Treatment strategy and thought on classical herbal formulae for coronavirus disease 2019 / 中国中药杂志

Coronavirus disease 2019(COVID-19) refers to the pneumonia caused by novel coronavirus(2019-nCoV) infection in 2019. It is highly infectious, with quick spreading and a wide range of impact. It has been broken out in many countries around the world and has become a public health emergency of international concern. Chinese medicine has a long history in treating plague, and viral disease is the clinical advantage in Chinese medicine. Under the premise that there is currently no specific drug treatment, Chinese medicine has achieved certain effects in the treatment of COVID-19, which has attracted much attention and has been upgraded to a national strategy. Regarding the treatment of COVID-19 with Chinese medicine, it is believed that in terms of the name of Chinese medicine, the modern connotation of "uniform of typhoid and febrile disease" should be re-recognized, and it is advisable to use drugs based on specific clinical prescriptions and indications. In terms of pathogenesis, the COVID-19 has the pathogenesis rules including from the mild to severe conditions, from the surface to the inside, from the excess syndrome to the deficiency syndrome. We should pay attention to the Taiyang syndrome damaged by wet disease in initial stage, Shaoyang syndrome complicated with Yangming syndrome in the middle stage, phlegm-heat obstructing lung in critical period, lung and spleen deficiency in the recovery stage. In terms of clinical treatment strategies, Dayuan Yin is recommended to induce sweat and disperse the stasis in early stage. Xiaochaihu Decoction and Maxing Shigan Decoction is used to relieve both exterior and interior symptoms in middle stage. In critical stage, Tingli Dazao Xiefei Decoction, Weijing Decoction, Xuanbai Chengqi Decoction, Xiaoxianxiong Decoction, and Sanzi Yangqin Decoction are considered to reduce phlegm and clear heat. We should pay attention to nourishing Qi and strengthening the spleen by Zhuye Shigao Decoction, Sha-shen Maidong Decoction, and Liujunzi Decoction in the later recovery period. It shall be noted that, no matter in the initial mild stage, the middle and critical stages, or in the later recovery stage, Chinese medicine plays an important role, including preventing mild to severe disease, shortening the fever time, improving cough symptoms, increasing blood oxygen saturation and reducing mortality. Many studies have shown that the classical herbal formulae can alleviate the cytokine storm, regulate the immune imbalance, and produce the potential effect of synergistic treatment for COVID-19 through multiple components, multiple targets, and multiple pathways.

Analysis of an improved workflow of endoscope reprocessing for bedside endoscopic diagnosis and treatment on COVID-19 patients / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Severe cases infected with the coronavirus disease 2019 (COVID-19), named by the World Health Organization (WHO) on Feb. 11, 2020, tend to present a hypercatabolic state because of severe systemic consumption, and are susceptible to stress ulcers and even life-threatening gastrointestinal bleeding. Endoscopic diagnosis and treatment constitute an irreplaceable part in the handling of severe COVID-19 cases. Endoscopes, as reusable precision instruments with complicated structures, require more techniques than other medical devices in cleaning, disinfection, sterilization, and other reprocessing procedures. From 2016 to 2019, health care-acquired infection caused by improper endoscope reprocessing has always been among the top 5 on the list of top 10 health technology hazards issued by the Emergency Care Research Institute. Considering the highly infective nature of COVID-19 and the potential aerosol contamination therefrom, it is of pivotal significance to ensure that endoscopes are strictly reprocessed between uses. In accordance with the national standard “Regulation for Cleaning and Disinfection Technique of Flexible Endoscope (WS507-2016),” we improved the workflow of endoscope reprocessing including the selection of chemicals in an effort to ensure quality control throughout the clinical management towards COVID-19 patients. Based on the experience we attained from the 12 severe COVID-19 cases in our hospital who underwent endoscopy 23 times in total, the article provides an improved version of endoscopic reprocessing guidelines for bedside endoscopic diagnosis and treatment on COVID-19 patients for reference.

Research strategy of drugs against 2019-novel coronavirus based on supramolecular “qi chromatography” theory of TCM / 中草药

At present, the 2019-novel coronavirus (2019-nCoV) is rampant all over the country, and controlling the spread of its epidemic has become a top priority. It is very difficult to control the epidemic spreading because there is no specific drug to fight against it. Therefore, it is urgent task for us to develop a specific drug as soon as possible, and attracting worldwide attention. The studies on anti-2019-nCoV drugs were generally carried out in three modes, as vaccine, chemical drugs and traditional Chinese medicine (TCM). Because the developing on vaccines and chemicals takes too long, it is hard to solve the urgent problem. Moreover, the RNA of coronavirus has been recombined so quickly that the vaccines and drugs studied with great efforts not only may miss the epidemic time, but also cannot be used in the next generation of new coronavirus treatment, as a result that the work of epidemic prevention is formidable. However, the prescriptions from traditional Chinese medicine theory can cure the epidemic disease, but how to develop it into a specific drug with clear chemical composition and clear pharmacologic mechanism, is also an urgent problem to be solved. In this paper, the new coronavirus and its drug development are reviewed, while the advantages and disadvantages are analyzed, and the drug dilemma research phenomenon is clarified by using the supramolecular “qi chromatography” theory. It is suggested that the strategy of anti-coronavirus drug developing should be put forward based on the impact of “qi chromatography” of biological supramolecular “imprinting template”, in order to develop new drugs against 2019-nCoV to control the spread of the epidemic as quick as we can, and establish a new research and development model of anti-coronavirus drug on integration of traditional Chinese and Western medicine, turning passive into active.

Analysis of an improved workflow of endoscope reprocessing for bedside endoscopic diagnosis and treatment on COVID-19 patients / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Severe cases infected with the coronavirus disease 2019 (COVID-19), named by the World Health Organization (WHO) on Feb. 11, 2020, tend to present a hypercatabolic state because of severe systemic consumption, and are susceptible to stress ulcers and even life-threatening gastrointestinal bleeding. Endoscopic diagnosis and treatment constitute an irreplaceable part in the handling of severe COVID-19 cases. Endoscopes, as reusable precision instruments with complicated structures, require more techniques than other medical devices in cleaning, disinfection, sterilization, and other reprocessing procedures. From 2016 to 2019, health care-acquired infection caused by improper endoscope reprocessing has always been among the top 5 on the list of top 10 health technology hazards issued by the Emergency Care Research Institute. Considering the highly infective nature of COVID-19 and the potential aerosol contamination therefrom, it is of pivotal significance to ensure that endoscopes are strictly reprocessed between uses. In accordance with the national standard "Regulation for Cleaning and Disinfection Technique of Flexible Endoscope (WS507-2016)," we improved the workflow of endoscope reprocessing including the selection of chemicals in an effort to ensure quality control throughout the clinical management towards COVID-19 patients. Based on the experience we attained from the 12 severe COVID-19 cases in our hospital who underwent endoscopy 23 times in total, the article provides an improved version of endoscopic reprocessing guidelines for bedside endoscopic diagnosis and treatment on COVID-19 patients for reference.

Exploring the mechanism of liver enzyme abnormalities in patients with novel coronavirus-infected pneumonia / 中华肝脏病杂志

Objective@#To explore and analyze the possible mechanism of liver injury in patients with coronavirus disease 2019 (novel coronavirus pneumonia, NCP).@*Methods@#The correlation between ALT, AST and other liver enzyme changes condition and NCP patients’ disease status reported in the literature was comprehensively analyzed. ACE2 expression in liver tissue for novel coronavirus was analyzed based on single cell sequencing (GSE115469) data. RNA-Seq method was used to analyze Ace2 expression and transcription factors related to its expression in liver tissues at various time-points after hepatectomy in mouse model of acute liver injury with partial hepatectomy. t-test or Spearman rank correlation analysis was used for statistical analysis.@*Results@#ALT and AST were abnormally elevated in some patients with novel coronavirus infection, and the rate and extent of ALT and AST elevation in severe NCP patients were higher than those in non-severe patients. Liver tissue results of single cell sequencing and immunohistochemistry showed that ACE2 was only expressed in bile duct epithelial cells of normal liver tissues, and very low in hepatocytes. In a mouse model of acute liver injury with partial hepatectomy, Ace2 expression was down-regulated on the first day, but it was elevated up to twice of the normal level on the third day, and returned to normal level on seventh day when the liver recovered and hepatocyte proliferation stopped. Whether this phenomenon suggests that the bile duct epithelial cells with positive expression of Ace2 participate in the process of liver regeneration after partial hepatectomy deserves further study. In RNA-Seq data, 77 transcription factors were positively correlated with the expression of ACE2 (r > 0.2, FDR < 0.05), which were mainly enriched in the development, differentiation, morphogenesis and cell proliferation of glandular epithelial cells.@*Conclusion@#We assumed that in addition to the over activated inflammatory response in patients with NCP, the up-regulation of ACE2 expression in liver tissue caused by compensatory proliferation of hepatocytes derived from bile duct epithelial cells may also be the possible mechanism of liver tissue injury caused by 2019 novel coronavirus infection.

Key points for the prevention and treatment of the novel coronavirus pneumonia in the elderly / 中华老年医学杂志

The population is commonly susceptible to the 2019 novel coronavirus(2019-nCoV), especially the elderly with comorbidities.Elderly patients infected with 2019-nCoV tend to have higher rates of severe illnesses and mortality.Immunoaging is an important cause of severe novel coronavirus pneumonia(NCP)in the elderly.Due to the combination of underlying diseases, elderly patients may exhibit a typical manifestations in clinical symptoms, supplementary examinations and pulmonary imaging, deserving particular attention.The general condition of the elderly should be considered during diagnosis and treatment.In addition to routine care and measures such as oxygen therapy, antiviral therapy and respiratory support, treatment of underlying disease, nutritional support, sputum expectoration, complication prevention and psychological support should also be considered for elderly patients.Based on literature review and expert panel discussion, we drafted the Key Points for the Prevention and Treatment of the Novel Coronavirus Pneumonia in the elderly, aiming to provide help with the prevention and treatment of NCP and the reduction of harm to the elderly population.

Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model / 中华医学杂志(英文版)

Background@#Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those without such facilities or 2019-novel coronavirus (2019-nCoV). This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV related coronavirus model.@*Methods@#A 2019-nCoV related pangolin coronavirus GX_P2V/pangolin/2017/ Guangxi was described. Whether GX_P2X uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA) -mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2X infection. The antiviral activities and antiviral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively.@*Results@#The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs-cepharanthine (CEP), selamectin and mefloquine hydrochloride exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48±0.02]×10-4 vs. 1.00±0.12, t=150.38, P<0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP has potent antiviral activities against both viral entry (1.00±0.37 vs. 0.46±0.12, t=2.42, P<0.05) and viral replication (1.00±0.43 vs. [6.18±0.95]×10-4, t=3.98, P<0.05).@*Conclusions@#Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and clinical trial of CEP for treatment of 2019-nCoV infection is warranted.

Epidemiological and clinical characteristics analysis of 30 childhood cases with 2019 novel coronavirus infection in Shenzhen / 中华传染病杂志

Objectives@#To analyze the epidemiological and clinical characteristics of children with 2019 novel coronavirus (2019-nCoV) infection in Shenzhen.@*Methods@#The data of 30 children diagnosed with 2019-nCoV infection in the Third People’s Hospital of Shenzhen from 16th January 2020 to 9th February 2020were collected.@*Results@#Among the 30 children, 14 were boys and 16 were girls. There were 10 mild cases, 13 common cases and one severe case, and six cases with asymptomatic infection. The age ranged from 7 months to 18 years old with the median age of 7 years old. Twenty out of 30 cases (66.7%) were school children. The common clinical characteristics were fever (30.0%, 9/30) and cough (23.3%, 7/30). The body temperature waved below 37.5 ℃. Mostly the auscultations of the lungs were no rales and there was no extrapulmonary complication. A total number of one case had wheezes and hypoxia, and one case had diarrhea and vomiting. There was no critical and death case. There were 29 cases with travelling experience in Hubei province within two weeks, and 24 cases (80.0%) had relatives (parents or grandparents) diagnosed with 2019-nCoV infection. Elevated white blood cell counts (﹥12×109/L), C reaction protein level, lactate dehydrogenase level and the low proportion of T help cells occurred in three, five, five and three cases, respectively. Some cases were coinfected with human respiratory syncytial virus, mycoplasma pneumonia, human herpesvirus, influenza B virus and rubella virus. The predominant pattern of computed tomography findings of childhood patients with 2019-nCoV infection presented with patchy film and ground-glass opacities in bilateral or unilateral lung. The median time for nucleic acid to turn negative was eight days among the enrolled cases. All the cases were cured and discharged home, and the days in hospital waved from 5 - 16 days (the median time was 12 days).@*Conclusions@#The majority of the childhood cases are the school-age children with family cluster. Most cases present mild and common symptoms with good prognosis. Some patients may be complicated with multiple infections.

Exploring the mechanism of liver enzyme abnormalities in patients with novel coronavirus-infected pneumonia / 中华肝脏病杂志

To explore and analyze the possible mechanism of liver injury in patients with coronavirus disease 2019 (novel coronavirus pneumonia, NCP). The correlation between ALT, AST and other liver enzyme changes condition and NCP patients' disease status reported in the literature was comprehensively analyzed. ACE2 expression in liver tissue for novel coronavirus was analyzed based on single cell sequencing (GSE115469) data. RNA-Seq method was used to analyze Ace2 expression and transcription factors related to its expression in liver tissues at various time-points after hepatectomy in mouse model of acute liver injury with partial hepatectomy. -test or Spearman rank correlation analysis was used for statistical analysis. ALT and AST were abnormally elevated in some patients with novel coronavirus infection, and the rate and extent of ALT and AST elevation in severe NCP patients were higher than those in non-severe patients. Liver tissue results of single cell sequencing and immunohistochemistry showed that ACE2 was only expressed in bile duct epithelial cells of normal liver tissues, and very low in hepatocytes. In a mouse model of acute liver injury with partial hepatectomy, Ace2 expression was down-regulated on the first day, but it was elevated up to twice of the normal level on the third day, and returned to normal level on seventh day when the liver recovered and hepatocyte proliferation stopped. Whether this phenomenon suggests that the bile duct epithelial cells with positive expression of Ace2 participate in the process of liver regeneration after partial hepatectomy deserves further study. In RNA-Seq data, 77 transcription factors were positively correlated with the expression of ACE2 (r > 0.2, FDR < 0.05), which were mainly enriched in the development, differentiation, morphogenesis and cell proliferation of glandular epithelial cells. We assumed that in addition to the over activated inflammatory response in patients with NCP, the up-regulation of ACE2 expression in liver tissue caused by compensatory proliferation of hepatocytes derived from bile duct epithelial cells may also be the possible mechanism of liver tissue injury caused by 2019 novel coronavirus infection.