ObjectiveTo prepare triptolide-Chuanxiong Rhizoma extract ethanol transfersomes（TP-CX@TESs）， conduct its quality evaluation， and investigate its in vitro anti-inflammatory efficacy and the underlying mechanisms. MethodsTP-CX@TESs was prepared via the ultrasonic injection method. With encapsulation efficiency and particle size as evaluation indicators， Box-Behnken design-response surface methodology（BBD-RSM） was employed to optimize the formulation process. The TP-CX@TESs prepared under the optimal process was characterized and evaluated for in vitro transdermal performance. A lipopolysaccharide（LPS）-induced RAW264.7 cell inflammation model was established. After 24 h of drug intervention， the levels of inflammatory factors such as nitric oxide（NO）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α） in the cell supernatant were detected. Western blot was used to determine the protein expression levels of Janus kinase 2（JAK2）， signal transducer and activator of transcription 3（STAT3）， and α7 nicotinic acetylcholine receptor（α7nAChR）， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was applied to measure the mRNA expression levels of JAK2， STAT3， the encoding gene of α7nAChR（CHRNA7）， and nuclear transcription factor-κB（NF-κB）. ResultsResults of BBD-RSM showed that the optimal formulation for preparing TP-CX@TESs was as follows：egg yolk lecithin content of 2.3%， ethanol volume fraction of 30%， and ratio of polysorbate-80 to egg yolk lecithin of 2∶5. Microscopic characterization revealed that TP-CX@TESs exhibited a spherical-like structure with a particle size of （105.60±3.85） nm， a polydispersity index of 0.19±0.03， and a Zeta potential of （-15.89±0.98） mV. The encapsulation efficiencies of triptolide， ferulic acid， and ligustilide were （76.88±4.40）%， （78.84±4.40）%， and （65.88±0.06）%， respectively. Both in vitro release and transdermal penetration of triptolide， ferulic acid， and ligustilide in TP-CX@TESs all followed the first-order kinetic model， showing a certain sustained-release property. Experimental results in RAW264.7 cells indicated that TP-CX@TESs significantly inhibited the release of NO， TNF-α， and IL-6（P<0.01）， remarkably upregulated the protein expression levels of STAT3 and α7nAChR（P<0.01）， increased the mRNA expression level of CHRNA7， and significantly downregulated the mRNA expression level of NF-κB（P<0.05， P<0.01）. ConclusionThe optimized formulation process of TP-CX@TESs is simple and feasible， along with favorable in vitro release property， good transdermal permeability， and excellent in vitro anti-inflammatory activity， the mechanism is related to the inhibition of NF-κB.

ObjectiveTo prepare triptolide-Chuanxiong Rhizoma extract ethanol transfersomes（TP-CX@TESs）， conduct its quality evaluation， and investigate its in vitro anti-inflammatory efficacy and the underlying mechanisms. MethodsTP-CX@TESs was prepared via the ultrasonic injection method. With encapsulation efficiency and particle size as evaluation indicators， Box-Behnken design-response surface methodology（BBD-RSM） was employed to optimize the formulation process. The TP-CX@TESs prepared under the optimal process was characterized and evaluated for in vitro transdermal performance. A lipopolysaccharide（LPS）-induced RAW264.7 cell inflammation model was established. After 24 h of drug intervention， the levels of inflammatory factors such as nitric oxide（NO）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α） in the cell supernatant were detected. Western blot was used to determine the protein expression levels of Janus kinase 2（JAK2）， signal transducer and activator of transcription 3（STAT3）， and α7 nicotinic acetylcholine receptor（α7nAChR）， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was applied to measure the mRNA expression levels of JAK2， STAT3， the encoding gene of α7nAChR（CHRNA7）， and nuclear transcription factor-κB（NF-κB）. ResultsResults of BBD-RSM showed that the optimal formulation for preparing TP-CX@TESs was as follows：egg yolk lecithin content of 2.3%， ethanol volume fraction of 30%， and ratio of polysorbate-80 to egg yolk lecithin of 2∶5. Microscopic characterization revealed that TP-CX@TESs exhibited a spherical-like structure with a particle size of （105.60±3.85） nm， a polydispersity index of 0.19±0.03， and a Zeta potential of （-15.89±0.98） mV. The encapsulation efficiencies of triptolide， ferulic acid， and ligustilide were （76.88±4.40）%， （78.84±4.40）%， and （65.88±0.06）%， respectively. Both in vitro release and transdermal penetration of triptolide， ferulic acid， and ligustilide in TP-CX@TESs all followed the first-order kinetic model， showing a certain sustained-release property. Experimental results in RAW264.7 cells indicated that TP-CX@TESs significantly inhibited the release of NO， TNF-α， and IL-6（P<0.01）， remarkably upregulated the protein expression levels of STAT3 and α7nAChR（P<0.01）， increased the mRNA expression level of CHRNA7， and significantly downregulated the mRNA expression level of NF-κB（P<0.05， P<0.01）. ConclusionThe optimized formulation process of TP-CX@TESs is simple and feasible， along with favorable in vitro release property， good transdermal permeability， and excellent in vitro anti-inflammatory activity， the mechanism is related to the inhibition of NF-κB.

Objective To investigate the effects of dapagliflozin on inflammatory factors and prognosis in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI). Methods In a randomized, double-blind trial, 146 patients with T2DM and AMI (within 7 days of onset) were divided into dapagliflozin (dapagliflozin 10 mg/d combining AMI standard therapy) and control (AMI standard therapy) groups, and were followed up for 12 months. Serum levels of interleukin-1β (IL-1β), IL-6, high-sensitivity C reactive protein (hs-CRP) at baseline, 1, 3, 6, and 12 months, and left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP), and major adverse cardiovascular events (MACE) rate at 12 months were compared between the two groups. Kaplan-Meier curves were used to analyze the cumulative incidences of MACE in the two groups. Results Three patients were withdrawn or dropped out. At 12 months, IL-1β, IL-6, and hs-CRP levels were significantly lower in dapagliflozin group (n＝71) than those in control group (n＝72, P＜0.01), approaching normal levels. Compared with the control group, LVEF was higher (P＜0.01), BNP was lower (P＜0.01), MACE incidence was lower (P＝0.047) in dapagliflozin group at 12 months. Generalized linear mixed models showed significant group-time interactions in IL-1β, IL-6, and hs-CRP (P＜0.001), and these factors declined faster in the dapagliflozin group. Kaplan-Meier curve showed the cumulative incidences of MACE and heart failure were lower in dapagliflozin group than those in non-dapagliflozin group (P＜0.05). Conclusions For patients with T2DM patients and AMI, dapagliflozin has good anti-inflammatory and cardioprotective effects.

BACKGROUND:Exosomes derived from mesenchymal stem cells play pivotal roles in cell communication and epigenetic regulation due to their low immunogenicity and targeted delivery effects,and have been clinically applied in the treatment of various diseases.OBJECTIVE:To review the isolation,purification,identification methods,and application progress of mesenchymal stem cell-derived exosomes,and to facilitate the development of large-scale preparation techniques and clinical translation of mesenchymal stem cell-derived exosomes.METHODS:The Chinese search terms"exosome,mesenchymal stem cells,isolation,purification,characterization,clinical application"and the English search terms"exosome,extracellular vesicles,mesenchymal stem cells,isolation,characterization,application"were used to search the literature published before September 2024 in CNKI,PubMed,and Web of Science databases.Articles with poor relevance to the topic,outdated,or duplicated content were excluded,and finally,109 articles were included for review.RESULTS AND CONCLUSION:(1)This paper reviews recent methods for isolating and purifying exosomes,comparing the characteristics of ultracentrifugation,ultrafiltration,size-exclusion chromatography,polymer precipitation,immunoaffinity,microfluidic methods,and other novel approaches based on their underlying principles.(2)Methods for identifying exosomes can be categorized into physical and biochemical analyses,characterizing exosomes based on their shape,size,and characteristic proteins.(3)Mesenchymal stem cell-derived exosomes have broad applications in multiple fields such as medical aesthetics,wound repair,and cancer treatment,due to their immune-regulatory properties and ability to cross biological barriers.(4)The clinical translation of exosomes faces challenges due to their complex structure,lack of universal isolation techniques,and poor stability,making it difficult to achieve in a short period of time.

BACKGROUND:Exosomes derived from mesenchymal stem cells play pivotal roles in cell communication and epigenetic regulation due to their low immunogenicity and targeted delivery effects,and have been clinically applied in the treatment of various diseases.OBJECTIVE:To review the isolation,purification,identification methods,and application progress of mesenchymal stem cell-derived exosomes,and to facilitate the development of large-scale preparation techniques and clinical translation of mesenchymal stem cell-derived exosomes.METHODS:The Chinese search terms"exosome,mesenchymal stem cells,isolation,purification,characterization,clinical application"and the English search terms"exosome,extracellular vesicles,mesenchymal stem cells,isolation,characterization,application"were used to search the literature published before September 2024 in CNKI,PubMed,and Web of Science databases.Articles with poor relevance to the topic,outdated,or duplicated content were excluded,and finally,109 articles were included for review.RESULTS AND CONCLUSION:(1)This paper reviews recent methods for isolating and purifying exosomes,comparing the characteristics of ultracentrifugation,ultrafiltration,size-exclusion chromatography,polymer precipitation,immunoaffinity,microfluidic methods,and other novel approaches based on their underlying principles.(2)Methods for identifying exosomes can be categorized into physical and biochemical analyses,characterizing exosomes based on their shape,size,and characteristic proteins.(3)Mesenchymal stem cell-derived exosomes have broad applications in multiple fields such as medical aesthetics,wound repair,and cancer treatment,due to their immune-regulatory properties and ability to cross biological barriers.(4)The clinical translation of exosomes faces challenges due to their complex structure,lack of universal isolation techniques,and poor stability,making it difficult to achieve in a short period of time.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

OBJECTIVE: To explore the effects and mechanisms of the C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4) signaling axis on apoptosis and autophagy in SH-SY5Y neuronal cells subjected to oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro. METHODS: SH-SY5Y cells were divided into the following groups: OGD/R group and non-OGD/R group, with the OGD/R group subjected to OGD/R modeling and the non-OGD/R group receiving no treatment. Cells were also divided into CXCL12⁺ and CXCL12^- groups; the CXCL12⁺ group received 0.1 mg/L exogenous recombinant CXCL12 (rhCXCL12) at reoxygenation, while the CXCL12^- group did not. Another set of cells was divided into CXCL12+AMD3100 and CXCL12 groups; the CXCL12+AMD3100 group was pretreated with 2.5 mg/L AMD3100, a CXCR4 inhibitor, for 2 hours before OGD/R and received both 2.5 mg/L AMD3100 and 0.1 mg/L rhCXCL12 at reoxygenation, whereas the CXCL12 group received rhCXCL12 only. Additionally, cells were divided into small interfering RNA CXCR4 (siCXCR4) and small interfering RNA negative control (siNC) groups; the siCXCR4 group underwent CXCR4 knockdown before OGD/R modeling and received 0.1 mg/L rhCXCL12 at reoxygenation, while the siNC group, transfected with a negative control, received the same treatment. Protein expression of autophagy-related 16 (ATG16), microtubule-associated protein 1 light chain 3 (LC3), aquaporin-3 (AQP3), and CXCR4 was detected by Western blotting. Apoptosis rate and CXCR4 expression were measured by flow cytometry. RESULTS: Compared with the non-OGD/R group, the OGD/R group showed a significantly increased apoptosis rate and markedly decreased protein expression levels of ATG16, LC3, AQP3, and CXCR4 (all P < 0.05). CXCR4 fluorescent expression was also significantly reduced, suggesting that OGD/R simultaneously affects neuronal apoptosis and autophagy while inhibiting CXCR4 and AQP3 expression in SH-SY5Y cells. Compared with the CXCL12^- group, the CXCL12⁺ group exhibited no significant change in apoptosis rate but demonstrated significantly increased protein expression of ATG16, LC3, and AQP3 (ATG16/GAPDH: 1.21±0.10 vs. 1.00±0.00; LC3/β-actin: 1.22±0.10 vs. 1.00±0.00; AQP3/β-actin: 1.26±0.04 vs. 1.00±0.00; all P < 0.05). CXCR4 expression was also significantly enhanced (fluorescence intensity: 1.19±0.05 vs. 1.00±0.00, P < 0.05), indicating that CXCL12 may promote autophagy in OGD/R-injured SH-SY5Y cells via the CXCR4/AQP3 pathway. Compared with the CXCL12 group, the CXCL12+AMD3100 group showed no significant difference in apoptosis rate but significantly lower protein levels of ATG16 and LC3 (ATG16/GAPDH: 0.75±0.08 vs. 1.00±0.00; LC3/GAPDH: 0.86±0.07 vs. 1.00±0.00; both P < 0.05), suggesting that CXCL12 induces autophagy in OGD/R SH-SY5Y cells through CXCR4. Compared with the siNC group, the siCXCR4 group showed no significant change in apoptosis rate but significantly reduced protein expression of ATG16, LC3, AQP3, and CXCR4 (ATG16/GAPDH: 0.76±0.06 vs. 1.00±0.00; LC3/GAPDH: 0.79±0.11 vs. 1.00±0.00; AQP3/GAPDH: 0.81±0.05 vs. 1.00±0.00; CXCR4/GAPDH: 0.86±0.04 vs. 1.00±0.00; all P < 0.05), indicating that CXCR4 knockdown suppresses OGD/R-induced autophagy in SH-SY5Y cells likely via AQP3. CONCLUSIONS The CXCL12/CXCR4 signaling axis can regulate OGD/R-induced autophagy in SH-SY5Y cells through AQP3 without affecting apoptosis, indicating a role for this pathway in neuronal autophagy during cerebral ischemia/reperfusion injury.
Humans ; Receptors, CXCR4/metabolism* ; Chemokine CXCL12/metabolism* ; Autophagy ; Glucose/metabolism* ; Apoptosis ; Neurons/cytology* ; Oxygen/metabolism* ; Signal Transduction ; Cell Line, Tumor ; Cell Hypoxia ; Benzylamines ; Cyclams

ObjectiveTo investigate the value of prealbumin-to-total bilirubin （PA/TBil） ratio on admission in predicting 90-day mortality or liver transplantation in patients with HBV-related acute-on-chronic liver failure （HBV-ACLF）， as well as the effect of its combination with Model for End-Stage Liver Disease （MELD） score on the predictive performance for short-term prognosis. MethodsA retrospective analysis was performed for the clinical data of 216 HBV-ACLF patients who were admitted to Department of Infectious Diseases in the First Affiliated Hospital of Soochow University from April 2020 to May 2025， and the patients were followed up for 3 months. According to the outcome， the patients were divided into survival group with 104 patients and death/transplantation group with 112 patients. The Kolmogorov-Smirnov test was used to check whether the continuous data was in accordance with the normal distribution； the two-independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups. The chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate binary Logistic regression analyses were used to investigate the influencing factors for prognosis， and the receiver operating characteristic （ROC） curve was used to analyze the performance of each indicator in predicting the prognosis of ACLF. The area under the ROC curve （AUC） was calculated， and the Delong test was used for comparison of AUC. ResultsA total of 216 patients were enrolled in this study， with a 90-day survival rate of 48.15% （104/216）. Compared with the death/transplantation group， the survival group had significantly higher platelet count， lymphocyte count， albumin， and PA/TBil ratio （all P<0.05） and significantly lower age， white blood cell count， neutrophil count， prothrombin time， international normalized ratio， aspartate aminotransferase， total bilirubin， creatinine， and MELD score （all P<0.05）. The multivariate Logistic regression analysis showed that age （odds ratio ［OR］=1.05， 95% confidence interval ［CI］： 1.02 — 1.09， P<0.001）， PA/TBil ratio （OR=0.16， 95%CI： 0.05 — 0.46， P<0.001）， and MELD score （OR=1.09， 95%CI： 1.01 — 1.17， P=0.024） were independent influencing factors for 90-day prognosis in HBV-ACLF patients. PA/TBil ratio and MELD score used alone or in combination had an AUC of 0.760， 0.779， and 0.811， respectively， in predicting the prognosis of HBV-ACLF patients， and PA/TBil ratio combined with MELD score had a better AUC than PA/TBil ratio or MELD score used alone （Z=-2.058 and 2.017， both P<0.05）. ConclusionBoth serum PA/TBil ratio and MELD score can effectively predict the prognosis of patients with HBV-ACLF， and a combination of the two indicators had a better predictive performance than MELD score alone， which provides an important reference for clinical risk stratification management and timely intervention.

Objective:To explore the influence of artificial intelligence(AI)-assisted compressive sensing(ACS)technique with different acceleration factors on the image quality and scan time of three dimensional time-of-flight magnetic resonance angiography(3D-TOF-MRA)for brain.Methods:Thirty participants who underwent brain magnetic resonance imaging(MRI)at Tongzhou Branch of Beijing Friendship Hospital were recruited.All subjects underwent imaging scans about four different parameters:a non-accelerated technique(control group),ACS technique integrated with acceleration factor of 4.03(ACS4 group),ACS technique integrated with acceleration factor of 5.02(ACS5 group),and ACS technique integrated with acceleration factor of 6.06(ACS6 group).The image clarity,ranking of imaging capabilities of distal branch blood vessels and the ratio of pseudo-stenosis were qualitatively analyzed.The signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),edge sharpness,and scan time were quantitatively analyzed.Results:There was not difference in vessel clarity among three ACS groups at the proximal and middle intracranial segments.For distal segments of blood vessel,the ACS4 group[3.0(3.0,3.0)]and ACS5 group[3.0(3.0,3.0)]were better than ACS6[2.5(2.0,3.0)](q=29.800,27.500,P<0.05).The imaging capabilities of distal-branch vessel of ACS4 group and ACS5 group were better than ACS6 group.There was no stenosis in the proximal and middle segments of the images of the three ACS group,and there were no stenosis in the images of distal vessels of ACS4 group and ACS5 group.A total of 5 cases were pseudo-stenosis in the distal vessels of ACS6 group.Compared with the control group,the incidence of pseudo-stenosis in the distal vessels of ACS6 group was 16.7%.The SNR and CNR values of quantitative analysis for proximal vessels in ACS6 group were higher than them in ACS4 group(q=27.800,26.200,P<0.05),and there was not significant difference in them among ACS4 group,ACS6 group and ACS5 group(P>0.05).The differences of SNR and CNR values in the middle and distal segments of blood vessels among different groups were not significant(P>0.05).There was not significant difference in the edge sharpness of blood vessels among ACS4 group,ACS5 group,and ACS6 group(P>0.05),while all of them were higher than those of control group,and the differences were significant(q=48.150,53.367,44.883,P<0.001).Compared with control group,the scan-time of ACS4 group was reduced by 55.19%,and that of ACS5 group was reduced by 64.07%,and that of ACS6 group was reduced by 70%.Conclusion:ACS technique can accelerate the imaging speed of brain 3D-TOF-MRA and ensure image quality.It is clinically recommended to set the ACS acceleration factor as 5.02 to undergo brain 3D-TOF-MRA scans.