Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Vectors used to carry foreign genes play an important role in gene therapy, among which, the adeno-associated virus (AAV) has many advantages, such as nonpathogenicity, low immunogenicity, stable and long-term expression and multiple-tissue-type infection, etc. These advantages have made AAV one of the most potential vectors in gene therapy, and widely used in many clinical researches, for example, Parkinson's disease. This paper introduces the biological characteristics of AAV and the latest research progress of AAV carrying neurotrophic factor, dopamine synthesis related enzymes and glutamic acid decarboxylase gene in the gene therapy of Parkinson's disease.

Objective To analysis the clinical effects of biliary-pancreatic double stents in pancreatic cancer patients with obstructive jaundice.Methods From July 2008 to October 2011,a total of 60 patients with advanced pancreatic cancer were randomly divided into two groups to receive biliary-pancreatic double stents (n =28) or biliary stent only (n =32) according to the odd and even numbers of their admission date.Changes in liver function,abdominal pain,quality of life scores (QOL) were compared between two groups.Results The stents were placed successfully in 54 patients (90.0％),in which symptoms were relieved or gradually disappeared in all patients after the procedure.One week after stents placement,the serum total bilirubin decreased significantly from 164.32 ±45.16 μmol/L before ERCP to 63.25 ±27.06 μmol/L (P ＜ 0.05),other parameters including ALT,AST,AKP and r-GT were also decreased significantly compared with those of pre-ERCP (P ＜ 0.01),but there was no significant difference between the two groups (P ＞ 0.05).25 cases in double-stents group and 29 cases in single-stent group had varying degrees of pain relief at 7d after ERCP,but the overall pain relief rate and complete pain relief rate in double-stent group were significantly higher than those in single-stent group (92.0％ vs.55.2％; 64.0％ vs.34.5％,P＜0.05).At 7d and 14d after ERCP,Karnofsky QOL score were improved significantly in double-stent group (P ＜ 0.05).It was significantly better than single-stent group at 14d after ERCP (P ＜0.05).No death or other severe ERCP-related complications were observed.Conclusion Biliary-pancreatic stent placement for pancreatic cancer could significantly improve liver function and relieve obstructive pain.In the ways of alleviating pain and improving quality of life scores,it was better than ERCP biliary stent placement,especially for patients with pancreatic cancer combined obstructive pain.It indicated that biliary-pancreatic stent placement was better than simple biliary stent placement for advanced pancreatic head cancer patients with obstructive pain.

Aptamers are capable of binding a wide range of biomolecular targets with high affinity and specificity. It has been widely developed for diagnostic and therapeutic purposes. Because of unique three dimensional structures and cell-membrane penetration, aptamers inhibit virus infection not only through binding specific target, such as the viral envelope, genomic site, enzyme, or other viral components, but also can be connected to each other or with siRNA jointly achieve antiviral activity. Taking human immunodeficiency virus and hepatitis C virus as examples, this paper reviewed the effects and mechanisms of aptamers on disturbing viral infection and replication steps. It may provide an insight to the development of aptamer-based new antiviral drugs.

High mobility group A2 protein (HMGA2), an architectural factor, is highly expressed in various cancer types including lung cancers. It is a candidate target for cancer therapy. RNAi is an effective gene silencing method with low cost and less time-consuming. It is possible to exploit this technology in therapy. Here, 5 siRNAs targeting Hmga2 gene (HMGA2 siRNA1-5) were designed and synthesized. MTT assay, colony formation assay, transwell assay and flow cytometry were used to evaluate the effects of these siRNAs on lung cancer cell lines (NCI-H446 and A549). Results from cell proliferation, clone formation, migration and apoptosis showed that HMGA2 siRNA1, 3, 5 could affect these aspects for both lung cancer cell lines. Among the five siRNAs, HMGA2 siRNA5 showed the greatest inhibition effects. The inhibition effects of HMGA2 siRNA5 are sequence specific and are not due to the induction of interferon response. Taken together, siRNAs targeting Hmga2 gene are potential candidates for lung cancer gene therapy.

The aim of this study was to reveal the protection role and the related mechanism of cytoglobin on the oxidation induced hepatic stellate cell damage. We applied siRNA to interfere the endogenous cytoglobin gene, used recombinant cytoglobin protein to treat the completely activated human hepatic stellate cell line LX-2 and the incompletely activated primary rat hepatic stellate cells, or over-expressed cytoglobin protein in LX-2 cells. We used two different oxidative-stress related models, the hydrogen peroxide model and the iron-overload model in our experiments and investigated the proliferation status and the intracellular superoxide level of the cells. The results showed that endogenous cytoglobin exerted significant protective effects on hydrogen peroxide or iron-overload induced LX-2 cell damage, confirming that upregulation of cytoglobin was the protective response of activated hepatic stellate cells to oxidative stress. Recombinant cytoglobin protein could protect LX-2 cells from oxidation induced damage, and prevent primary rat hepatic stellate cells from excessive proliferation and injury. The cytoplasmic reactive oxygen species (ROS) scavenging capacity of the recombinant cytoglobin protein was not as good as its capacity in scavenging ROS outside the cells, likely owing to the lack of active transporting mechanisms. Intracellular over-expression of cytoglobin protein could exert significant protective effect on LX-2 cells treated with hydrogen peroxide or iron-overload. Our results would accelerate the exploitation of new anti-fibrotic targets.
Animals ; Cell Line ; Globins ; genetics ; pharmacology ; Hepatic Stellate Cells ; cytology ; pathology ; Humans ; Hydrogen Peroxide ; toxicity ; Oxidative Stress ; drug effects ; Protective Agents ; pharmacology ; RNA, Small Interfering ; genetics ; Rats ; Reactive Oxygen Species ; metabolism

Recombinant adeno-associated viral vectors (rAAV) have been widely used as gene therapy vectors in clinical trials. Here, we reviewed the genomic structures and replication mechanisms of wt-AAV. Then, the assembly of capsid and the encapsidation of genomic DNA, two major events during AAV pakaging, was discussed in detail. Although the overall pattern of virus assembly and encapsidation is known, the molecular mechanisms and the structure-function relationship involved in these processes are not well understood. Further elucidatation of these processes may improve the production technology of rAAV and develop gene drug based on rAAV.
Capsid ; physiology ; Capsid Proteins ; genetics ; DNA, Viral ; genetics ; Dependovirus ; genetics ; physiology ; Genetic Vectors ; Genome, Viral ; Virus Assembly ; genetics ; physiology

Objective To explore the strategies for diagnosis and treatment of anomalous junction of pancreaticobiliary duct (AJPBD) complicated by acute pancreatitis. Methods The clinical dataof 22 patients with abnormal pancreaticobiliary junction were analyzed retrospectively. Results The incidence of acute pancreatitis in this series was 31.8 % (7/22), thereinto, 5 cases(71.4%) in C-Ptype (the common bile duct joining the pancreatic duct) and 2(28.6%) in P-C type (the pancreatic duct joining the common bile duct). Seven patients underwent ERCP+ EST+ ENBD. Two patients with common bile duct stones were treated with stone basket and cholecystectomy was performed in two cases with gallstone. All patients were successfully treated. The follow-up for l year showed that there was no recurrence of pancreatitis. Conclusion Acute pancreatitis usually occurs in patients with AJPBD, especially in C-P type or with gallbladder stone or common bile duct stone. ERCP+EST+ENBD and prophylactic cholecystectomy are effective to prevent and treat acute pancreatitis.

1263 patients with choledocholithiasis were treated with endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) from January 2005 to December 2008, with 1235 (97.8%) cases successfully treated. One-time ERCP removal of the stones was successful in 982 patients, with two times in 129 patients and three times in 124. 1130 patients (89. 5% ) underwent endoscopic nasal biliary drainage (ENBD) after the procedure. 56 patients with refractory stone were treated with intrabiliary plastic stent, among whom 42 were cured through endoscopic retrograde biliary drainage (ERBD) of 1 -3 times. Complications occurred in 29 patients (2. 3% ) with hemorrhage in 8 patients,acute pancreatitis in 17 and perforations in 4. Mortality rate was 0. We concluded that the majority cases of choledocholithiasis can be successfully treated by ERCP, while intrahepatic cholelithiasis and refractory common bile duct stone remained therapeutic challenges. It is also mandatory to evaluate long-term efficacy and complications of ERCP.

Numerous studies and clinical trials have demonstrated the efficacy of recombinant adeno-associated virus gene delivery vectors. However, prior to expression, it is necessary to convert the single-stranded DNA genome into double-stranded DNA, which hinders the efficiency of these vectors. We can entirely circumvent this step through the use of self-complementary recombinant adeno-associated virus vector (scrAAV). ScrAAV packages an inverted repeat genome that can fold into double-stranded DNA without the requirement for DNA synthesis or base-pairing between multiple vector genomes. By using scrAAV, we could increase expression efficiency and reduce immune response caused by vectors themselves. Therefore, it is a promising vector for gene therapy. So far, it has been used in the treatment of hepatic diseases, central nervous system diseases, and eye diseases. It has also been used in the modifications of stem cells and as vectors for siRNA/miRNA and ribozymes. In this review, we focused on the preparation, expression and location of scrAAV both in vitro and in vivo. We mainly introduced the recent progress of scrAAV based therapy of Hemophilia B, in order to elucidate the potential and prospects of scrAAV in gene therapy.
Animals ; Base Sequence ; DNA ; genetics ; DNA, Complementary ; genetics ; DNA, Single-Stranded ; genetics ; Dependovirus ; genetics ; metabolism ; Gene Transfer Techniques ; Genetic Therapy ; methods ; trends ; Genetic Vectors ; genetics ; Hemophilia B ; therapy ; Humans ; Molecular Sequence Data