The gut microbiome actively regulates host immunity,digestive processes,and the function of the intesti-nal endocrine system.Additionally,it modulates host neural signal transmission and nutrient metabolism through metabo-lite generation.Vascular calcification involves the deposition of calcium phosphate in blood vessel walls,secondary to metabolic disorders such as chronic kidney disease,atherosclerosis,diabetes,and osteoporosis.Recent research spanning the past two decades has indicated a close correlation between shifts in the composition and functionality of the gut microbiota,along with its metabolites,and the onset of metabolic disease-related vascular calcification.This paper pres-ents a comprehensive review of the roles and mechanisms of the gut microbiota in this context.

BACKGROUND:Obesity negatively affects dynamic balance during walking,and crossing barriers is a more routine functional activity that requires more stability in controlling body posture. OBJECTIVE:To investigate the differences in dynamic stability between obese and average males,and to assess the balance ability of obese males using a relatively more challenging obstacle crossing. METHODS:A total of 24 male youths(12 each in the obese and normal groups)were recruited to complete the tests of walking on level ground and crossing obstacles of different heights(4 cm,11 cm,15 cm)in random order.Kinematic and dynamic data were collected using the Qualisys motion capture system and Kistler force stage.Statistical analysis was performed using two-factor(2 groups * 4 movement types)repeated measures analysis of variance. RESULTS AND CONCLUSION:The obese group had a lower step speed than the normal group(P<0.05),the proportion of the first single support period decreased and the proportion of the second double support period increased when crossing the 11 cm versus 15 cm hurdles(P<0.05).When walking on level ground,the margin of stability in the internal and external directions in the normal group was greater than that of the obese group(P<0.05).When crossing the 4 cm hurdles,the margin of stability in the obese group was less than that in the normal group(P<0.05).When crossing the 11 cm hurdles,there was no significant difference between the two groups in the anterior-posterior direction(P>0.05),while there was a significant difference in the internal-external direction(P<0.05).When crossing the 15 cm hurdles,the margin of stability in the obese group was lower than that in the normal group(P<0.05).Overall,obesity decreases the body's ability to control the body,reduces dynamic stability during crossing the barrier,and increases the risk of falls compared with the general population.In addition,compared with level ground walking,the decrease in the dynamic stability when crossing barriers is more significant in the obese group than the general population.

Background and Aims:Centrally located breast cancer(CLBC),due to its proximity to the nipple-areolar complex,has long been treated primarily with mastectomy,while the oncologic safety of breast-conserving surgery(BCS)remains controversial.This study,based on a large-scale database combined with a real-world cohort,compared the survival outcomes of BCS and mastectomy to evaluate the feasibility and oncologic safety of BCS in CLBC patients.Methods:Data of 10 325 female CLBC patients diagnosed between 2010 and 2015 were extracted from the SEER database,including 5 601 patients who underwent BCS and 4 724 who underwent mastectomy.Propensity score matching(PSM)yielded 1 951 matched pairs,and disease-specific survival(DSS)and overall survival(OS)were compared between groups.Cox regression analyses were performed to identify prognostic factors,and subgroup analyses were conducted.Additionally,an independent validation cohort from Xiangya Hospital,Central South University(2015-2016)included 221 BCS and 636 mastectomy patients,with OS and progression-free survival(PFS)assessed.Results:After PSM,baseline characteristics between groups were well balanced.Kaplan-Meier analysis demonstrated no significant differences in DSS or OS between BCS and mastectomy,and 5-,7-,and 10-year OS rates were comparable(all P＞0.05).Subgroup analyses revealed equivalent outcomes for BCS and mastectomy in patients with T1/T2 disease,different HER2 statuses,and those receiving chemotherapy,while in patients receiving radiotherapy,BCS showed significantly better DSS and OS than mastectomy(both P＜0.05).Multivariate Cox regression identified T,N,and M stage,histologic grade,molecular subtype,ER/PR status,and chemotherapy as independent prognostic factors(all P＜0.05),whereas surgical type was not(P＞0.05).The validation cohort confirmed the SEER findings,with no significant differences in OS or PFS between the two groups(both P＞0.05).Conclusions:BCS provides DSS and OS comparable to mastectomy in CLBC patients and may confer additional survival benefits when combined with radiotherapy.These findings suggest that CLBC should not be considered a contraindication to BCS,supporting BCS as a feasible and safe surgical strategy that offers valuable evidence for individualized clinical decision-making and may help improve patients' quality of life.

Background and Aims:Centrally located breast cancer(CLBC),due to its proximity to the nipple-areolar complex,has long been treated primarily with mastectomy,while the oncologic safety of breast-conserving surgery(BCS)remains controversial.This study,based on a large-scale database combined with a real-world cohort,compared the survival outcomes of BCS and mastectomy to evaluate the feasibility and oncologic safety of BCS in CLBC patients.Methods:Data of 10 325 female CLBC patients diagnosed between 2010 and 2015 were extracted from the SEER database,including 5 601 patients who underwent BCS and 4 724 who underwent mastectomy.Propensity score matching(PSM)yielded 1 951 matched pairs,and disease-specific survival(DSS)and overall survival(OS)were compared between groups.Cox regression analyses were performed to identify prognostic factors,and subgroup analyses were conducted.Additionally,an independent validation cohort from Xiangya Hospital,Central South University(2015-2016)included 221 BCS and 636 mastectomy patients,with OS and progression-free survival(PFS)assessed.Results:After PSM,baseline characteristics between groups were well balanced.Kaplan-Meier analysis demonstrated no significant differences in DSS or OS between BCS and mastectomy,and 5-,7-,and 10-year OS rates were comparable(all P＞0.05).Subgroup analyses revealed equivalent outcomes for BCS and mastectomy in patients with T1/T2 disease,different HER2 statuses,and those receiving chemotherapy,while in patients receiving radiotherapy,BCS showed significantly better DSS and OS than mastectomy(both P＜0.05).Multivariate Cox regression identified T,N,and M stage,histologic grade,molecular subtype,ER/PR status,and chemotherapy as independent prognostic factors(all P＜0.05),whereas surgical type was not(P＞0.05).The validation cohort confirmed the SEER findings,with no significant differences in OS or PFS between the two groups(both P＞0.05).Conclusions:BCS provides DSS and OS comparable to mastectomy in CLBC patients and may confer additional survival benefits when combined with radiotherapy.These findings suggest that CLBC should not be considered a contraindication to BCS,supporting BCS as a feasible and safe surgical strategy that offers valuable evidence for individualized clinical decision-making and may help improve patients' quality of life.

The gut microbiome actively regulates host immunity,digestive processes,and the function of the intesti-nal endocrine system.Additionally,it modulates host neural signal transmission and nutrient metabolism through metabo-lite generation.Vascular calcification involves the deposition of calcium phosphate in blood vessel walls,secondary to metabolic disorders such as chronic kidney disease,atherosclerosis,diabetes,and osteoporosis.Recent research spanning the past two decades has indicated a close correlation between shifts in the composition and functionality of the gut microbiota,along with its metabolites,and the onset of metabolic disease-related vascular calcification.This paper pres-ents a comprehensive review of the roles and mechanisms of the gut microbiota in this context.

Animal experiments are widely used in biomedical research for safety assessment,toxicological analysis,efficacy evaluation,and mechanism exploration.In recent years,the ethical review system has become more stringent,and awareness of animal welfare has continuously increased.To promote more efficient and cost-effective drug research and development,the United States passed the Food and Drug Administration(FDA)Modernization Act 2.0 in September 2022,which removed the federal mandate requiring animal testing in preclinical drug research.In April 2025,the FDA further proposed to adopt a series of"new alternative methods"in the research and development of drugs such as monoclonal antibodies,which included artificial intelligence computing models,organoid toxicity tests,and 3D micro-physiological systems,thereby gradually phasing out traditional animal experiment models.Among these cutting-edge technologies,3D bioprinting models are a significant alternative and complement to animal models,owing to their high biomimetic properties,reproducibility,and scalability.This review provides a comprehensive overview of advancements and applications of 3D bioprinting technology in the fields of biomedical and pharmaceutical research.It starts by detailing the essential elements of 3D bioprinting,including the selection and functional design of biomaterials,along with an explanation of the principles and characteristics of various printing strategies,highlighting the advantages in constructing complex multicellular spatial structures,regulating microenvironments,and guiding cell fate.It then discusses the typical applications of 3D bioprinting in drug research and development,including high-throughput screening of drug efficacy by constructing disease models such as tumors,infectious diseases,and rare diseases,as well as conducting drug toxicology research by building organ-specific models such as those of liver and heart.Additionally,the review examines the role of 3D bioprinting in tissue engineering,discussing its contributions to the construction of functional tissues such as bone,cartilage,skin,and blood vessels,as well as the latest progress in regeneration and replacement.Furthermore,this review analyzes the complementary advantages of 3D bioprinting models and animal models in the research of disease progression,drug mechanisms,precision medicine,drug development,and tissue regeneration,and discusses the potential and challenges of their integration in improving model accuracy and physiological relevance.In conclusion,as a cutting-edge in vitro modeling and manufacturing technology,3D bioprinting is gradually establishing a comprehensive application system covering disease modeling,drug screening,toxicity prediction,and tissue regeneration.

Objective To explore the mechanism of ferroptosis induced by endoplasmic reticulum stress(ERs)in acute respiratory distress syndrome(ARDS).Methods In order to determine the effects of LPS on oxidative stress and Fe2+level of mouse capillary alveolar epithelial cells(MLE12 cells),the cells were treated with LPS(0,1,2,5 μg/ml)for 24 h.To verify the role of ferroptosis in lipopolysaccharide(LPS)-induced cell death,MLE12 cells were divided into control(Con)group,iron removal inhibitor(Fer-1)group,LPS group and LPS+Fer-1 group.LPS+Fer-1 group was pretreated with 10 μmol/L Fer-1 for 6 h,then the cells were exposed to 5 μg/ml LPS for 24 h.Con group was treated with solvent DMSO for 24 h.Fer-1 group was pretreated with 10 μmol/L Fer-1 for 6 h,and then treated with DMSO for 24 h.The cells in LPS group were exposed to 5 μg/ml LPS for 24 h.The MLE12 cells were divided into three groups:Con+Vector group,Con+sequence similarity family 134 mem-ber B(FAM134B)group,LPS+Vector group and LPS+FAM134B group.After transfected with vector or FAM134B overexpression plasmid for 48 h,the cells were exposed or not exposed to 5 μg/ml LPS for 24 h.Cell vi-ability was measured by CCK-8.The levels of malondialdehyde(MDA),glutathione and iron,the protein levels of ferroptosis markers[cyclooxygenase 2(PTGS2),glutathione peroxidase 4(GPX4)]and ERs markers[glucose reg-ulatory protein 78(GRP78),activated transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)]were measured in different groups.In order to further confirm the results of in vitro cell experiments,40 mice were randomly divided into Con+Vector group,Con+FAM134B group,LPS+Vector group and LPS+FAM134B group,with 10 mice in each group.LPS-induced sepsis models were established in LPS+Vector group and LPS+FAM134B group,and the levels of GPX4 and ERs in lung tissue were evaluated by immunofluorescence staining and protein blot.Results LPS treatment increased the levels of PTGS2 and MDA,and decreased the levels of GPX4 and GSH in MLE12 cells in a dose-dependent manner.Compared with LPS group,the cell viability,GPX4 and GSH levels in LPS+Fer-1 group increased significantly(P<0.05),while the PTGS2 protein level and MDA level decreased significantly(P<0.05).Compared with LPS+Vector group,LPS+FAM134B group significantly increased cell viability(P<0.05),decreased PTGS2 protein level(P<0.05)and increased GPX4 level(P<0.05).At the same time,the level of MDA in LPS+FAM134B group was lower than that in LPS+Vector group(P<0.05),and the level of GSH was higher than that in LPS+Vector group(P<0.05).In animal experiment,compared with LPS+Vector group,the expression levels of 4-HNE,ATF4 and CHOP in lung tissue of LPS+FAM134B group decreased significantly(P<0.05),and the expression levels of GPX4,FAM134B group in-creased significantly(P<0.05).Conclusion LPS induces ferroptosis and ERs in MLE12 cells in a dose-depend-ent manner.Activating the endoplasmic reticulum autophagy associated FAM134B receptor helps to inhibit ERs and alleviate cell ferroptosis.

Objective To investigate the efficacy of antibacterial photodynamic therapy(aPDT)as an adjunct to subgingival scaling and root planning in the treatment of chronic periodontitis.Methods This study followed medical ethics guidelines,and informed consent was obtained from all patients.Sixteen patients were recruited for this random-ized split-mouth controlled trial.The control group underwent subgingival scaling and root planning(SRP),while the ex-perimental group received subgingival scaling and root planing plus aPDT treatment using Perowave? with a toluidine blue O solution photosensitizer.The probing pocket depth(PD),recession,plaque index(PLI),bleeding index(BI)and proportion of positive sites of bleeding on probing(BOP)(BOP%)at all sites were examined at baseline(before treat-ment)and at 1,3 and 6 months after treatment.Results Follow-up was completed for 13 patients.On the control side,356 teeth were tested at 2 136 sites.A total of 360 teeth on the test side and 2 160 sites were included in the study.Before treatment,there was no significant difference in the baseline indicators between the two groups.After treatment,both groups showed significant improvement in clinical parameters,including PD,PLI,BI,and BOP%,compared with baseline.At 3 months,the BOP%and PLI in the experimental group were significantly lower than those in the control group(P＜0.05).The improvement in BOP%and PLI in the experimental group was significantly greater than that in the control group 3 months after treatment(P＜0.05).Conclusion aPDT,as an adjuvant treatment to SRP for chronic periodontitis,can improve gingival bleeding and control periodontal inflammation in the early stage.

【Objective】To observe the effect of acupuncture mainly on cleft points on chemical radiculitis rats and to explore the therapeutic mechanism of acupuncture on lumbar disc prolapse.【Methods】Twenty-four rats with chemical radiculitis were equally randomized into acupuncture group and model group,and another 12 normal rats were in the blank control group.Acupuncture group received acupuncture on acupoints of Jiaji(EX-B2)and Weizhong(BL40)and cleft points of Foot-Shaoyang Meridian and Foot-Taiyang Meridian for 28 days.After treatment,rat behavioral changes and morphological features of nerve cells were observed,the weight of inflammation filter paper was detected,and hemorheologic parameters,nitric oxide (NO) and interleukin 6(IL-6) were assayed.【Results】Acupuncture improved the motor function of affected limb,recovered the senses of pain and tough,improved hemorheologic parameters,reduced the inflammatory reaction,relieved degeneration of nerve root,and decreased the contents of inflammatory factors(P