The stability of deoxyribonucleoside triphosphate (dNTP) pool is essential for the normal synthesis of nuclear and mitochondrial DNA. The lack or excess of any dNTP may cause DNA damage and genomic instability, and increase mutation rate. Present studies have confirmed that the instability of dNTP pool is closely related to a variety of tumorigenesis. In addition, dNTP pool is involved in the development of tumor via multiple pathways, while the mechanisms of tumors caused by the instability of dNTP are complicated. This paper discusses the relationship between the stability of dNTP pool and DNA damage repair to provide a theoretical basis for early diagnosis and targeted treatment of tumors.

December 2019 witnessed the outbreak of COVID-19 in Wuhan and spread of the epidemic across the country. As a provincial designated hospital for critical patients, the First Affiliated Hospital of Zhejiang University responded rapidly since then by advocating the four-concentration principles, namely " concentrating patients, experts, resources and treatment" . In its rescue of critical patients, the hospital formulated comprehensive emergency plans, optimized hospital-wide resources, effectively arranged rescue spacing, established medical echelons, and implemented multi-disciplinary strategy. These efforts ensured efficient rescue and treatment, achieving a cure rate up to 98.7% of such patients, with no deaths.

Clinical trial management system is independently developed by our hospital, which basically realized the whole process management and data collection of clinical trials. Based on the platform, the functional architecture of data remote monitoring and auditing was established. By desensitizing and encrypting of data, the project and subject hologram were visualized to facilitate to review of data. The data remote monitoring and auditing cloud platform adopts the B/S architecture pattern. Users register to apply for an account through the cloud platform, and access to the account via HTTPS security protocol. The authorized users were able to view the relevant items online to ensure the secure data transmission and easy operating. The electronic management of data is the direction of future efforts. By compliance with laws and regulations, the remote monitoring/auditing can be realized, and the data security and personal privacy can be ensured with the application of information technology. In this paper, the feasibility of remote monitoring/auditing mode is explored, specific technical schemes and system functions are suggested, and the realization scenarios are conceived in case of major public health emergencies.

Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on ( 6), and -19: , we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.
Adrenal Cortex Hormones ; adverse effects ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Antiviral Agents ; adverse effects ; therapeutic use ; Betacoronavirus ; isolation & purification ; Coronavirus Infections ; drug therapy ; Critical Illness ; Drug Therapy ; Humans ; Nutritional Support ; Pandemics ; Pneumonia, Viral ; drug therapy ; Probiotics ; administration & dosage

The current epidemic situation of coronavirus disease 2019 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance" strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinary personalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in 10%patients' blood samples at acute period and 50%of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifying cytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance" strategy effectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviral effects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favored the balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short period of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as and , so nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore,we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.
Betacoronavirus ; isolation & purification ; China ; epidemiology ; Coronavirus Infections ; diagnosis ; epidemiology ; therapy ; virology ; Disease Management ; Early Diagnosis ; Feces ; virology ; Humans ; Pandemics ; Pneumonia, Viral ; diagnosis ; epidemiology ; therapy ; virology ; Sputum ; virology

The current epidemic situation of corona virus disease-19 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 inZhejiang Province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance"strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinarypersonalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in10% patients'blood samples at acute periodand 50% of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifyingcytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance"strategyeffectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviraleffects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favoredthe balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis should be prescribed rationally and was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbialdysbiosis with decreasedprobiotics such as and . Nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the SARS-CoV-2 infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience above and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.

Objective: To investigate the expression and clinical significance of ribonucleotide reductase small subunit M2 (RRM2) in chronic hepatitis B virus (HBV) infection and related liver diseases. Methods: A total of 428 patients with chronic HBV infection and liver disease were enrolled from Songyang County People’s Hospital from October 2017 to September 2019. There were 166 cases of chronic hepatitis B (CHB), 53 cases of HBV-related cirrhosis, 28 cases of non-HBV-related cirrhosis, 57 cases of HBV-related liver cancer, 33 cases of non-HBV-related liver cancer, and 91 cases of non-viral hepatitis. In addition, 36 healthy subjects were selected as the control group. Among 166 cases of CHB, there were 87 patients with high viral load group (HBV DNA ≥4.0 lg IU/mL) and 79 patients with low viral load group (HBV DNA <4.0 lg IU/mL); while in 87 high viral load patients, 56 had high alanine transaminase (ALT) (≥40 U/L) and 31 had normal ALT (<40 U/L). The expression level of serum RRM2 protein in patients was detected by enzyme-linked immunosorbent assay (ELISA), and the relationship of RRM2 expression with HBV DNA and liver function was analyzed. SPSS 23.0 and PRISM 8.0 statistical software were used to analyze data. Correlation analysis was performed using Spearman analysis. Results: The serum ALT and RRM2 levels in patients with high viral load CHB were higher than those in low viral load group (Z=-6.68, t=6.80, P<0.01). Patients with HBV-related cirrhosis had higher serum RRM2 levels than those with non-HBV-related cirrhosis (t=9.16, P<0.01). The serum RRM2 level was higher in patients with HBV-related liver cancer than that in patients with non-HBV-related liver cancer (t=12.42, P<0.01). Among patients with high viral load CHB, there was no significant difference in serum RRM2 levels between patients with ALT ≥40 U/L group and patients with ALT <40 U/L group (t=0.51, P>0.05). The level of ALT in the non-viral hepatitis group was higher than that in the healthy control group (Z=-8.43, P<0.01), but there was no significant difference in serum RRM2 levels between the two groups (t=1.03, P>0.05). Correlation analysis showed that serum RRM2 level was positively correlated with HBV DNA load (r=0.51, P<0.01), but not correlated with liver function indicators such as ALT and aspartate aminotransferase (all P>0.05) in patients with chronic HBV infection and related liver diseases. Conclusions Serum RRM2 level is positively correlated with HBV DNA load and has no significant correlation with ALT. RRM2 might be used as a target for the development of new hepatitis B drugs.

Enterococcus is an opportunistic pathogen of nosocomial infection.In recent years, the resistance rate of Enterococcus to antimicrobial agents is increasing with the widespread use of antibiotics, even leading to the development of vancomycin-resistant Enterococcus(VRE).Linezolid is a synthetic oxazolidinone antibiotic, which less likely to generates the cross-resistance with other antimicrobial agents that inhibit bacterial protein synthesis,so it has been regarded as the last line of defense for VRE.However, since the linezolid has appeared on the market, the reports of linezolid-resistant Enterococcus have also emerged.This article reviews the resistance mechanisms of Enterococcus to linezolid in order to provide reference for resistance surveillance as well as the research and development of new antimicrobial agents.

The First Affiliated Hospital of Zhejiang University founded an online hospital campus leveraging the Internet-plus environment. Supported by the offline hospital, this campus made full use of Internet features and advantages in its attempts to optimize the distribution of medical resources,to improve the accessibility of medical service, to reduce medical costs, and to expand the service coverage among others. Meanwhile,this online system, via interconnection with the hospital′s HIS system, achieved online medical insurance payment,prescriptions checking and drug delivery service.

Ribonucleotide reductase ( RR ) is a rate-limiting enzyme, and it is responsible for reducing ribonucleotides to their corresponding deoxyribonucleotides , which are the building blocks required for DNA replication and repair .Recent studies have revealed that RR activity is associated with DNA replication in virus , and RR inhibitors have been used for clinical antiviral treatment .This paper reviews research progress on RR and its inhibitors , including the classification , structure and function of RR; the classification, mechanism and clinical application of RR inhibitors in antiviral therapy and the future prospects of RR inhibitors .