AIM: To investigate expression differences and mechanism of action of serine/threonine kinase 1(AKT1), ATP synthase F1 subunit(ATP5F1), and Bcl-2-associated anti-apoptotic gene 3(BAG3)in the occurrence and progression of pterygium.METHODS:Pterygium-related gene expression data were retrieved from GEO database to screen differentially expressed genes(DEGs). String and Cytoscape were used to construct protein-protein interaction(PPI)networks and identify core targets. GO/KEGG enrichment analyzed mitochondrial metabolic pathways. The pterygium samples(head/body)were collected; pathological features were evaluated by HE staining, and the expression of AKT1, ATP5F1, and BAG3 was detected via immunohistochemistry(IHC).RESULTS:A total of 1 264 DEGs were identified(585 upregulated, 679 downregulated). GO analysis showed significant enrichment of mitochondrial pathways regarding to biological processes, cell components and molecular functions; KEGG analysis highlighted oxidative phosphorylation and chemical carcinogenesis-reactive oxygen species(ROS)pathways. The head and body pterygium samples were collected from 28 cases(28 eyes)that received pterygium surgery, including 7 males(7 eyes)and 21 females(21 eyes), with a mean age of 69.32±8.98 years. HE staining showed more severe dysplasia, disordered stroma, and inflammation in the pterygium head versus the body. IHC detection confirmed significantly lower AKT1, ATP5F1, and BAG3 expression in the head compared with the body(all P<0.05).CONCLUSION:GEO-based bioinformatics and experiments confirmed that AKT1/ATP5F1/BAG3(mitochondrial genes)had significant differential expression in pterygium, correlating with pathological progression. They may regulate mitochondrial metabolism to mediate pterygium progression, offering new insights for targeted therapy.

ObjectiveTo analyze the effects of the progestin-primed ovarian stimulation （PPOS） protocol on embryo euploidy rate and clinical pregnancy outcomes in infertile patients. MethodsWomen who underwent Preimplantation genetic testing for aneuploidy （PGT-A） cycles were selected as study participants （a total of 656 cycles and 3 081 blastocysts）. Participants were divided into two age groups （≤35 years and >35 years） and further stratified by ovarian stimulation protocol： the Progestin-Primed Ovarian Stimulation （PPOS） group （n=48 and 60， respectively）， the Luteal Phase Long Protocol （LP） group （n=160 and 57， respectively）， and the Gonadotropin-Releasing Hormone Antagonist Protocol （AP） group （n=220 and 111， respectively）. Baseline characteristics， ovarian stimulation outcomes， and embryo development parameters were compared among the three protocols within each age group. Additionally， clinical pregnancy outcomes of the first frozen embryo transfer （FET） cycle were compared. The primary outcome measure was the embryo euploidy rate. Results① In the ≤35 years age group， baseline follicle-stimulating hormone （bFSH） levels were significantly higher in the PPOS group compared to the LP and AP groups， and the bFSH/bLH ratio was significantly higher in the PPOS group than in the AP group （P < 0.05）. In the >35 years age group， bFSH levels in both the PPOS and AP groups were significantly higher than in the LP group （P < 0.05）.② In the ≤35 years group， there were no significant differences in the rates of metaphase II （MII） oocytes， 2-pronuclei （2 PN） zygotes， cleavage， 2 PN cleavage， blastocyst formation， high-quality embryos， or embryo euploidy between the PPOS group and either the LP or AP groups. However， the PPOS group showed significantly lower values for the following parameters compared to the other two groups： total oocytes retrieved， number of MII oocytes， number of 2 PN zygotes， number of cleaved embryos， number of 2 PN cleaved embryos， number of blastocysts formed， number of high-quality embryos， number of high-grade blastocysts， number of transferable embryos， number of cryopreserved embryos， number of biopsied blastocysts， number of euploid embryos， and the rate of obtaining at least one euploid embryo. In the >35 years group， no significant differences were observed among the PPOS， LP， and AP groups in the rates of MII oocytes， 2 PN cleavage， blastocyst formation， or in the number of euploid embryos， euploidy rate， and the rate of obtaining at least one euploid embryo. However， the PPOS group had significantly lower numbers of total oocytes retrieved， MII oocytes， 2 PN zygotes， cleaved embryos， 2 PN cleaved embryos， blastocysts formed， transferable embryos， and cryopreserved embryos compared to the LP group （P<0.05）. The high-quality embryo rate was significantly lower in the PPOS group than in the AP group （P<0.05）. The numbers of high-quality embryos， high-grade blastocysts， and biopsied blastocysts were significantly lower in the PPOS group than in both the LP and AP groups （P<0.05）. Notably， the 2 PN fertilization rate was significantly higher in the PPOS group than in the AP group， and the cleavage rate was significantly higher in the PPOS group than in both the LP and AP groups （P<0.05）.③ No significant differences were found among the three groups in the biochemical pregnancy rate， clinical pregnancy rate， live birth rate， early miscarriage rate， and late miscarriage rate following the first FET cycle. ConclusionCompared to the other two protocols， the PPOS protocol does not significantly affect embryo euploidy or clinical pregnancy rates. However， in freeze-all cycles with PGT-A， the PPOS protocol does not reduce the rate of chromosomally normal embryos but may decrease the total number of available embryos. It may not be the optimal choice for younger women， but it can be considered as a viable option for women of advanced maternal age.

ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

BACKGROUND:Cannabidiol has anti-inflammatory,antioxidant,and other pharmacological effects,and has no mental activity,so the research in liver disease is increasing day by day,but its effect on transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells is not clear.OBJECTIVE:To investigate the effect of cannabidiol on transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells and its possible mechanism of anti-hepatic fibrosis.METHODS:(1)In vitro experiment:Rat hepatic stellate cell line(HSC-T6)was selected and cultured in six groups.The control group was routinely cultured for 24 hours.The simple drug group was cultured with cannabidiol for 24 hours.The modeling group was cultured with transforming growth factor β1 for 24 hours.The modeling+low-dose drug group,the modeling+high-dose drug group,and the modeling+positive control group were cultured with transforming growth factor β1 for 24 hours,1,5 μmol/L cannabidiol and silymarin were cultured for 24 hours.After culture,the mRNA expression of α-smooth muscle actin and type Ⅰ collagen,the levels of interleukin 1β and tumor necrosis factor α,and the protein expression of type Ⅰ collagen and transforming growth factor β1/Smad signal transduction pathway were detected in each group.(2)In vivo experiments:C57BL/6J mice were randomly divided into five groups with eight mice in each group.Models were not established in the sham operation group.The liver fibrosis models were established by biliary ligation in the modeling group,the modeling+low-dose drug group,the modeling+high-dose drug group,and the modeling+positive control group.At 3 weeks after the modeling,4,8 mg/kg cannabidiol or silymarin were injected intraperitoneally,once a day,for 7 consecutive days.After administration,the liver function,liver pathological morphology,expression levels of α-smooth muscle actin,type Ⅰ collagen,and transforming growth factor β1/Smad signal transduction pathway related protein were detected in each group.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with the control group,mRNA expression of α-smooth muscle actin and type Ⅰ collagen,interleukin 1β and tumor necrosis factor α,and protein expression of type Ⅰ collagen,transforming growth factor β1 and p-Smad2/3 in HSC-T6 cells were increased(P<0.05),while Smad7 protein expression was decreased(P<0.05)in the modeling group.Two doses of cannabidiol could improve the above changes in HSC-T6 cells induced by transforming growth factor β1,and the improvement was more obvious in the modeling+high-dose drug group.(2)In vivo experiment:Compared with sham operation group,the activities of serum alanine aminotransferase and aspartate aminotransferase were increased(P<0.05),inflammatory cell infiltration and collagen content in liver tissue were increased(P<0.05),and the transforming growth factor β1/Smad signal transduction pathway was activated;α-smooth muscle actin and type Ⅰ collagen expression levels were increased(P<0.05)in the modeling group.Two doses of cannabidiol could reduce the changes of the above indexes in the modeling mice,and the effect was more obvious in the modeling+high-dose drug group.(3)It is indicated that cannabidiol inhibits hepatic fibrosis by suppressing the activation of transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells.

AIM:This study aims to investigate the therapeutic effects of Xiaozhen Fang(XZF)on epidermal growth factor receptor(EGFR)inhibitor,erlotinib-induced skin toxicity in mice,with a focus on the underlying functional mechanisms.METHODS:A mouse model of skin toxicity was established and divided into three groups(n=5 per group):blank,erlotinib(150 mg/kg),and erlotinib(150 mg/kg)combined with XZF(45 g/kg)groups.Skin toxicity se-verity and body weight were evaluated.Western blot was performed to detect protein levels of gasdermin D(GSDMD),caspase-1,and interleukin-1β(IL-1β)in skin tissue.Immunofluorescence was employed to analyze gasdermin E,IL-1β,caspase-1,and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)expression in skin tissue.In vitro,HacaT cells were cultured and treated with erlotinib followed by different concentrations of XZF-containing se-rum.Cell viability was assessed by MTT assay.Cell ultrastructure was observed by transmission electron microscopy,and p53-binding protein 1(53BP1)expression was analyzed by immunofluorescence staining.RESULTS:The XZF signifi-cantly alleviated erlotinib-induced skin toxicity in mouse model,as evidenced by reduced rash incidence,alleviated limb swelling,and increased body weight(P<0.05).Expression of Gasdermins,IL-1β,caspase-1,and NLRP3 was distinctly down-regulated in dorsal skin tissue(P<0.05 or P<0.01).In vitro,XZF-containing serum markedly suppressed pyropto-sis in HacaT cells(P<0.01),preserved cell membrane integrity,and significantly reduced 53BP1 fluorescence intensity(P<0.01).CONCLUSION:The XZF mitigates EGFR inhibitor,erlotinib-induced skin toxicity in mice,potentially by regulating pyroptosis through the NLRP3/caspase-1/GSDMD signaling pathway.This mechanism exerts a cytoprotective ef-fect and alleviates erlotinib-induced skin toxicity.

Animal surgery courses are a critical component of medical training;however,teaching practices have demonstrated problems,such as the difficulty of interdisciplinary teaching,students' weak concepts of sterility,poor clinical thinking,insufficient teamwork,shallow emotional investment,and ineffective value guidance.By integrating the characteristics of student learning and utilizing virtual simulation experiments alongside peer role models,an emotional-guidance teaching model has been established to enhance the effectiveness of"life education",through strengthened emotional identification and improved value guidance.The result indicate that this teaching model forms a closed-loop teaching process,aligns with students' cognitive patterns and cultivates their comprehensive abilities,and enhances teaching effectiveness.

The integration of medical treatment and disease prevention(hereinafter referred to as"med-prevent integra-tion")constitutes a vital strategy for achieving universal health objectives.Party-building initiatives in university-affiliated hospi-tals present a novel approach to enhance this integration at the primary care level.This study identifies three major challenges in current practice,including insufficient conceptual integration between medical and preventive services,inadequate cross-depart-mental coordination and resource allocation,and imperfect accountability mechanisms within Party-building frameworks.From the perspective of integrated governance,we propose a comprehensive pathway where party-building facilitates the systematic conver-gence of ideological orientation,organizational structure,cultural values,and institutional mechanisms.These findings provide both theoretical framework and practical guidance for university-affiliated hospitals to deepen primary-level med-prevent integration through Party-building initiatives.

The etiologies and clinical manifestations of central nervous system diseases in children are complex and diverse.Some patients may have sequelae that will affect the neurological function and quality of life of children for a lifetime.Mesenchymal stem cells are a potentially effective treatment method for nervous system diseases.In recent years，there has been an increasing number of related studies targeting the pediatric population.This article introduced the mechanism of mesenchymal stem cells in the treatment of central nervous system diseases and reviewed the progress of clinical application research in the field of children.

BACKGROUND:Both calorie restriction and time-restricted feeding,as two common dietary patterns,have been shown to improve health by regulating metabolism.However,the difference between these dietary patterns,metabolic indices,as well as the gut microbiota still requires further attention.OBJECTIVE:To explore the differences of calorie restriction and time-restricted feeding on the metabolic indices and gut microbiota of mice.METHODS:The C57BL/6J mice were randomly divided into three groups of ad libitum,calorie restriction,and time-restricted feeding(n=6 per group)for 28 weeks of dietary intervention.Various parameters such as body weight,food intake,glucose tolerance,serum fasting insulin,Homeostasis Model Assessment of Insulin Resistance,and leptin were measured.The impact of different interventions on the gut microbiota structure in mice was explored using 16S rRNA sequence analysis.Key operational taxonomic units responsive to dietary interventions were identified through LEfSe analysis.RESULTS AND CONCLUSION:(1)Compared with the ad libitum group,the body weight,food intake,area under the glucose tolerance curve of the calorie restriction and time-restricted feeding groups were decreased(P＜0.01),and the serum leptin was decreased(P＜0.05).The fasting insulin level and serum leptin level of the calorie restriction group were decreased(P＜0.05)and were significantly lower than those of the time-restricted feeding group(P＜0.05);homeostasis model assessment of insulin resistance decreased in the calorie restriction group(P＜0.01).(2)Compared with the ad libitum group,the αdiversity of gut microbiota in the calorie restriction group and the time-restricted feeding group was decreased(P＜0.05),but the diversity of the time-restricted feeding group was slightly lower than that in the calorie restriction group.(3)There were 15 key operational taxonomic units related to calorie restriction and the time-restricted feeding intervention,of which 8 were positively correlated with metabolic phenotypes and their abundance decreased,and 3 were negatively correlated with metabolic phenotypes and their abundance increased(P＜0.05).OTU819 Lachnospiraceae_UCG-006 was positively correlated with body weight,area under the glucose tolerance curve,homeostasis model assessment of insulin resistance,and fasting insulin,while OTU1397 Muribaculaceae was negatively correlated with these indicators.The results show that both calorie restriction and the time-restricted feeding intervention can improve the weight and glucose metabolism of mice,and both intervention modes caused the remodeling of the gut microbiota,which helped to improve the metabolic disorders.

Objective To investigate the protective effects and possible mechanisms of sofalcone on small intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs(NSAIDs)in rats.Methods In the first group of animal experiments,rats were randomly divided into five groups:normal control group,diclofenac group(diclofenac 7.5 mg·kg-1),and sofalcone high-doses groups(sofalcone 10 mg·kg-1+diclofenac 7.5 mg·kg-1),sofalcone medium-doses groups(sofalcone 5 mg·kg-1+diclofenac 7.5 mg·kg-1),and sofalcone low-doses groups(sofalcone 2 mg·kg-1+diclofenac 7.5 mg·kg-1).Each group received daily gavage for seven days.Serum D-lactate levels were measured,and histological damage to the small intestine was assessed through HE staining and pathological scoring.In the second group,rats were separated into three groups:normal control group,diclofenac group(diclofenac 7.5 mg·kg-1),and sofalcone group(sofalcone 2 mg·kg-1+diclofenac 7.5 mg·kg-1).Concurrently,the rats'body mass,24-hour diet,and water intake were monitored.Additionally,serum levels of pro-inflammatory cytokines such as IL-6,IFN-γ,TNF-α,inflammatory markers CRP and D-lactate,as well as measurements of tissue reactive oxygen species(ROS),lactate dehydrogenase(LDH),and mitochondrial membrane potential were conducted using appropriate kits.Western blotting was applied to assess the expression levels of intercellular junction proteins(Occludin,Claudin-1,α-Catenin),programmed necrosis pathway-associated proteins including receptor-interacting protein kinase 1(RIPK1),RIPK3,and mixed lineage kinase domain-like pseudokinase(MLKL)along with p-MLKL.Results In the first experiment,the diclofenac group exhibited significant histological damage to the small intestine,with elevated levels of D-lactic acid and pathological scores compared to the normal control group(P<0.01).Following intervention with sofalcone,both the histological damage and the levels of D-lactic acid and pathological scores in the small intestine were notably reduced(P<0.05 or P<0.01).However,there was no substantial difference in pathological scores among different doses of sofaclone groups(P>0.05).In the second experiment,compared with normal control group,rats in the diclofenac group showed decreased body mass,24-hour average diet and water intake,along with elevated levels of IL-6,IFN-γ,TNF-α,CRP,D-lactic acid,tissue ROS,LDH activity,RIPK1,RIPK3,and p-MLKL/MLKL protein expression levels,as well as mitochondrial membrane potential(P<0.05 or P<0.01).Moreover,Occludin,Claudin-1,and α-Catenin protein expression levels were reduced(P<0.05 or P<0.01).Following sofalcone intervention,the previously mentioned parameters were reversed(P<0.05 or P<0.01).Notably,there was no statistically significant difference observed in the reduction of RIPK1 protein expression(P>0.05).Conclusions Sofalcone reduces NSAID-induced small intestinal mucosal injury in rats by inhibiting the RIPK1/RIPK3/MLKL-dependent programmed necrosis pathway.