Objective To explore the effects and mechanisms of human umbilical cord mesenchymal stem cell (HUC-MSC)-derived exosomes (Exo) pretreated with Huangkui capsules on renal ischemia-reperfusion injury (IRI). Methods HUC-MSCs were cultured in media containing different concentrations of Huangkui capsules for 24 hours to determine cell viability and select an appropriate concentration for subsequent experiments. HUC-MSCs were pretreated with 50 μg/mL Huangkui capsules for 24 hours, and Exo were extracted using an exosome extraction kit. The morphology was observed under a transmission electron microscope, particle size was measured by nanoparticle tracking analysis, and the expression of exosomal membrane surface marker proteins was detected by Western blot. Human renal tubular epithelial cells (HK-2 cells) were randomly divided into hypoxia/reoxygenation group (M group), hypoxia/reoxygenation + Exo group (E group), and hypoxia/reoxygenation + Huangkui capsules pretreated Exo group (H group). Western blotting was used to measure the expression of endoplasmic reticulum stress (ERS)-related proteins, and real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to measure the expression of ERS-related gene messenger RNA (mRNA). Mice were randomly divided into sham operation group (Sham group), ischemia-reperfusion group (I/R group), ischemia-reperfusion + Exo group (E group), and ischemia-reperfusion + Huangkui capsules pretreated Exo group (H group). Renal histological assessment, serum creatinine (Scr), blood urea nitrogen (BUN) measurement and inflammatory factor detection were performed 24 hours later. Results Both Exo and Huangkui capsules prereated Exo had a bilayer membrane structure and a cup-shaped morphology; their average particle sizes were 116.8 nm and 81.3 nm, respectively. Both expressed CD9, CD63, TSG101. Compared with the M group, the E group had decreased relative expression of transcription factor 6 (ATF6) and protein kinase R-like endoplasmic reticulum kinase (PERK) proteins, increased mRNA relative expression, increased relative expression of C/EBP homologous protein (CHOP) protein, and decreased mRNA relative expression. Compared with the E group, the H group had decreased relative expression of ATF6, PERK, CHOP proteins, and decreased mRNA relative expression of ATF6 and PERK (all P<0.05). Animal experimental results showed that compared with the Sham group, the I/R group had increased renal tubular injury scores, Scr, BUN, interleukin (IL)-1β, IL-10, IL-18, tumor necrosis factor (TNF)-α levels. Compared with the I/R group, the E and H groups had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels. Compared with the E group, the H group had decreased renal tubular injury scores and Scr, BUN, IL-1β, IL-10, IL-18, TNF-α levels (all P<0.05). Conclusions Huangkui capsules pretreatment HUC-MSC-derived Exo may alleviate renal IRI by inhibiting ERS.

Objective:To evaluate the feasibility of transjugular transcatheter tricuspid valve replacement (TTVR) using the LuX-Valve Plus system (Ningbo Jenscare Scientific, China) for the treatment of severe tricuspid regurgitation in real-world clinical settings.Methods:This prospective study enrolled 81 patients with severe ricuspid regurgitation (≥3+) who underwent TTVR with the LuX-Valve Plus system at the Department of Cardiology, West China Hospital of Sichuan University between May 2022 and March 2024. Among them, 44 patients were from a compassionate-use study, and 37 were from two premarket clinical trials. Baseline clinical data, preprocedural imaging, procedural outcomes, and postprocedural follow-up data were collected. The primary endpoint events included device success, procedural success, and 30 d composite adverse events.Results:The age of the cohort was (74.5±7.8) years, with 54 females (67%). Device success and procedural success rates were both 90% (73/81). Post-procedural tricuspid regurgitation improved, with a 6% (5/81) incidence of moderate-to-severe paravalvular leakage. The rate of permanent pacemaker implantation was 12% (10/81), of which 5% (4/81) had pre-existing indications for pacemaker implantation. Major bleeding events occurred in 10% (8/81) of patients, and the 30 d composite endpoint rate was 25% (20/81).Conclusion:TTVR using the LuX-Valve Plus system demonstrates promising feasibility for high-risk surgical patients with severe tricuspid regurgitation, effectively reducing or eliminating regurgitation with acceptable safety. However, challenges remain in reducing risks of major adverse events, including permanent pacemaker implantation and severe bleeding.

Objective:To develop a deep learning-based segmentation model MT-UNet to automatically segment bone metastases and benign bone lesions in bone scintigraphy with SPECT/CT.Methods:A total of 93 patients (48 males and 45 females, age 28-84 years) who underwent bone SPECT/CT in the Department of Nuclear Medicine, General Hospital of Northern Theater Command from June 2023 to December 2023 were enrolled retrospectively in this study, with a total of 184 bone lesions (94 benign lesions and 90 metastatic tumors). The MT-UNet was employed to segment bone lesions in SPECT, CT and SPECT/CT images respectively. Comparative analysis with 8 segmentation models was performed. The training set and validation set were divided by using 5-fold cross-validation and transfer learning was introduced to further enhance the robustness of the model. An additional cohort of 22 patients (15 males and 7 females, age 37-87 years) who received bone SPECT/CT in the Department of Nuclear Medicine, General Hospital of Northern Theater Command from April 2023 to May 2023 were included, comprising 40 bone lesions (22 benign lesions and 18 metastatic tumors) as the test set of MT-UNet. Segmentation performance of different models was assessed using accuracy, sensitivity, specificity, AUC, intersection over union and Dice similarity coefficient (DSC). Delong test was used to compare the segmentation efficacy among different models in the test set.Results:In the validation set, MT-UNet demonstrated DSC of 0.940, 0.962, and 0.963 for SPECT, CT, and SPECT/CT bone lesion segmentation, respectively, which were outperformed other models. Following transfer learning implementation, the SPECT/CT model′s DSC was improved to 0.984. In the test set, MT-UNet maintained comparable segmentation performance to the validation set, with significant AUC differences among the three models ( Z values: from -15.42 to -9.27, all P<0.01). Compared with conventional image interpretation, MT-UNet-based segmentation reduced physician interpretation time from 164min to 102min. Conclusion:MT-UNet has shown good performance in automatic segmentation of bone metastases and benign bone lesions, and is expected to become an important part of SPECT/CT image intelligent diagnosis system for bone metastases.

Objective:To develop a deep learning-based segmentation model MT-UNet to automatically segment bone metastases and benign bone lesions in bone scintigraphy with SPECT/CT.Methods:A total of 93 patients (48 males and 45 females, age 28-84 years) who underwent bone SPECT/CT in the Department of Nuclear Medicine, General Hospital of Northern Theater Command from June 2023 to December 2023 were enrolled retrospectively in this study, with a total of 184 bone lesions (94 benign lesions and 90 metastatic tumors). The MT-UNet was employed to segment bone lesions in SPECT, CT and SPECT/CT images respectively. Comparative analysis with 8 segmentation models was performed. The training set and validation set were divided by using 5-fold cross-validation and transfer learning was introduced to further enhance the robustness of the model. An additional cohort of 22 patients (15 males and 7 females, age 37-87 years) who received bone SPECT/CT in the Department of Nuclear Medicine, General Hospital of Northern Theater Command from April 2023 to May 2023 were included, comprising 40 bone lesions (22 benign lesions and 18 metastatic tumors) as the test set of MT-UNet. Segmentation performance of different models was assessed using accuracy, sensitivity, specificity, AUC, intersection over union and Dice similarity coefficient (DSC). Delong test was used to compare the segmentation efficacy among different models in the test set.Results:In the validation set, MT-UNet demonstrated DSC of 0.940, 0.962, and 0.963 for SPECT, CT, and SPECT/CT bone lesion segmentation, respectively, which were outperformed other models. Following transfer learning implementation, the SPECT/CT model′s DSC was improved to 0.984. In the test set, MT-UNet maintained comparable segmentation performance to the validation set, with significant AUC differences among the three models ( Z values: from -15.42 to -9.27, all P<0.01). Compared with conventional image interpretation, MT-UNet-based segmentation reduced physician interpretation time from 164min to 102min. Conclusion:MT-UNet has shown good performance in automatic segmentation of bone metastases and benign bone lesions, and is expected to become an important part of SPECT/CT image intelligent diagnosis system for bone metastases.

BACKGROUND:Macrophages are an important part of innate immunity.When the internal environment of the body changes,macrophages can produce different polarization phenotypes and play the corresponding inflammatory immune function.Mesenchymal stem cells can secrete a large number of extracellular vesicles into the internal environment of the body,which have the functions of intercellular signaling and immune regulation.Studies have shown that mesenchymal stem cells and mesenchymal stem cells-extracellular vesicles can affect the M1/M2 polarization balance of macrophages so as to treat immune inflammatory diseases.OBJECTIVE:To explore the signaling mechanism of how mesenchymal stem cells and their extracellular vesicles interfere with autoimmune diseases by regulating the polarization of macrophages,as well as the related research progress of engineered extracellular vesicles in this field.METHODS:The first author searched the relevant literature published in PubMed,CNKI and other databases until June 2024.Chinese search terms were"mesenchymal stem cells,extracellular vesicles,exosomes,apoptotic bodies,apoptotic vesicles,macrophage polarization,M1 polarization,M2 polarization,autoimmune diseases,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,type 1 diabetes mellitus,inflammatory bowel disease,autoimmune dacryadenitis,engineered extracellular vesicles,engineering exosomes,drug delivery."English search terms were"macrophage polarization,M1 macrophage,M2 macrophage,autoimmune disease,type 1 diabetes,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,autoimmune dacryadenitis,inflammatory bowel disease,mesenchymal stem cells,extracellular vesicles,engineered extracellular vesicles,engineering exosomes,drug delivery."The title and abstract of each paper were read and initially screened.Finally,70 articles were selected for induction and analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cells can regulate M1/M2 polarization by releasing or indirectly acting on functional proteins.(2)Mesenchymal stem cells can regulate macrophage M2 polarization through inflammasome.(3)Mesenchymal stem cells can be combined with commonly used drugs to enhance drug efficacy.(4)Mesenchymal stem cells can regulate the release of mesenchymal stem cells-extracellular vesicles after inflammatory stimulation and affect the polarization of macrophages.(5)Mesenchymal stem cells-extracellular vesicles can regulate autoimmune diseases by targeting macrophage polarization through PTEN,NOTCH,nuclear factor κB,Toll-like receptors,PI3K/AKT and other pathways.(6)Engineered extracellular vesicles can achieve non-invasive targeted drug delivery,prolong the half-life of drugs,promote the oral administration of exosomes,reduce allograft reaction,improve the bioavailability of Chinese herbs and overcome the blood-brain barrier,opening up a new path for drug delivery.

BACKGROUND:Macrophages are an important part of innate immunity.When the internal environment of the body changes,macrophages can produce different polarization phenotypes and play the corresponding inflammatory immune function.Mesenchymal stem cells can secrete a large number of extracellular vesicles into the internal environment of the body,which have the functions of intercellular signaling and immune regulation.Studies have shown that mesenchymal stem cells and mesenchymal stem cells-extracellular vesicles can affect the M1/M2 polarization balance of macrophages so as to treat immune inflammatory diseases.OBJECTIVE:To explore the signaling mechanism of how mesenchymal stem cells and their extracellular vesicles interfere with autoimmune diseases by regulating the polarization of macrophages,as well as the related research progress of engineered extracellular vesicles in this field.METHODS:The first author searched the relevant literature published in PubMed,CNKI and other databases until June 2024.Chinese search terms were"mesenchymal stem cells,extracellular vesicles,exosomes,apoptotic bodies,apoptotic vesicles,macrophage polarization,M1 polarization,M2 polarization,autoimmune diseases,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,type 1 diabetes mellitus,inflammatory bowel disease,autoimmune dacryadenitis,engineered extracellular vesicles,engineering exosomes,drug delivery."English search terms were"macrophage polarization,M1 macrophage,M2 macrophage,autoimmune disease,type 1 diabetes,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,autoimmune dacryadenitis,inflammatory bowel disease,mesenchymal stem cells,extracellular vesicles,engineered extracellular vesicles,engineering exosomes,drug delivery."The title and abstract of each paper were read and initially screened.Finally,70 articles were selected for induction and analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cells can regulate M1/M2 polarization by releasing or indirectly acting on functional proteins.(2)Mesenchymal stem cells can regulate macrophage M2 polarization through inflammasome.(3)Mesenchymal stem cells can be combined with commonly used drugs to enhance drug efficacy.(4)Mesenchymal stem cells can regulate the release of mesenchymal stem cells-extracellular vesicles after inflammatory stimulation and affect the polarization of macrophages.(5)Mesenchymal stem cells-extracellular vesicles can regulate autoimmune diseases by targeting macrophage polarization through PTEN,NOTCH,nuclear factor κB,Toll-like receptors,PI3K/AKT and other pathways.(6)Engineered extracellular vesicles can achieve non-invasive targeted drug delivery,prolong the half-life of drugs,promote the oral administration of exosomes,reduce allograft reaction,improve the bioavailability of Chinese herbs and overcome the blood-brain barrier,opening up a new path for drug delivery.

Objective:To evaluate the feasibility of transjugular transcatheter tricuspid valve replacement (TTVR) using the LuX-Valve Plus system (Ningbo Jenscare Scientific, China) for the treatment of severe tricuspid regurgitation in real-world clinical settings.Methods:This prospective study enrolled 81 patients with severe ricuspid regurgitation (≥3+) who underwent TTVR with the LuX-Valve Plus system at the Department of Cardiology, West China Hospital of Sichuan University between May 2022 and March 2024. Among them, 44 patients were from a compassionate-use study, and 37 were from two premarket clinical trials. Baseline clinical data, preprocedural imaging, procedural outcomes, and postprocedural follow-up data were collected. The primary endpoint events included device success, procedural success, and 30 d composite adverse events.Results:The age of the cohort was (74.5±7.8) years, with 54 females (67%). Device success and procedural success rates were both 90% (73/81). Post-procedural tricuspid regurgitation improved, with a 6% (5/81) incidence of moderate-to-severe paravalvular leakage. The rate of permanent pacemaker implantation was 12% (10/81), of which 5% (4/81) had pre-existing indications for pacemaker implantation. Major bleeding events occurred in 10% (8/81) of patients, and the 30 d composite endpoint rate was 25% (20/81).Conclusion:TTVR using the LuX-Valve Plus system demonstrates promising feasibility for high-risk surgical patients with severe tricuspid regurgitation, effectively reducing or eliminating regurgitation with acceptable safety. However, challenges remain in reducing risks of major adverse events, including permanent pacemaker implantation and severe bleeding.

ObjectiveTo investigate the effects and mechanism of Zuogui Jiangtang Tongmai prescription （ZJTP） on human umbilical vein endothelial cells （HUVECs） damaged by high glucose combined with lipopolysaccharide （LPS）. MethodThe survival rate of cells was determined by cell counting kit-8 （CCK-8）， and the level of tumor necrosis factor-α （TNF-α） was determined by enzyme-linked immunosorbent assay （ELISA） to determine the optimal injury concentration and action time of LPS， as well as the optimal action concentration of ZJTP drug-containing serum. HUVECs were divided into a blank control group， a model group， a ZJTP drug-containing serum group， and an SCFA mixed liquid group. ELISA was used to detect the level of endothelin-1 （ET-1）， nitric oxide （NO）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and TNF-α. Western blot was performed to detect the protein expression of G protein-coupled receptor43 （GPR43）， β-suppressor protein-2 （β-arrestin-2）， nuclear factor-κB suppressor α （IκBα）， and nuclear factor κB p65 （NF-κB p65）. The nucleation of NF-κB p65 was observed by immunofluorescence staining （IF）. The role of GPR43 in the regulation of inflammatory injury was observed by means of small interfering ribonucleic acid （siRNA）. The cells after intervention were divided into an empty carrier group， a ZJTP drug-containing serum group， a Si-GPR43 group， and a Si-GPR43 + ZJTP drug-containing serum group. The content of IL-1β， IL-6， and TNF-α was detected by ELISA. The protein expression of pathways was detected by Western blot. IF was used to observe the nucleation of NF-κB p65. ResultThe optimal molding condition was 1 mg·L^-1 LPS for 24 h. The optimal drug intervention condition was 5% ZJTP drug-containing serum for 24 h. Compared with the blank control group， the content of ET-1 in the model group was significantly increased， and the content of NO was significantly decreased （P<0.01）. The levels of inflammatory factors were significantly increased （P<0.01）. The expressions of GPR43 and IκBα were significantly decreased， while the protein expressions of β-arrestin-2 and NF-κB p65 were significantly increased （P<0.01）. NF-κB p65 protein was transferred from the extranuclear to the intranuclear （P<0.01）. Compared with the model group， the content of ET-1 in the ZJTP drug-containing serum group was decreased， and the content of NO was increased （P<0.05）. The levels of inflammatory factors decreased （P<0.05）. The protein expressions of GPR43 and IκBα were increased， while the expressions of β-arrestin-2 and NF-κB p65 were decreased （P<0.05）. The amount of NF-κB p65 transferred from the intranuclear to the extranuclear decreased （P<0.01）. The mechanism study showed that compared with the Si-GPR43 group， the content of IL-1β， IL-6， and TNF-α were significantly decreased after treatment with ZJTP drug-containing serum （P<0.01）. The protein expressions of GPR43 and IκBα were significantly increased （P<0.01）， while the protein expressions of β-arrestin-2 and NF-κB p65 were significantly decreased （P<0.01）. The amount of NF-κB p65 transferred from the extranuclear to the intranuclear decreased （P<0.01）. ConclusionZJTP has a protective effect on HUVECs with high glucose and LPS-induced inflammatory injury， which may be related to the regulation of GPR43/β-arrestin-2/IκBα/NF-κB pathway.

Based on the neurovascular unit(NVU), neurovascular coupling functions as a barrier to maintain the homeostasis of the microenvironment by regulating the signaling and metabolic activity of nerve cells and capillaries. Widely dispersed across the retina, the NVU is essential to preserving its normal physiological function. A disturbance in retinal neurovascular homeostasis produced by a range of factors can result in a variety of retinal disorders, such as diabetic retinopathy(DR), glaucoma, retinitis pigmentosa(RP)and age-related macular degeneration(ARMD). The retina also has a widespread distribution of brain-derived neurotrophic factor(BDNF), which functions to promote neuron growth and repair damage by binding to its receptor TrkB. In recent years, BDNF was found to play a protective role against damage in the early stage of retinal neurovascular homeostasis imbalance, often known as the neurodegenerative stage. It also helps to reduce the production of pro-angiogenic substances of neurological origin and offers a fresh approach for the early detection and treatment of associated eye disorders.

Objective:To systematically review the risk prediction models for cognitive impairment in stroke patients, aiming to provide references for clinical healthcare professionals in selecting or constructing high-quality risk assessment tools.Methods:A computerized search was conducted in PubMed, Embase, Web of Science, OVID, Cochrane Library, SinoMed, CNKI, Wanfang Database, and VIP to identify studies related to risk prediction models for cognitive impairment in stroke patients. The search was limited to articles published up to August 1, 2023. Two researchers independently screened the literature, extracted data, and assessed the risk of bias and applicability of the included studies using PROBAST.Results:A total of 26 articles were included. The applicability of the studies was generally good, but all studies had some degree of bias risk, mainly arising from unreasonable study designs, inappropriate time intervals between predictor assessment and outcome determination, insufficient sample sizes, unreasonable handling of continuous variables, omission of missing data, lack of reporting of calibration, and overfitting of the models. Meta-analysis results showed that age ( OR=0.05, 95% CI: 0.033-0.057), education level ( OR=-0.13, 95% CI: -0.171 - -0.082), history of diabetes ( OR=2.32, 95% CI: 1.867-2.881), history of hypertension ( OR=0.67, 95% CI: 0.420-0.918), and NIHSS score ( OR=0.40, 95% CI: 0.331-0.469) were factors for cognitive impairment in stroke patients. Conclusions:While various risk prediction models for cognitive impairment in stroke patients exist, they suffer from methodological flaws and high bias risks, with some commonalities and controversies in predictors. Future research should adhere to the principles of transparent reporting of individual prognosis or diagnosis of multivariate prediction models, develop localized prediction models with low bias risk and good applicability, and conduct internal and external validations to demonstrate their applicability and feasibility in clinical practice.