Network pharmacology research of mechanism of Maxing Shigan Decoction in treating COVID-19

Background: The COVID-19 has a huge negative impact on people's health. Traditional Chinese Medicine (TCM) has a good effect on viral pneumonia. It is of great practical significance to study its pharmacology. Methods: The ingredients and targets of each herb in Maxing Shigan Decoction which obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the related targets of COVID-19 were screened by GeneCards database based on the network pharmacology. Venn was used to analyze the intersection target between active ingredients and diseases. Cytoscape software was used to construct an active ingredient-disease target network. The protein-protein interaction network was constructed by STRING database and Cytohubba was used to screen out the key targets. Gene Ontology (GO) functional enrichment analysis and KEGG pathway analysis were performed by DAVID database. Results: In this study, a total of 134 active ingredients and 229 related targets, 198 targets of COVID-19 and 48 common targets of drug-disease were chosen. Enrichment items and pathways were obtained through GO and KEGG pathway analysis. The predicted active ingredients were quercetin, kaempferol, luteolin, naringenin, glycyrol, and the key targets involved IL6, MAPK3, MAPK8, CASP3, IL10, etc. The results showed that the active ingredients of Maxing Shigan Decoction acted on multiple targets which played roles in the treatment of COVID-19 by regulating inflammation, immune system and other pathways. Conclusions: The main contribution of this paper is to use data to mine the principles of the treatment of COVID-19 from the pharmacology of these prescriptions, and the results can be provided theoretical reference for medical workers. © The Author (s) 2023. Published by Higher Education Press.

[Experience in emergency response to 2019-nCoV positive cases in an international test competition].

Objective: To analyze the performance of emergency response to 2019 novel coronavirus (2019-nCoV) positive cases in an international test competition in an Winter Olympic Game venue and provide evidences for the COVID-19 prevention and control in similar competitions. Methods: A retrospective analysis on the epidemiological investigation and nucleic acid test results of the cases, the implementation of prevention and control measures, including the communication with sport teams and others, was conducted. Results: The positive cases of 2019-nCoV among entering people were detected before entry, at airport, hotel and venue. Two positive cases were reported before entry, 2 positive cases infected previously and 3 asymptomatic cases were reported after the entry. The venue public health team and local CDC conducted epidemiological investigation and contact assessment jointly in a timely and efficient manner. No local secondary transmission occurred, but the nucleic acid test results of positive persons fluctuated, posing serious challenges to the implementation of prevention and control measures. Conclusion: In large scale international competition, there is high risk of imported COVID-19. It is necessary to fully consider the fluctuation of nucleic acid test results, the criteria for determination and cancellation of positive results and give warm care to positive cases in the emergency response.

Optimal Scheduling of COVID-19 Pandemic Supply Disruptions Under Uncertainty

With the outbreak of COVID-19 pandemic, the problem of supply chain emergency scheduling has had a great influence on economic benefits of enterprises. The uncertainty of the COVID-19 pandemic and uncertainty of supply chain have made the problem of emergency scheduling more complicated. In this study, a multiobjective multiperiod mixed-integer programming optimization model was developed, in which two conflicting benefit factors, cost and service level were taken as the optimization target of the model. Cost and service level were normalized, and the weighted sum was taken as the objective function, which transformed the problem into a multiperiod nonlinear one. Two algorithms of Bi-level Modified Hybrid Genetic Algorithm (BMHGA) and Bi-level Hybrid Genetic Algorithm (BHGA) were designed to solve the model. Three emergency strategies have been proposed, including enabling alternative suppliers, repairing failure nodes and enabling internal suppliers' flexibility. The parameter of disruption scenario and its solution method were designed. Finally, the practicability of the proposed model and algorithm was demonstrated through application to a case study of an electronics supply chain. The results indicated that the optimal solution of two algorithms was between 2%-5%, and BMHGA could obtain a better optimal solution.

Keeping Fun Alive: an Experience Report on Running Online Coding Camps

The outbreak of the COVID-19 pandemic prohibited radically the collocation and face-to-face interactions of participants in coding bootcamps and similar experiences, which are key characteristics that help participants to advance technical work. Several specific issues are faced and need to be solved when running online coding camps, which can achieve the same level of positive outcomes for participants. One of such issues is how to keep the same level of fun that participants obtained through physical activities and interactions in the face-to-face settings. In this paper, we report on our experience and insights gained from designing and running a fully remote coding camp that exposes high school students to Agile-based Software Engineering practices to enhance their ability to develop high-quality software. To design the online coding camp, we adapted the face-to-face version of the coding camp to keep the same "level of fun", i.e., adaptations aimed at increasing communication, engaging participants, and introducing fun items to reduce fatigue due to prolonged computer use, while preserving the technical curriculum that enables students to attain the learning goals originally planned. The comparison with the results of the face-to-face coding camp shows that we succeeded in keeping the fun alive in the online edition, and the participants of online camp were able to produce the results at the same level of quality in terms of product and process as in the face-to-face edition. From our experience, we synthesize lessons learned, and we sketch some guidelines for educators.

Extradosed cable-stayed Peljesac Bridje in Croatia Fabrication of steel box girders and on-site installation

The new Peljeac Bridge and access road project, which links Mainland Croatia to the Peljeac Peninsula, is the most significant social infrastructure project in Croatia under construction at present. The bridge site lies in the highly active seismic region with ground acceleration a(g) = 0.34g and a maximum average ten-minute wind speed above 33.7 m/s. As a result, the execution class for the steel structure was judged to be EXC4 based on the recommended matrix in standard EN 1090-2, which defines execution classes according to consequence class, service category, and production category. The correspondingly determined quality level was class B+, which equates to quality class B under ISO 5817 with supplementary requirements for bridge decks from EN 1090-2. This article describes the whole fabrication process in the workshop, the long-distance transportation and the installation on the bridge site. To satisfy such high-quality technical requirements, the heavy steel structures were fabricated using a wide variety of mechanized equipment and automatic welding techniques. This helped to ensure a more efficient fabrication process and more consistent product quality. The length of the large side span segments was designed to suit the capabilities of the floating cranes and transit barges, thereby making on-site installation more efficient. Against the backdrop of the global Covid-19 pandemic, the contractor CRBC overcame seemingly unsurmountable obstacles beyond their control to successfully complete this challenging assignment in two years.

Safety and efficacy of oral lopinavir/ritonavir in pediatric patients with coronavirus disease: a nationwide comparative analysis.

OBJECTIVE: Because of the limited treatment options available, oral lopinavir/ritonavir (LPR) was used for treating coronavirus disease (COVID-19) in pediatric patients. This study aimed to assess the efficacy and safety of LPR in COVID-19 pediatric patients with mild symptoms. PATIENTS AND METHODS: This retrospective multicenter analysis included hospitalized children with mild COVID-19 who received LPR at one of 13 hospitals in China from January 1, 2020, to June 1, 2020. Patients treated with LPR were matched with patients not treated with LPR (1:4) according to age, sex, and length of symptom onset and hospitalization. Descriptive statistics and non-parametric tests were applied to compare differences between groups. Kaplan-Meier probability curves and Cox regression models were used to analyze nasal swab turning negative time (recovery time) and hospital discharge days. RESULTS: In total, 23 patients treated with LPR were matched with 92 untreated controls. The median age of patients was 6 years, and 56.52% of them were male. All patients were discharged from the hospital after being cured. The treatment group had a longer nasal swab turning negative time (hazard ratio [HR] 5.33; 95% CI: 1.94-14.67; p = 0.001) than the control group. LPR treatment was also associated with a longer hospitalization time (HR 2.01; 95% CI: 1.24-3.29; p = 0.005). After adjusting for the influence of LPR treatment, adverse drug reaction events were associated with a longer nasopharyngeal swab negative time (HR 4.67; 95% CI 1.35-16.11; p = 0.015). CONCLUSIONS: For children with mild COVID-19, LPR is inferior to conventional treatment in reducing virus shedding time and hospitalization duration and is associated with increased adverse reactions.

[Analysis of CT features of 15 children with 2019 novel coronavirus infection].

Objective: To explore imaging characteristics of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: A retrospective analysis was performed on clinical data and chest CT images of 15 children diagnosed with 2019-nCoV infection. They were admitted to the Third People's Hospital of Shenzhen from January 16 to February 6, 2020. The distribution and morphology of pulmonary lesions on chest CT images were analyzed. Results: Among the 15 children, 5 were males and 10 females, aged from 4 to 14 years. Five of the 15 children were febrile and 10 were asymptomatic on the first visit. The first nasal or pharyngeal swab samples in all the 15 cases were positive for 2019-nCoV nucleic acid. For their first chest CT images, 6 patients had no lesions, while 9 patients had pulmonary inflammatory lesions. Seven cases had small nodular ground glass opacities and 2 cases had speckled ground glass opacities. After 3 to 5 days of treatment, 2019-nCoV nucleic acid in a second respiratory sample turned negative in 6 cases. Among them, chest CT images showed less lesions in 2 cases, no lesion in 3 cases, and no improvement in 1 case. The remaining 9 cases were still positive in a second nucleic acid test. Six patients showed similar chest CT inflammation, while 3 patients had new lesions, which were all small nodular ground glass opacities. Conclusions: The early chest CT images of children with 2019-nCoV infection are mostly small nodular ground glass opacities. The clinical symptoms of children with 2019-nCoV infection are nonspecific. Dynamic reexamination of chest CT and nucleic acid are important.

Clinical efficacy of lopinavir/ritonavir in the treatment of Coronavirus disease 2019.

OBJECTIVE: The Coronavirus disease 2019 (COVID-19) which outbroke in December 2019 is highly contagious with a low cure rate. In view of this, there is an urgent need to find a more appropriate therapeutic scheme against COVID-19. The study aimed to investigate whether lopinavir/ritonavir (LPV/r) in combination with other pneumonia-associated adjuvant drugs has a better therapeutic effect on COVID-19. PATIENTS AND METHODS: Totally 47 patients with COVID-19 infection who were admitted to Rui'an People's Hospital between January 22 and January 29, 2020 were collected. The patients were divided into the test group and the control group according to whether they had been treated with LPV/r or not during hospitalization. Patients in the test group were treated with LPV/r combined with adjuvant medicine, while those in the control group were just treated with adjuvant medicine. The changes of body temperature, blood routine and blood biochemistry between the two groups were observed and compared. RESULTS: Both groups achieved good therapeutic effect with the body temperature of patients decreased gradually from admission to the 10th day of treatment. But the body temperature of patients in the test group decreased faster than that of the control group. Blood routine indexes showed that compared with the control group, the abnormal proportion of white blood cells, lymphocytes and C-reactive protein of the test group could be reduced to some extent. Blood biochemical indexes exhibited that the proportion of patients with abnormal alanine aminotransferase and aspartate aminotransferase in the test group were lower than the control group. The number of days for nCoV-RNA turning negative after treatment was significantly decreased in the test group than that in the control group. CONCLUSIONS: Compared with the treatment of pneumonia-associated adjuvant drugs alone, the combination treatment with LPV/r and adjuvant drugs has a more evident therapeutic effect in lowering the body temperature and restoring normal physiological mechanisms with no evident toxic and side effects. In view of these conclusions, we suggested that the use of LPV/r combined with pneumonia-associated adjuvant drugs in the clinical treatment for patients with COVID-19 should be promoted.

[Analysis of CT features of 15 Children with 2019 novel coronavirus infection].

Objective: To explore imaging characteristics of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: A retrospective analysis was performed on clinical data and chest CT images of 15 children diagnosed with 2019-nCoV. They were admitted to the third people's Hospital of Shenzhen from January 16 to February 6, 2020. The distribution and morphology of pulmonary lesions on chest CT images were analyzed. Results: Among the 15 children, there were 5 males and 10 females, aged from 4 to 14 years old. Five of the 15 children were febrile and 10 were asymptomatic on first visit. The first nasal or pharyngeal swab samples in all the 15 cases were positive for 2019-nCoV nucleic acid. For their first chest CT images, 6 patients had no lesions, while 9 patients had pulmonary inflammation lesions. Seven cases of small nodular ground glass opacities and 2 cases of speckled ground glass opacities were found. After 3 to 5 days of treatment, 2019-nCoV nucleic acid in a second respiratory sample turned negative in 6 cases. Among them, chest CT images showed less lesions in 2 cases, no lesion in 3 cases, and no improvement in 1 case. Other 9 cases were still positive in a second nucleic acid test. Six patients showed similar chest CT inflammation, while 3 patients had new lesions, which were all small nodular ground glass opacities. Conclusions: The early chest CT images of children with 2019-nCoV infection are mostly small nodular ground glass opacities. The clinical symptoms of children with 2019-nCoV infection are nonspecific. Dynamic reexamination of chest CT and nucleic acid are important.