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.

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.

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 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.

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.

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.