ObjectiveTo compare the differences between the ultrafiltration method and the dextran gel filtration method during the purification of Tfn-modified PCL micelles by using purification efficiency and micelle purity as indicators. MethodsCoumarin-6 （C6） was used as a fluorescent probe and was loaded into HOOC-PEG-PCL to form PCL micelles by the film-dispersion method. Tfn was then conjugated to the surface of PCL micelles via an amidation reaction， resulting in two types of micelles： Tfn/PCL_H and Tfn/PCL_L. The pharmaceutical properties of the two types of micelles were characterized. The micelles were then purified through ultrafiltration method and dextran gel method respectively， and the efficiency of the two methods， along with the purity of the final micelles， was compared. The density of Tfn on the surface of PCL micelles was also calculated. ResultsThe hydrated diameter of PCL micelles was approximately 73 nm， and the C6 loading efficiency was around 0.046%. The size increased to 134 nm and 158 nm for Tfn/PCL_L and Tfn/PCL_H， respectively. The micelle population was monodisperse. The purification results showed that， for the ultrafiltration method， after two and one rounds of purification， the Tfn/C6 ratio stabilized at 23.6 and 3.4 for Tfn/PCL_H and Tfn/PCL_L， respectively. For the dextran gel filtration method， the Tfn/C6 ratio reached 23.7 for the Tfn/PCL_H group after two rounds of purification. However， for the Tfn/PCL_L group， the Tfn/C6 ratio increased during four rounds of dextran gel purification， and a significant difference （P = 0.042 4） was observed between the first and last filtrations. The density of Tfn in the final micelles were calculated. For the ultrafiltration method， the Tfn density of Tfn/PCL_H and Tfn/PCL_L were 94.9% and 13.8%， respectively. For the dextran gel filtration method， the density of the two micelles were 95.6% and 14.4%， respectively. For Tfn/PCL_L group， the density results revealing a statistically significant difference （P=0.000 2）. ConclusionThe purification efficiency of the two methods is comparable. However， the purity of the final micelles shows a significant difference， with the dextran gel filtration method resulting in higher purity， particularly for the Tfn/PCL_L micelles.

ObjectiveTo analyze the epidemiological characteristics of a local dengue fever cluster outbreak in Qingpu District of Shanghai in 2024, and to provide a reference for subsequent dengue fever prevention and control. MethodsSeven confirmed local dengue fever cases reported through the National Notifiable Infectious Diseases Surveillance System in Qingpu District of Shanghai in 2024 were selected as the research subjects. Descriptive epidemiological methods were used to conduct investigation and analysis from the aspects of onset, medical treatment and reporting, clinical symptoms, travel and contact history within 15 days before onset, and activity trajectories. ResultsA total of 7 cases were identified in this outbreak. None of the cases had a travel history to dengue-endemic areas within 15 days prior to onset, while all had shared exposure environments and mosquito bite histories, indicating a local clustered transmission pattern. The main clinical manifestations included fever (100.00%) and myalgia (42.86%). All 7 cases were positive for dengue virus serotype 2 (DENV-2) by nucleic acid testing. Genetic sequencing showed that the virus strains belonged to the Cosmopolitan genotype and were most closely related to the epidemic DENV strains circulating in southern China in recent years. ConclusionThis outbreak might be a local secondary infection caused by the short-term stay of dengue fever-infected individuals, and the possible source of importation was dengue fever endemic areas in southern China.

Lung cancer， with persistently high incidence and mortality rates， remains a significant global health challenge. By taking the study on the experience in diagnosis and treatment of lung cancer with phlegm-dampness and blood stasis syndrome by distinguished traditional Chinese medicine physicians of the Sichuan School as an example， the diagnosis and treatment system for lung cancer with phlegm-dampness and blood stasis syndrome， which was formed in response to the humid and foggy environment of the Sichuan Basin， possesses unique value. However， traditional inheritance modes face challenges such as fragmentation， lack of standardization， and insufficient quantification， which hinder the promotion and application of this experience. This research focused on how to leverage multimodal data and artificial intelligence-generated content （AIGC） to achieve precise analysis， intelligent inheritance， and clinical innovation of the experience in diagnosis and treatment of lung cancer with phlegm-dampness and blood stasis syndrome by distinguished traditional Chinese medicine physicians of the Sichuan School. By integrating multimodal data （encompassing four diagnostic methods of traditional Chinese medicine， modern medical imaging， clinical laboratory tests， molecular biology， and regional environmental information）， a precise diagnosis and treatment system integrating macro and micro perspectives for the "disease， syndrome， and pathogenesis" was constructed. The research yielded the following results： （1） In precise syndrome differentiation， the objective quantification of the phlegm-dampness and blood stasis syndrome was achieved. By constructing a "four diagnostic methods， imaging， and molecule" correlation model， the study revealed intrinsic links between tongue and pulse parameters and the tumor microenvironment， as well as between regional climatic factors and syndrome characteristics， enabling real-time dynamic monitoring of efficacy. （2） In elucidating patterns， the study systematically explored the syndrome differentiation thoughts of Sichuan School physicians， such as the timing of purgation and tonification. A "pathogenesis， syndrome complex， and prescriptions and herb" network model was constructed， which accurately elucidated the synergistic action mechanisms of core herb pairs and quantified the dynamic compatibility patterns of reinforcing healthy Qi and eliminating pathogenic factors. （3） In intelligent empowerment， an auxiliary system integrating intelligent syndrome differentiation， treatment plan generation， and efficacy evaluation was built. This system can fuse regional characteristics with individual data， dynamically generate and optimize personalized prescriptions aligned with the experience of Sichuan School， and predict efficacy trends and potential adverse reactions. The integration of multimodal data and AIGC can effectively facilitate the structured inheritance and clinical translation of distinguished physicians' experience. The established intelligent diagnosis and treatment model integrating traditional Chinese medicine and Western medicine demonstrates clear potential in prolonging patients' progression-free survival， alleviating symptoms， and reducing adverse reactions to treatment. This study provides a referential methodological framework for the traditional Chinese medicine experience in diagnosis and treatment of lung cancer， especially the empirical inheritance and modernized development of regional academic schools. It contributes to advancing clinical diagnosis and treatment toward greater precision and personalization.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

AIM:To investigate the effect of resistance exercise on the function of endothelial progenitor cells(EPCs)in type 2 diabetic rats and explore the mechanism of myokine irisin in this process.METHODS:Forty 6-week-old healthy male SD rats were selected,ten of which were used as control group,and the rest were fed with high-fat and high-sugar diet combined with streptozotocin injection for diabetic modeling.The rats were randomly divided into model group and model exercise group,with 15 rats in each group.The animals in the control and model groups were kept quiet-ly,and those of model exercise group underwent tail-loaded ladder climbing training for 12 weeks(3 times/week).72 hours after the last training,plasma,gastrocnemius and femur were separated.The irisin content of each tissue and mRNA as well as protein expression of fibronectin type Ⅲ domain-containing protein 5(FNDC5)in the gastrocnemius and femur were measured.Bone marrow endothelial progenitor cells were isolated and cultivated,and then treated with exoge-nous irisin for 48 hours.The cell viability and adhesion function of endothelial progenitor cells were detected by CCK-8 and adhesion assay,respectively.The endothelial repair ability was detected by carotid artery injury model in nude mice.The protein expression of phosphatidylinositol 3-kinase(PI3-K)/Akt/endothelial nitric oxide synthase(eNOS)signaling pathway was detected by Western blot.RESULTS:(1)In vivo experiment:compared with the control group,the model group showed a decrease in plasma,gastrocnemius muscle,and femoral irisin content,as well as a decrease in gastrocne-mius muscle FNDC5 mRNA and protein expression levels(P＜0.05).Compared with the model group,the levels of irisin in plasma,gastrocnemius muscle and femur,as well as the expression of FNDC5 mRNA and protein in gastrocnemius mus-cle,increased in the model exercise group(P＜0.05).There was no significant change in the expression of FNDC5 mRNA and protein in the femurs of each group(P＜0.05).(2)Cell experiment:① endothelial progenitor cells without irisin treatment:compared with the control group,the cell viability,adhesion function,and endothelial injury repair ability of endothelial progenitor cells reduced(P＜0.05),and the expression of PI3-K,Akt,eNOS signaling pathway down-regulated in the model group(P＜0.05).Compared with the model group,the model exercise group showed improvement in endothe-lial progenitor cell function(P＜0.05)and up-regulation of protein expression in the PI3-K/Akt/eNOS signaling pathway(P＜0.05).② Endothelial progenitor cells treated with irisin:supplementation with irisin improved the function of endotheli-al progenitor cells and increased the expression of various proteins in the PI3-K/Akt/eNOS signaling pathway in the model group and model exercise group compared with those without irisin treatment(P＜0.05).CONCLUSION:Regular resis-tance exercise can improve the function of endothelial progenitor cells in type 2 diabetic rats,and its mechanism may be re-lated to the regulation of PI3-K/Akt/eNOS signaling pathway by myokine irisin released from skeletal muscle.

Objective To investigate the effects of exosomes derived from hypoxia-treated mesenchymal stem cells on chondrocyte injury.Methods After mesenchymal stem cells were subjected to hypoxic treatment,the secreted exosomes were collected and co-cultured with IL-1β-stimulated chondrocytes.Cell viability was assessed using the CCK-8 assay,while apoptosis was evaluated by flow cytometry and the measurement of Caspase-3 and PARP activities.Intracellular levels of ROS,Fe2+,and MDA were quantified using commercial assay kits.The expression of GPX4,SLC7A11,and ACSL4 was analyzed at both mRNA and protein levels via qRT-PCR and Western blot,respectively.Additionally,the secretion of COL2A1,MMP13,ADAMTS5,TNF-α,IL-6,and PGE2 was determined by ELISA.Results Chondrocyte viability was significantly enhanced following the uptake of exosomes derived from hypoxia-treated mesenchymal stem cells(H-Exo)(P<0.05).IL-1β treatment reduced chondrocyte viability,increased Caspase-3 and PARP activities,and promoted apoptosis(P<0.05);however,H-Exo effectively reversed IL-1 β-induced apoptotic effects.Furthermore,IL-1 β markedly down-regulated the expression of GPX4 and SLC7A11,up-regulated ACSL4 expression,and elevated intracellular levels of ROS,Fe2+,and MDA(P<0.05),indicating the induction of ferroptosis.Both the ferroptosis inhibitor and H-Exo significantly attenuated IL-1β-triggered ferroptosis,and H-Exo counteracted the detrimental effects of IL-1β as well as those induced by a ferroptosis inducer.Additionally,IL-1β suppressed the expression of the chondrogenic marker COL2A1,up-regulated the catabolic enzymes MMP13 and ADAMTS5,and enhanced the secretion of pro-inflammatory cyto-kines TNF-α,IL-6,and PGE2(P<0.05).Notably,H-Exo alleviated IL-1β-mediated inflammation and restored the balance between chondrogenic anabolism and catabolism.Conclusions Exosomes secreted by mesenchymal stem cells under hypoxic conditions can effectively inhibit chondrocyte apoptosis and ferroptosis,thereby alleviating cellular injury.These findings suggest that such exosomes exert a protective effect on chondrocytes and hold prom-ise as a novel therapeutic strategy for cartilage repair.

The concept of"musculoskeletal imbalance with soft tissue primacy"posits that tendon injury induced by intervertebral disc degeneration constitutes the core pathogenesis of spinal musculoskeletal imbalance.This study systematically elucidates the pathological mechanisms through which tendon injury leads to spinal instability by integrating traditional Chinese medicine(TCM)"musculoskeletal balance"theory with contemporary biomechanical research on disc degeneration.In the process of intervertebral disc degeneration,the change of stress distribution revealed by modern biomechanics is highly consistent with the TCM principle of"tendon impairment affecting bone".Finite element analysis revealing the"stability-instability-restabilization"process further validates the pathological progression from musculoskeletal imbalance to rebalance.This integrated TCM-Western medicine perspective establishes a novel theoretical framework for predicting disease progression and developing personalized therapeutic strategies,particularly in guiding clinical practice of"treating bone disorders through tendon regulation".

Objective:To compare the effects of regional nerve block and general anaesthesia in elderly patients undergoing traumatic lower limb fracture surgery.Methods:A total of 100 patients over 60 years old with traumatic lower extremity fracture who received surgical treatment in Yan′an People′s Hospital from October 2021 to October 2023 were prospectively selected as the study objects and divided into two groups with 50 cases in each group by random number table method. The control group was given general anesthesia, and the observation group was given regional nerve block. Both groups were given patient controlled intravenous analgesia (PCIA) after surgery. Perioperative hemodynamic indexes, surgical conditions, postoperative visual analogue scale (VAS) score, analgesia recovery rate and stress response indexes before and after surgery were compared between the two groups, and the incidence of complications were compared between the two groups.Results:The mean arterial pressure (MAP) and heart rate (HR) at the beginning of 5 min (T 1) and at the end of the operation (T 2) were decreased compared with the time point before entry (T 0), and there were no statistical differences of MAP, HR at 30 min after the operation (T 3) between the two groups ( P>0.05). The MAP and HR at T 1 and T 2 time points in the observation group were higher than those in the control group, there were statistical differences ( P<0.05). The amount of infusion in the observation group was lower than that in the control group: (443.63 ± 31.47) ml vs. (645.25 ± 45.85) ml, there was statistical difference ( P<0.01). There were no statistical differences in operation time and postoperative hospital stay between the two groups ( P>0.05). The VAS scores in the observation group at 6, 12, 24 and 48 h after surgery were lower than those in the control group: (3.21 ± 0.61) scores vs. (3.89 ± 0.74) scores, (3.45 ± 0.67) scores vs. (4.12 ± 0.78) scores, (2.57 ± 0.47) scores vs. (3.04 ± 0.64) scores, (1.96 ± 0.34) scores vs. (2.34 ± 0.45) scores; and the analgesic relief rate was lower than that in the control group: 8.00%(4/50) vs. 24.00%(12/50), there were statistical differences ( P<0.05). The levels of cortisol (Cor), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and β-endorpeptide (β-EP) at 24 h postoperative in the observation group were lower than those in the control group: (134.74 ± 28.94) ng/L vs. (158.52 ± 35.63) ng/L, (102.53 ± 15.41) μg/L vs. (128.95 ± 18.74) μg/L, (47.54 ± 5.72) ng/L vs. (59.74 ± 6.98) ng/L, (38.74 ± 4.17) μg/L vs. (45.75 ± 5.12) μg/L, there were statistical differences ( P<0.05). There was no statistical difference in complication rate between the two groups ( P>0.05). Conclusions:Regional nerve block can stabilize the intraoperative hemodynamics, reduce the stress response of the body and have a good analgesic effect in the operation of lower extremity fracture in the elderly.

The concept of"musculoskeletal imbalance with soft tissue primacy"posits that tendon injury induced by intervertebral disc degeneration constitutes the core pathogenesis of spinal musculoskeletal imbalance.This study systematically elucidates the pathological mechanisms through which tendon injury leads to spinal instability by integrating traditional Chinese medicine(TCM)"musculoskeletal balance"theory with contemporary biomechanical research on disc degeneration.In the process of intervertebral disc degeneration,the change of stress distribution revealed by modern biomechanics is highly consistent with the TCM principle of"tendon impairment affecting bone".Finite element analysis revealing the"stability-instability-restabilization"process further validates the pathological progression from musculoskeletal imbalance to rebalance.This integrated TCM-Western medicine perspective establishes a novel theoretical framework for predicting disease progression and developing personalized therapeutic strategies,particularly in guiding clinical practice of"treating bone disorders through tendon regulation".

With population aging worldwide,Alzheimer's disease(AD)has become a serious human health issue.Owing in part to the complexity of the pathogenesis of AD,effective therapeutic options are lacking.Mesenchymal stem cell-derived exosomes(MSC-Exos)have powerful regenerative properties and repair functions,providing a new direction for treatment.They are donor-derived,easily stored,natural carriers,with low immunogenicity and a low risk of tumor formation.They have shown great potential in the treatment of AD and post-treatment rehabilitation.This article introduces the pathological mechanisms of AD and characteristics of MSC-Exos,provides a detailed review of the roles of MSC-Exos in the treatment of AD,including anti-inflammatory effects,immunomodulatory effects,and related signaling pathway modulation,and summarizes recent research progress,with the aim of providing a basis for the development of novel therapeutic approaches to AD.