Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

Plant-derived extracellular vesicles (PDEVs) are nanoscale extracellular vesicles secreted by plant cells, characterized by a lipid bilayer structure. These vesicles carry a variety of bioactive molecules, including proteins, nucleic acids, and lipids, and play essential roles in intercellular communication and physiological regulation in plants. Compared to animal-derived extracellular vesicles, PDEVs offer several advantages, such as a broad range of sources, high biocompatibility, low immunogenicity, and low production costs. Furthermore, PDEVs have demonstrated remarkable potential as natural nanocarriers for drug delivery, due to their ability to efficiently traverse biological barriers, such as the blood-brain barrier, making them promising candidates for drug delivery systems. This review systematically elaborates on the complex composition of PDEVs, which consists of lipids, proteins, and nucleic acids, the typical structural characteristics of their lipid bilayers ranging from 30 to 150 nm, and their versatile loading capabilities as drug carriers, efficiently encapsulating various types of therapeutic agents such as hydrophilic small molecules, hydrophobic drugs, nucleic acids, and proteins. We systematically summarize the recent advancements in strategies for enhancing the loading efficiency of PDEVs, which include methods such as co-incubation, ultrasound-assisted loading, electroporation, freeze-thaw cycles, and microfluidic technology. These techniques are evaluated based on their underlying principles, suitable drug types, and their respective advantages. In addition to loading strategies, we focus on the engineered approaches to achieve targeted delivery using PDEVs, such as genetic engineering modifications, chemical ligand conjugation, membrane fusion technology, and polyethylene glycol (PEG) modification. We discuss the mechanisms of these strategies in enhancing targeting efficiency, prolonging in vivo circulation time, and improving therapeutic efficacy. Further, this review highlights the application of PDEVs in various disease models, including tumor, skin inflammation, metabolic disorders, and neurodegenerative diseases, showcasing their therapeutic potential as multifunctional delivery platforms. The ability of PDEVs to encapsulate diverse therapeutic agents and target specific tissues or cells opens up new avenues for the treatment of complex diseases, offering advantages over conventional drug delivery systems. However, despite the promising applications of PDEVs, several challenges remain in their development and clinical translation. These challenges include variability in source materials, standardization of preparation processes, quality control, scalability of production, and the need for clinical validation. To overcome these obstacles, the integration of advanced technologies such as artificial intelligence-assisted design and multi-omics analysis is proposed as a way to facilitate the precise development of PDEVs. These emerging technologies hold the potential to further enhance the precision and effectiveness of plant-based drug delivery systems, ultimately advancing the field of precision medicine. In conclusion, the use of PDEVs as a platform for drug delivery represents a promising area of research with the potential to revolutionize therapeutic strategies. Their ability to encapsulate and deliver a wide variety of bioactive molecules, along with their inherent advantages in biocompatibility and versatility, makes them a valuable tool in the development of more efficient and targeted therapeutic interventions. Continued research and innovation in this field will pave the way for the clinical implementation of PDEVs in the treatment of various diseases, offering new hope for more effective and sustainable therapeutic options.

Objective To investigate the clinical safety and efficacy of predictive extracorporeal membrane oxygenation (ECMO) support during liver transplantation in high-risk recipients. Methods A single-center retrospective study was conducted. A total of 35 liver transplant recipients who underwent predictive ECMO assistance during surgery at the Second Affiliated Hospital of Guangxi Medical University from January 2021 to April 2025 were included. Baseline characteristics, ECMO application, ECMO operating parameters and hemodynamic conditions during ECMO operation were analyzed. The cumulative survival rate was calculated using the Kaplan-Meier method and survival curves were plotted. Results Veno-arterial ECMO in 35 recipients was established after induction of general anesthesia. The median ECMO operation time was 8.5 h, and the success rate of weaning from ECMO was 97%. The cardiac index (CI) during the non-liver period and the new liver period was higher than that before cannulation, and CI increased during the non-liver period and before weaning (all P<0.001). The mean invasive arterial pressure and central venous pressure remained stable. No ECMO-related complications occurred in the recipients. The average survival time was (25 ± 3) months. The main causes of death were severe pulmonary infection and multiple organ failure. Conclusions For liver transplant recipients with severe cardiopulmonary dysfunction, hemodynamic disorders, or multiple organ failure risk factors, implementing predictive ECMO support during liver transplantation through active risk prediction is a safe and effective circulatory guarantee strategy.

ObjectiveTo investigate the current status of ethical sensitivity among clinical nursing interns in the context of artificial intelligence （AI） and analyze its influencing factors. MethodsAdopting mixed research methods and convenience sampling， a total of 237 nursing interns from a tertiary A hospital in Xi’an were selected as research subjects. Data were collected using a general information questionnaire and the Nursing Students’ Ethical Sensitivity Scale， and semi-structured interviews were conducted with 8 nursing interns. ResultsThe total score of ethical sensitivity among nursing interns was （33.98±6.32）， which was at a moderate level. Multiple linear regression analysis revealed that academic degree （undergraduate： β=0.147， P<0.05； postgraduate： β=0.139， P<0.05）， affinity for the nursing profession （β=0.118， P<0.05）， whether they had taken nursing ethics courses （β=-0.124， P<0.05）， and familiarity with artificial intelligence （β=-0.159，P<0.05） were influencing factors of ethical sensitivity among nursing interns. Four themes were extracted from semi-structured interviews， namely， the incomplete mastery of nursing ethics-related knowledge among nursing interns， weakened ethical sensitivity in the AI teaching scenario of nursing interns， insufficient professional identity affecting the development of nursing interns’ ethical sensitivity， and technological dependence leading to the lack of humanistic care among nursing interns. ConclusionEthical sensitivity of nursing interns represents a moderate level， primarily influenced by educational background， degree of fondness for the nursing profession， learning experience of nursing ethics courses， and familiarity with AI. Nursing educators and clinical administrators urgently need to establish a sustainable school-hospital collaborative model of nursing ethics education， attach importance to the cultivation of ethical awareness and value guidance for nursing interns， and strengthen the intensity and depth of nursing ethics education among nursing interns， thereby improving their level of ethical sensitivity in the context of AI.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Objective:To explore the correlation between thyroid hormone levels and the 90-day prognosis in patients with severe pulmonary tuberculosis, with a particular focus on the impact of age.Methods:This retrospective cohort study included 156 patients(43 females, 113 males; ages ranging from 21 to 93 years)diagnosed with severe pulmonary tuberculosis between January 2022 and December 2023.Patients were categorized into deceased( n=46)and survived( n=110)groups based on their 90-day survival status.Further subcategorization into elderly and non-elderly subgroups was conducted.Thyroid hormone levels and other relevant laboratory markers were measured and analyzed. Results:Total triiodothyronine(TT3) [(0.92±0.36)nmol/L] and free triiodothyronine(FT3) [(2.19±0.87)pmol/L] in deceased group were lower than in survival group [TT3(1.09±0.38)nmol/L], FT3 [(2.79±0.99)pmol/L], both P<0.05.T3 levels positively correlated with 90-day survival (TT3: r=-0.202, P=0.011; FT3: r=-0.276, P<0.001).In elderly patients, this correlation was weakened (TT3: r=-0.071, P=0.526; FT3: r=-0.206, P=0.059), but remained significant in non-elderly patients (TT3: r=-0.360, P=0.002; FT3: r=-0.345, P=0.003).FT3 was a better prognostic indicator than TT3. Conclusions:Low serum T3 levels are indicative of a poor prognosis in severe pulmonary tuberculosis; however, their predictive value diminishes in elderly patients.

Objective:To retrospectively analyze the short-term curative effects of various treatment methods for displaced femoral neck fractures in young and healthy elderly individuals aged 65 to 74 years, while also exploring the surgical treatment options available for this population.Methods:A retrospective analysis was conducted on 159 patients with displaced femoral neck fractures(Garden types Ⅲ and Ⅳ)who were treated at Zhengzhou Orthopedic Hospital from July 2019 to June 2021.Among these patients, 75 were male and 84 were female, with ages ranging from 65 to 74 years, and an average age of 69.1±2.9 years.Patients were categorized based on the treatment method received: the total hip arthroplasty(THA)group comprised 77 cases, the hemiarthroplasty(HA)group included 42 cases, and the internal fixation(IF)group contained 40 cases.We compared intraoperative blood loss, operation time, Harris hip joint function scores one-year post-operation, and the incidence of secondary surgeries across the groups.Results:All 159 patients were followed up for a duration of 36 to 60 months(mean 45.1 months)postoperatively.Intraoperative blood loss was recorded as follows: IF group(19.3±7.0 ml), HA group(303.7±33.8 ml, P<0.001), and THA group(453.6±75.6 ml), with statistically significant differences in pairwise comparisons among the three groups(all P<0.001).The operation times were: IF group(40.7±13.1 min), HA group(53.2±7.5 min), and THA group(96.8±23.6 min), again showing statistically significant differences between each pair of groups(all P<0.001).The Harris hip score at one year postoperatively was(82.1±8.0)points, with an excellent and good rate of 82.4%.Specifically, the THA group scored(82.1±8.1)points with an excellent and good rate of 83.1%; the HA group scored(82.3±7.5)points with an excellent and good rate of 83.3%; and the IF group scored(81.8±8.0)points with an excellent and good rate of 80.0%.No statistically significant differences were observed in the excellent and good rates among the three groups(all P>0.05).A chi-square test performed on the overall postoperative complications among the three groups revealed no statistically significant differences( P=0.115). Conclusions:For relatively healthy elderly patients aged 65 to 74 with femoral neck fractures, hip replacement is not the sole treatment option.Treatment plans should be individualized based on patients' health conditions, transcending age limitations, to effectively address the growing challenges posed by femoral neck fractures in an aging society.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To evaluate the clinical efficacy of Modified Buyang Huanwu Decoction combined with Ningxin Jieyu Electroacupuncture in treating post-stroke depression(PSD)and explore its potential mechanisms.Methods A total of 120 PSD patients diagnosed at Shaanxi Provincial Hospital of Traditional Chinese Medicine(inpatient and outpatient departments)from October 2021 to October 2023 were enrolled and randomly divided into an observation group and a control group using a random number table,with 60 cases in each group.Both groups received conventional therapy.The control group additionally received oral administration of Escitalopram Oxalate Tablets,while the observation group underwent Modified Buyang Huanwu Decoction combined with Ningxin Jieyu Electroacupuncture.Both groups were treated for 4 weeks.The clinical efficacy,24-item Hamilton Depression Scale(HAMD-24)scores,National Institutes of Health Stroke Scale(NIHSS)scores,cerebral blood volume(CBV),cerebral blood flow(CBF),serum neurotransmitter levels[norepinephrine(NE),dopamine(DA),5-hydroxytryptamine(5-HT)],and inflammatory cytokines[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)]were evaluated after one-month treatment.Results(1)After treatment,the HAMD-24 scores and NIHSS scores of patients in the two groups significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the HAMD-24 scores and NIHSS scores,and the difference was statistically significant(P＜0.05).(2)After treatment,the cerebral blood flow and cerebral blood volume of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving cerebral blood flow and cerebral blood volume,with statistically significant differences(P＜0.05).(3)After treatment,the serum NE,DA,and 5-HT levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving serum NE,DA,and 5-HT levels,with statistically significant differences(P＜0.05).(4)After treatment,the serum TNF-α and IL-6 levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving serum TNF-α and IL-6 levels,with statistically significant differences(P＜0.05).(5)The total effective rate was 93.33%(56/60)in the observation group and 76.67%(46/60)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion Modified Buyang Huanwu Decoction combined with Ningxin Jieyu Electroacupuncture effectively alleviates depressive symptoms,enhances neurological function,and improves cerebrovascular perfusion in PSD patients.The therapeutic mechanism may involve modulation of neurotransmitter levels and inflammatory cytokines.

Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.