Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

Dry eye,also known as keratoconjunctivitis sicca,is clinically manifested as dry eyes,itching,burning,blurred vision and other symptoms,which seriously affects the life quality of patients.In recent years,the incidence of dry eye has increased year by year,and it has become one of the common clinical diseases in ophthalmology.At present,the treatment methods of dry eye mainly include drug treatment,surgical treatment and clinical nursing,among which drug is the most commonly used method for the treatment of dry eye.Therefore,this paper summarizes the application and research progress of clinical medication of dry eye based on permeation pathways and inflammatory pathways in recent years,so as to provide some ideas for the follow-up treatment of dry eye and drug development.

Objective To study the effect of self-monitoring of blood glucose information management platform based on the medical consortium on the level of blood glucose control by improving the implementation rate of self-monitoring of blood glucose prescriptions for type 2 diabetes patients in the community.Methods A convenient sampling method was used to select 121 patients with type 2 diabetes from April 2021 to April 2023 who were enrolled in a community of a tertiary hospital medical consortium in Beijing.They were randomly divided into 61 patients in an experimental group and 60 patients in a control group.The control group received routine blood glucose monitoring and guidance education,while the experimental group was managed by a self-monitoring of blood glucose information management platform based on the medical consortium with nurses as the main body.Glycated hemoglobin,glucose test,fasting blood sugar,blood glucose 2 hours after meal,and the completion of self blood glucose monitoring prescriptions were evaluated and analyzed in the first week and the twelfth week of the 2 groups.Results 61 cases in the experimental group and 58 cases in the control group completed the follow-up,and the patients who completed the follow-up were analyzed.There was no statistically significant difference in glycated hemoglobin between the 2 groups at baseline(P=0.117).After 12 weeks,the reduction standard-reaching rate in glycated hemoglobin in the experimental group was significantly different from that in the control group(P=0.014).The number of self-monitoring of fasting blood glucose and the total number of other time periods in experimental group were significantly higher than those in the control group(P＜0.001);the implementation rate of self-monitoring prescription in the experimental group was better than that in the control group(P＜0.001).Conclusion A self blood glucose monitoring information platform was built to manage community type 2 diabetes patients,so that patients can master and implement the personalized blood glucose monitoring prescription formulated by the medical union team with nurses as the main body,and it is conducive to improving the frequency of blood glucose monitoring and the level of blood glucose control of diabetes patients.

Objective:To analyze the feasibility of free disinfection of central venous catheter infusion connector after using disposable disinfection caps.Methods:Using the convenient sampling method, a total of 132 patients who were hospitalized in the Department of Hematology of a Class Ⅲ Grade A hospital in Beijing from January to August of 2020 were selected as the research objects. According to the order of hospitalization, they were divided into the experimental group (group A) and the control group (group B) . Group A used disposable disinfection caps to connect the infusion connector, while group B repeatedly wiped the infusion connector for 15 s with 70%-80% alcohol cotton before infusion. According to infusion interval of 8 and 12 h and sampling timing, group A was divided into group A1-8 h and group A2-12 h, while group B was divided into group B1-8 h and group B1-12 h, with 33 cases in each group. Samples from infusion connectors of the 4 groups were collected for bacterial culture and bacterial inhibition on the surface of infusion connectors was compared.Results:There were 2 cases of detachment in A1-8 h group, 3 cases in A2-12 h group and 1 case in B2-12 h group. A total of 126 patients completed the study. A total of 18 patients in group A had bacteria at the infusion connector, which was more than 0 patients in group B, and the difference was statistically significant ( P<0.01) . In A1-8 h group, there was statistically significant difference in the presence of bacteria before and after using disinfection caps ( P<0.01) . There was no statistically significant difference in the presence or absence of bacteria in the infusion connector before and after the use of the infusion caps in the A2-12 h group ( P>0.05) . Conclusions:The disinfection effect of the disposable infusion connector disinfection cap is not the same as that of the disposable alcohol cotton pad disinfection method, but it can inhibit the growth of bacteria on the infusion connector surface within 8 h.

Objective To establish a liquid chromatography-tandem mass spectrometric ( LC-MS/MS ) for determination of clopidogrel in human plasma and stability of clopidogrel under different conditions,which was used subsequently to investigate the pharmacokinetics of clopidogrel in healthy Chinese volunteers. Methods Clopidogrel-d4 hydrogen sulfate was used as an internal standard. Separation was achieved on a WATERS Xterra? RP18 column (4.6 mm× 100 mm,3.5μm) with a mobile phase consisting of acetonitrile-0.1% formic acid (66:34) at a flow rate of 1.0 mL.min-1 within 3.2 min. ESI source was applied and operated in positive ion mode and multiple reaction monitoring (MRM). Plasma samples were pretreated by acetonitrile precipitation. Results A good linearity of clopidogrel was obtained in the concentration range of ( 5-5 000 ) ng.L-1. The lower limit of quantification was 5 ng.L-1. The intra-and inter-run precisions at three quality control levels were within 1.3%–9.9%,the relative deviation of the assay was within -6.2%-14.3%. The blood samples were stable when chilled with crushed ice ( 0℃) and cold water ( 4℃) ,as well as kept at room temperature ( 20℃) for 40 min. The plasma QC samples were stable at room temperature ( 20 ℃) for 4 h,at -70℃ for 38 days and during three freeze-thaw cycles. Hemolysis in blood sample drawn didn’ t affect the plasma concentration. The determination and the result of incurred sample reanalysis met the requirements. Conclusion A specific, rapid, sensitive and stable LC-MS/MS method is developed and validated for determination of clopidogrel in human plasma. The method is proven to be suitable for study of the pharmacokinetics of clopidogrel in healthy Chinese volunteers after a single oral dose of 75 mg clopidogrel hydrogen sulphate tablet.

Objective To construct an Apoptin prokaryotic vector,aiming to produce antigenic fusion protein Apoptin. Methods The Apoptin gene was amplified from the template of plasmid pSSCHG/NT4-Apoptin-HA2-TAT by PCR.The Apoptin was sub-cloned into the multiple clone sites of plasmid pET-28a(+) to get the prokaryotic vector of pET-28a(+)-Apoptin,which was transformed into E.coli BL21(DE3).Expression of E.coli BL21(DE3) was induced by IPTG.The specific protein expression was detected by SDS-PAGE. Results The fusion protein was expressed with high efficiency in E.coli BL21(DE3) transformed by pET-28a(+)-Apoptin after induction with IPTG.The specific fusion protein had an apparent related molecular weight of about 17 000 ku as indicated by SDA-PAGE analysis. Conclusion The Apoptin prokaryotic expression vector with pET-28a(+)-Apoptin can effectively express Apoptin fusion protein,laying a foundation for further study of Apoptin and preparation of antibodies against Apoptin.