Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

The Guangdong Province Laboratory Animals Ordinance(the GPLAO),officially enacted and implemented in October 2010,marked a new phase of legal management in the administration of laboratory animals in Guangdong Province.The GPLAO clearly authorizes the laboratory animal monitoring institutes in Guangdong Province to conduct laboratory animal quality monitoring and assume corresponding legal responsibilities.It also specifies the standards for the production and use of laboratory animals,while bringing attention to laboratory animal welfare and ethics.Through the formulation of supporting documents,the active promotion of the standardization and regulation of administrative law enforcement,and the implementation of measures to delegate power,streamline administration,and optimize government services,significant improvements have been made in the standardized management of laboratory animals in Guangdong Province and in supporting the innovative development of biomedicine.Moreover,notable achievements have been made in areas such as the construction of experimental animal technology platforms,standardization work,the preservation and development of unique resources,and talent pool development.However,with the advancements in science and technology,social economy,and legislative work,some aspects in the GPLAO have been identified for improvement.These include the need for clearer provisions on laboratory animal welfare,more specific guidelines for the management of genetically engineered animals,improved regulations on the safety and welfare of practitioners,further refined implementation of the"one-vote veto system",continued promotion of laboratory animal standardization,and the exploration of effective mechanisms for resource sharing.This paper reviews and summarizes the institutional characteristics,post-legislation implementation,and effectiveness of the GPLAO,as well as the issues and countermeasures identified during the implementation.It concludes the laboratory animals management practices in Guangdong Province during the past 10 years,aiming to provide a reference for laboratory animal legislation.

Breast cancer has become the most commonly diagnosed cancer type in the world. A combination of chemotherapy and photothermal therapy (PTT) has emerged as a promising strategy for breast cancer therapy. However, the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Therefore, to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect, a multifunctional nanoparticle system (PCRHNs) is developed, which is grafted onto the prussian blue nanoparticles (PB NPs) by reduction-responsive camptothecin (CPT) prodrug copolymer, and then modified with tumor-targeting peptide cyclo(Asp-d-Phe-Lys-Arg-Gly) (cRGD) and hyaluronic acid (HA). PCRHNs exhibited nano-sized structure with good monodispersity, high load efficiency of CPT, triggered CPT release in response to reduction environment, and excellent photothermal conversion under laser irradiation. Furthermore, PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT. In vivo studies indicate that PCRHNs exhibited excellent biocompatibility, prolonged blood circulation, enhanced tumor accumulation, allow tumor-specific chemo-photothermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity. Moreover, hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT. Collectively, PCRHNs may be a promising therapeutic way for breast cancer therapy.

【Objective】 To provide reference for formulating relatively unified quality control strategies and meeting the requirements of homogenization construction of blood banks across Chongqing area by retrospectively analyzing sampling results of different blood components during the past two years in all levels of blood banks in Chongqing area. 【Methods】 The key quality data of blood components prepared by 6 blood banks in Chongqing were analyzed retrospectively. According to the issuing units to the clinical during the past two years, the research objects were selected as leukocyte-depleted suspended RBCs, cryoprecipitate, pathogen inactivated fresh frozen plasma(FFP) and apheresis platelets. The quality data of the above-mentioned blood components from January 2019 to June 2021 were collected and analyzed. 【Results】 For leukocyte-depleted suspended RBCs(1U)prepared by 5 blood banks, statistically significant differences in Hb, residual white blood cells and hemolysis rate at the end of storage, except for Hct, were noticed(P<0.05). For cryoprecipitate, the content of blood coagulation factor Ⅷ and fibrinogen were statistically different among 3 blood banks in 1U specification(P<0.05) and among 5 blood banks in 2U specification(P<0.05). For pathogen inactivated FFP, the content of blood coagulation factor Ⅷ, plasma proteins, and residual methylene blue were statistically different among 3 blood banks(P<0.05). For apheresis platelets, Plt, white/red blood cells contamination and pH at the end of storage were statistically different among 3 blood banks(P<0.05). 【Conclusion】 The quality data of blood components, prepared by different blood banks, meet the requirements of national standard, however, certain differences are existing among blood banks.Key points during the process of collection, preparation, storage and transportation need to be cleared and unified, so as to reduce the differences between each other, and determine the direction and basis for homogeneity construction in the next step.

【Objective】 To study the status and conduct effect evaluation of blood donation recruitment of blood services in Chongqing, and explore its influencing factors, so as to provide reference for the regional homogenization of blood services in Chongqing. 【Methods】 19 blood services in Chongqing were investigated by questionnaire in terms of the input in human resources and funds, recruitment methods, document construction and effect evaluation. The statistical analysis was conducted. 【Results】 The average number of blood donors per 1 000 population in 19 blood services in Chongqing was 9.35±3.35. Among the 19 blood services, blood inventory warning occurred in 18, 6 of them reached Level 2 and 1 of them was Level 1. The number of blood donations per 1 000 population in blood banks with no more than 5 recruits or with less than 100 000 yuan/year recruitment fund was significantly lower than that in blood banks with more than 5 recruits or with more than 100 000 yuan/year recruitment fund(P<0.05). SMS and telephone recruitment were most commonly used in blood donation recruitment. Most blood banks have established corresponding system documents, but only one has established the method to evaluate the effect of blood donation recruitment. 【Conclusion】 The number of blood donations per 1 000 population in 19 blood services in Chongqing varies greatly, and the pressure of blood inventory warning is widespread. The input of human resources and financial fund have a certain impact on the number of blood donations per 1000 population, but not the alone factor. The recruitment method is a little bit more on the traditional side, and the blood donation recruitment and efficacy evaluation is in lack of documentary supporting. Regional homogenization should be achieved by integrating the resources of blood services, establishing the document framework of blood donation recruitment and effect evaluation, clarifying the evaluation content and unifying the evaluation standard.

The previous pharmacokinetic methods can be only limited to drug analysis in vitro, which provide less information on the distribution and metabolismof drugs, and limit the interpretation and assessment of pharmacokinetics, the determination of metabolic principles, and evaluation of treatment effect. The objective of the study was to investigate the pharmacokinetic characteristics of gene recombination angiogenesis inhibitor Kringle 5 in vivo. The SPECT/CT and specific 131I-Kringle 5 marked by Iodogen method were both applied to explore the pharmacokinetic characteristics of 131I-Kringle 5 in vivo, and to investigate the dynamic distributions of 131I-Kringle 5 in target organs. Labeling recombinant angio-genesis inhibitor Kringle 5 using 131I with longer half-life and imaging in vivo using SPECT instead of PET, could overcome the limitations of previous methods. When the doses of 131I-Kringle 5 were 10.0, 7.5 and 5.0 g/kg, respectively, the two-compartment open models can be determined within all the metabolic process in vivo. There were no significant differences in t1/2α, t1/2β, apparent volume of distribution and CL between those three levels. The ratio of AUC(0 ? 1) among three different groups of 10.0, 7.5 and 5.0 g/kg was 2.56:1.44:1.0, which was close to the ratio (2:1.5:1.0). It could be clear that in the range of 5.0–10.0 g/kg, Kringle 5 was characterized by the first-order pharmacokinetics. Approximately 30 min after 131I-Kringle 5 was injected, 131I-Kringle 5 could be observed to concentrate in the heart, kidneys, liver and other organs by means of planar imaging and tomography. After 1 h of being injected, more radionuclide retained in the bladder, but not in intestinal. It could be concluded that 131I-Kringle 5 is mainly excreted through the kidneys. About 2 h after the injection of 131I-Kringle 5, the radionuclide in the heart, kidneys, liver and other organs was gradually reduced, while more radionuclide was concentrated in the bladder. The radionuclide was completely metabolized within 24 h, and the distribution of radioactivity in rats was similar to normal levels. In our study, the specific marker 131I-Kringle 5 and SPECT/CT were suc-cessfully used to explore pharmacokinetic characteristics of Kringle 5 in rats. The study could provide a new evaluation platform of the specific, in vivo and real-time functional imaging and pharmacokinetics for the clinical application of 131I-Kringle 5.

Objective To determine the causes and risk factors of antimicrobial treatment failure in patients with community-acquired pneumonia(CAP). Methods Hospitalized adults with CAP from January 2006 to December 2006 were analyzed retrospectively. Treatment failure was defined as appearance of nonresponding pneumonia and progressive pneumonia. Patient's clinical features were analyzed. Results All of 378 patients were involved in this study. Total antimicrobial treatment failure was happened in 50 patients(32 patients with non-responding pneumonia and 18 patients with progressive pneumonia). The causes were infectious (35 patients,70% ), non-infectious (11 patients,22% ) and undetermined (4 patients,8% ).Mortality of antimicrobial treatment failure was 18%(9/50, 8 patients died of infectious cause, 1 patient had no clear cause of death). Stepwise Logistic regression analysis showed that C-reactive protein, multilobar pneumonia,albumin < 30 g/L,renal function lesion,liver function lesion were related with antimicrobial treatment failure. Independent factors of treatment failure were multilobar pneumonia (P= 0.002) ,albumin <30 g/L(P = 0.001 ) and renal function lesion (P = 0.000). Conclusion The major challenge associated with antimicrobial treatment failure in hospitalized patients with CAP is infection, most of which is infection of drug resistant strain.

OBJECTIVE To find the distribution of pathogens and their antibiotics sensitivity in patients with bile duct diseases in order to guide clinical uses of antibiotics. METHODS Totally 128 bile samples were collected for bacterial cultures and sensitivity tests. RESULTS Pathogens were found in 68 samples(53.0%).The common pathogens were Escherichia coli(22.9%),Klebsiella pneumoniae(15.7%),Pseudomonas aeruginosa(11.4%) and Enterococcus faecalis(10.0%).Most bacteria were sensitive to imipenem,vancomycin,imipenem/cilastatin(Tienam),third and fourth generation cephalosporins;but resistant to penicillins,second-generation cephalosporins,macrolides and quinolones. CONCLUSIONS The most pathogenic bacteria in biles are E.coli,K.pneumoniae and Ent.faecalis and the antibiotic sensitivity tests can help clinical application of antibiotics.

Human FceR I a subunit extracellular domain was cloned and expressed with 2 different expressing systems and Dot blot was used to detect its biological activity to bind with IgE,providing reference for binding mechanism of human FceR I a subunit extracellular domain with IgE. It was shown that FceR I a subunit extracellular domain from pBAD/g I A expressing system could bind with IgE, but the one from PQE30 expressing system could not bind with IgE. It is suggested that FceR I a subunit extracellular domain alone is sufficient to bind with IgE without P and Y subunit. The proper space configuration and disulfide bond of FceR I a subunit is necessary for binding with IgE, but its glycosylation is unnecessary.

Objective:To show whether the Fas Ligand gene induces mast cells apoptosis.Methods:RT-PCR was used to amplify the gene of rat Fas ligand extracelluar domain and transmembrane domain and cloned it into eukaryotic expression plasmid pcDNA3.1.Transcent transfect RBL-2H3,the expression of Fas ligand RBL-2H3 was detected by RT-PCR、Western blot.The Annexin V FCM was used to detect the RBL-2H3 apoptosis after the transfection of Fas Ligand.Results:It is successful to obtain the gene of rat Fas Ligand extracellular domain and transmembrane segment,cloning it into pcDNA3.1,FasL was expressed on the surface of RBL-2H3 and it's supernatant after the transfection of pcDNA3.1/FasL.The cell start to be apoptosis.Conclusion:Our study reveals that Fas Ligand gene transfection in RBL-2H3 can effectively induced apoptosis.It is a promising strategy for Fas Ligand to be used in the therapy of allergic disease. [