ObjectiveTo investigate the protective effect of liver-targeted fibroblast growth factor 21 （FGF21） overexpression against CCl₄-induced acute liver injury （ALI） and its association with silent information regulator 1/glutathione peroxidase 4 （SIRT1/GPX4） expression and ferroptosis-related markers. MethodsFemale ICR mice （8 weeks old） were randomly divided into Control， CCl₄， adeno-associated virus （AAV）-FGF21， and AAV-FGF21 + CCl₄ groups. Liver-targeted FGF21 overexpression was achieved via tail vein injection of AAV8-FGF21 virus with green fluorescent protein （GFP） labeling. ALI was induced by intraperitoneal injection of CCl₄ （0.3 mL/kg）， with sample collection at 12 hours. Body weight and liver weight were recorded to calculate the liver weight/body weight. Alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using a biochemical analyzer. FGF21 expression in liver tissues was detected by immunofluorescence. Hepatic histopathology was evaluated by HE staining. RT-qPCR was performed to assess mRNA expression of ferroptosis and iron metabolism-related genes （ACSL4， PTGS2， HJV， FPN， GPX4）， FGF21， and SIRT1. Protein expression of FGF21， SIRT1， and GPX4 were determined by Western blot. Iron content， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD） activity in liver homogenate were quantified using assay kits. ResultsCompared with the Control group， the FGF21 mRNA and protein expression elevated in CCl₄ group； serum ALT/AST levels and liver weight/body weigh increased. The HE staining results showed that the liver cell membranes were ruptured. The mRNA levels of ACSL4 and PTGS2， the iron content and MDA levels all increased （P<0.01）. The mRNA levels of SIRT1， GPX4， HJV， and FPN， the GSH level and SOD activity all decreased （P<0.05）， and the protein levels of SIRT1 and GPX4 both decreased （P<0.05）. Compared with the CCl₄ group， the serum levels of ALT and AST in the AAV-FGF21 + CCl4 group were decreased （P<0.01）， and the liver/body ratio of mice decreased （P<0.01）. The results of HE staining showed that the degree of liver injury was alleviated. The mRNA levels of ACSL4 and PTGS2， iron content and MDA level all decreased （P<0.01）， while the mRNA levels of SIRT1， GPX4， HJV， FPN， GSH level and SOD activity all increased （P<0.05）. The protein levels of SIRT1 and GPX4 both increased （P<0.05）. ConclusionFGF21 overexpression is associated with enhanced SIRT1/GPX4 expression and suppression of ferroptosis features， thereby contributing to the alleviation of CCl₄-induced ALI.

Plant exosome-like nanovesicles(PELNs)are extracellular nanoparticles(30 to 300 nm in diameter)secreted by plant cells,characterized by a unique lipid-protein-nucleic acid compo-sition and functional attributes.These vesicles play pivotal roles in plant metabolism,immune de-fense,and the regulation of cellular physiological activities across species.This review systematically summarized recent research advances in PELNs,encompassing their biogenesis pathways,composi-tional analysis,extraction/isolation protocols,storage stability,identification methodologies,and ap-plications in skeletal system disorders.Critical challenges and future research directions in this field also discussed,providing valuable references for subsequent investigations.

AIM To investigate the protective effects and mechanisms of aqueous extract of Cimicifugae Rhizoma on intestinal mucosa in a mouse model of ulcerative colitis(UC).METHODS The UC mouse models established by sodium dextran sulfate were allocated into different groups and administered with sulfasalazine(200 mg/kg)or aqueous extract of Cimicifugae Rhizoma(3.9,7.8 g/kg)by gavage,respectively.The mice had their changes of body weight,defecation patterns,disease activity index(DAI)and colon length recorded;their colon tissue pathological alterations and goblet cell quantification analyzed through HE and AB-PAS staining;their ROS levels in colon tissue measured via ELISA;their mRNA expressions of inflammatory cytokines,Nrf2/HO-1 signaling pathway components and NLRP3/Caspase-1/GSDMD pathway regulators in colon tissue assessed by RT-qPCR;their protein expressions of Nrf2/HO-1 and NLRP3/Caspase-1/GSDMD pathway verified by immunohistochemistry;and their ZO1 and Occludin tight junction proteins in colon tissues quantified by Western blot analysis.RESULTS Compared to the model group,the high-dose Cimicifugae Rhizoma aqueous extract group demonstrated significantly increased body weight,colon length and DAI scores(P＜0.01);mitigated intestinal mucosal barrier damage;reduced ROS levels in colon tissue(P＜0.01);suppressed mRNA levels of pro-inflammatory factors IL-1β,IL-6 and TNF-α in colon(P＜0.01);elevated expressions of tight junction protein ZO1 and Occludin in colon tissue(P＜0.05);upregulated mRNA and protein expressions of Nrf2,NQO1 and HO-1 in colon tissue(P＜0.05,P＜0.01);downregulated mRNA and protein expressions of Keap1(P＜0.05);and reduced expressions of NLRP3 inflammasome components(ASC,Caspase-1,GSDMD)in mRNA and protein(P＜0.05,P＜0.01).CONCLUSION The aqueous extract of Cimicifugae Rhizoma exerts protective effects against UC through dual mechanisms involving redox regulation and pyroptosis inhibition by reducing ROS level via Nrf2/HO-1 pathway activation and attenuating NLRP3-mediated pyroptosis via Caspase-1/GSDMD pathway inhibition,and thereby synergistically preserves the structural and functional integrity of intestinal mucosal barrier and mitigates UC progression.

ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop （TTFL） of biorhythm in the rat model of non-alcoholic fatty liver disease （NAFLD） and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank （n=20）， model （n=15）， and low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） modified Ditan tang （n=10） groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage， and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid （NEFA） assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining， and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 （BMAL1/ARNTL） in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1， circadian locomotor output cycles kaput （CLOCK）， period circadian clock 2 （PER2）， and cryptochrome1 （Cry1） in the hypothalamus and liver were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed elevated levels of TG， TC， LDL-C， AST， and ALT （P<0.01） and a lowered level of HDL-C （P<0.05） in the serum， elevated levels of TG and NEFA in the liver （P<0.01）， pyknosis and deep staining of hypothalamic neuron cells， and a large number of vacuoles in the brain area. In addition， the model group showed lipid deposition in the liver， up-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.01）， and down-regulated mRNA and protein levels of Cry1 and PER2 （P<0.01） in the hypothalamus and liver. Compared with the model group， all the three modified Ditan tang groups showed lowered levels of TG， TC， LDL-C， ALT， and AST （P<0.05， P<0.01） and an elevated level of HDL-C （P<0.05） in the serum， and lowered levels of TG and NEFA （P<0.05， P<0.01） in the liver. Furthermore， the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells， reduced lipid deposition in the liver， down-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.05， P<0.01）， and up-regulated mRNA and protein levels of Cry1 and PER2 （P<0.05， P<0.01） in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK， BMAL1， Cry1， and PER2 in the TTFL of NAFLD rats.

AIM: To analyze the influencing factors of capsular constriction syndrome(CCS)in cataract patients after phacoemulsification(Phaco)combined with intraocular lens(IOL)implantation.METHODS: Retrospective study. The data of 2 900 cataract patients(2 900 eyes)in our hospital's information system from January 2021 to January 2024 were collected. All patients were treated with Phaco combined with IOL implantation, and the incidence of CCS within 30 wk after surgery was recorded. Patients were categorized into CCS(116 cases, 116 eyes)and N-CCS group(2 784 cases, 2 784 eyes)based on the occurrence of CCS. The basic data of the two groups were compared, and the influencing factors of CCS within 30 wk after Phaco combined with IOL implantation in cataract patients were analyzed by multivariate Logistic regression.RESULTS: Among 2 900 patients(2 900 eyes)included, 116 cataract patients(116 eyes)developed CCS within 30 wk after Phaco combined with IOL implantation, with an incidence rate of 4.00%. The single factor and multi-factor Logistic regression analysis showed that the complicated diabetes, high myopia, complicated glaucoma, and axial length(AL)>30 mm were the risk factors for the occurrence of CCS after Phaco IOL implantation in cataract patients(all P<0.05).CONCLUSION: Attention should be paid to cataract patients with diabetes, high myopia, glaucoma and AL>30 mm, which will increase the risk of CCS within 30 wk after Phaco combined with IOL implantation in cataract patients.

Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.

Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.

Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective To design an electric ice blanket system for prehospital emergency care of patients of heat sroke disease.Methods The electric ice blanket system consisted of a cooling host and cooling accessories.The cooling host had its chassis made of acrylonitrile-butadiene-styrene(ABS),which was equipped externally with an lithium battery and a DC power adapter,and integrated internally a cooling system,an internal circulation pump,an external circulation pump and a main control system;the cooling accessories included a cooling blanket,a cooling cap and a cooling vest,which had the inner layer made of thermoplastic polyurethane(TPU)elastomer and the outer layer made of Oxford cloth or polyester fiber.The system was compared with the existing subcooling therapeutic apparatus on the market in terms of cooling effect with a water bag simulation cooling experiment.Results The cooling experiment showed that the system was comparable to the existing subcooling therapeutic apparatus on the market in terms of cooling effect while behaved well in size and weight.Conclusion The system developed has a high cooling effect and advantages in portability and compatibility to the environment without power supply,which can be used for the early treatment of patients of heat stroke disease.[Chinese Medical Equipment Journal,2025,46(9):16-21]