Objective To explore the mechanism of high mobility group AT-hook 1(Hmga1)in regulating the osteogenic differentiation of bone marrow mesenchymal stem cell(BMSC)through the Wnt/β-catenin pathway in the treatment of osteopo-rosis.Methods Hmga1-overexpressing lentiviral vector(LV)was constructed in vitro to transfect rat BMSC,and the Wnt signal inhibitor Dickkopf-1(DKK1)was used for intervention.Osteogenic differentiation-related indices were analyzed by qRT-PCR,Western blot,alkaline phosphatase(ALP)activity detection and Alizarin red staining.Ovariectomized(OVX)osteoporosis rat model was established,and Hmga1-LV was injected into the bone marrow cavity.Micro-CT,histological staining and immuno-fluorescence techniques were used to evaluate the bone microstructure and the expression of osteogenic differentiation-related proteins.Results Hmga1 expression was upregulated in a time-dependent manner during osteogenic differentiation of BMSC,while Hmga1 expression was significantly decreased in the bone tissue of OVX rats.Overexpression of Hmga1 significantly en-hanced the ALP activity and mineralized nodule formation of BMSC,and upregulated the expression of Runt-related transcrip-tion factor 2(Runx2)and osteocalcin(Ocn).The effect was partially reversed by DKK1.Hmga1 overexpression activated the Wnt/β-catenin pathway by promoting the nuclear translocation of β-catenin.In vivo experiments showed that Hmga1-LV treat-ment significantly improved trabecular thickness(Tb.Th)and bone volume fraction(BV/TV)in OVX rats,and reduced trabecu-lar separation(Tb.Sp),but had no significant effect on osteoclast differentiation.Conclusion Hmga1 promotes BMSC osteogen-ic differentiation and reverses OVX-induced bone loss by activating the Wnt/β-catenin signaling pathway,providing a potential target for gene therapy of postmenopausal osteoporosis.

Objective To compare and analyze the disease burden of stroke related to high systolic blood pressure(HSBP)in China and globally.Methods Data were collected and organized from the GBD 2021 on the age-specific and sex-specific mortali-ty rates and disability-adjusted life years(DALY)rates for stroke attributable to HSBP in China and globally from 1990 to 2021.The Joinpoint regression model was used to analyze trends in the disease burden of stroke attributable to HSBP.The Bayesian age-period-cohort(BAPC)model was applied to predict future disease burden of stroke attributable to HSBP in China and globally.Results From 1990 to 2021,the age-standardized mortality rate(ASMR)and age-standardized disability-adjusted life years(ASDR)for stroke attributable to HSBP in China were both higher than the global trends,and the rate of decline was slower than that of the global trend.The decline was slower in males compared to females.By 2021,China's ASMR and ASDR had decreased to 77.73 per 100000(AAPC=-1.31％)and 1484.39 per 100000 person-years(AAPC=-1.34％),respective-ly.The disease burden of stroke attributable to HSBP both in China and globally was primarily concentrated in the elderly popu-lation.In China,except for the 25-34 age group,the mortality rate and DALY rate in all other age groups showed a downward trend.It is projected that,over the next 10 years,both China's and the global ASMR and ASDR for stroke attributable to HSBP will continue to decline,and the decline in China was expected to be greater than the global trend.Conclusion Although the ASMR and ASDR for stroke attributable to HSBP in China show a declining trend,the prevention and treatment situation re-mains challenging.The disease burden is higher among the elderly and males,and the lack of improvement in the disease burden among the 25-34 age group requires attention.In the future,preventive and treatment measures for stroke related to HSBP should be further refined based on existing experience.

Objective To analyze the expression of monocyte surface antigen-presenting factors CD86+and HLA-DR in the subacute phase of burn injury,and the molecular mechanism of monocytes contributing to persistent inflammation.Methods The mice were divided into the sham group and the burn group,and a mouse model of 30％body surface burn was estab-lished.Spleens were collected from mice on the 8th day after burn injury,and monocytes were isolated for transcriptomic analy-sis.A mouse model of Notch1 lentiviral transfection was constructed,and models of sham burn+blank control(sham-NC),burn+blank control(burn-NC),sham burn+Notch1 shRNA(sham-sh),and burn+Notch1 shRNA(burn-sh)were estab-lished.The qRT-PCR and Western blot were used to detect the expressions of monocyte surface antigens CD86+and HLA-DR.Immunofluorescence was performed to analyze the expression of CD86+and HLA-DR in splenic monocytes.ELISA was used to analyze serum levels of IL-10 and CRP.Results On the 8th day after burn injury,compared with the sham burn group,the expressions of monocyte surface antigens CD86+and HLA-DR were decreased,while serum levels of IL-10 and CRP were increased in the burn group.Contents of IL-10 and CRP showed significant negative correlations with CD86+and HLA-DR,re-spectively.Transcriptomic analysis revealed 258 significantly upregulated genes and 360 significantly downregulated genes in splenic monocytes from the burn group.The differentially expressed genes primarily enriched in the Notch signaling path-way.Western blot results showed a significant upregulation of Notch1 expression.After lentiviral inhibition of Notch1 signaling invivo,compared with the burn-NC group,expressions of CD86+and HLA-DR on monocyte surfaces were increased,and ser-um levels of IL-10 and CRP were decreased in the burn-sh group.Conclusion The functional inhibition of splenic monocytes is mediated by Notch1 signaling pathway in the subacute phase of burn injury.Inhibition of Notch1 signaling in vivo improves the antigen-presenting capacity of monocytes after burn injury and inhibits the secretion of inflammatory factors.

Objective To detect the expression of CD99 in breast cancer and its effects on proliferation and migration of MDA-MB-435S cell.Methods Expression of CD99 was detected by immunohistochemical examination in tissues from 80 cases of breast cancer,40 cases of ductal carcinoma in situ,60 cases of benign breast hyperplasia,and 20 cases of normal breast.A cell line MDA-MB-435S-SiCD99 and the negative control cell line MDA-MB-435S-SiNC were constructed,which were transfected with SiCD99 and its negative control.Western blot was used to detect the protein levels of CD99 after CD99 silencing in MDA-MB-435S cell.The effects of CD99 on MDA-MB-435S cell proliferation and migration were evaluated using cell counting kit-8(CCK-8),transwell and wound healing assays via silencing CD99 in MDA-MB-435S cell.Results The expression of CD99 in breast cancer tissue was higher than that in tissue of ductal carcinoma in situ,benign breast hyperplasia tissue and normal breast tissue(P＜0.01).Western blot result showed that the expression of CD99 was decreased after CD99 silencing in MDA-MB-435S cell(P＜0.01).Compared with the MDA-MB-435S-SiNC,the proliferation rate was lower(P＜0.01,CCK-8 test),the scratch distance was shorter(P＜0.01,wound healing assay),and the migration abilities was obviously decreased(P＜0.01,tr-answell assay)in MDA-MB-435S-SiCD99.Conclusion CD99 is upregulated in the breast cancer and silencing CD99 obviously inhibited the proliferation and migration of breast cancer cells,providing evidence for diagnosis and potential treatment of breast cancer.

Brain computer interface(BCI)is a cutting-edge technology that involves the cross-fertilisation of multiple disci-plines such as neuroscience,computer science,bioengineering,electrical engineering,psychology,etc.It can establish a direct communication path between the brain and external devices,providing the possibility for patients with spinal cord injury(SCI),stroke,amyotrophic lateral sclerosis and other conditions to restore their motor or communication abilities.From the first re-cording of brain electrical activity by Hans Berger,to the gradual development of BCI technology,it shows the continuous pro-gress of BCI technology.According to the signal acquisition method,BCI can be classified as noninvasive and invasive types,and the application scenarios of the two experimental paradigms are different.This review explores the current applications of BCI in spinal cord injury,including the treatment of paraplegic patients and the relief of neuropathic pain.BCI devices will develop to-wards the directions of personalization,household use and intelligence,and BCI technology is expected to demonstrate its unique value and potential in more fields.

Pain is a distressing experience in sensory,emotional,cognitive,and social dimensions associated with existed or potential tissue damage.Studies have demonstrated the efficacy of acupuncture analgesia,but the underlying mechanisms are not fully understood.Bioelectrical signals,as one of the basic characteristics of life activities,play a key role in the process of acu-puncture analgesia.Through advanced neurophysiological techniques and multimodal imaging,it has been found that acupuncture can trigger specific changes in bioelectric signals,thus producing analgesic effects.With the rapid development of modern medi-cal technology,the study of bioelectrical signals has gradually delved into the cellular and molecular levels,providing more possi-bilities to reveal the analgesic mechanism of acupuncture.This review focuses on the close connection between bioelectrical sig-naling phenomena and acupuncture analgesia mechanism,summarizes the current research status of bioelectrical signaling phe-nomena in acupuncture analgesia mechanism by collating related literature.The future research directions were prospected,ai-ming to provide theoretical basis and new ideas for further understanding and applying acupuncture analgesia.

Objective To systematically explore influencing factors of internet addiction behaviors among junior school students across different grades from multiple dimensions.Methods This study enrolled all students from a junior high school in Wuhan.Annual questionnaire surveys were conducted from October 2021 to September 2024 to collect data on demographic characteristics,study and living situation,mental health,and internet addiction behaviors.Students were combined according to grade level during the survey period.An exposure-wide association analysis(ExWAS)strategy was employed to identify grade-specific influencing factors in each dimension of internet addiction.Results Common influencing factors across all three grades included academic interest(OR=0.45～0.50,95％CI:0.29～0.76)in the study dimension and living situation dimension and stress(OR=1.06,95％CI:1.03～1.10)in mental health dimension.Grade-specific influences of internet addiction existed in these two dimensions:In grade 7,the affinity with father(OR=0.97,95％CI:0.94～1.00),alcohol experimentation(OR=2.33,95％CI:1.54～3.53),and perpetrating bullying(OR=2.16,95％CI:1.04～4.49)were the main factors;In grade 8,mod-erate-to-high intensity physical activity(OR=0.50,95％CI:0.31～0.81),the affinity with father(OR=0.97,95％CI:0.94～1.00),bullying victimization(OR=2.32,95％CI:1.50～3.60),and anxiety symptoms(OR=2.01,95％CI:1.26～3.20)were the main factors;In grade 9,perpetrating bullying(OR=3.19,95％CI:1.31～7.78)and anxiety symptoms(OR=1.91,95％CI:1.18～3.10)were the main factors.Conclusion Influencing factors of internet addiction behaviors vary across grades in junior high school.Prevention and control strategies should incorporate grade-specific characteristics to implement targeted measures,thereby enhancing early identification capabilities and intervention effectiveness.

Objective To explore the effects of apolipoprotein E gene(ApoE)polymorphism on cerebral oxygen metabolism and postoperative cognitive function in patients undergoing laparoscopic general anesthesia surgery.Methods In this study,210 patients who underwent laparoscopic cholecystectomy in our hospital from January 2020 to January 2024 were selected and di-vided into ApoE ε2 group(45 cases,ε2/ε2,ε2/ε3),ApoE ε3 group(98 cases,ε3/ε3),and ApoE ε4 group(67 cases,ε3/ε4,ε4/ε4)based on their ApoE genotype.The general information,blood lipid levels,and cerebral oxygen metabolism index levels of each group were compared.Multiple linear regression analysis was conducted to investigate the relationship between ApoE gene poly-morphism,blood lipid levels,and cerebral oxygen metabolism indicators,and to analyze the correlation between blood lipid levels and oxygen metabolism indicators under different genotypes.Patients were divided into cognitive impairment group(n=54)and non-cognitive impairment group(n=156)based on whether they experienced cognitive impairment after surgery.General infor-mation,blood lipid levels,and cerebral oxygen metabolism indicators were compared between the two groups.Multivariate logis-tic regression analysis was conducted to identify the influencing factors of cognitive dysfunction.Restrictive cubic spline method was used to analyze the dose-response relationship between blood lipid levels,cerebral oxygen metabolism indicators,and cogni-tive impairment.The adjusted odds ratio(OR)and 95％confidence interval(CI)of ApoE gene polymorphism and cerebral oxygen metabolism indicators to the risk of cognitive impairment were estimated,and the interaction between ApoE gene polymorphism and cerebral oxygen metabolism indicators on cognitive impairment was analyzed.Results Among 210 patients undergoing lap-aroscopic general anesthesia surgery,the frequency of the ε3 allele was the highest,accounting for 71.67％,while the ε2 and ε4 alleles accounted for 11.90％and 16.43％,respectively.The highest proportion of the ε3/ε3 genotype was 46.67％(98/210),while the others were ε3/ε4(65/210),ε2/ε3(40/210),ε2/ε2(5/210),and ε4/ε4(2/210)in descending order.The total cholester-ol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)of ApoE ε4 group patients were higher than those of ApoE ε2 group and ApoE ε3 group patients,while high-density lipoprotein cholesterol(HDL-C)was lower than that of ApoE ε2 group and ApoE ε3 group patients,and the differences were statistically significant(all P＜0.05).The difference in radial artery and internal jugular vein bulb oxygen content(DajvO2)in ApoE ε4 group patients was higher than that in ApoE ε2 group and ApoE ε3 group.The cerebral oxygen uptake rate(COER),internal jugular vein bulb oxygen content(CjvO2),and internal jugu-lar vein bulb oxygen saturation(SjvO2)were lower than those in ApoE ε2 group and ApoE ε3 group patients,and the differences were statistically significant(all P＜0.05).The TC,TG,LDL-C,HDL-C,COER,DajvO2,CjvO2,and SjvO2 levels were not cor-related with ApoE ε2 and ApoE ε3 types,but were correlated with ApoE ε4 type.The TC,TG,LDL-C,DajvO2 levels were posi-tively correlated with ApoE ε4 type,while HDL-C,COER,CjvO2,SjvO2 were negatively correlated with ApoE ε4 type(all P＜0.05).Under different genotypes,TC,TG,LDL-C were positively correlated with COER,CjvO2,and SjvO2(all P＜0.05),and negatively correlated with DajvO2(P＜0.05).HDL-C was negatively correlated with COER,CjvO2,and SjvO2(all P＜0.05),and positively correlated with DajvO2(P＜0.05).The differences in ApoE gene polymorphism,TC,TG,LDL-C,HDL,COER,DajvO2,CjvO2,and SjvO2 between patients with cognitive impairment and those without cognitive impairment were statistically significant(all P＜0.05).Multivariate logistic regression analysis showed that high TC,high TG,and ApoE ε4 genotypes were independent risk factors for cognitive dysfunction(all P＜0.05),while high COER and high SjvO2 were independent protective factors for cognitive dysfunction.The association intensity between TC,TG,LDL-C,HDL,COER,DajvO2,CjvO2,and SjvO2 and cognitive impairment showed a nonlinear dose-response relationship(P＜0.05).TC,TG,LDL-C,DajvO2 were positively correlated with the risk of cognitive impairment,while HDL-C,COER,CjvO2,and SjvO2 were negatively correlated with the risk of cognitive impairment.The interaction analysis of the generalized multifactor dimensionality reduction model showed that ApoE ε4 had interactions with COER,DajvO2,CjvO2,and SjvO2.Conclusion The polymorphism of ApoE gene is associated with cerebral oxygen metabolism in patients undergoing laparoscopic general anesthesia surgery.Among them,patients with ApoE ε4 genotype have a higher risk of cognitive dysfunction after surgery than those with ApoE ε2 and ApoE ε3 genotypes.Clinically,patients with ApoE ε4 genotype should strengthen intraoperative cerebral oxygen monitoring and achieve more accurate individualized anesthesia management based on their genotype.

Objective To elucidate the mechanistic role of ferrostatin-1(Fer-1)in the pathogenesis of diabetic nephropathy(DN).Methods Twenty spontaneous diabetic mice and ten negative control mice were used for in vivo experiments.The for-mer were randomly divided into a model group and a Fer-1 treatment group,with the treatment group receiving intraperitoneal injections of Fer-1(1 mg/kg).Levels of BUN,Scr,glucose,microalbuminuria,GSH,and iron were measured in the mice.Renal histopathological staining was performed to observe renal morphology.Western blot and immunohistochemistry were used to detect the expression of ferroptosis marker proteins,heat shock factor 1(HSF-1),and heme oxygenase-1(HO-1)in renal tis-sues.Human renal cortical proximal tubular epithelial cells(HK-2)were cultured and divided into three groups during in vitro experiments:control group,high glucose group(30 mmol/L),and Fer-1 treatment group(1μmol/L).Levels of GSH,MDA,4-HNE,and iron content were measured.Immunofluorescence experiment was used to assess the level of reactive oxygen species(ROS).Western blot was performed to detect the expressions of ferroptosis marker proteins,kidney injury molecule-1,neutro-phil gelatinase-associated lipocalin,HO-1,and HSF-1 in HK-2 cells.Results In the model group,renal pathological changes,in-cluding glomerular hypertrophy,mesangial matrix expansion,glycogen accumulation,and fibrosis,were observed.Compared with the control group,levels of BUN,Scr,glucose,and urinary microalbumin were increased,GSH content was decreased,and iron level was elevated in the model group(all P＜0.05).The expression of HSF-1 protein in the kidneys of the model group was lower than that in the control group,while HO-1 protein expression was higher.The Fer-1 treatment group exhibited the oppo-site trend.(both P＜0.05).GSH expression was decreased,and iron content,MDA,and 4-HNE levels were increased in the high glucose group(all P＜0.05).Immunofluorescence result revealed that,compared with the control group,ROS level was higher in the high glucose group(all P＜0.05).Additionally,the high glucose group showed increased expressions of KIM-1,NGAL,and HO-1,along with reduced HSF-1 expression,whereas the Fer-1 treatment group exhibited the opposite trend.(all P＜0.05).Conclusion Both in vivo and in vitro experiments have demonstrated that ferroptosis plays a significant role in the de-velopment and progression of DN.Fer-1 may alleviate DN injury by upregulating ferroptosis through the HSF-1/HO-1 signaling pathway.

In the general state,Th17 cells can promote inflammatory responses,while Treg cells have anti-inflammatory and immunomodulatory functions.In obesity individuals,the body is often in a chronic low-grade inflammatory state,and the Th17/Treg cell balance is disrupted,leading to an increase in the number and hyperfunction of Th17 cells and a decrease in the number and hypofunction of Treg cells,which exacerbates the development of obesity and related metabolic diseases.In this paper,the relationship between Th17/Treg cell balance and obesity,and the mechanism of Th17/Treg cell imbalance leading to the occur-rence and development of obesity are reviewed according to relevant research progress in recent years,with a view to exploring new targets for the treatment of obesity.