study

Background: The rapid spread of coronavirus disease 2019 (COVID-19) has attracted worldwide attention. There were also reported gastrointestinal symptoms in patients with COVID-19. This work aims to analyze the global research trends in COVID-19 and digestive disease. Methods: The related papers on COVID-19 and digestive disease were identified with Pubmed and web of science core collection on September 3, 2021. Bibliometric visualization was conducted through VOSviewer and CiteSpace. Results: The analytic research was based on original articles and reviews. There were 997 articles found, with citations ranging from 0 to 878. These articles were distributed among 86 countries and 355 journals. The USA mainly contributed (288 articles), where 3 of the top 10 institutions were located. Followed by China (215 articles) and Italy (160 articles). The highest level of scientific collaboration has been formed between the USA to China. The World Journal of Gastroenterology (39 papers) published the most significant number of articles. Concerning the research topic, the colon/small bowel had the largest number of articles, followed by the liver and pancreaticobiliary. "Liver injury,” "inflammatory bowel disease,” "management,” and "endoscopy” were the hotspot keywords. The largest cluster of liver transplantation had offered hints regarding research frontiers. Conclusion: The analytic results showed that the liver, especially liver transplantation, and inflammatory bowel disease were the 2 most influential research topics in COVID-19 and digestive disease.

The Effect of Digital Transformation on the Pharmaceutical Sustainable Supply Chain Performance: The Mediating Role of Information Sharing and Traceability Using Structural Equation Modeling

As the global pharmaceutical market continues to expand, the demand for pharmaceutical supply chain is increasing. In the context of "Industry 4.0”, the pharmaceutical supply chain sector needs to accelerate digital construction. Pharmaceutical companies need to strengthen risk management in order to cope with supply disruptions. From the perspective of sustainable development, the pharmaceutical supply chain can achieve sustainable supply performance in social, economic and environmental dimensions through digital transformation. There is a lack of research on digital transformation of pharmaceutical supply chain management. Further research is needed on what specific digital management pharmaceutical companies need to enhance to improve supply performance. This study uses empirical analysis to examine the impact of digital transformation on sustainable supply chain performance and to explore the role of information sharing and traceability as mediators. The aim is to guide the pharmaceutical supply chain to clearly manage the development of digital transformation and obtain sustainable supply performance. This study presents hypotheses based on cutting-edge theoretical findings. In total, 298 Chinese pharmaceutical company supply chain managers were surveyed and Structural equation analysis was conducted using SPSS26.0 and AMOS24.0. The results show that digital transformation significantly and positively impacts sustainable supply chain performance. Traceability plays a mediating role. The mediating role of information sharing is not significant. However, information sharing and traceability as two separate trends can have synergistic effects that together affect sustainable supply performance. The conclusion is that the pharmaceutical supply chain should accelerate digital construction, eliminate the uneven development of digital technology among supply chain members, and reduce the impact of technological uncertainty on performance. Companies are enhancing supply chain security management through information sharing and traceability systems, and are continuously focusing on the role of digital transformation as a driver for sustainable development.

Assessing the medical resources in COVID-19 based on evolutionary game.

COVID-19 has brought a great challenge to the medical system. A key scientific question is how to make a balance between home quarantine and staying in the hospital. To this end, we propose a game-based susceptible-exposed-asymptomatic -symptomatic- hospitalized-recovery-dead model to reveal such a situation. In this new framework, time-varying cure rate and mortality are employed and a parameter m is introduced to regulate the probability that individuals are willing to go to the hospital. Through extensive simulations, we find that (1) for low transmission rates (ß < 0.2), the high value of m (the willingness to stay in the hospital) indicates the full use of medical resources, and thus the pandemic can be easily contained; (2) for high transmission rates (ß > 0.2), large values of m lead to breakdown of the healthcare system, which will further increase the cumulative number of confirmed cases and death cases. Finally, we conduct the empirical analysis using the data from Japan and other typical countries to illustrate the proposed model and to test how our model explains reality.

Effects of short-term quarantine on growth and development of children aged 1-36 months during the Omicron outbreak.

Consequences of epidemic quarantine on children's well-being are not clear and there are scarce data about the short-term impact of epidemic quarantine on children's growth and development. The study aimed to explore and analyze the potential impacts of the Omicron outbreak on children's growth and development during the lockdown in Shanghai, China. Totally, 4565 children aged 1-36 months who had a routine physical examination in the child health departments of hospitals before (June 1, 2021, to July 6, 2021) and after (June 1, 2022, to July 6, 2022) Shanghai's lockdown were included in this study. A population-based cross-sectional study was conducted by using the Infant Toddler Growth Development Screening Test (ITGDST). The children's growth and development in these two periods were compared with a propensity score matching (PSM) approach. After 1:1 matching, a total of 2462 children aged 1-36 months were analyzed. After PSM, there was no significant difference in terms of overall development, gross motor, fine motor, and language development for children before and after the Omicron lockdown. However, statistically significant decrease of wasting was observed for children after the lockdown (p < 0.05). Further interaction analysis indicated older age group (OR = 0.26, 95% CI 0.11-0.59) and the group of second parity (OR = 0.30, 95% CI 0.11-0.83) were favorable to language development during the lockdown.  Conclusion: Short-term quarantine had no significant adverse, but rather beneficial, effects on growth and development of children aged 1-36 months during the Omicron epidemic in Shanghai, China. What is Known: • Consequences of epidemic quarantine on children's well-being are not clear. Long-term psychological effects of coronavirus disease 2019 pandemic on children have been reported. However, there are scarce data about the short-term impact of epidemic quarantine on children's growth and development. What is New: • Short-term quarantine had no significant adverse, but rather beneficial, effects on growth and development of children aged 1-36 months during the Omicron epidemic in Shanghai, China.

Effects of physical activity and use of digital devices on visual acuity in children and adolescents during the COVID-19 pandemic: A cross-sectional study.

Purpose: To determine the association between poor visual acuity, the use of digital devices and physical activity (PA) during the COVID-19 pandemic. Methods: A total of 327,646 Chinese children and adolescents were included in the analysis using a cluster random sampling method; this is a case-control study, of those 144,708 children and adolescents with poor visual acuity were included in the case group, while 182,938 who did not have poor visual acuity were included in the control group. A logistic regression model was used to assess the contribution of PA and the use of digital devices to poor visual acuity. Results: A total of 144,708 children and adolescents experienced poor visual acuity during the COVID-19 pandemic; 54.8% were male, and 55.2% live in rural areas. Compared to controls, children and adolescents with poor visual acuity exhibited more time for the use of digital devices (4.51 ± 2.44 vs. 3.79 ± 2.34 for cases and controls, respectively; P < 0.001) and PA (3.07 ± 0.92 vs. 2.85 ± 1.00 for cases and controls, respectively; P < 0.001). During the COVID-19 pandemic, risk factors related to poor visual acuity among children and adolescents included the use of digital devices (OR 1.135; 95% CI 1.132-1.139), and PA (OR 1.269; 95%CI 1.259-1.278). The results of interaction analysis show that for children and adolescents aged 12 to 17, the positive association between the use of digital devices and poor visual acuity decreased. The interaction effect between PA and digital devices is 0.987. Conclusions: Children and adolescents were at risk of poor visual acuity during the COVID-19 pandemic. Extended use of the digital devices increased the risk of poor visual acuity, especially for children aged 6-11 years. But the risk of poor visual acuity among children and adolescents decreases as the time spent on PA increases.

Prevalence of Post-traumatic Stress Disorder Status Among Healthcare Workers and Its Impact on Their Mental Health During the Crisis of COVID-19: A Cross-Sectional Study.

Objective: After the unprecedented coronavirus disease 2019 (COVID-19) outbreak, the health status of the general population has suffered a huge threat, and the mental health of front-line healthcare providers has also encountered great challenges. Therefore, this study aims to: (1) investigate the prevalence and influencing factors of post-traumatic stress disorder (PTSD) among healthcare providers, and (2) verify the moderating role of self-efficacy in the influence of PTSD on mental health. Methods: A cross-sectional study was conducted using an online survey of 1993 participants. The presence of depression, anxiety, self-efficacy, and PTSD was evaluated using screening tests from March 1. Sociodemographic and COVID-19-related data were also collected. A data analysis was performed using descriptive statistics, Pearson's correlation coefficient, and multiple linear regression. Results: The prevalence of PTSD among healthcare providers was 9.3%. PTSD was negatively correlated with self-efficacy (r = -0.265, P < 0.01), anxiety (r = -0.453, P < 0.01), and depression (r = 0.708, P < 0.01). Profession, daily working hours, maximum continuous working days, and daily sleep time were influencing factors of PTSD. A binary logistic regression analysis showed that physicians (OR = 2.254, 95% CI = 1.298, 3.914) and nurses (OR = 2.176, 95% CI = 1.337, 3.541) were more likely to experience PTSD than other healthcare providers. Conclusion: Self-efficacy has a moderating effect on the influence of PTSD on anxiety and depression. This suggests that health managers need to respond to the current psychological crisis of healthcare providers, implement appropriate psychological interventions, and minimize the psychological harm caused by COVID-19.

Safety and efficacy of mesenchymal stem cells in severe/critical patients with COVID-19: A systematic review and meta-analysis.

Background: The present study aims to better understand the efficacy and safety of mesenchymal stromal cells (MSCs) in treating severe/critical patients with COVID-19. Methods: PubMed, the Cochrane Library, and the Chinese electronic database CNKI were searched from inception up to Dec 19, 2021. Original comparative studies for MSC treatment + standard treatment for severe/critical patients with COVID-19, with placebo or standard treatment as the control group, were included. The primary outcomes were in-hospital mortality and adverse events (AEs). A meta-analysis was performed to compare the mortality rates between the two groups. Then, a subgroup analysis was performed according to the category of the disease (severe or critical) and MSC dose. Afterwards, a descriptive analysis was performed for AEs and secondary outcomes. The funnel plot and Egger's test were used for the publication bias assessment. Findings: Compared to placebo or standard care, MSCs provide significant benefit in the treatment of patients with severe/critical COVID-19, in terms of in-hospital mortality rate (odds ratio: 0.52, 95% CI 0.32-0.84), with very low heterogeneity (P=0.998 [Q test], I 2=0.0%) and less AEs. No significant difference was found in mortality rate due to the different disease categories or MSC doses. Furthermore, no publication bias was found. Interpretation: The present study demonstrates that MSCs are highly likely to reduce mortality and are safe to use for patients with severe or critical COVID-19, regardless of whether 1-3 doses are applied. However, due to the small sample size of the included studies, further high-quality, large-scale trials are needed to confirm this statement in the future. Funding: The National Key Research and Development Program of China (No. 2020YFC0860900), the Science and Technology Project of Wuhan (No. 2020020602012112), the Tianjin Science and Technology Research Program (18PTSYJC00070 and 16PTWYHZ00030), Haihe Laboratory of Cell Ecosystem Innovation Fund (HH22KYZX0046), and the Tianjin Free Trade Zone Innovation Development Project (ZMCY-03-2021002-01) funded the study. We are also grateful for the support from the 3551 Talent Plan of China Optics Valley.