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.

Transcranial temporal interference stimulation (tTIS) is a novel non-invasive neuromodulation technique with the potential to precisely target deep brain structures. This study explores the neural and behavioral effects of tTIS on the superior colliculus (SC), a region involved in eye movement control, in mice. Computational modeling revealed that tTIS delivers more focused stimulation to the SC than traditional transcranial alternating current stimulation. In vivo experiments, including Ca²⁺ signal recordings and eye movement tracking, showed that tTIS effectively modulates SC neural activity and induces eye movements. A significant correlation was found between stimulation frequency and saccade frequency, suggesting direct tTIS-induced modulation of SC activity. These results demonstrate the precision of tTIS in targeting deep brain regions and regulating eye movements, highlighting its potential for neuroscientific research and therapeutic applications.
Animals ; Superior Colliculi/physiology* ; Transcranial Direct Current Stimulation/methods* ; Eye Movements/physiology* ; Male ; Mice ; Mice, Inbred C57BL

Objective To understand the genotyping of human immunodeficiency virus (HIV) co-infected hepatitis C virus (HCV) patients in Yunnan Province, and to analyze the differences in viral load, biochemical indicators, and blood routine indicators among different genotypes, in order to provide a laboratory basis for the diagnosis and clinical treatment of HIV/HCV co-infected patients. Methods From November 2022 to June 2023, the serum samples and basic information of patients diagnosed with HIV/HCV co-infection were collected in the antiviral outpatient clinic of Yunnan Provincial Hospital of Infectious Diseases. The HCV viral load was detected by one-step qRT-PCR amplification, the positive samples were sequenced, and genotyping was determined based on NS5 gene sequence. The differences in biochemical and blood routine indexes between HIV patients co-infected with different HCV genotypes and low/high viral loads were analyzed. Results A total of 126 HIV/HCV co-infected patients were collected, including 20 HCV genotype 1 (15.9%), 91 HCV genotype 3 (72.2%), and 15 HCV genotype 6 (11.9%). The maximum and minimum viral load of the three HCV genotypes were as follows: HCV type 1 (1.0×108, 4.8×104 IU/mL), HCV type 3 (2.2×108, 2.9×102 IU/mL), and HCV type 6 (8.1×107, 6.8×104 IU/mL). The results showed that there was no significant difference between HIV co-infection with different genotypes of HCV and three HIV treatment schemes, including nucleoside reverse transcriptase inhibitors+integrase strand transfer inhibitors (NRTIs+INSTIs), nucleoside reverse transcriptase inhibitors+non-nucleoside reverse transcriptase inhibitors (NRTIs+NNRTIs) and nucleoside reverse transcriptase inhibitors+protease inhibitor (NRTIs+PLs), and the viral load of patients (P>0.05). The analysis of biochemical indexes such as total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA), and blood routine indexes such as white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), platelet (PLT), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) among different HCV genotypes and low/high viral loads showed that there was no significant difference in biochemical indexes and blood routine indexes between low/high viral loads of HIV co-infected HCV patients (P>0.05); however, the biochemical indicators TBIL, IBIL and MCHC were significantly different statistically between patients with genotype 3 HCV infection and those with genotype 1 HCV infection (P<0.05), while other biochemical and blood routine indexes were not statistically different among different HCV genotypes (P>0.05). Conclusions There are six subtypes of HCV co-infection in HIV patients in Kunming, Yunnan Province, including three genes of genotype 1, 3, and 6. Among them, genotype 3 HCV is the main prevalent genetic virus among HIV co-infected populations. The TBIL, IBIL and MCHC values of HIV patients co-infected with HCV type 3 are different from those infected with HCV type 1.

Objective:To explore the current status of catheterization technology training for tunnel peripherally inserted central catheter (PICC) intravenous therapy specialist nurses, so as to provide reference for promoting the application of this technology and conducting systematic specialized training.Methods:From May to June 2023, convenience sampling was used to select 279 intravenous therapy specialist nurses from 150 hospitals in 24 provinces, autonomous regions, and municipalities directly under the central government as the research subject. A self-designed questionnaire was used to survey the research subject in the form of an electronic questionnaire.Results:A total of 279 questionnaires were distributed, and 279 valid questionnaires were collected, with an effective response rate of 100.0% (279/279). The hospitals where 141 nurses were located implemented tunnel PICC catheterization technology, of which 93 nurses implemented this technology in their departments, 34 nurses were able to independently complete this technique. A total of 113 nurses received tunnel PICC training, and 141 nurses believed that the primary factor affecting the implementation and development of this technology was the level of technical mastery of specialist nurses, 248 nurses expressed that training effectiveness could be effectively improved through workshops.Conclusions:The training and promotion of tunnel PICC catheterization technology need to be strengthened. It is urgent to further increase the re-certification of intravenous therapy specialist nurses and perfect the platform and standardization of specialized training to improve the nursing quality of intravenous therapy.

Objective:To construct a hypoglycemia random forest prediction model for older adults with type 2 diabetes, and assess the model′s prognostication performance through internal and external verification.Methods:From August 2022 to January 2023, 300 older adults with type 2 diabetes in Beijing Hospital were selected. The demographic characteristics, medical history, laboratory tests, and other data of the patients were collected, and the data set was randomly divided into the training set and verification set in a ratio of 7∶3. The hypoglycemia prediction model for older adults with type 2 diabetes was constructed and optimized based on the random forest algorithm. The calibration curve was used to evaluate the model′s calibration, and the ROC was used to evaluate the model′s discrimination. The clinical applicability of the model was assessed by the decision curve analysis. The risk factors for hypoglycemia in the older adults were explored by prioritizing the contributions of variables in prediction. The Bootstrap method was used for internal validation, and the validation set was used for external validation.Results:Among the 300 older adults with type 2 diabetes, 128 cases (42.67%) experienced hypoglycemia within one week. The predictive contributions of risk factors in the model were ranked as follows: the number of episodes of hypoglycemia in one month, HDL-C, heart disease, diabetes knowledge and education, combination therapy, age, duration of diabetes, staple food restriction, glycosylated hemoglobin, and gender. The internal and external calibration curves of the hypoglycemia random forest model for the older adults with type 2 diabetes fluctuated around the diagonal, indicating that the calibration degree of the predictive model is good. The AUROC of internal verification was 0.823 (95% CI 0.752-0.894), the sensitivity and specificity were 0.867 and 0.698, respectively. The external verification was 0.859 (95% CI 0.817 - 0.902), and sensitivity and specificity were 0.789 and 0.804, respectively, showing that the overall discrimination of the prediction model was good. The DCA curves were far from the all-positive line and all-negative line, which indicated that the prediction model had good clinical applicability. Conclusions:The predictive effect of this model is good, and it is suitable for predicting the risk of hypoglycemia in older adults with type 2 diabetes, and it provides a reference for early hypoglycemia screening and predictive intervention for this kind of patients.

Objective:To explore the experience and demand of diabetic patients for exercise management platform and provide reference for building scientific exercise management platform module content for diabetic patients.Methods:Using the phenomenological research method, with data saturation as the sample size selection criteria, a total of 11 diabetic patients from Department of Endocrinology of two Class Ⅲ Grade A hospitals in Beijing from June to August 2021 were selected for semi-structured in-depth interviews. Colaizzi 7-step analysis method was used to analyze data and extract themes.Results:Diabetic patients had a high degree of acceptance to use the exercise management platform. The demand could be summarized into five themes, which are professional service demand, effect analysis demand, personalized monitoring demand, simplicity of operation demand and interest stimulating demand.Conclusions:The development of diabetes exercise management platform should be diversified and personalized. Multi-disciplinary professional cooperation teams should be used to provide scientific and high-quality services and guidance for diabetes patients on the platform, so as to help diabetes patients form regular and effective exercise habits.

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 investigate the effect and mechanism of miR-885-3p on the radiosensitivity of colorectal cancer cell HT-29. Methods The expression of miR-885-3p in HT-29 cells irradiated with different doses (0, 2, 4, 6, 8 Gy) of X-rays was detected by qPCR. The effect of miR-885-3p in modulating cell radiosensitivity was assessed in HT-29 cells with miR-885-3p overexpression. Bioinformatics prediction and dual luciferase reporter gene assay were employed to identify the direct target gene of miR-885-3p. Relationship between miR-885-3p and target gene tyrosine kinase 1 (AKT1) was investigated via regulation of miR-885-3p expression. The effect of AKT1 on radiosensitivity in HT-29 cells was evaluated through knockdown AKT1. The effect of AKT1 on miR-885-3p-induced radiosensitivity was detected by co-transferring miR-885-3p and AKT1 gene into HT-29 cells. Results miR-885-3p expression was up-regulated in radiation-induced HT-29 cells (F=46. 64, P<0. 05). Over-expression of miR-885-3p and knockdown of AKT1 enhanced cell radiosensitization by inhibiting survival and promoting apoptosis (t=12. 33, 12. 95, P <0. 05) with SER of 1. 602 and 1. 946, respectively. Inhibition of miR-885-3p promoted radioresistance by increasing cell survival and inhibiting apoptosis (t=11. 94, P<0. 05) with a SER of 0. 839. AKT1 is a target gene downstream of miR-885-3p, overexpression of AKT1 reversed the effect of miR-885-3p on cell radiosensitivity with a SER of 0. 680. Conclusions miR-885-3p can enhance the radiosensitivity of colorectal cancer HT-29 cells by directly targeting AKT1, which provides a target for improving the radiosensitivity of clinical colorectal cancer.

Objective To explore the best method for first Rituximab transfusion, in order to reduce the incidence of anaphylaxis. Methods A total of 157 non Hodgkin lymphoma patients with first Rituximab transfusion were divided into three groups according to random number table, within 55 cases in control group and the patients of control group undergoing Rituximab instruction advised transfusion method (50 ml/h). There were 62 patients in observation 1 group who received the beginning transfusion speed 10 ml/h and changed the speed every 30 min. There were 40 cases in observation 2 group who accepted the beginning speed 20 ml/h and changed speed every 30 min. The anaphylaxis in the three groups were observed and statistically analyzed. Results The anaphylaxis rates were 9. 7% in the observation 1 group and 25. 7% in the observation 2 group and 30. 9% in the control group. Compared three groups, the differences of anaphylaxis incidence were statistically significant between observation 1 group and the observation 2 group, control group (P<0. 05). The difference of anaphylxis incidences were not statistically significant between the observation 2 group and the control group (P>0. 05). Conclusions For first Rituximab transfusion, the beginning of 10 ml/h transfusion speed and changing speed every 30 min can effectively minimize anaphylxis incidence caused by Rituximab transfusion.

Objective To develop a quantitative immunohistochemistry assay for duck hepatitis B virus core antigen (DHB-cAg)in duck liver tissue.Methods By comparison with no repair antigen and repair antigen with high pressure,microwave and trypsin,the best solution of antigen retrieval was determined.By optimizing the parameter of image acquisition and de-ducting blank area,mean density of yellow areas was calculated using Image-Pro Plus 6.0 software.Using the assay devel-oped to determine the level of DHBcAg in liver tissue from duck infected by DHBV,anti-DHBV activity of DHBcMAb-TAT PTD conj ugate was examined.Results SABC method with no repair antigen was selected,which was better than other methods.DHBcAg expression in duck liver tissue could be objectively and accurately quantified by setting Image-Pro Plus 6.0 software parameters and calculating mean density of yellow areas.By comparison with the differences between mean densityat baseline of treatment and end of treatment,it was showed that DHBcMAb-TATPTD conjugate treatment dose-de-pendently reduced the levels of DHBcAg in liver tissue,which show that the assay developed could effectively evaluate the anti-DHBV activity of agent.Conclusion The immunohistochemistry assay developed in this study can objectively and accu-rately evaluate the level of DHBcAg in duck liver tissue.