AIM:To investigate the modulatory role of E3 ubiquitin-protein ligase ITCH in Alzheimer disease(AD)-like pathology through the thioredoxin-interacting protein(TXNIP)-nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)signaling pathway using both in vivo and in vitro experimental models.METHODS:(1)Ten 5×FAD(AD model)mice and 10 wild-type(WT)mice at 2-,4-and 6-month-old were randomly allocated into AD and WT groups.Amyloid β-protein(Aβ)plaque burden in the brain was detected by thioflavin-S and immunofluorescence staining,with the latter method additionally applied to assess TXNIP protein expression.The protein levels of ITCH and TXNIP were determined by Western blot,while their interaction was verified by co-immunoprecipitation.(2)Mouse mi-croglia BV2 cells stimulated by lipopolysaccharide(LPS)were used to construct neuroinflammation model,and were di-vided into control(CON)group and LPS+ATP treatment group.The BV2 cells stimulated by Aβ were used to construct AD inflammation model.According to the different treatment time,they were divided into CON,and 12,24 and 48 h treatment groups.Western blot was used to evaluate the expression of ITCH,TXNIP,and NLRP3 inflammasome compo-nents(NLRP3 and caspase-1)as well as the downstream IL-1β.Adenovirus-mediated ITCH overexpression(OE-ITCH)in Aβ-stimulated BV2 cells comprised three experimental groups:negative control group,Aβ oligomer stimulation group,and OE-ITCH group,with subsequent immunoblotting of inflammatory mediators.RESULTS:The deposition of Aβ plaques in the cortex and hippocampus of 5×FAD transgenic mice exhibited an age-dependent progression(P<0.01).Compared with WT mice,the levels of TXNIP protein increased synchronously,and the levels of ubiquitin ligase ITCH was significantly down-regulated(P<0.05).Co-immunoprecipitation confirmed the interaction between ITCH and TXNIP proteins in the brain of 2-and 4-month-old 5×FAD mice,which exhibited marked attenuation by 4 months of age.In BV2 microglial models,Aβ/LPS stimulation provoked significant ITCH suppression,concurrently up-regulating TXNIP,core NLRP3 inflammasome components(NLRP3 and caspase-1),and downstream IL-1β(P<0.05).Overexpression of ITCH significantly inhibited Aβ-induced activation of TXNIP and NLRP3 and therelated inflammatory factors in BV2 cells.CONCLUSION:The results of in vitro and in vivo experiments showed that ITCH protein exerts effects against AD-like pathology by inhibiting the expression of TXNIP-NLRP3 signaling pathway.

Objective To introduce a modified technique of right ventricular outflow tract (RVOT) reconstruction using a handmade bicuspid pulmonary valve crafted from expanded polytetrafluoroethylene (ePTFE) and to summarize the early single-center experience. Methods Patients with complex congenital heart diseases (CHD) who underwent RVOT reconstruction with a handmade ePTFE bicuspid pulmonary valve due to pulmonary regurgitation at Guangdong Provincial People’s Hospital from April 2021 to February 2022 were selected. Postoperative artificial valve function and right heart function indicators were evaluated. Results A total of 17 patients were included, comprising 10 males and 7 females, with a mean age of (18.18±12.14) years and a mean body weight of (40.94±19.45) kg. Sixteen patients underwent reconstruction with a handmade valved conduit, with conduit sizes ranging from 18 to 24 mm. No patients required mechanical circulatory support, and no in-hospital deaths occurred. During a mean follow-up period of 12.89 months, only one patient developed valve dysfunction, and no related complications or adverse events were observed. The degree of pulmonary regurgitation was significantly improved post-RVOT reconstruction and during follow-up compared to preoperative levels (P<0.001). Postoperative right atrial diameter, right ventricular diameter, and tricuspid regurgitation area were all significantly reduced compared to preoperative values (P<0.05). Conclusion The use of a 0.1 mm ePTFE handmade bicuspid pulmonary valve for RVOT reconstruction in complex CHD is a feasible, effective, and safe technique.

Objective:To analyze the echocardiographic features of different subtypes of Takayasu arteritis（TA）complicated with heart failure（HF），and to explore the clinical application value of echocardiography in the assessment of TA-HF.Methods:Comprehensive clinical and echocardiographic data were collected from 328 consecutive patients with TA who were admitted to the First Affiliated Hospital of China Medical University between January 2010 and December 2023. HF was diagnosed and classified according to the criteria outlined in the China guidelines for the diagnosis and treatment of heart failure 2024. A total of 38 TA-HF patients was selected and enrolled. Based on left ventricular ejection fraction（LVEF），they were grouped into preserved LVEF（HFpEF）group（LVEF≥50%， n=22）and the reduced LVEF（HFmr/rEF）group（LVEF<50%， n=16）. Clinical and echocardiographic data were compared between the HFpEF group and the HFmr/rEF group. Multivariate analysis was performed to evaluate the risk factors for the occurrence of heart failure. Results:① The incidence of HF was 11.6% in patients with TA（38/328）. In the patients with TA-HF，Numano Type Ⅴ accounted for 52.6%（20/38）. According to HF classification standard，TA-HF most commonly manifested as HFpEF at 57.9%（22/38），HFmrEF and HFrEF each accounted for 21.05%（8/38）respectively. ②Echocardiographic analysis revealed the following findings in TA-HF patients：34（89.5%）patients exhibited left heart dilation，4（10.5%）patients demonstrated right heart dilation，23（60.5%）patients presented with left ventricular myocardial hypertrophy，18（47.4%）patients had moderate/severe aortic valve regurgitation，9（23.7%）patients showed diffuse left ventricular myocardial wall motion abnormalities，8（21.1%）patients displayed segmental left ventricular myocardial wall motion abnormalities，and 11（28.9%）patients were diagnosed with pulmonary hypertension. ③Intergroup comparisons demonstrated significantly lower levels of erythrocyte sedimentation rate，reduced proportions of patients in clinical active phase，and lower incidence of moderate/severe aortic regurgitation in HFmr/rEF group versus HFpEF group（all P<0.05）. Conversely，HFmr/rEF group exhibited significantly higher rates of myocardial motion abnormalities，left atrial anteroposterior diameter，left ventricular end-systolic anteroposterior diameter，and left ventricular end-systolic volume compared to HFpEF group（all P<0.05）. ④Multivariate regression analysis identified left ventricular wall motion abnormality，pulmonary hypertension，moderate/severe aortic regurgitation and left ventricular myocardial hypertrophy as independent risk factors for TA-HF development. Conclusions:TA-HF exhibits diverse echocardiographic manifestations，with distinct echocardiographic features observed among different subtypes. Echocardiography plays a crucial role in the diagnosis，classification，and risk stratification of TA-HF.

AIM:To investigate the modulatory role of E3 ubiquitin-protein ligase ITCH in Alzheimer disease(AD)-like pathology through the thioredoxin-interacting protein(TXNIP)-nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)signaling pathway using both in vivo and in vitro experimental models.METHODS:(1)Ten 5×FAD(AD model)mice and 10 wild-type(WT)mice at 2-,4-and 6-month-old were randomly allocated into AD and WT groups.Amyloid β-protein(Aβ)plaque burden in the brain was detected by thioflavin-S and immunofluorescence staining,with the latter method additionally applied to assess TXNIP protein expression.The protein levels of ITCH and TXNIP were determined by Western blot,while their interaction was verified by co-immunoprecipitation.(2)Mouse mi-croglia BV2 cells stimulated by lipopolysaccharide(LPS)were used to construct neuroinflammation model,and were di-vided into control(CON)group and LPS+ATP treatment group.The BV2 cells stimulated by Aβ were used to construct AD inflammation model.According to the different treatment time,they were divided into CON,and 12,24 and 48 h treatment groups.Western blot was used to evaluate the expression of ITCH,TXNIP,and NLRP3 inflammasome compo-nents(NLRP3 and caspase-1)as well as the downstream IL-1β.Adenovirus-mediated ITCH overexpression(OE-ITCH)in Aβ-stimulated BV2 cells comprised three experimental groups:negative control group,Aβ oligomer stimulation group,and OE-ITCH group,with subsequent immunoblotting of inflammatory mediators.RESULTS:The deposition of Aβ plaques in the cortex and hippocampus of 5×FAD transgenic mice exhibited an age-dependent progression(P<0.01).Compared with WT mice,the levels of TXNIP protein increased synchronously,and the levels of ubiquitin ligase ITCH was significantly down-regulated(P<0.05).Co-immunoprecipitation confirmed the interaction between ITCH and TXNIP proteins in the brain of 2-and 4-month-old 5×FAD mice,which exhibited marked attenuation by 4 months of age.In BV2 microglial models,Aβ/LPS stimulation provoked significant ITCH suppression,concurrently up-regulating TXNIP,core NLRP3 inflammasome components(NLRP3 and caspase-1),and downstream IL-1β(P<0.05).Overexpression of ITCH significantly inhibited Aβ-induced activation of TXNIP and NLRP3 and therelated inflammatory factors in BV2 cells.CONCLUSION:The results of in vitro and in vivo experiments showed that ITCH protein exerts effects against AD-like pathology by inhibiting the expression of TXNIP-NLRP3 signaling pathway.

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.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

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.

Objective:To analyze the echocardiographic features of different subtypes of Takayasu arteritis（TA）complicated with heart failure（HF），and to explore the clinical application value of echocardiography in the assessment of TA-HF.Methods:Comprehensive clinical and echocardiographic data were collected from 328 consecutive patients with TA who were admitted to the First Affiliated Hospital of China Medical University between January 2010 and December 2023. HF was diagnosed and classified according to the criteria outlined in the China guidelines for the diagnosis and treatment of heart failure 2024. A total of 38 TA-HF patients was selected and enrolled. Based on left ventricular ejection fraction（LVEF），they were grouped into preserved LVEF（HFpEF）group（LVEF≥50%， n=22）and the reduced LVEF（HFmr/rEF）group（LVEF<50%， n=16）. Clinical and echocardiographic data were compared between the HFpEF group and the HFmr/rEF group. Multivariate analysis was performed to evaluate the risk factors for the occurrence of heart failure. Results:① The incidence of HF was 11.6% in patients with TA（38/328）. In the patients with TA-HF，Numano Type Ⅴ accounted for 52.6%（20/38）. According to HF classification standard，TA-HF most commonly manifested as HFpEF at 57.9%（22/38），HFmrEF and HFrEF each accounted for 21.05%（8/38）respectively. ②Echocardiographic analysis revealed the following findings in TA-HF patients：34（89.5%）patients exhibited left heart dilation，4（10.5%）patients demonstrated right heart dilation，23（60.5%）patients presented with left ventricular myocardial hypertrophy，18（47.4%）patients had moderate/severe aortic valve regurgitation，9（23.7%）patients showed diffuse left ventricular myocardial wall motion abnormalities，8（21.1%）patients displayed segmental left ventricular myocardial wall motion abnormalities，and 11（28.9%）patients were diagnosed with pulmonary hypertension. ③Intergroup comparisons demonstrated significantly lower levels of erythrocyte sedimentation rate，reduced proportions of patients in clinical active phase，and lower incidence of moderate/severe aortic regurgitation in HFmr/rEF group versus HFpEF group（all P<0.05）. Conversely，HFmr/rEF group exhibited significantly higher rates of myocardial motion abnormalities，left atrial anteroposterior diameter，left ventricular end-systolic anteroposterior diameter，and left ventricular end-systolic volume compared to HFpEF group（all P<0.05）. ④Multivariate regression analysis identified left ventricular wall motion abnormality，pulmonary hypertension，moderate/severe aortic regurgitation and left ventricular myocardial hypertrophy as independent risk factors for TA-HF development. Conclusions:TA-HF exhibits diverse echocardiographic manifestations，with distinct echocardiographic features observed among different subtypes. Echocardiography plays a crucial role in the diagnosis，classification，and risk stratification of TA-HF.

Objective:To investigate the expression of homeobox protein C4(HOXC4)in gastric cancer tissues and cells,as well as its effects on the proliferation,migration and invasion of gastric cancer cells and the underlying mechanisms.Methods:The cancer and adjacent tissue specimens surgically removed from 16 patients with advanced gastric cancer at the Department of Oncology,Nanyang First People's Hospital,between May 2020 and April 2021 were collected.Additionally,human normal gastric epithelial cells(GES-1)and gastric cancer cell lines(AGS,SGC-790,and MGC-803)were included.Western blot(WB)was performed to detect HOXC4 expression in gastric cancer tissues and cells.RNA interference technology was used to knockdown or overexpress HOXC4 in SGC-790 and AGS cells,with experimental groups divided as follows:the sh-HOXC4#1 group,sh-HOXC4#2 group,sh-Con group,sh-HOXC4+pc-integrin β1 group,pc-HOXC4 group,pc-Con group,and pc-HOXC4+pc-integrin β1 group.EdU assay,CCK-8 assay,and Transwell assay were employed to evaluate the effects of HOXC4 knockdown or overexpression on cell viability,proliferation,migration,invasion,and integrin β1 expression in each group.A tumor-bearing mouse model was established using HOXC4-knockdown AGS cells to observe the impact of HOXC4 knockdown on tumor volume and the expressions of Ki67 and integrin β1 proteins in xenograft tissues.Results:The expression of HOXC4 in gastric cancer tissues and cells was significantly up-regulated(all P<0.01).Compared with those in the sh-Con group,the expression levels of HOXC4 and integrin β1 in SGC-790 and AGS cells,and the cell viability,proliferation,migration and invasion ability decreased significantly in sh-HOXC4#1 and sh-HOXC4#2 groups(all P<0.01).Compared with those in the sh-HOXC4 group,the cell viability,invasion and migration abilities of cells in the sh-HOXC4+pc-integrin β1 group increased significantly(all P<0.01).Compared with those in the pc-Con group,the cell viability,invasion and migration abilities of cells in the pc-HOXC4 group increased significantly(all P<0.01).Compared with those in the pc-HOXC4 group,the cell viability,invasion and migration abilities of cells in the pc-HOXC4+integrin β1-shRNA group decreased significantly(all P<0.01).Compared with those in the sh-Con group,the tumor grew slowly,and the volume decreased,and the expressions of Ki67 and integrin β1 decreased significantly in the sh-HOXC4#1 and sh-HOXC4#2 groups(all P<0.01).Conclusion:The expression of HOXC4 is up-regulated in gastric cancer tissues and cells,and it promotes the proliferation,migration and invasion of gastric cancer cells by activating the integrin β1 signaling pathway.

BACKGROUND:Previous studies have confirmed that the new compound cottonrose hibiscus leaf gel plaster has a good effect in the treatment of acute soft tissue swelling. OBJECTIVE:To observe the clinical efficacy of compound cottonrose hibiscus leaf gel plaster in the treatment of synovitis of the knee joint. METHODS:Seventy-two patients with knee synovitis were selected from Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2019 to May 2021.These patients were randomly divided into a trial group and a control group,with 36 cases in each group.The trial group was treated with compound cottonrose hibiscus leaf gel plaster,once a day,12 hours each time,while the control group was treated with Diclofenac Diethylamine Emulgel,twice a day.After 28 days of treatment,visual analog scale score,WOMAC Osteoarthritis Index score,quality of life score(SF-36),thickness of knee synovium and comprehensive curative effect were compared between the two groups. RESULTS AND CONCLUSION:(1)Visual analog scale scores after treatment were lower than those before treatment(P<0.05).Visual analog scale scores in the trial group after 7,14 and 28 days of treatment were lower than those in the control group(P<0.05).The WOMAC Osteoarthritis Index scores of the two groups after treatment were lower than those before treatment(P<0.05),and the WOMAC Osteoarthritis Index scores in the trial group after 7,14 and 28 days of treatment were lower than those in the control group(P<0.05).(3)The SF-36 quality of life score in the two groups after 28 days of treatment was higher than that before treatment(P<0.05).SF-36 quality of life score in the trial group after 28 days of treatment was higher than that in the control group(P<0.05).(4)After 28 days of treatment,the thickness of knee synovium in the trial group was less than that in the control group(P<0.05),and the effective rate in the trial group was higher than that in the control group(P<0.05).(5)These findings indicate that compared with Diclofenac Diethylamine Emulgel,the compound cottonrose hibiscus leaf gel plaster can better relieve knee pain,enhance knee joint function,reduce synovial hyperplasia,and elevate the overall quality of life of patients.