ObjectiveTo investigate the effects of metformin on the immune functions of immature dendritic cells （imDCs） and the underlying mechanisms. MethodsMouse bone marrow-derived imDCs were treated with different concentrations of metformin. The working concentration and treatment time of metformin in this study were determined based on the results of cell apoptosis and cell viability assays. The effects of metformin on the phagocytic capacity of imDCs was evaluated using an antigen endocytosis assay. The expression of cluster of differentiation 205 （CD205）， the polymerization of filamentous actin （F-actin）， and the underlying regulatory mechanisms were investigated through flow cytometry， laser confocal fluorescence microscopy， and Western blot. ResultsThe working concentrations of metformin were 1， 2， 4 mmol/L for 24 h determined by the apoptosis and cell viability assays.Metformin significantly suppressed the phagocytic capacity of imDCs， down-regulated the expression of the mannose receptor CD205 on the cell surface， which was closely associated with phagocytic function； metformin inhibited the RhoA-ROCK1-LIMK1-Cofilin signaling pathway， which inhibited the polymerization of F-actin and disturbed its dynamic remodeling of imDCs. ConclusionMetformin can inhibit the expression of CD205 and disrupt the remodeling of F-actin， thereby suppressing the antigen-capturing capacity of imDCs.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

Objective:To explore the clinical outcomes and recent follow-up results of the Modified Diamond Protocol in patients with low ejection fraction heart failure (HF) during the perioperative period of cardiac surgery.Methods:Retrospectively collected clinical data of 62 patients who underwent open heart surgery in the cardiac surgery department of Nanjing Drum Tower Hospital from August 2022 to January 2024, including 48 males and 14 females with mean age of (63.3±11.5)years old. All patients were diagnosed with low ejection fraction heart failure preoperatively, with left ventricular ejection fraction (LVEF) ≤0.35. Based on the indications of postoperative heart failure medication, 21 patients who received the Modified Diamond Protocol treatment were included in the Modified group, and 41 patients who received the standard treatment plan were included in the Control group. The baseline clinical characteristics and data of the two groups were compared. The left ventricular end-diastolic diameter (LVDd), pulmonary artery pressure (PH), LVEF, postoperative heart failure improvement, mortality, and readmission rates at preoperative, postoperative, and final discharge follow-up times of the two groups were analyzed.Results:There was no statistical difference in baseline data between the control group and the modified diamond regimen group ( P>0.05). There were no perioperative deaths in either group of patients. Compared to preoperative levels, there were significant decrease in PH, a significant reduction in LVDd, and significant increase in LVEF within each group ( P<0.05). Compared to control group, the Modified group demonstrated a greater reduction in PH (-17 mmHg vs. -12 mmHg, 1 mmHg=0.133 kPa), a greater reduction in LVDd (-0.59 mm vs. -0.57 mm), and a greater increase in LVEF (0.08 vs. 0.03), indicating an overall better improvement in cardiac function in the Modified group. However, there were no statistically significant differences between two groups ( P>0.05). All patients were followed up for 3-12 months. The overall mortality rate within 1 year was 12.9%(8/62). During the final follow-up for cardiac function, when comparing within each group, both groups showed a decrease in PH, a reduction in LVDd, and an increase in LVEF, all of which were improvements compared to preoperative levels, with statistically significant differences( P<0.05). Compared to control group, the Modified group showed a greater decrease in pulmonary hypertension (PH) (-17 mmHg vs. -12 mmHg), a greater reduction in LVDd(-0.58 mm vs. -0.57 mm), and a greater increase in left ventricular ejection fraction (LVEF) (0.06 vs. 0.07). The overall improvement in cardiac function was similar between the two groups, with no statistically significant differences( P>0.05). The readmission rate in the Modified group was significantly lower than in the Control group (9.5% vs. 36.6%, P=0.02), and the mortality rate was relatively lower (4.8% vs. 19.5%, P=0.11). Conclusion:The Modified Diamond Protocol is an effective approach to enhance postoperative cardiac function in patients with low ejection fraction undergoing cardiac surgery, contributing to early recovery and reduced readmission rates, but the long-term trend in mortality rates remain to be observed.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.

Objective:To explore the effect of Lactobacillus reuteri on testicular injury in mice exposed to neonicotinoid insec-ticides(NNI).Methods:Fifteen C57BL/6 male mice were randomly divided into control group(CTRI.group),exposure group(NNI group)and Lactobacillus intervention group(NNI-L group).The mice in CTRL group were given 0.02ml/g of 0.5％carboxym-ethyl cellulose sodium solution by gavage for 14 days.The mice in NNI group were given 0.02 ml/g of NNI mixture by gavage for 14 days.The mice in NNI-L group were given 0.02 ml/g of NNI mixture by gavage and 5 × 108cfu/ml of Lactobacillus reuteri powder so-lution for 14 days.Then,the histomorphology and function of testicle were evaluated by hematoxylin-eosin staining,immunofluores-cence staining and RNA sequencing.Results:Compared with CTRL group,the thickness of testicular seminiferous epithelium in the NNI group was significantly thinner.And the decline in the number of spermatogenic cells and sperm was observed.And the expression of spermatogonial stem cell marker UCHL1 was down-regulated which was significantly improved in NNI-L group compared with the NNI group.The abnormal expressions of hormone and sperm methylation related genes in testis of NNI group were detected by RNA sequen-cing,with significant down-regulation being found in NPFF and IGF2.While the expression of HSD3B8 was significantly up-regulated.The abnormal expression of these genes could be significantly improved after oral administration of Lactobacillus reuteri.Conclusion:Testicular spermatogenesis and endocrine function can be damaged by NNI exposure.And oral administration of Lactoba-cillus reuteri protects testis from the adverse effects of NNI toxicity.

Objective:To investigate the glymphatic system dysfunction and white matter microstructural damage in type 2 diabetic mellitus patients with diabetic peripheral neuropathy (DPN), and to identify the early diagnostic imaging biomarkers.Methods:Thirty-one DPN patients and 31 type 2 diabetes mellitus (T2DM) patients who attended the First People's Hospital of Yancheng from March 2022 to October 2023 were included. In addition, 40 healthy controls (HC) were recruited. All subjects underwent 3.0T MRI scan with diffusion tensor imaging and 3D-T1WI sequences, and the diffusion tensor imaging analysis along the perivascular space(DTI-ALPS) index, perivascular space volume fraction in white matter(PVSVF-WM) and peak width of skeletonized mean diffusivity (PSMD) were calculated. SPSS 26.0 software was used to perform one-way ANOVA, t-tests, and Chi-square tests to compare clinical data and imaging indicators among the three groups. Partial correlation analysis was used to explore the relationships between DTI-ALPS index, PVSVF-WM, PSMD and clinical indicators in DPN patients. Finally, receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic value of DTI-ALPS index, PVSVF-WM, and PSMD for DPN. Results:The DPN group(1.46±0.19)had considerably lower DTI-ALPS index than the T2DM group (1.59±0.14) and HC group (1.60±0.17) (both P<0.05, Bonferroni correction). The DPN group (1.44±0.11) had significantly higher PVSVF-WM than both the T2DM group (1.35±0.14) and HC group (1.26±0.13) (both P<0.05, Bonferroni correction). The DPN group (1.84±0.31) and the T2DM group (1.83±0.25) had higher PSMD than HC group (1.60±0.24) (both P<0.05, Bonferroni correction), but the difference between the DPN group and the T2DM group was not statistically significant ( P>0.05). The DTI-ALPS index in the DPN group were negatively correlated with PSMD ( r=-0.379, P=0.035). The DTI-ALPS index was negatively correlated with the Toronto clinical scoring system (TCSS) score ( r=-0.456, P=0.01), while PSMD was positively correlated with TCSS scores ( r=0.686, P<0.001) in DPN group. The ROC curves showed that the area under the curve (AUC) was 0.777 ( P<0.001) for the combined diagnosis of DPN with the DTI-ALPS index, PVSVF-WM and PSMD. Conclusion:DPN patients exhibit glymphatic system dysfunction and white matter microstructural damage. The DTI-ALPS index and PSMD can serve as objective markers for assessing DPN severity. The combination of glymphatic system function indicators and white matter microstructural damage markers has moderate diagnostic value for peripheral neuropathy in T2DM patients.

Objective Radial artery occlusion(RAO)is one of the common complications following coronary intervention via the traditional radial artery approach.This study aims to evaluate the clinical effectiveness of retrograde recanalization of occluded radial arteries through the distal transradial approach(dTRA)approach.Methods A total of 35 patients with RAO admitted to the cardiovascular department of the Anhui Chest hospital between December 2022 and April 2024,who were scheduled to undergo coronary intervention and had attempted recanalization of RAO via dTRA approach were selected.The primary result was the success rate of recanalizing RAO via dTRA.The secondary results included factors influencing the failure of recanalization via dTRA,postoperative puncture complications,and the patency rate at the 3-month follow-up.Results This study divided the patients into a successful group(29 cases,82.9％)and a failed group(6 cases,17.1％)based on whether the distal radial artery was successfully opened and occluded.The proportion of smoking(100.00％vs.17.24％,P=0.040),history of diabetes(100.00％vs.10.34％,P=0.025),and chronic total occlusion of coronary artery(83.33％vs.17.24％,P=0.030)in the failure group were higher than those in the success group,and the difference was statistically significant.The application rate of balloon tracking assisted technology in the failed group(16.67％vs.58.62％,P=0.045),and the diameter of the radial artery at 3 days after surgery[(1.63±0.13)mm vs.(2.13±0.32)mm,P=0.021]and the peak radial artery blood flow velocity at 3 days postoperatively[(0.10±0.78)m/s vs.(0.50±0.13)m/s,P＜0.001]were all lower in the successful group,and the differences were statistically significant.Logistic regression analysis 3 days after surgery showed that chronic complete occlusion of the coronary artery was an independent risk factor for surgical opening failure(OR 0.042,95％CI 0.004-0.438,P=0.008).After 3 months of follow-up,the patency rate of the successful group was 55.2％.Conclusions Retrograde recanalization of RAO via dTRA is safe and feasible,but its long-term patency rate is not high.

The mammary gland is one of the most important glands in human body, and the abnormal changes of its tissue mechanics are often closely related to the occurrence and development of mammary gland diseases. With the development of two new interdisciplines, biomechanics and mechanobiology, their theoretical research results have been gradually transformed into clinical applications, resulting in two new clinical disciplines, mechanodiagnostics and mechanotherapy. However, many clinicians still lack a systematic and in-depth understanding of the biomechanical characteristics and mechanobiology of breast tissue, and their potential value in the clinical diagnosis and treatment of breast diseases. In view of this, we elaborated the evolution law of the biomechanical characteristics and mechanobiological mechanism of breast diseases from four aspects: breast biomechanics, breast mechanobiology, breast mechanodiagnostics, and breast mechanotherapy, analyzed their role in the occurrence and development of breast diseases, and discussed the mechanical principles involved in the traditional diagnosis and treatment of breast diseases, to provide new ideas and schemes for the diagnosis and treatment of breast diseases.