Methodology for designing intrahospital transportation of patients with suspected infectious disease that limits infection spread risk in China.

Aims: The transport of patients suspected of having COVID-19 requires careful consideration. Using paths selected at random and not accounting for person flow along the path are risk factors for infection spread. Intrahospital transportation (IHT) protocols and guidelines should be used to help reduce the risk of secondary virus transmission during transport. This study aimed to propose optimal IHT for patients with an infectious disease presenting in an out-patient area. Design: The map of a West China Hospital was used. We also used field investigation findings and simulated person flow to establish pathway length and transportation time. We identified three optimum pathways and estimated safety boundary marks, including a patient transportation border (PTB) and safety transportation border (STB). Finally, IHT, PTB, and STP formed a virtual transport pipeline (VTP) and a traceable IHT management system, which can generate a virtual isolation space. Results: The three pathways met efficiency, accessibility, and by-stander flow criteria. No facility characteristic modification was required. Conclusions: Using virtual models to identify pathways through out-patient hospital areas may help reduce the risk of infection spread.

Advances in the use of nanomaterials for nucleic acid detection in point-of-care testing devices: A review

The outbreak of the coronavirus (COVID-19) has heightened awareness of the importance of quick and easy testing. The convenience, speed, and timely results from point-of-care testing (POCT) in all vitro diagnostic devices has drawn the strong interest of researchers. However, there are still many challenges in the development of POCT devices, such as the pretreatment of samples, detection sensitivity, specificity, and so on. It is anticipated that the unique properties of nanomaterials, e.g., their magnetic, optical, thermal, and electrically conductive features, will address the deficiencies that currently exist in POCT devices. In this review, we mainly analyze the work processes of POCT devices, especially in nucleic acid detection, and summarize how novel nanomaterials used in various aspects of POCT products can improve performance, with the ultimate aims of offering new ideas for the application of nanomaterials and the overall development of POCT devices.

Impact and the delivery of loco-regional treatment for hepatocellular carcinoma during the COVID-19 pandemic.

Hepatocellular carcinoma (HCC) is the second most lethal tumour, with therapies broadly divided into curative and palliative intent. Unfortunately, the majority of HCCs were found to be unresectable at diagnosis. Advances in novel loco-regional therapies have given patients with unresectable HCC a vital chance for disease control and survival. However, the COVID-19 pandemic has greatly shaped and impacted treatment protocols and delivery for HCC patients. This review article aims to describe the impact of the COVID-19 pandemic on the delivery of loco-regional treatment modalities for HCC and compare treatment trends between the pre -pandemic and pandemic eras. Treatment of HCC involves complex collaboration between clinical professionals within their local and global healthcare institutions. The COVID-19 pandemic has had a profound impact on the treatment of HCC. The delivery of loco-regional treatment for HCC will need to adapt to each healthcare system's unique structure.

Integrated network pharmacology analysis, molecular docking, LC-MS analysis and bioassays revealed the potential active ingredients and underlying mechanism of Scutellariae radix for COVID-19

Scutellariae radix (“Huang-Qin” in Chinese) is a well-known traditional herbal medicine and popular dietary supplement in the world, extensively used in prescriptions of TCMs as adjuvant treatments for coronavirus pneumonia 2019 (COVID-19) patients in China. According to the differences in its appearance, Scutellariae radix can be classified into two kinds: ZiQin (1∼3 year-old Scutellariae baicalensis with hard roots) and KuQin (more than 3 year-old S. baicalensis with withered pithy roots). In accordance with the clinical theory of TCM, KuQin is superior to ZiQin in cooling down the heat in the lung. However, the potential active ingredients and underlying mechanisms of Scutellariae radix for the treatment of COVID-19 remain largely unexplored. It is still not clear whether there is a difference in the curative effect of ZiQin and KuQin for the treatment of COVID-19. In this research, network pharmacology, LC-MS based plant metabolomics, and in vitro bioassays were integrated to explore both the potential active components and mechanism of Scutellariae radix for the treatment of COVID-19. As the results, network pharmacology combined with molecular docking analysis indicated that Scutellariae radix primarily regulates the MAPK and NF-κB signaling pathways via active components such as baicalein and scutellarin, and blocks SARS-CoV-2 spike binding to human ACE2 receptors. In vitro bioassays showed that baicalein and scutellarein exhibited more potent anti-inflammatory and anti-infectious effects than baicalin, the component with the highest content in Scutellariae radix. Moreover, baicalein inhibited SARS-CoV-2’s entry into Vero E6 cells with an IC50 value of 142.50 μM in a plaque formation assay. Taken together, baicalein was considered to be the most crucial active component of Scutellariae radix for the treatment of COVID-19 by integrative analysis. In addition, our bioassay study revealed that KuQin outperforms ZiQin in the treatment of COVID-19. Meanwhile, plant metabolomics revealed that baicalein was the compound with the most significant increase in KuQin compared to ZiQin, implying the primary reason for the superiority of KuQin over ZiQin in the treatment of COVID-19.

Structures, biomimetic synthesis, and anti-SARS-CoV-2 activity of two pairs of enantiomeric phenylpropanoid-conjugated protoberberine alkaloids from the rhizomes of Corydalis decumbens.

(±)-Decumicorine A (1) and (±)-epi-decumicorine A (2), two pairs of enantiomeric isoquinoline alkaloids featuring a novel phenylpropanoid-conjugated protoberberine skeleton, were isolated and purified from the rhizomes of Corydalis decumbens. The separation of (±)-1 and (±)-2 was achieved by chiral HPLC to produce four optically pure enantiomers. The structures and absolute configurations of compounds (-)-1, (+)-1, (-)-2, and (+)-2 were elucidated by spectroscopic analysis, ECD calculations, and X-ray crystallographic analyses. The two racemates were generated from a Diels-Alder [4 + 2] cycloaddition between jatrorrhizine and ferulic acid in the proposed biosynthetic pathways, which were fully verified by a biomimetic synthesis. Moreover, compound (+)-1 exhibited an antiviral entry effect on SARS-CoV-2 pseudovirus by blocking spike binding to the ACE2 receptor on HEK-293T-ACE2h host cells.

Polypyridyl ruthenium complexes as bifunctional TAR RNA binders and HIV-1 reverse transcriptase inhibitors.

Inhibitors of type 1 human immunodeficiency virus (HIV-1) reverse transcriptase are central to anti-HIV therapy. Most of their targets are enzymes, while very few could bind to viral RNA. Here we designed four new polypyridyl Ru(II) complexes, which could bind HIV-1 TAR RNA tightly and selectively by molecular recognition of hydrogen bonds, further stabilize the Ru(II)-RNA bound system by electrostatic attraction, and efficiently inhibit the Moloney murine leukemia virus (M-MuLV) and HIV-1 reverse transcriptase. The polypyridyl Ru(II) complexes also have physical and chemical advantages, including high chemical stability and photostability, sensitive spectroscopic responses to HIV TAR RNA, and low toxicity to normal cells. This work also provides valuable drug design strategies for acquired immune deficiency syndrome (AIDS) and other reverse transcriptase related disease research, such as hepatitis C virus (HCV), Ebola virus (EBOV), influenza A virus, and most recently the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Terpyridyl ruthenium complexes as visible spectral probe for poly(A) RNA and bifunctional TAR RNA binders and HIV-1 reverse transcriptase inhibitors

HIV-1 reverse transcriptase (RT) inhibitors play essential role in anti-HIV therapy. The vast majority of them target the enzymes, while very few are able to bind to the viral RNA. Here we designed and synthesized two new terpyridyl Ru(II) complexes with HIV-1 TAR RNA binding groups. The complex RuTz2 exhibited a remarkable selectivity for poly(A) RNA over calf thymus DNA, total RNA and yeast transfer RNA, generated significant visible spectral response and inhibited the reverse transcription of poly(A) RNA to poly(dT) cDNA by M-MuLV RT. Moreover, RuTz2 was found to target the HIV-1 TAR RNA tightly and selectively by molecular recognition of hydrogen bonds, further stabilize the Ru(II)-RNA binding complex by electrostatic attraction, and efficiently inhibit the HIV-1 RT. These terpyridyl Ru(II) complexes also showed low toxicity to normal cells, which would greatly reduce its harmful side-effect on normal cells in drug application. This work also provides valuable drug design strategies for AIDS and other RT related diseases researches, such as HCV, EBOV and SARS-CoV-2.

Prognostic Value of Machine Learning in Patients with Acute Myocardial Infarction.

(1) Background: Patients with acute myocardial infarction (AMI) still experience many major adverse cardiovascular events (MACEs), including myocardial infarction, heart failure, kidney failure, coronary events, cerebrovascular events, and death. This retrospective study aims to assess the prognostic value of machine learning (ML) for the prediction of MACEs. (2) Methods: Five-hundred patients diagnosed with AMI and who had undergone successful percutaneous coronary intervention were included in the study. Logistic regression (LR) analysis was used to assess the relevance of MACEs and 24 selected clinical variables. Six ML models were developed with five-fold cross-validation in the training dataset and their ability to predict MACEs was compared to LR with the testing dataset. (3) Results: The MACE rate was calculated as 30.6% after a mean follow-up of 1.42 years. Killip classification (Killip IV vs. I class, odds ratio 4.386, 95% confidence interval 1.943-9.904), drug compliance (irregular vs. regular compliance, 3.06, 1.721-5.438), age (per year, 1.025, 1.006-1.044), and creatinine (1 µmol/L, 1.007, 1.002-1.012) and cholesterol levels (1 mmol/L, 0.708, 0.556-0.903) were independent predictors of MACEs. In the training dataset, the best performing model was the random forest (RDF) model with an area under the curve of (0.749, 0.644-0.853) and accuracy of (0.734, 0.647-0.820). In the testing dataset, the RDF showed the most significant survival difference (log-rank p = 0.017) in distinguishing patients with and without MACEs. (4) Conclusions: The RDF model has been identified as superior to other models for MACE prediction in this study. ML methods can be promising for improving optimal predictor selection and clinical outcomes in patients with AMI.

A rare case of drug-induced bradycardia associated with the just low dose use of methylprednisolone in a child with COVID-19.

Methylprednisolone (MP) is usually used to reduce inflammation reaction and tissue damage, which may have a beneficial treatment effect on coronavirus disease 2019 (COVID-19). However, we present the case of a child who manifests significant bradycardia with the use of just low dose MP on the premise of the long-term use of arbidol. Arbidol can affect the activity of CYP3A4, which is also a key metabolic enzyme of MP by competitive inhibition, and which is easy to aggravate the side effects of MP. Therefore, more attention should be paid to bradycardia occurrence in the patient with COVID-19 when MP is considered in COVID-19.

Nineteen New Flavanol-Fatty Alcohol Hybrids with α-Glucosidase and PTP1B Dual Inhibition: One Unusual Type of Antidiabetic Constituent from Amomum tsao-ko.

The dried fruits of Amomum tsao-ko were first revealed to have hypoglycemic effects on db/db mice at a concentration of 200 mg/kg. In order to clarify the antidiabetic constituents, 19 new flavanol-fatty alcohol hybrids, tsaokoflavanols A-S (1-19), were isolated and determined by extensive spectroscopic data and ECD calculations. Most of the compounds showed α-glucosidase and PTP1B dual inhibition, among which 1, 2, 6, 11, and 18 exhibited obvious activity against α-glucosidase with IC50 values of 5.2-9.0 µM, 20-35 times stronger than that of acarbose (IC50, 180.0 µM); meanwhile, 6, 10-12, and 19 were PTP1B/TCPTP-selective inhibitors with IC50 values of 56.4-80.4 µM, 2-4 times stronger than that of suramin sodium (IC50, 200.5 µM). Enzyme kinetics study indicated that compounds 1, 2, 6, and 11 were α-glucosidase and PTP1B mixed-type inhibitors with Ki values of 13.0, 11.7, 2.9, and 5.3 µM and 142.3, 88.9, 39.2, and 40.8 µM, respectively. Docking simulations proved the importance of hemiacetal hydroxy, the orientation of 3,4-dihydroxyphenyl, and the length of alkyl in binding with α-glucosidase and PTP1B.

The point-of-care-testing of nucleic acids by chip, cartridge and paper sensors

ABSTRACT Point-of-care nucleic acid testing (POCNAT) has played an important role in the outbreak of infectious diseases (e.g., COVID-19) over recent years. POCNAT aims to realize the rapid, simple and automatic detection of nucleic acid. Thanks to the development of manufacturing technology, electronic information technology, artificial intelligence technology, and biological information technology in recent years, the development of the POCNAT device has led to significant advancement. Instead of the normal nucleic acid detection methods used in the laboratory, some novel experimental carriers have been applied, such as chips, cartridges and papers. The application of these experimental carriers has realized the automation and integration of nucleic acid detection. The entire process of nucleic acid detection is normally divided into three steps (nucleic acid extraction, target amplification and signal detection). All of the reagents required by the process can be pre-stored on these experimental carriers, without unnecessary manual operation. Furthermore, all of the processes are carried out in this experimental carrier, with the assistance of a specific control device. Although they are complicated to manufacture and precise in design, their application provides a significant step forwards in nucleic acid detection and realizes the integration of nucleic acid detection. This technology has great potential in the field of point-of-care molecular diagnostics in the future. This paper focuses on the relevant content of these experimental carriers.

Trends of interventional radiology procedures during the COVID-19 pandemic: the first 27 weeks in the eye of the storm.

OBJECTIVES: While the Novel Coronavirus (COVID-19) pandemic looks to persist, institutions promote delaying procedures. Understanding trends and demands of interventional radiology (IR) procedures in the infected and COVID-free populations are needed in long-term planning. We detail IR procedure trends in the first 27 weeks of the pandemic and compare with the pre-pandemic era. METHODS: In this IRB approved retrospective electronic case review, all IR patients in our institution from 1 January to 9 July 2020, the same period in 2019 pre-pandemic and the Severe Acute Respiratory Syndrome (SARS-CoV) outbreak were included. IR procedures were classified using Interventional Radiology-Procedure Acuity Scale (IR-PAS) and category of IR procedures. Along with descriptive frequencies, the Mann-Whitney U test and Chi-square test of independence were performed. RESULTS: During the pandemic, 3655 IR procedures were performed compared to 3851 procedures pre-pandemic. No statistically significant difference in weekly IR caseloads across IR-PAS tiers between both periods (p = .088) and category of procedure (p = .054) were noted. General intervention procedures remained the largest proportion and musculoskeletal procedures the minority, in both periods. More general intervention radiology and oncology procedures were performed during the COVID-19 pandemic compared to the SARS-CoV outbreak. Thirty-four (0.93%) IR procedures were performed on 30 COVID-19 patients. There was no IR procedure-related COVID-19 cross-transmission. CONCLUSIONS: Demand for IR procedures among COVID-free patients remains high, and IR procedures involving COVID-19 represents a fraction of the IR caseload. A sustainable model in providing timely IR services to COVID-free patients needs to be considered.

Trends of Interventional Radiology procedures during the Covid-19 pandemic: The first 27 weeks in the eye of the storm (preprint)

ObjectivesWhile the Novel Coronavirus (COVID-19) pandemic looks to persist, institutions promote delaying procedures. Understanding trends and demands of interventional radiology (IR) procedures in the infected and COVID-free populations are needed in long-term planning. We detail IR procedure trends in the first 27 weeks of the pandemic and compare with the pre-pandemic era. MethodsIn this IRB approved retrospective electronic case review, all IR patients in our institution from 1 January to 9 July 2020, the same period in 2019 pre-pandemic and the Severe Acute Respiratory Syndrome (SARS-CoV) outbreak were included. IR procedures were classified using Interventional Radiology – Procedure Acuity Scale (IR-PAS) and category of IR procedures. Along with descriptive frequencies, the Mann-Whitney U test and Chi-square test of independence were performed.ResultsDuring the pandemic, 3655 IR procedures were performed compared to 3851 procedures pre-pandemic. No statistically significant difference in weekly IR caseloads across IR-PAS tiers between both periods (p = .088) and category of procedure (p = .054) were noted. General intervention procedures remained the largest proportion and musculoskeletal procedures the minority, in both periods. More general intervention radiology and oncology procedures were performed during the Covid-19 pandemic compared to the SARS-CoV outbreak. Thirty-four (0.93%) IR procedures were performed on 30 COVID-19 patients. There was no IR procedure-related COVID-19 cross-transmission. ConclusionsDemand for IR procedures among COVID-free patients remains high, and IR procedures involving COVID-19 represents a fraction of the IR caseload. A sustainable model in providing timely IR services to COVID-free patients needs to be considered.

Characteristics of Renal Function in Patients Diagnosed With COVID-19: An Observational Study.

Objective: The aim of the study was to analyze the characteristics of renal function in patients diagnosed with COVID-19. Methods: In this retrospective, single-center study, we included all confirmed cases of COVID-19 in a tertiary hospital in Guangdong, China from January 20, 2020 to March 20, 2020. Blood and urine laboratory findings related to renal function were summarized, and the estimated glomerular filtration rate (eGFR) and endogenous creatinine clearance (Ccr) were also calculated to assess the renal function. Results: A total of 12 admitted hospital patients were diagnosed with COVID-19, included 3 severe cases, and 9 common cases. Serum creatinine (Scr) was not abnormally elevated in all of the patients, and blood urea nitrogen (BUN) was abnormally elevated in only 25.0% of the patients. However, compared with the recovery period, the patient's Scr and BUN increased significantly in peak of disease (p-scr = 0.002 & p-bun < 0.001). By observing the fluctuations in Scr and BUN from admission to recovery, it was found that the peak of Scr and BUN appeared within the first 14 day of the course of the disease. Urinary microprotein detection indicated that the abnormally elevated rates of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), and urine transferring (TRU) standardized by urinary creatinine in peak of disease were 41.7, 41.7, 50.0, and 16.7%, respectively. The abnormal rates of the calculated eGFR and Ccr were 66.7 and 41.7%. Conclusion: Scr and BUN were generally increased during the course of COVID-19. Detection of urinary microproteins and application of multiple indicators assessment could be helpful for discovering abnormal renal function in patients with COVID-19. However, the evidence is limited due to the small sample size and observational nature. Additional studies, especially large prospective cohort studies, are required to confirm these findings.

Analysis of early renal injury in COVID-19 and diagnostic value of multi-index combined detection (preprint)

Objectives The aim of the study was to analyze the incidence of COVID-19 with early renal injury, and to explore the value of multi-index combined detection in diagnosis of early renal injury in COVID-19. Design The study was an observational, descriptive study. Setting This study was carried out in a tertiary hospital in Guangdong, China. Participants 12 patients diagnosed with COVID-19 from January 20, 2020 to February 20, 2020. Primary and secondary outcome measures The primary outcome was to evaluate the incidence of early renal injury in COVID-19. In this study, the estimated glomerular filtration rate (eGFR), endogenous creatinine clearance (Ccr) and urine microalbumin / urinary creatinine ratio (UACR) were calculated to assess the incidence of early renal injury. Secondary outcomes were the diagnostic value of urine microalbumin (UMA), 1-microglobulin (A1M), urine immunoglobulin-G (IGU), urine transferring (TRU) alone and in combination in diagnosis of COVID-19 with early renal injury. Results While all patients had no significant abnormalities in serum creatinine (Scr) and blood urea nitrogen (BUN), the abnormal rates of eGFR, Ccr, and UACR were 66.7%, 41.7%, and 41.7%, respectively. Urinary microprotein detection indicated that the area under curve (AUC) of multi-index combined to diagnose early renal injury in COVID-19 was 0.875, which was higher than UMA (0,813), A1M (0.813), IGU (0.750) and TRU (0.750) alone. Spearman analysis showed that the degree of early renal injury was significantly related to C-reactive protein (CRP) and neutrophil ratio (NER), suggesting that the more severe the infection, the more obvious the early renal injury. Hypokalemia and hyponatremia were common in patients with COVID-19, and there was a correlation with the degree of renal injury. Conclusions Early renal injury was common in patients with COVID-19. Combined detection of UMA, A1M, IGU, and TRU was helpful for the diagnosis of early renal injury in COVID-19.