Risk spillover network in the supply chain system during the COVID-19 crisis: Evidence from China.

The COVID-19 crisis seriously impacted the global economy and supply chain system. Unlike previous studies, this paper examines the risk spillover effects within the supply chain system rather than between financial and other specific industries. The hypotheses are proposed by developing and simulating an agent-based model; the copula-conditional value at risk model is employed to empirically validate these hypotheses in China during the COVID-19 crisis. The findings reveal that risks are transmitted and amplified from downstream, through midstream to upstream. Additionally, the financial industry amplifies the risk spillover from the midstream to the upstream and downstream. Moreover, the risk spillovers exhibit significant time-varying characteristics, and policy interventions can potentially mitigate the effect of such spillovers. This paper provides a theoretical basis and empirical evidence for risk spillover in supply chain systems and offers suggestions for industrial practitioners and regulators.

New progresses on cell surface protein HSPA5/BiP/GRP78 in cancers and COVID-19.

Heat-shock-protein family A (Hsp70) member 5 (HSPA5), aliases GRP78 or BiP, is a protein encoded with 654 amino acids by the HSPA5 gene located on human chromosome 9q33.3. When the endoplasmic reticulum (ER) was stressed, HSPA5 translocated to the cell surface, the mitochondria, and the nucleus complexed with other proteins to execute its functions. On the cell surface, HSPA5/BiP/GRP78 can play diverse functional roles in cell viability, proliferation, apoptosis, attachments, and innate and adaptive immunity regulations, which lead to various diseases, including cancers and coronavirus disease 2019 (COVID-19). COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which caused the pandemic since the first outbreak in late December 2019. HSPA5, highly expressed in the malignant tumors, likely plays a critical role in SARS-CoV-2 invasion/attack in cancer patients via tumor tissues. In the current study, we review the newest research progresses on cell surface protein HSPA5 expressions, functions, and mechanisms for cancers and SARS-CoV-2 invasion. The therapeutic and prognostic significances and prospects in cancers and COVID-19 disease by targeting HSPA5 are also discussed. Targeting HSPA5 expression by natural products may imply the significance in clinical for both anti-COVID-19 and anti-cancers in the future.

Variable radiographic and histologic presentations of amiodarone-related interstitial lung disease and the importance of avoiding re-exposure.

Amiodarone is a commonly used antiarrhythmic agent but exhibits potential pulmonary toxicity. In this case series, we describe the clinical, radiographic, and histologic manifestations of three patients who developed interstitial lung disease (ILD) following amiodarone treatment for variable lengths of time with different dosages. The presentations on computed tomographic images and in pulmonary pathology differed among the three patients. All three had immediate discontinuation of amiodarone and received treatment with systemic corticosteroids. One patient eventually died from ventilator-associated pneumonia after an initial improvement. The other two patients recovered well but later experienced ILD recurrence following brief re-exposure to amiodarone. Through this case series, we aim to demonstrate the variable features of amiodarone-related ILD, and highlight the importance of timely amiodarone cessation and avoiding re-exposure to prevent the progression and recurrence of ILD.

Treatment cost assessment for COVID-19 inpatients in Shenzhen, China 2020-2021: facts and suggestions.

Background: Knowledge regarding the treatment cost of coronavirus disease 2019 (COVID-19) in the real world is vital for disease burden forecasts and health resources planning. However, it is greatly hindered by obtaining reliable cost data from actual patients. To address this knowledge gap, this study aims to estimate the treatment cost and specific cost components for COVID-19 inpatients in Shenzhen city, China in 2020-2021. Methods: It is a 2 years' cross-sectional study. The de-identified discharge claims were collected from the hospital information system (HIS) of COVID-19 designated hospital in Shenzhen, China. One thousand three hundred ninety-eight inpatients with a discharge diagnosis for COVID-19 from January 10, 2020 (the first COVID-19 case admitted in the hospital in Shenzhen) to December 31, 2021. A comparison was made of treatment cost and cost components of COVID-19 inpatients among seven COVID-19 clinical classifications (asymptomatic, mild, moderate, severe, critical, convalescent and re-positive cases) and three admission stages (divided by the implementation of different treatment guidelines). The multi-variable linear regression models were used to conduct the analysis. Results: The treatment cost for included COVID-19 inpatients was USD 3,328.8. The number of convalescent cases accounted for the largest proportion of all COVID-19 inpatients (42.7%). The severe and critical cases incurred more than 40% of treatment cost on western medicine, while the other five COVID-19 clinical classifications spent the largest proportion (32%-51%) on lab testing. Compared with asymptomatic cases, significant increases of treatment cost were observed in mild cases (by 30.0%), moderate cases (by 49.2%), severe cases (by 228.7%) and critical cases (by 680.7%), while reductions were shown in re-positive cases (by 43.1%) and convalescent cases (by 38.6%). The decreasing trend of treatment cost was observed during the latter two stages by 7.6 and 17.9%, respectively. Conclusions: Our findings identified the difference of inpatient treatment cost across seven COVID-19 clinical classifications and the changes at three admission stages. It is highly suggestive to inform the financial burden experienced by the health insurance fund and the Government, to emphasize the rational use of lab tests and western medicine in the COVID-19 treatment guideline, and to design suitable treatment and control policy for convalescent cases.

Degradation and dechlorination of trichloroacetic acid induced by an in situ 222 nm KrCl* excimer radiation.

Since the coronavirus disease 2019 (COVID-19) pandemic epidemic, the excessive usage of chlorinated disinfectants raised the substantial risks of disinfection by-products (DBPs) exposure. While several technologies may remove the typical carcinogenic DBPs, trichloroacetic acid (TCAA), their application for continuous treatment is limited due to their complexity and expensive or hazardous inputs. In this study, degradation and dechlorination of TCAA induced by an in situ 222 nm KrCl* excimer radiation as well as role of oxygen in the reaction pathway were investigated. Quantum chemical calculation methods were used to help predict the reaction mechanism. Experimental results showed that UV irradiance increased with increasing input power and decreased when the input power exceeded 60 W. Decomposition and dechlorination were simultaneously achieved, where around 78% of TCAA (0.62 mM) can be eliminated and 78% dechlorination within 200 min. Dissolved oxygen showed little effect on the TCAA degradation but greatly boosted the dechlorination as it can additionally generate hydroxyl radical (•OH) in the reaction process. Computational results showed that under 222 nm irradiation, TCAA was excited from S0 to S1 state and then decayed by internal crossing process to T1 state, and a reaction without potential energy barrier followed, resulting in the breaking of C-Cl bond and finally returning to S0 state. Subsequent C-Cl bond cleavage occurred by a barrierless •OH insertion and HCl elimination (27.9 kcal/mol). Finally, the •OH attacked (14.6 kcal/mol) the intermediate byproducts, leading to complete dechlorination and decomposition. The KrCl* excimer radiation has obvious advantages in terms of energy efficiency compared to other competitive methods. These results provide insight into the mechanisms of TCAA dechlorination and decomposition under KrCl* excimer radiation, as well as important information for guiding research toward direct and indirect photolysis of halogenated DBPs.

Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury.

Introdcution: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary. Methods: We assessed the ability of anti-CD31-ORI-NPs to penetrate endothelial cell barriers and specifically accumulate in lung tissues using an animal model. We also compared the efficacy of anti-CD31-ORI-NPs to that of free oridonin in ameliorating acute lung injury and evaluated the cytotoxicity of both treatments on endothelial cells. Results: Compared to free ORI, the amount of anti-CD31-ORI-NPs accumulated in lung tissues increase at least three times. Accordingly, anti-CD31-ORI-NPs improve the efficacy three times on suppressing IL-6 and TNF-a secretion, ROS production, eventually ameliorating acute lung injury in animal model. Importantly, anti-CD31-ORI-NPs significantly decrease the cytotoxicity at least two times than free oridonin on endothelial cells. Discussion: Our results from this study will not only offer a novel therapeutic strategy with high efficacy and low toxicity, but also provide the rational design of nanomaterials of a potential drug for acute lung injury therapy.

Discovering a Dihydrofluorescein Analogue as a Promising Fluorescence Substrate to HRP

Horseradish peroxidase (HRP) combined with its fluorescence substrates is attracting increasing attention for biochemical analysis. Amplex red is the most widely used fluorescence substrate to HRP;however, it suffers from some drawbacks, such as nonspecific responsiveness toward carboxylesterases. Discovering a new small molecular fluorescence substrate with improved sensitivity and selectivity for HRP is thus desired. Herein, three dihydrofluorescein derivatives (DCFHs) are presented to serve as HRP substrates through fluorescence turn-on methods. The most promising one, 2,7-dichloro-9-(2-(hydroxymethyl)phenyl)-9H-xanthene-3,6-diol (DCFH-1), exhibited excellent sensitivity in the detection of HRP. Moreover, DCFH-1 does not respond to carboxylesterase, thus holding advantages over Amplex red. In the further study, the detection reagent in the commercial ELISA kits was replaced with DCFH-1 to establish a new fluorescence ELISA, which works very well in the quantification of inflammatory cytokine biomarkers from in vitro models.

Superiority of UV222 radiation by in situ aquatic electrode KrCl excimer in disinfecting waterborne pathogens: Mechanism and efficacy.

Microbial safety in water has always been the focus of attention, especially during the COVID-19 pandemic. Development of green, efficient and safe disinfection technology is the key to control the spread of pathogenic microorganisms. Here, an in situ aquatic electrode KrCl excimer radiation with main emission wavelength 222 nm (UV222) was designed and used to disinfect model waterborne virus and bacteria, i.e. phage MS2, E. coli and S. aureus. High inactivation efficacy and diversity of inactivation mechanisms of UV222 were proved by comparision with those of commercial UV254. UV222 could totally inactivate MS2, E. coli and S. aureus with initial concentrations of ∼107 PFU or CFU mL-1 within 20, 15, and 36 mJ/cm2, respectively. The UV dose required by UV254 to inactivate the same logarithmic pathogenic microorganism is at least twice that of UV222. The protein, genomic and cell membrane irreparable damage contributed to the microbial inactivation by UV222, but UV254 only act on nucleic acid of the target microorganisms. We found that UV222 damage nucleic acid with almost the same or even higher efficacy with UV254. In addition, free base damage of UV222 in similar ways with UV254(dimer and hydrate). But due to the quantum yield of free base degradation of UV222 was greater than UV254, the photolysis rates of UV222 to A, G, C and U four bases were 11.5, 1.2, 3.2 and 1 times as those of UV254, respectively. Excellent disinfection performance in UV222 irradiation was also achieved in real water matrices (WWTP and Lake). In addition, it was proved that coexisting HCO3- or HPO42 - in real and synthetic water matrices can produce • OH to promote UV222 disinfection. This study provided novel insight into the UV222 disinfection process and demonstrated its possibility to take place of the conventional ultraviolet mercury lamp in water purification.

Canine Coronavirus Infection Modulates the Biogenesis and Composition of Cell-Derived Extracellular Vesicles.

Coronavirus (CoV) has persistently become a global health concern causing various diseases in a wide variety of hosts, including humans, birds, and companion animals. However, the virus-mediated responses in animal hosts have not been studied extensively due to pathogenesis complexity and disease developments. Extracellular vesicles (EVs) are widely explored in viral infections for their intercellular communication, nanocarrier, and immunomodulatory properties. We proposed that coronavirus hijacks the host exosomal pathway and modulates the EV biogenesis, composition, and protein trafficking in the host. In the present study, Crandell-Rees feline kidney (CRFK) cells were infected with canine coronavirus (CCoV) in an exosome-free medium at the multiplicity of infection (MOI) of 400 infectious units (IFU) at various time points. The cell viability was significantly decreased over time, as determined by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Post-infection EVs were isolated, and transmission electron microscopy (TEM) showed the presence of small EVs (sEVs) after infection. NanoSight particle tracking analysis (NTA) revealed that EV sizes averaged between 100 and 200 nm at both incubation times; however, the mean size of infection-derived EVs was significantly decreased at 48 h when compared to uninfected control EVs. Quantitative analysis of protein levels performed by dot blot scanning showed that the expression levels of ACE-2, annexin-V, flotillin-1, TLR-7, LAMP, TNF-α, caspase-1, caspase-8, and others were altered in EVs after infection. Our findings suggested that coronavirus infection impacts cell viability, modulates EV biogenesis, and alters cargo composition and protein trafficking in the host, which could impact viral progression and disease development. Future experiments with different animal CoVs will provide a detailed understanding of host EV biology in infection pathogenesis and progression. Hence, EVs could offer a diagnostic and therapeutic tool to study virus-mediated host responses that could be extended to study the interspecies jump of animal CoVs to cause infection in humans.

Highly Sensitive Poly-N-isopropylacrylamide Microgel-based Electrochemical Biosensor for the Detection of SARS-COV-2 Spike Protein.

Objective: Late 2019 witnessed the outbreak and widespread transmission of coronavirus disease 2019 (COVID-19), a new, highly contagious disease caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Consequently, considerable attention has been paid to the development of new diagnostic tools for the early detection of SARS-CoV-2. Methods: In this study, a new poly-N-isopropylacrylamide microgel-based electrochemical sensor was explored to detect the SARS-CoV-2 spike protein (S protein) in human saliva. The microgel was composed of a copolymer of N-isopropylacrylamide and acrylic acid, and gold nanoparticles were encapsulated within the microgel through facile and economical fabrication. The electrochemical performance of the sensor was evaluated through differential pulse voltammetry. Results: Under optimal experimental conditions, the linear range of the sensor was 10 -13-10 -9 mg/mL, whereas the detection limit was 9.55 fg/mL. Furthermore, the S protein was instilled in artificial saliva as the infected human saliva model, and the sensing platform showed satisfactory detection capability. Conclusion: The sensing platform exhibited excellent specificity and sensitivity in detecting spike protein, indicating its potential application for the time-saving and inexpensive detection of SARS-CoV-2.

Emerging Role of Neutrophil Extracellular Traps in Gastrointestinal Tumors: A Narrative Review.

Neutrophil extracellular traps (NETs) are extracellular fibrous networks consisting of depolymerized chromatin DNA skeletons with a variety of antimicrobial proteins. They are secreted by activated neutrophils and play key roles in host defense and immune responses. Gastrointestinal (GI) malignancies are globally known for their high mortality and morbidity. Increasing research suggests that NETs contribute to the progression and metastasis of digestive tract tumors, among them gastric, colon, liver, and pancreatic cancers. This article explores the formation of NETs and reviews the role that NETs play in the gastrointestinal oncologic microenvironment, tumor proliferation and metastasis, tumor-related thrombosis, and surgical stress. At the same time, we analyze the qualitative and quantitative detection methods of NETs in recent years and found that NETs are specific markers of coronavirus disease 2019 (COVID-19). Then, we explore the possibility of NET inhibitors for the treatment of digestive tract tumor diseases to provide a new, efficient, and safe solution for the future therapy of gastrointestinal tumors.

Analysis of the Influencing Factors of Seeking Intention on COVID-19 Risk Information: A Cross-Sectional Study.

Background: Information seeking, as an important part of the prevention and control of infectious diseases, can lead to positive outcomes by reducing uncertainty and alleviating panic. However, most previous studies have limited their analysis to individual-level psychosocial factors, and little is known about how social-level factors influence individuals' information-seeking intentions. Methods: The cross-sectional survey was conducted from July 30, 2020 to August 15, 2020 in China. We used a convenience sampling strategy to recruit participants from among the Internet users. The structural equation model was used to identify the incentives associated with coronavirus disease 2019 (COVID-19) risk information-seeking intention. Results: In this study, the responses of 871 Internet users who reflected a response rate of 85% were analyzed. Information-seeking intention was found to be directed by informational subjective norms (ISNs), perceived information need, risk knowledge, the sense of community (SOC), and negative affective responses, and ISNs were found to be the strongest driving factor. Individuals with a stronger SOC, which was associated with greater pressure and expectations, show negative affective responses. COVID-19 risk knowledge can affect the information-seeking intention of Internet users not only directly but also indirectly through their perceived information need. In addition, more risk knowledge was associated with a lower perceived risk likelihood. Conclusion: When formulating risk communication strategies, governments and health institutions should take targeted measures to improve the public's SOC and knowledge. This will provide an opportunity to explore the role of individual cognition and environmental risk information in public health.

Applying two behavioral theories to predict the willingness to receive COVID-19 vaccine booster in the elderly: A cross-sectional study.

BACKGROUND: The COVID-19 vaccination booster can effectively protect the elderly from infection while also lowering the risk of serious illness and death. However, barriers remain in willingness of the elderly to boost vaccination. OBJECTIVE: Using the protection motivation theory (PMT) and the theory of planned behavior (TPB), to study the factors that influence willingness of the elderly to get the COVID-19 vaccine booster. METHODS: The elderly who visited three randomly selected medical institutions in Nanjing's core urban region between March and April 2022 were chosen as study participants. A face-to-face survey was conducted using purposeful sampling and a self-designed questionnaire. The questionnaire contained sociodemographic characteristics, the elderly's willingness to obtain a COVID-19 vaccine booster, and psychosocial cognitive components based on the PMT and TPB. SmartPLS 3.0 was used to conduct structural equation modeling. RESULTS: 214 participants were included in the analysis. The combined model of the two behavioral theories explained the willingness to accept COVID-19 vaccine booster well with R2 of 0.490. Self-efficacy (ß = 0.315) was the strongest predictor of vaccine booster willingness. Subjective norms (ß = 0.160), perceived severity (ß = 0.157), and perceived vulnerability (ß = 0.159) also showed positive effects on vaccine booster willingness, while response cost (ß = -0.143) had a negative effect on the willingness. No significant association between attitudes, response efficacy and the willingness was discovered. CONCLUSION: The willingness of the elderly to receive the COVID-19 vaccine booster was affected by psychosocial cognitive factors. This study supports the applicability of the PMT and TPB models to interpret the willingness of the elderly in such areas.

SARS‐CoV‐2 modulation of RIG‐I‐MAVS signaling: Potential mechanisms of impairment on host antiviral immunity and therapeutic approaches

The coronavirus disease 2019 (COVID‐19) is a global infectious disease aroused by RNA virus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Patients may suffer from severe respiratory failure or even die, posing a huge challenge to global public health. Retinoic acid‐inducible gene I (RIG‐I) is one of the major pattern recognition receptors, function to recognize RNA viruses and mediate the innate immune response. RIG‐1 and melanoma differentiation‐associated gene 5 contain an N‐terminal caspase recruitment domain that is activated upon detection of viral RNA in the cytoplasm of virus‐infected cells. Activated RIG‐I and mitochondrial antiviral signaling (MAVS) protein trigger a series of corresponding immune responses such as the production of type I interferon against viral infection. In this review, we are summarizing the role of the structural, nonstructural, and accessory proteins from SARS‐CoV‐2 on the RIG‐I‐MAVS pathway, and exploring the potential mechanism how SARS‐CoV‐2 could evade the host antiviral response. We then proposed that modulation of the RIG‐I‐MAVS signaling pathway might be a novel and effective therapeutic strategy to against COVID‐19 as well as the constantly mutating coronavirus. The retinoic acid‐inducible gene I mitochondrial antiviral signaling (RIG‐I‐MAVS) axis is designated as a major signaling pathway in the innate immune response for RNA viruses. This review summarized the role of various proteins derived from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) on the RIG‐I‐MAVS pathway and explored the underlying mechanism of SARS‐CoV‐2 to escape the host antiviral response. Regulation of RIG‐I‐MAVS pathway might be a potentially therapeutic strategy to boost immunity against COVID‐19.

A Retrospective Analysis of National-Scale Agricultural Development in Saudi Arabia from 1990 to 2021

Agricultural intensification has resulted in the depletion of groundwater resources in many regions of the world. A prime example is Saudi Arabia, which witnessed dramatic agricultural expansion since the 1970s. To explore the influence of policy interventions aimed to better manage water resources, accurate information on the changes in the number and acreage of center-pivot fields is required. To quantify these metrics, we apply a hybrid machine learning framework, consisting of Density-Based Spatial Clustering of Applications with Noise, Convolutional Neural Networks, and Spectral Clustering, to the annual maximum Normalized Differential Vegetation Index maps obtained from Landsat imagery collected between 1990 to 2021. When evaluated against more than 28,000 manually delineated fields, the approach demonstrated producer's accuracies ranging from 83.7% to 94.8% and user's accuracies ranging from 90.2% to 97.9%. The coefficient of determination (R2) between framework-delineated and manually delineated fields was higher than 0.97. Nationally, we found that most fields pre-dated 1990 (covering 8841 km2 in that year) and were primarily located within the central regions covering Hail, Qassim, Riyadh, and Wadi ad-Dawasir. A small decreasing trend in field acreage was observed for the period 1990-2010. However, by 2015, the acreage had increased to approximately 33,000 fields covering 9310 km2. While a maximum extent was achieved in 2016, recent decreases have seen levels return to pre-1990 levels. The gradual decrease between 1990 to 2010 was related to policy initiatives designed to phase-out wheat, while increases between 2010 to 2015 were linked to fodder crop expansion. There is evidence of an agricultural uptick starting in 2021, which is likely in response to global influences such as the COVID-19 pandemic or the conflict in Ukraine. Overall, this work offers the first detailed assessment of long-term agricultural development in Saudi Arabia, and provides important insights related to production metrics such as crop types, crop water consumption, and crop phenology and the overarching impacts of agricultural policy interventions.

Risk factors for postoperative medical morbidity and 3-month mortality in elderly patients with hip fracture following hip arthroplasty during COVID-19 pandemic.

BACKGROUND: The purpose of the current study was to investigate the incidence of postoperative medical complications and 3-month mortality in patients ≥ 70 years old with hip fracture following hip arthroplasty (HA) and independent risk factors associated with postoperative medical complications and 3-month mortality during the Coronavirus Disease 2019 (COVID-19) pandemic. METHODS: A multicenter retrospective study was conducted, patients ≥ 70 years old with HA for hip fracture under general anesthesia were included during COVID-19 and before COVID-19 pandemic. The outcome was defined as postoperative medical complications and 3-month mortality. The baseline characteristics and risk factors were collected, multivariable logistic regression was used to identify independent risk factors for postoperative medical complications and 3-month mortality. RESULTS: A total of 1096 patients were included during COVID-19 pandemic and 1149 were included before COVID-19 pandemic in the study. Patients ≥ 70 years with hip fracture for HA had longer fracture to operation duration (7.10 ± 3.52 vs. 5.31 ± 1.29, P < 0.001), and the incidence of postoperative medical complications (21.90% vs. 12.53%, P < 0.001) and 3-month mortality (5.20% vs. 3.22%, P = 0.025) was higher during COVID-2019 pandemic. Multivariate logistic regression analysis showed that dementia (OR 2.73; 95% CI 1.37-5.44; P = 0.004), chronic obstructive pulmonary disease (COPD) (OR 3.00; 95% CI 1.92-4.71; P < 0.001), longer fracture to operation duration (OR 1.24; 95% CI 1.19-1.30; P < 0.001) were associated with increased risk for postoperative medical complications. COPD (OR 2.10; 95% CI 1.05-4.17; P = 0.035), dementia (OR 3.00; 95% CI 1.11-7.94; P = 0.031), postoperative medical complications (OR 4.99; 95% CI 2.68-9.28; P < 0.001), longer fracture to operation duration (OR 1.11; 95% CI 1.04-1.19; P = 0.002) were associated with increased risk for 3-month mortality. CONCLUSIONS: In conclusion, we found that postoperative medical morbidity and 3-month mortality in patients with hip fracture underwent HA were 21.90% and 5.20%, respectively, during the COVID-19. COPD, dementia and longer fracture to operation duration were associated with negative outcome in patients with hip fracture underwent HA during the COVID-19.

Compound lidocaine/prilocaine cream combined with tetracaine prevents cough caused by extubation after general anaesthesia: a randomised controlled trial.

BACKGROUND: Coughing caused by tracheal extubation is common following general anaesthesia. Heavy aerosol production by coughing during recovery from general anaesthesia in patients with respiratory infections (especially COVID-19) may be one of the highest risk factors for infection in healthcare workers. The application of local anaesthetics to the endotracheal tube is an effective method to reduce coughing. The most commonly used anaesthetics are compound lidocaine/prilocaine cream and tetracaine spray. However, coughing still occurs when the two anaesthetics are used alone. We speculated that the application of compound lidocaine/prilocaine combined with tetracaine spray would better prevent coughing caused by tracheal extubation. METHODS: Patients scheduled for laparoscopic cholecystectomy or cholecystectomy combined with common bile duct exploration under general anaesthesia were randomly assigned to Group C (saline spray), Group L (2 g compound lidocaine/prilocaine cream contains 5 mg of lidocaine and 5 mg prilocaine)), Group T (tetracaine) and Group F (compound lidocaine/prilocaine cream combined with tetracaine). The incidence of coughing, the endotracheal tube tolerance assessment, the incidence of agitation, the active extubation rate, the incidence of postoperative pharyngeal pain and the incidence of postoperative cough were recorded and analysed. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and the plasma concentrations of epinephrine and norepinephrine were measured immediately before extubation and 1 min after extubation. RESULTS: A total of 211 patients were randomly assigned to Group C (53 cases), Group L (52 cases), Group T (52 cases) and Group F (54 cases). The primary result is assessment of the incidence of cough. The patients emerged from general anaesthesia, 96% of Group C had cough, which was significantly reduced in Group L (61.5%, P < 0.001), Group T (75%, P < 0.05) and Group F (22.2%, P < 0.001). Group F had a significantly reduced incidence of cough compared to Group L and Group T (P < 0.05 or P < 0.01, respectively). The secondary results were assessed. The endotracheal tube tolerance score in Group C ((1, 3) 4, P < 0.001) was higher than Group L ((0, 1) 2), Group T ((0, 1.25) 3) and Group F ((0, 0) 1). Group F had a significantly lower score than Group L and Group T (P < 0.05, P < 0.01, respectively). The incidence of agitation and the active extubation rate were also higher in Group C (96.2% and 71.7%, respectively, P < 0.001) than Group L (48.1% and 15.4%, respectively), Group T (61.5% and 26.9%, respectively) and Group F (17.3% and 7.7%, respectively). Blood pressure, HR and plasma concentrations of epinephrine and norepinephrine were significantly higher in Group C than in all other groups at the time of extubation and 1 min after extubation (P < 0.001). Group F exhibited significantly reduced blood pressure, heart rate and plasma concentrations of epinephrine and norepinephrine compared to Group L and Group T (P < 0.05, P < 0.01 or P < 0.001, respectively). The incidence of postoperative pharyngeal pain and the incidence of postoperative cough were not significantly different among the groups. CONCLUSIONS: Compound lidocaine/prilocaine cream combined with tetracaine may be a more effective approach for preventing coughing and stabilising circulation during extubation following general anaesthesia. This may play an important role in preventing medical staff from contracting respiratory infectious diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200058429 (registration date: 09-04-2022) "retrospectively registered".

Antiviral Potential of Small Molecules Cordycepin, Thymoquinone, and N6, N6-Dimethyladenosine Targeting SARS-CoV-2 Entry Protein ADAM17.

COVID-19 is an acute respiratory disease caused by SARS-CoV-2 that has spawned a worldwide pandemic. ADAM17 is a sheddase associated with the modulation of the receptor ACE2 of SARS-CoV-2. Studies have revealed that malignant phenotypes of several cancer types are closely relevant to highly expressed ADAM17. However, ADAM17 regulation in SARS-CoV-2 invasion and its role on small molecules are unclear. Here, we evaluated the ADAM17 inhibitory effects of cordycepin (CD), thymoquinone (TQ), and N6, N6-dimethyladenosine (m62A), on cancer cells and predicted the anti-COVID-19 potential of the three compounds and their underlying signaling pathways by network pharmacology. It was found that CD, TQ, and m62A repressed the ADAM17 expression upon different cancer cells remarkably. Moreover, CD inhibited GFP-positive syncytia formation significantly, suggesting its potential against SARS-CoV-2. Pharmacological analysis by constructing CD-, TQ-, and m62A-based drug-target COVID-19 networks further indicated that ADAM17 is a potential target for anti-COVID-19 therapy with these compounds, and the mechanism might be relevant to viral infection and transmembrane receptors-mediated signal transduction. These findings imply that ADAM17 is of potentially medical significance for cancer patients infected with SARS-CoV-2, which provides potential new targets and insights for developing innovative drugs against COVID-19.

Mental health problems of preschool children during the COVID-19 home quarantine: A cross-sectional study in Shanghai, China.

Objective: As the coronavirus disease 2019 (COVID-19) pandemic spread across Shanghai, China, in late February 2022 and protective measures to mitigate its impact were enacted, this study aimed to estimate how home quarantine affected the mental health of preschool children in Shanghai, China and explore the association between lifestyle factors and mental health during this special period. Methods: A cross-sectional online survey of 2,110 preschool students from Shanghai, China, was conducted during May 20-25,2022. Preschooler' mental health (Strengths and Difficulties Questionnaire, SDQ) and daily activities were reported by parents. Results: The sample involved 2,110 children with a mean age of 4.65 years [standard deviation (SD): 0.91, range: 3-6 years]. Boys and children whose mother's education level were college and high school had higher rate of mental health problems. Boys had significantly higher rates of peer problems and prosocial behaviors than girls. The 3-year-old group had significantly higher rates of prosocial behaviors than other groups. As compared to the Shanghai norm and the SDQ results of preschool children in Shanghai in 2019 (SH2019), there were a significant decrease in emotional symptoms score, as well as a significant increase in conduct problems score. Additionally, peer problems score significantly increased compared to SH2019. Decreased time spent on daily sleep was associated with the increased risk for preschoolers' mental health problems. Conclusion: There was an increase in the frequency of emotional and behavioral problems, especially regarding conduct problems and peer problems, in preschool children during the COVID-19 home quarantine in Shanghai, China. Boys, younger preschool children and children whose mother's education level were college and high school may be especially vulnerable to emotional and behavioral problems. It was also found that decreased time spent on sleep may aggravate preschool children's mental health problems. It may be beneficial to differentiate and focus on conducting psychoeducation and implementing psycho-behavioral interventions to solve these issues.