Antibody-based therapies are one of the crucial tumor-targeted therapies,enabling pre-cise elimination of tumor cells by specifically binding to antigens on the tumor cell surface.However,their wide applications in solid tumor therapy are often limited by on-target toxicity.Recent advance-ments in antibody engineering have led to the development of novel tumor-targeted masking antibod-ies,which are specifically designed to address these limitations.Masking antibodies typically consist of an antibody domain,a masking domain and a linker.These antibodies are characterized by selective activation and other functional properties.Currently,various masking antibody technologies with distinct characteristics have been developed and have demonstrated favorable safety profiles in animal studies.This review summarizes the structure and characteristics of tumor-targeted masking antibodies outlines common masking technologies and their drug development in order to offer new lines of thought for the design and development of next-generation tumor-targeted therapeutics.

The 16S rRNA sequencing,whole genome sequencing and drug sensitivity tests were used to identify the isolates molecularly and to detect and analyse their virulence genes,resistance genes and drug resistance.The results showed that the isolate was highly homologous to Klebsiella pneumoniae X4 and located on the same branch by 16S rRNA sequence analysis,and it was named as KLKp10.Whole genome sequencing results showed that the KLKp10 genome was 5 342 841 bp in length,containing 5 138 genes,346 repetitive segments,6 rRNAs and 81 tRNAs,with a GC con-tent of 57.30％.MLST analysis showed that KLKp10 belongs to the ST-4263 type.The functions of 4 097 of the genes encoding proteins were classified and annotated by COG,and there were also 382 genes with unknown functions.A total of 50 functional classifications were involved in the an-notation results based on the GO database;33 kinds of signaling pathways were covered based on the signaling pathway annotations in the KEGG database.A total of 443 virulence genes were screened in the VFDB database,of which 339 belonged to the Set A database and could encode 124 virulence factors.The 101 resistance genes were predicted by comparing with the CARD database,among which there were more resistance genes against β-lactam antibiotics.The results of drug sensitivity test showed that KLKp10 was highly sensitive to ceftazidime,gentamicin,azithro-mycin,chloramphenicol,norfloxacin,ofloxacin,and enrofloxacin;moderately sensitive to ceftriax-one,neomycin,kanamycin,and streptomycin;and resistant to ciprofloxacin,tetracycline,amoxicil-lin,and penicillin.In this study,we systematically revealed the gene-wide characterization,virulence factors and drug resistance of Klebsiella pneumoniae KLKp10 of Kole pig origin,which provides important data support for the study of Klebsiella pneumoniae at the overall level of its genome.

The 16S rRNA sequencing,whole genome sequencing and drug sensitivity tests were used to identify the isolates molecularly and to detect and analyse their virulence genes,resistance genes and drug resistance.The results showed that the isolate was highly homologous to Klebsiella pneumoniae X4 and located on the same branch by 16S rRNA sequence analysis,and it was named as KLKp10.Whole genome sequencing results showed that the KLKp10 genome was 5 342 841 bp in length,containing 5 138 genes,346 repetitive segments,6 rRNAs and 81 tRNAs,with a GC con-tent of 57.30％.MLST analysis showed that KLKp10 belongs to the ST-4263 type.The functions of 4 097 of the genes encoding proteins were classified and annotated by COG,and there were also 382 genes with unknown functions.A total of 50 functional classifications were involved in the an-notation results based on the GO database;33 kinds of signaling pathways were covered based on the signaling pathway annotations in the KEGG database.A total of 443 virulence genes were screened in the VFDB database,of which 339 belonged to the Set A database and could encode 124 virulence factors.The 101 resistance genes were predicted by comparing with the CARD database,among which there were more resistance genes against β-lactam antibiotics.The results of drug sensitivity test showed that KLKp10 was highly sensitive to ceftazidime,gentamicin,azithro-mycin,chloramphenicol,norfloxacin,ofloxacin,and enrofloxacin;moderately sensitive to ceftriax-one,neomycin,kanamycin,and streptomycin;and resistant to ciprofloxacin,tetracycline,amoxicil-lin,and penicillin.In this study,we systematically revealed the gene-wide characterization,virulence factors and drug resistance of Klebsiella pneumoniae KLKp10 of Kole pig origin,which provides important data support for the study of Klebsiella pneumoniae at the overall level of its genome.

Antibody-based therapies are one of the crucial tumor-targeted therapies,enabling pre-cise elimination of tumor cells by specifically binding to antigens on the tumor cell surface.However,their wide applications in solid tumor therapy are often limited by on-target toxicity.Recent advance-ments in antibody engineering have led to the development of novel tumor-targeted masking antibod-ies,which are specifically designed to address these limitations.Masking antibodies typically consist of an antibody domain,a masking domain and a linker.These antibodies are characterized by selective activation and other functional properties.Currently,various masking antibody technologies with distinct characteristics have been developed and have demonstrated favorable safety profiles in animal studies.This review summarizes the structure and characteristics of tumor-targeted masking antibodies outlines common masking technologies and their drug development in order to offer new lines of thought for the design and development of next-generation tumor-targeted therapeutics.

Objective To investigate the clinical feature and antibiotic resistance profile of K.pneumoniae isolates from patients for better management of K.pneumoniae infections.Methods Nonduplicate K.pneumoniae strains were collected from January to December in 2015.K.pneumoniae strains were identified by VITEK 2-Compact 60 and tested for antimicrobial susceptibility by KirbyBauer method.Results A total of 753 strains ofK.pneumoniae were included,most (40.9％,308/753) of which were isolated from sputum,followed by urine (18.2％,137/753).Most of the strains were from old patients at least 60 years of age (40.8％,307/753),and primarily from intensive care units (16.7％,126/753) and Department of Respiratory Medicine (13.7％,103/753).Respiratory tract infection was found in 144 patients,of which 71.5％ (103/144) were due to K.pneumoniae.More than half of the K.pneumoniae strains were resistant to piperacillin (66.3 ％),cefazolin (60.8 ％) and cefitroxime (59.4 ％).Only a few strain were resistant to imipenem (2.4 ％) and meropenem (2.0).ESBLs were produced in 410 (54.4 ％) of the 753 strains,and 29 (3.9 ％) strains were carbapenem-resistant,492 (65.3 ％) strains were resistant to multiple antimicrobial agents.Conclusions Clinical K.pneumoniae isolates are highly resistant to most of the antimicrobial agents tested.The strains were mostly isolated from sputum and urine,and positive for ESBLs.MDR K.pneumoniae sWains are emerging.K.pneumoniae isolates are still very susceptible to carbapenems in vitro.

Objective To evaluate the safety and immunogenicity of one booster dose of inactivated hepatitis A vaccine in young adults.Methods The subjects were selected from participants in the clinical trial of immunogenicity of inactivated and attenuated live hepatitis A vaccine in young adults.Eligible subjects were those who had received one dose of inactivated or attenuated hepatitis A vaccine,could be contacted and were sero-negative before primary vaccination.All qualified subjects were immunized with one booster dose of inactivated hepatitis A vaccine.The blood samples were collected before booster dose vaccination and 28 days after the immunization.Anti-HAV antibody titer ≥20 mIU/ml was considered to be sero-protected against hepatitis A virus.Results The GMCs in the inactivated HAV vaccine group and attenuated live vaccine group before booster dose vaccination were 70.80 mIU/ml and 50.12 mIU/ml,respectively,and the sero-protection rates were 94.7％ and 65.0％,respectively.After the vaccination of the booster dose,the sero-protection rates in both groups were 100.0％,and the GMCs were 2 816.09 mIU/ml and 2 654.55 mIU/ml,respectively.Conclusion The GMCs and sero-protection rates of anti-HAV antibody in young adults declined after three years of the primary vaccination.However,the higher GMC and sero-protection rate were observed in the inactivated vaccine group than in the attenuated live vaccine group.Significant increases of GMC levels were observed in both groups after one booster dose vaccination.

Targeted therapy means transporting drugs to certain tissue,aiming at increasing the utilization of drugs as well as reducing cytotoxicity.Chemotherapy drugs carried by carbon nanotube have high pharmaceutical activity and tumor control rate,compared with drugs alone.Carbon nanotube combined with immunotherapy drugs and nucleic acid can treat tumors at immunology and gene level.

ObjectiveTo guide fluid management and evaluate the clinical index through monitoring extravascular lung water index(EVLWI) of patients with pulmonary contusion.MethodsThirtyone severe chest trauma patients with pulmonary contusion were selected,performed with central venous catheterization or femoral artery catheterization,and connected to pulse index continuous cardiac output (PICCO).EVLWI after pulmonary contusion were measured by using thermal dilution.The intake and output of patients were recorded in detail,fluid intake was controlled,furosemide was prescribed,and the changes and correlations of oxygenation index,EVLWI and liquid balance difference at different time points were evaluated.ResultsEVLWI after pulmonary contusion at 1st to 7th d after hospitalization was respectively (9.25 ±0.71),(8.98 ±0.61),(8.61 ±0.59),(7.75±0.53),(6.64 ±0.49),(6.22±0.36),(5.59 ±0.39) ml/kg.Comparing with 1st d after hospitalization,EVLWI declined from 3rd d (P ＜ 0.05).Oxygenation index at Ist to 7th d after hospitallzation was respectively( 145.76±23.61 ),( 144.19±20.24),( 146.67±19.25 ),(159.33±15.42),(177.38±14.25),(199.33±19.04),(213.71±18.51) mm Hg(1 mm Hg =0.133 kPa).Comparing with 1st d,oxygenation index from 4th to 7th d had significant difference (P ＜ 0.05 ).The fluid volume at 1st d to 7th d were all negative balance,that of 3rd d to 6th d had significant difference comparing with 1st d [(-431.43±121.17),(-601.43±127.09),(-629.52±140.69),(-320.01 ±93.71) ml vs.(-213.81±63.91 ) ml](P ＜ 0.05 ).Oxygenation index and EVLWI had negative correlation(r =-0.824,P＜0.01).Liquid balance difference and the changes of oxygenation index and EVLWI had no correlation.ConclusionEVLWI effectively monitoring after pulmonary contusion can not only evaluate the changes of pulmonary vascular permeability of patients with pulmonary contusion,but also have important significance to guide fluid management.

OBJECTIVE: To determine Ginsenoside Rg1,Ginsenoside Re and Ginsenoside Rb1 in Yixin fumai granula by HPLC.METHODS: Samples were determined on a Diamond C18(150 mm?4.6 mm,5 ?m).The mobile phase consisted of accetonitrile-water by gradient elution with flow rate at 1 mL?min-1,UV detection wavelength at 203 nm,column temperature at 25 ℃ and sample size at 10 ?L.RESULTS: The linear ranges of Ginsenoside Rg1,Ginsenoside Re and Ginsenoside Rb1 were 0.645～6.450 ?g(r=0.999 8),0.54～5.40 ?g(r=0.999 7) and 0.605～6.050 ?g(r=0.999 9),respectively;the average recoveries were 100.59%(RSD=2.03%),98.70%(RSD=1.46%)and 98.99%(RSD=1.19%),respectively.CONCLUSION: The method is sensitive,simple and accurate,and it can be used for the quality control of Yixin fumai granula.