Interferon (IFN) is one of the commonly used anti-HBV drug in clinic,in which IFN-λ is a new type of IFN,including IFN-λ1,IFN-λ2 and IFN-λ3 (also called IL-29,IL-28A and IL-28B,respectively).Researches in recent years show that IFN-λ3 (IL-28B) polymorphism seems to be involved in the onset of hepatitis B,the response to antiviral therapy and the outcome of HBV infection.This paper reviews the correlations between IL-28B polymorphism and the spontaneous clearance of HBV,the progression of HBV infection,the occurrence of liver cancer and the therapeutic effect of IFN treatment.

The pharmacokinetics/pharmacodynamics ( PK/PD) of antimicrobials aims to establish and evaluate dose-concentration-response relationship, and subsequently to describe and predict the effect-time courses resulting from a drug dose.Nowadays, PK/PD is playing an important role in dosage regimen optimizing, reducing toxicity and drug tolerance of antibiotics.And it is also of great significance in determining susceptibility breakpoints and development in new drug.This paper reviews the progress on PK/PD studies of antibacterial and antifungal agents to provide theoretical basis for safe and effective individual dosage regimens.

Objective To investigate molecular types and drug resistance of methicillin-resistant Staphylococcus aureus (MRSA) in Zhejiang province.Methods One hundred and fourty-seven clinical MRSA isolates were collected from 11 grade A tertiary hospitals during January 2009 and December 2010 in Zhejiang province.Minimal inhibitory concentrations (MICs) of 13 antimicrobial agents were determined by agar dilution.Multilocus sequence typing (MLST),staphylococcal cassette chromosome mec (SCCmec) typing and spa typing were used to examine the homology of the strains,and drug resistance patterns were compared among different molecular types.Simpson index was used to determine the discriminatory power of three typing methods.Results Fourteen STs were identified in 147 MRSA isolates,of which ST239 (75 isolates),ST5 (24 isolates) and ST59 (23 isolates) were the most prevalent clones.Four SCCmec types (types Ⅱ to Ⅴ) were identified in 141 isolates,and 6 isolates were not typed.SCCmec type Ⅲ was the predominant type (76 isolates),which was followed by type Ⅳ (32 isolates),type Ⅱ (24 isolates) and type Ⅴ (9 isolates).All MRSA isolates yielded 23 spa types,in which t030 (57 strains),t437 (17 strains),t002 (15 strains) and t037 (12 strains) were the predominant spa types.MRSA strains were sensitive to linezolid,teicoplanin,vancomycin and norvancomycin,but were highly resistant to other antibacterial agents,especially in strains carrying clone ST239 or of SCCmec type Ⅲ.The discriminatory power of MLST,SCCmec and spa typing were 0.6885,0.6577 and 0.8165,respectively.Conclusion The predominant clone of MRSA strains in Zhejiang province was ST239-SCCmec Ⅲ-t030-MRSA,and these strains are highly resistant to most antibacterial agents,so that the surveillance of MRSA in hospital should be strengthened.

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 .

Objective To evaluate the safety and feasibility of the modified apnea test (MAT) for brain death evaluation. Method A prospective, controlled clinical study was carried out. Forty-three patients with suspected brain death underwent a total of 85 MATs. The patient's spontaneous breathing, hemodynamics and oxy genarion were monitored during MAT; arterial blood pH, PaCO2, PaO2 were measured before and after the MAT. Paired t test was used for statistical analysis to determine significant differences in measurements before and after MAT on the same patient. The Wilcoxon Signed-Rank Test was used to determine statistical significance for skew distribution of PaO2 before and after apnea testing. Informed consent was obtained from the kinfolk of all participants and all of the procedures were done in accordance with national and international laws and policies. Results Hemodynamics and oxygenarion were stable in all patients during MAT, and none regained spontaneous respiration. About 89.4% of tests were completed within 4 minutes, and 10.6% within 8 minutes. The mean value of Pa CO2 rise was (23.1 ±4.8), and the average rate of PaCO2 increase was 5.3 mmHg per minute. Conclusions Modified apnea test can be done safely for brain death evaluation and is a useful supplement to the common apnea test.

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.

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.

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.

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.

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.