Objective To evaluate the effectiveness of preoperative immunosuppressive therapy combined with surgical intervention for Behçet's disease. Methods A retrospective study was conducted on Behçet's disease patients who underwent cardiovascular surgery at Guangdong Provincial People's Hospital from 2012 to 2021. Patients were divided into an immunosuppressive group and a non-immunosuppressive group based on whether they received immunosuppressive therapy before surgery. The complications and long-term survival rates of the two groups were analyzed. Results A total of 28 patients were included, among which 2 patients underwent reoperation, a total of 30 surgeries were performed, including 16 males (53.3%), and the age at diagnosis was 37 (31, 45) years. There were 15 surgeries in the immunosuppressive group and 15 surgeries in the non-immunosuppressive group. Compared with the non-immunosuppressive group, the incidence of complications during hospitalization in the immunosuppressive group was lower (13.3% vs. 53.3%, P=0.008). One patient died in hospital, and the rest were discharged and followed up, with a median follow-up time of 38.7 (15.1, 57.3) months, and there was no statistically significant difference in long-term survival rate between the two groups (73.3% vs. 93.3%, P=0.158). There was no statistical difference in the cumulative incidence of complications one month (20% vs. 53%, P=0.058) and one year (27% vs. 60%, P=0.065) after surgery between the immunosuppressive group and the non-immunosuppressive group, but there was a statistical difference in the cumulative incidence of complications three years after surgery (47% vs. 92%, P=0.002). Conclusion Surgical treatment can save lives in Behçet's disease patients with cardiovascular diseases, but the incidence of postoperative complications is high. Timely use of immunosuppressants before cardiovascular surgery can reduce the incidence of postoperative complications.

Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.

Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.

Objective:To explore the effect of the defect area and volume of intra-articular impacted fragments (IAIF) on the contact stress of the ankle joint surface.Methods:A 23-year-old male volunteer, 168 cm in height and 60 kg in weight, with no history of trauma or anatomic abnormality of the ankle, was selected. On the basis of a normal ankle finite-element model, IAIF-defect finite-element models were established. The first group consisted of IAIF-defect models with identical area but different volumes: on the distal tibial articular surface the defect area was 4 mm × 5 mm (20 mm 2), and the heights were 2 mm, 3 mm, 4 mm, 5 mm and 6 mm. The second group consisted of IAIF-defect models with identical defect volume but different areas. The defect volume was 90 mm 3, while the defect areas on the distal tibial articular surface were 2 mm×3 mm, 3 mm×3 mm, 3 mm×5 mm, 3 mm×6 mm, and 5 mm×6 mm, with corresponding heights of 15 mm, 10 mm, 6 mm, 5 mm, and 3 mm. Under a 600 N vertical load the contact stress of the ankle joint was calculated, and the finite-element data were recorded and analyzed. Pearson correlation analysis was used to analyze, separately for the two groups, the correlation between IAIF defect and the maximum contact stress (MCS) of the distal tibial articular surface, and simple linear regression analysis was performed to obtain regression equations. Equivalence zero testing was used to verify the correlations and to compare their differences. Results:For IAIF defects with the same area but different volumes, including 4 mm×5 mm×2 mm, 4 mm×5 mm×3 mm, 4 mm×5 mm×4 mm, 4 mm×5 mm×5 mm, and 4 mm× 5 mm×6 mm, the corresponding maximum contact stress (MCS) on the distal tibial joint surface were 3.846 MPa, 3.839 MPa, 3.835 MPa, 3.833 MPa, and 3.831 MPa, respectively, with an average of 3.837 MPa. The mean ±1% range is from 3.799 MPa to 3.875 MPa. The correlation analysis showed that the IAIF defects with the same area but different volumes were negatively correlated with contact stress ( r=-0.956, P=0.011). The linear regression equation was MCS=-0.0002×VI+3.851, where VI denotes IAIF volume. Equivalence zero testing confirmed that all measured values lay within the predefined ±1 % margin, satisfying the equivalence null hypothesis. For IAIF defects of identical volume (90 mm 3) but varying articular surface areas—2 mm×3 mm, 3 mm×3 mm, 3 mm×5 mm, 3 mm×6 mm and 5 mm×6 mm—the corresponding MCS values were 2.147 MPa, 2.812 MPa, 3.622 MPa, 4.476 MPa and 6.186 MPa, respectively (mean 3.849 MPa; equivalence band 3.811-3.887 MPa at ±1% of the mean). Correlation analysis demonstrated a strong positive relationship between identical-volume varying-area IAIF defects and contact stress ( r=0.996, P<0.001). The linear regression equation was MCS=0.168×AI+1.236, where AI denotes IAIF area. Equivalence zero testing indicated that none of the measured values fell within the predefined ±1% margin, failing to satisfy the equivalence null hypothesis. Conclusion:In posterior ankle fractures, the volume change of IAIF defects has no clinical significance in relation to MCS, showing a small negative correlation. However, the area change of IAIF defects is clinically significant in relation to MCS, demonstrating a larger positive correlation.

Multimodal image fusion technique is a key technology that combines a variety of medical imaging methods to obtain compre-hensive diagnostic information,which has been widely used in clinical disease research.Finite element analysis is essentially a numerical method for solving differential equations,which simulates various physiological and pathological scenarios through combining with multimodal image fusion technique.It has been applied to many medical fields such as the whole lumbar spine,and plays an important role in anatomical research,biomechanical research,and the occurrence and development of diseases.This combination of technologies can simulate pathological processes such as vertebral loading,intervertebral disc degeneration and ligament ossification in three-dimensional space,thereby offering precise support for the elucidation of mechanical mechanisms,assessment of risk and design of surgical plan.This paper systematically reviewed the advances of finite element analysis based on multimodal image fusion in different anatomical units of the whole lumbar spine through literature collection and collation,and analyzed its key problems in model construction,material property assignment,validation methods and clinical transformation.The synergy of finite element analysis and multimodal image fusion provides clinicians with more basis for the diagnosis and treatment of lumbar spine diseases,and has broad application prospects.

Objective To investigate the characteristics of immune exhaustion in sepsis and analyze its association with gut microbiota translocation.Methods A total of 130 mice were randomly divided into a cecal ligation and puncture(CLP)group(n=100)and a Sham group(n=30)Mouse model of sepsis was established with CLP procedure.Flow cytometry was used to analyze the proportions of peripheral blood CD4+T and CD8+T cells and programmed cell death protein 1(PD-1)positive T cell subsets in mice.Bacterial colonization in organs such as the heart,liver and kidneys was quantified by plating homogenates of the organs.Pathological changes in immune organs were observed with HE staining.The expression and localization of CD4?,CD8?,and PD-1?cells in immune organs were detected with immunohistochemical staining,and Image J software was employed for subsequent quantification of the number of the positive cells.Results HE staining demonstrated that immune organs exhibited varying degrees of pathological damages with disease progression.Compared with the Sham mice,the CLP mice exhibited significantly increased bacterial colonization in parenchymal organs and peripheral blood(P<0.05),notably in the liver,which showed the most severe infection.In the CLP group,the proportion of CD4+T lymphocytes in peripheral blood at days 1,3,and 5 postoperatively was decreased by 56%,70.57%,and 87.42%,respectively,when compared with the Sham group(P<0.001).The proportion of CD8+T lymphocytes was decreased by 48.33%relative to the Sham group only at day 5(P<0.001).In contrast,the proportion of CD4+T cell subsets expressing PD-1 was increased to 673.08,423.08,and 600 times that of the Sham group,respectively,at the same postoperative time points(P<0.001).Immunohistochemical results showed that,in the CLP group,the proportion of CD4+T cells in the thymus,spleen,and mesenteric lymph nodes was increased to 7.65,2.66,and 3.7 times that of the Sham group,respectively,at the early-stage peak(P<0.001),and then these proportions were decreased by 82.8%(P<0.001),41.9%(P<0.01),and 60.15%(P<0.001),respectively,at the late-stage trough when compared with the early-stage peak in the corresponding organs.The proportion of CD8+positive cells was increased in the early stage and then decreased insignificantly,while the proportion of PD-1+positive cells was increased continuously,and reached 6.24,13.9,and 20.96 times that of the Sham group at the peak in the thymus,spleen,and mesenteric lymph nodes respectively(P<0.001),with their expression regions showing a rough overlap with those of CD4+cells.Conclusion During sepsis,the inflammatory response can cause severe damage to immune organs and persistent exhaustion of CD4?T lymphocytes,leading to declined defenses against infection,which may be the main causes for exacerbated gut microbiota translocation and then systemic infection.

BACKGROUND:The reduction of contact area,edge load,and stress increase of adjacent cartilage caused by knee cartilage defect are considered to easily cause degenerative changes in this tissue,which may develop into knee osteoarthritis.Growth factors are considered to be a treatment method to promote the healing of damaged cartilage and delay the progression of degenerative arthritis.OBJECTIVE:To analyze the hotspots and prospects of growth factor-promoted knee cartilage regeneration research by bibliometric methods.METHODS:The first author retrieved 321 articles related to growth factor-promoted knee cartilage regeneration research from the Web of Science core set database.VOSviewer 1.6.19 software was used to analyze the publication volume,country,institution,keyword,and literature citation status of the articles,and investigate the research hotspots.RESULTS AND CONCLUSION:(1)From 2000 to 2024,the annual number of publications in the field of growth factor-promoted knee cartilage regeneration showed an overall upward trend,with the highest number of publications in 2021.Harvard University in the United States published the most papers.(2)Keyword analysis showed that the frequency of keywords such as growth factor,cartilage,cartilage repair,platelet-rich plasma,and cartilage regeneration was high.In addition,the keyword co-occurrence network diagram showed that growth factor was closely related to keywords such as cartilage repair and cartilage regeneration,indicating that growth factor research plays an important role in the field of cartilage regeneration.(3)The results of literature citation analysis showed that the combination of platelet-rich plasma and muscle-derived stem cells may provide a new and effective treatment strategy for patients with osteoarthritis,which can deepen the understanding of cartilage repair mechanisms by promoting stem cell proliferation and cartilage formation.Fibroblast growth factor 2,fibroblast growth factor 18,and insulin growth factor 1 play a key role in cartilage repair and can promote chondrocyte proliferation and matrix synthesis.In particular,fibroblast growth factor 18 can promote the repair of damaged cartilage,thereby alleviating patients'pain and dysfunction,which deserves further in-depth study in the future.The latest research has developed a new Polyhedrin Delivery System(PODS)that can continuously release growth factors such as bone morphogenetic protein 2 and 7,significantly promoting chondrocyte proliferation and cartilage repair.This system provides a new perspective and potential therapy for the treatment of osteoarthritis.(4)Therefore,bone morphogenetic protein 2,7,insulin growth factor 1,and recombinant human fibroblast growth factor 18 are promising growth factor therapies for promoting cartilage regeneration.In the future,further in-depth research on the mechanism of action of growth factors,optimization of treatment strategies,and strengthening of long-term efficacy and safety evaluation are needed.

BACKGROUND:The reduction of contact area,edge load,and stress increase of adjacent cartilage caused by knee cartilage defect are considered to easily cause degenerative changes in this tissue,which may develop into knee osteoarthritis.Growth factors are considered to be a treatment method to promote the healing of damaged cartilage and delay the progression of degenerative arthritis.OBJECTIVE:To analyze the hotspots and prospects of growth factor-promoted knee cartilage regeneration research by bibliometric methods.METHODS:The first author retrieved 321 articles related to growth factor-promoted knee cartilage regeneration research from the Web of Science core set database.VOSviewer 1.6.19 software was used to analyze the publication volume,country,institution,keyword,and literature citation status of the articles,and investigate the research hotspots.RESULTS AND CONCLUSION:(1)From 2000 to 2024,the annual number of publications in the field of growth factor-promoted knee cartilage regeneration showed an overall upward trend,with the highest number of publications in 2021.Harvard University in the United States published the most papers.(2)Keyword analysis showed that the frequency of keywords such as growth factor,cartilage,cartilage repair,platelet-rich plasma,and cartilage regeneration was high.In addition,the keyword co-occurrence network diagram showed that growth factor was closely related to keywords such as cartilage repair and cartilage regeneration,indicating that growth factor research plays an important role in the field of cartilage regeneration.(3)The results of literature citation analysis showed that the combination of platelet-rich plasma and muscle-derived stem cells may provide a new and effective treatment strategy for patients with osteoarthritis,which can deepen the understanding of cartilage repair mechanisms by promoting stem cell proliferation and cartilage formation.Fibroblast growth factor 2,fibroblast growth factor 18,and insulin growth factor 1 play a key role in cartilage repair and can promote chondrocyte proliferation and matrix synthesis.In particular,fibroblast growth factor 18 can promote the repair of damaged cartilage,thereby alleviating patients'pain and dysfunction,which deserves further in-depth study in the future.The latest research has developed a new Polyhedrin Delivery System(PODS)that can continuously release growth factors such as bone morphogenetic protein 2 and 7,significantly promoting chondrocyte proliferation and cartilage repair.This system provides a new perspective and potential therapy for the treatment of osteoarthritis.(4)Therefore,bone morphogenetic protein 2,7,insulin growth factor 1,and recombinant human fibroblast growth factor 18 are promising growth factor therapies for promoting cartilage regeneration.In the future,further in-depth research on the mechanism of action of growth factors,optimization of treatment strategies,and strengthening of long-term efficacy and safety evaluation are needed.

Objective:To explore the effect of the defect area and volume of intra-articular impacted fragments (IAIF) on the contact stress of the ankle joint surface.Methods:A 23-year-old male volunteer, 168 cm in height and 60 kg in weight, with no history of trauma or anatomic abnormality of the ankle, was selected. On the basis of a normal ankle finite-element model, IAIF-defect finite-element models were established. The first group consisted of IAIF-defect models with identical area but different volumes: on the distal tibial articular surface the defect area was 4 mm × 5 mm (20 mm 2), and the heights were 2 mm, 3 mm, 4 mm, 5 mm and 6 mm. The second group consisted of IAIF-defect models with identical defect volume but different areas. The defect volume was 90 mm 3, while the defect areas on the distal tibial articular surface were 2 mm×3 mm, 3 mm×3 mm, 3 mm×5 mm, 3 mm×6 mm, and 5 mm×6 mm, with corresponding heights of 15 mm, 10 mm, 6 mm, 5 mm, and 3 mm. Under a 600 N vertical load the contact stress of the ankle joint was calculated, and the finite-element data were recorded and analyzed. Pearson correlation analysis was used to analyze, separately for the two groups, the correlation between IAIF defect and the maximum contact stress (MCS) of the distal tibial articular surface, and simple linear regression analysis was performed to obtain regression equations. Equivalence zero testing was used to verify the correlations and to compare their differences. Results:For IAIF defects with the same area but different volumes, including 4 mm×5 mm×2 mm, 4 mm×5 mm×3 mm, 4 mm×5 mm×4 mm, 4 mm×5 mm×5 mm, and 4 mm× 5 mm×6 mm, the corresponding maximum contact stress (MCS) on the distal tibial joint surface were 3.846 MPa, 3.839 MPa, 3.835 MPa, 3.833 MPa, and 3.831 MPa, respectively, with an average of 3.837 MPa. The mean ±1% range is from 3.799 MPa to 3.875 MPa. The correlation analysis showed that the IAIF defects with the same area but different volumes were negatively correlated with contact stress ( r=-0.956, P=0.011). The linear regression equation was MCS=-0.0002×VI+3.851, where VI denotes IAIF volume. Equivalence zero testing confirmed that all measured values lay within the predefined ±1 % margin, satisfying the equivalence null hypothesis. For IAIF defects of identical volume (90 mm 3) but varying articular surface areas—2 mm×3 mm, 3 mm×3 mm, 3 mm×5 mm, 3 mm×6 mm and 5 mm×6 mm—the corresponding MCS values were 2.147 MPa, 2.812 MPa, 3.622 MPa, 4.476 MPa and 6.186 MPa, respectively (mean 3.849 MPa; equivalence band 3.811-3.887 MPa at ±1% of the mean). Correlation analysis demonstrated a strong positive relationship between identical-volume varying-area IAIF defects and contact stress ( r=0.996, P<0.001). The linear regression equation was MCS=0.168×AI+1.236, where AI denotes IAIF area. Equivalence zero testing indicated that none of the measured values fell within the predefined ±1% margin, failing to satisfy the equivalence null hypothesis. Conclusion:In posterior ankle fractures, the volume change of IAIF defects has no clinical significance in relation to MCS, showing a small negative correlation. However, the area change of IAIF defects is clinically significant in relation to MCS, demonstrating a larger positive correlation.

This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Diabetic Nephropathies/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Inflammasomes/drug effects* ; Male ; Kidney/pathology* ; Endoplasmic Reticulum Chaperone BiP ; Humans ; Interleukin-18/genetics* ; Mice, Inbred C57BL