Neurological disorders such as post-stroke hemiplegia, spinal cord injury, and Parkinson disease represent a major global health burden. Brain-computer interface (BCI), which creates direct communication pathways between the nervous system and external devices, offers a promising strategy for functional restoration. The long-term efficacy of such BCI fundamentally depends on the performance of biomaterials at the neural interface. Ideal materials must concurrently satisfy biocompatibility, electrical conductivity, enduring chemical stability, and mechanical compatibility with brain tissue. This review systematically outlines the application of conductive polymers, inorganic nanomaterials, natural biomaterials, and composites in BCI, with a focus on how advanced designs, such as bionic and encapsulated electrodes, improve signal fidelity and surgical feasibility through structural innovation. It further summarizes key material-modification techniques and analyzes the complex foreign-body response orchestrated by microglia, astrocytes, and peripheral immune cells. Finally, it provides insights into future research directions and clinical translation of BCI-based neurorehabilitation, while highlighting critical challenges including long-term biosafety and the establishment of standardized evaluation frameworks, aiming to bridge the gap between laboratory innovation and effective clinical deployment.

Liver diseases are a group of complex clinical conditions caused by various factors and can lead to hepatocyte damage and liver dysfunction， posing a serious threat to human health. The cyclic GMP-AMP synthase （cGAS）-stimulator of interferon genes （STING） signaling pathway plays a key regulatory role in the course of liver diseases and is involved in the development， progression， and treatment of various diseases such as viral hepatitis， nonalcoholic fatty liver disease， liver fibrosis， and liver cancer. This article reviews the regulatory mechanisms of the cGAS-STING signaling pathway in processes such as inflammation， autophagy， antiviral response， and oxidative stress， analyzes its molecular function in liver diseases， and explores its application prospect as a potential target for the treatment of liver diseases， in order to provide a theoretical basis for developing novel therapeutic strategies for liver diseases.

OBJECTIVE To analyze the correlation of the peak blood concentration （cmax） of compound sulfamethoxazole （TMP/SMZ） and its metabolite N-acetyl sulfamethoxazole （NSMZ） with clinical efficacy and adverse reactions in critically ill patients. METHODS The data of critically ill patients treated with TMP/SMZ in various ICU of Hainan General Hospital from December 2023 to January 2025 were retrospectively collected. The patients were divided into success group and failure group based on the treatment outcome. Simple linear regression and Spearman correlation analysis were used to analyze the correlation of TMP cmax， SMZ cmax， and NSMZ cmax with clinical efficacy and adverse reactions. The receiver operating characteristic curve （ROC） was used to determine the cutoff values of cmax for predicting the occurrence of adverse reactions. RESULTS Among critically ill patients with an acute physiology and chronic health evaluation Ⅱ （APACHE-Ⅱ） ≥15 points 24 h of check-in at ICU， SMZ cmax of success group was significantly higher than failure group （P＜0.05）. The daily total dose of TMP/SMZ was positively correlated with TMP cmax and SMZ cmax（ P＜0.05）. TMP cmax was significantly correlated with hepatotoxicity and nephrotoxicity， SMZ cmax with hepatotoxicity， and NSMZ cmax with nephrotoxicity （P＜0.05）. The cutoff values of TMP cmax for predicting nephrotoxicity and hepatotoxicity were 7.25 μg/mL and 6.63 μg/mL， respectively. The cutoff value of SMZ cmax for predicting hepatotoxicity was 138.00 μg/mL， and that of NSMZ cmax for predicting nephrotoxicity was 60.76 μg/mL. CONCLUSIONS Among critically ill patients with an APACHE-Ⅱ ≥15 points 24 h of check-in at ICU， SMZ cmax is associated with treatment success. Hepatotoxicity risk significantly increases when TMP cmax ≥6.63 μg/mL or SMZ cmax ≥138.00 μg/mL； nephrotoxicity risk significantly increases when TMP cmax ≥7.25 μg/mL or NSMZ cmax ≥60.76 μg/mL.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

OBJECTIVES: To investigate the mechanism of DDX17 for regulating proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) during the development of pulmonary hypertension (PH). METHODS: In murine PASMCs cultured under normoxic or hypoxic conditions, the effects of transfection with si-Ddx17 and insulin treatment, alone or in combination, on cell proliferation and migration were evaluated using Ki-67 immunofluorescence staining, scratch assay and Transwell assay. Western Blotting was performed to detect the changes in protein expression levels of DDX17, 4EBP1, S6, p-4EBP1, and p-S6. In a mouse model of PH induced by intraperitoneal injection of monocrotaline (MCT), the changes in pulmonary vasculature were examined using HE staining following tail vein injection of AD-Ddx17i. RESULTS: The PASMCs in hypoxic culture exhibited significantly enhanced cell proliferation and migration and protein expressions of p-4EBP1 and p-S6, and these changes were obviously reversed by transfection with si-Ddx17. Treatment with insulin significantly attenuated the effect of si-Ddx17 against hypoxic exposure-induced changes in PASMCs. In the mouse model of MCT-induced PH, transfection with AD-Ddx17i obviously alleviated pulmonary vascular stenosis and intimal hyperplasia. CONCLUSIONS The expression of DDX17 is elevated in hypoxia-induced PASMCs and PH mice, and silencing DDX17 significantly inhibits PASMC proliferation and migration in vitro and pulmonary vascular remodeling in PH mice by reducing mTORC1 activity.
Animals ; Cell Proliferation ; Cell Movement ; DEAD-box RNA Helicases/metabolism* ; Myocytes, Smooth Muscle/metabolism* ; Mice ; Pulmonary Artery/cytology* ; Hypertension, Pulmonary/metabolism* ; Mechanistic Target of Rapamycin Complex 1 ; Cells, Cultured ; Muscle, Smooth, Vascular/cytology*

Biosensors have become powerful tools for real-time monitoring of specific small molecules and precise control of gene expression in biological systems. High-throughput sensors for 1, 4-butanediamine biosynthesis can greatly improve the screening efficiency of high-yielding 1, 4-butanediamine strains. However, the strategies for adapting the characteristics of biosensors are still rarely studied, which limits the applicability of 1, 4-butanediamine biosensors. In this paper, we propose the development of a 1, 4-butanediamine biosensor based on the transcriptional regulator PuuR, whose homologous operator puuO is installed in the constitutive promoter P_gapA of Escherichia coli to control the expression of the downstream superfolder green fluorescent protein (sfGFP) as the reporter protein. Finally, the biosensor showed a stable linear relationship between the GFP/OD₆₀₀ value and the concentration of 1, 4-butanediamine when the concentration of 1, 4-butanediamine was 0-50 mmol/L. The promoters with different strengths in the E. coli genome were used to modify the 1, 4-butanediamine biosensor, and the functional properties of the PuuR-based 1, 4-butanediamine biosensor were explored and improved, which laid the groundwork for high-throughput screening of engineered strains highly producing 1, 4-butanediamine.
Biosensing Techniques/methods* ; Escherichia coli/metabolism* ; Promoter Regions, Genetic/genetics* ; Green Fluorescent Proteins/metabolism* ; Transcription Factors/genetics* ; Escherichia coli Proteins/genetics* ; Diamines/metabolism* ; Gene Expression Regulation, Bacterial

Objective To develop and validate an early venous thromboembolism(VTE)risk assessment scale for emergency observation patients.Methods ① Based on the characteristics of emergency observation patients,the Delphi expert consultation method and literature review were used to determine scale items and construct a scoring system.②The newly developed VTE scale and its scoring system were analyzed for reliability and validity.③Primary application:collect non acute traumatic observation and rescue patients admitted to Zhejiang Hospital from June 2022 to June 2023 as the research subjects.Patients were divided into survival and non-survival groups based on 28-day outcomes.Differences in VTE scores between the two groups using the new scale,Caprini,and Padua models were compared.The optimal cut-off point was determined using the receiver operator characteristic curve(ROC curve),according to the optimal cut-off value of the new scale score,patients were divided into two groups,and Kaplan-Meier survival curves were used to analyze the 28-day cumulative survival of the two groups of patients.Results ①The preliminary version of the early VTE risk assessment scale for emergency observation patients was developed,comprising 8 items:age,pre examination triage level,underlying diseases,D-dimer levels,activities of daily living(ADL)assessment,coagulation-related indicators,anticoagulants and(or)antiplatelet drugs use,and unhealthy habits.② A total of 121 emergency observation patients were included in the analysis.The test-retest reliability correlation coefficient(R)of the new scale was 0.945(>0.850),split-half reliability was 0.741(>0.700),and Cronbach'sαcoefficient was>0.700.KMO value was 0.715(>0.700),and Bartlett's sphericity test yieldedχ2=167.079,P<0.001,confirming the suitability of the scale for factor analysis.Three factors were identified:basic information,initial assessment,and blood test indicators.Pearson correlation analysis showed the correlation coefficients between the new scale and the Caprini and Padua scores were 0.842 and 0.307,respectively,both P<0.01.③Area under the curve(AUC)of the new scale was 0.566,95%confidence interval(95%CI)was 0.444-0.688,with an optimal diagnostic cut-off value of 13.5 points based on the maximum Youden index.The results of the Kaplan-Meier regression indicated that survival analysis using the 13.5-point cut-off revealed that patients with scores≥13.5 had significantly lower 28-day survival rates than those with scores<13.5(Log-Rank test:χ2=5.609,P=0.018).④The survival group had significantly lower scores than the non-survival group across all scales(new score:10.06±2.84 vs.12.69±3.06,Caprini model:7.22±2.48 vs.9.41±2.64,Padua model:2.91±1.97 vs.4.59±1.07,all P<0.05).Conclusion The early VTE risk assessment scale for emergency observation patients was successfully developed,demonstrating good reliability and validity through statistical analysis.The new scale effectively predicts disease severity and prognosis in emergency observation patients.

Objective:To investigate the demand of rural elderly in Shenyang for integrated medical and elderly care service model,providing references for the improvement and development of rural integrated medical and elderly care services in Shenyang.Methods:Elderly individuals from selected rural areas in Shenyang were randomly sampled as study subjects.A questionnaire survey was conducted to analyze their basic demographics,satisfaction with current elderly care services,and demand levels for integrated medical and elderly care programs.Multiple linear regression analysis was used to identify factors influencing the demand for integrated medical and elderly care services among rural elderly.Results:The satisfaction scores of the rural elderly for medical care,cultural and recreational activities,spiritual comfort,and daily living assistance were 3.86±1.37,3.67±1.36,3.49±1.45,and 3.15±1.58,respectively.Multiple linear regression analysis showed that gender,monthly family income,occupation,insurance situation,living situation,and self-care ability were factors influencing the demand for integrated medical and elderly care services(P＜0.05).Conclusion:The demand for integrated medical and elderly care service model among rural elderly is affected by multiple factors.

Objective To investigate the diagnostic value of masseter muscle thickness fraction(MMTF)measured by ultrasound for the occurrence of dysphagia in patients with Parkinson's disease(PD).Methods A total of 100 patients were selected as the study group,and another 50 healthy individuals who received medical checkups with matched age,gender and body mass index(BMI)in our hospital during the same period were selected as the control group.The demographic data and disease characteristics of PD patients were recorded,and patients were divided into the dysphagia group(n=34)and the non-dysphagia group(n=66)according to the occurrence of dysphagia.The demographic data,and disease characteristics such as Hoehn-Yahr(H&Y)stage,Unified Parkinson's Disease Rating Scale(UPDRS)Ⅲ score,levodopa equivalent daily dose(LEDD)and MMT-related parameters measured by ultrasound were compared between the two groups.The indicators with P＜0.05 in univariate analysis were used as independent variables,and the influencing factors of dysphagia in patients with PD were investigated by binary Logistic regression analysis.The diagnostic efficacy of each index for dysphagia in patients with PD was evaluated by constructing receiver operating characteristic(ROC)curves,and the area under the curve(AUC)was calculated.Results The MMT during forceful biting and MMTF were lower in the study group than those in the control group(all P＜0.05).Compared with the non-dysphagia group,the dysphagia group was older and had higher H&Y stage and UPDRS III scores(all P＜0.05).The MMT during forceful biting and MMTF in the dysphagia group were lower than those in the non-dysphagia group(all P＜0.05).Multivariate Logistic regression analysis showed that increased UPDRSⅢ score was the risk factor for dysphagia in patients with PD,and increased MMT during forceful biting and MMTF were protective factors.The ROC curve analysis indicated that the AUC(95%CI)of UPDRS Ⅲ score,MMT during forceful biting and MMTF for diagnosing dysphagia in patients with PD were 0.714(0.615-0.800),0.744(0.647-0.826)and 0.888(0.809-0.942),respectively.The AUC of MMTF for diagnosing dysphagia in patients with PD was higher than those of UPDRS Ⅲscores and MMT during forceful biting(Z values were 2.611 and 2.208,respectively,P＜0.05).Conclusion MMTF is an independent influencing factor for dysphagia in patients with PD and can be used as a screening indicator for dysphagic patients.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.