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 Results Three patients were withdrawn or dropped out.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.

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.

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

Vascular cognitive impairment(VCI)is a type of cognitive dysfunction caused by cerebrovascular lesions,and its pathological mechanism includes mitochondrial damage.Therefore,maintaining mitochondrial homeostasis is crucial in the occurrence and progression of VCI.Mitochondrial homeostasis involves multiple levels,including biogenesis,autophagy,ion balance,protein quality control,membrane dynamics,and interactions with other organelles.This study outlines the regulatory mechanisms of mitochondrial homeostasis dysregulation at both the micro and macro levels,delves into the key role of mitochondrial homeostasis in VCI,analyzes potential therapeutic directions,and provides new scientific evidence and perspectives for the early diagnosis and treatment of VCI.

Objective:To analyze the comprehensive efficiency of resource allocation in urban public hospitals in 21cities of Guangdong Province from 2019 to 2023,aiming at providing empirical evidence for future medical policy makers and hospital managers in resource allocation and management.Methods:Using Data Envelopment Analysis and Malmquist index to evaluate the efficiency of health resource allocation in public hospitals in Guangdong.Results:From 2019 to 2023,the comprehensive efficiency of urban public hospitals in Guangdong Province was mildly ineffective,only 7 cities showing relative effectiveness,and there were significant regional differences in efficiency.Malmquist index analysis showed that the total factor productivity of health resource allocation in urban public hospitals in the province decreased from 2019 to 2020 and kept increasing from 2020 to 2023,mainly due to the increasing of the technological progress index and the scale efficiency index.Horizontally,the total factor productivity of 9 cities in the province has increased,while the total factor productivity of 12 cities has decreased,with significant regional differences.The input-output redundancy analysis shows that only 6 cities have no input-output redundancy.Conclusion:The overall efficiency of resource allocation in urban public hospitals in Guangdong Province from 2019 to 2023 is relatively low,with significant regional differences.In the future,it is necessary to coordinate and plan resource allocation,focus on refined management,strengthen talent training and technological improvement,improve the operational efficiency of existing resources,and promote high-quality development of hospitals.

Mitochondria are the center of intracellular energy metabolism.Mitochondrial dynamics refers to the dynamic process of mitochondrial fusion and fission,which plays an important role in maintaining mitochondrial homeostasis and central nervous system function.Optic atrophy 1(OPA1)is a key factor involved in mitochondrial dynamics.OPA1 acts by regulating mitochondrial fusion and fission,reducing oxidative stress,inhibiting apoptosis,and promoting mitochondrial autophagy,to maintain the dynamic changes in mitochondrial quantity,structure,and biological function.Numerous studies have shown that OPA1-mediated mitochondrial dynamics plays an important role in ischemic stroke,Alzheimer's disease,Parkinson's disease,spinal cord injury,multiple sclerosis,and other central nervous system diseases.Here we review the regulatory mechanism of OPA1 in terms of mitochondrial dynamics and the important role of mitochondrial function mediated by OPA1 in central nervous system diseases,to provide new ideas for clinical treatment.

Objective To investigate the efficacy and safety of blank microspheres combined with microcoils in treating hemopty-sis due to arteriae bronchiales(BA)malformation during bronchial arterial embolization(BAE).Methods A retrospective analysis was conducted on the preoperative data,embolization materials,technical success rate,clinical success rate,postoperative recurrence rate,and complications of 87 patients who underwent BAE using blank microspheres for hemoptysis due to BA malformation.Results There were 87 patients in this study,and BA computed tomography angiography(CTA)classification was as follows:32 cases(36.78％)of type Ⅰ,23 cases(26.44％)of type Ⅱ,19 cases(21.84％)of type Ⅲ,and 13 cases(14.94％)of other types(Ⅳ-Ⅸ).A total of 171 blood vessels were embolized in 87 patients,including 16 ectopic BA,and 130 embolized microspheres,including 104 microspheres of 500-700 μm and 26 of 700-900 μm.There were 265 microcoils,with a technical success rate of 100％,a 24 h clinical success rate of 100％,and a 30 d clinical success rate of 98.85％.The recurrence rate was 3.45％ at 6 months,5.75％ at 12 months,and 8.05％ at 24 months.Postopera-tive complications(Clavien-Dindo classification):complications of grade Ⅰ,embolic syndrome recurrence rate was 8.05％,chest pain incidence was 3.45％,dysphagia incidence was 2.30％,BA injury incidence was 3.45％;complications of grade Ⅳ,paraplegia inci-dence was 1.15％.Conclusion The use of blank microspheres combined with microcoils in the treatment of hemoptysis caused by BA malformation has high safety and clear efficacy.