Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Objective To analyze the influencing factors of pancreatic fat deposition in patients with type 2 diabetes mellitus(T2DM),and to explore the relationship between pancreatic fat deposition and islet function.Methods A survey on diabetes prevalence was conducted among 548 residents in the Nicheng community of Pudong New Area from October 2015 to December 2016,including 301 patients with T2DM and 247 subjects with normal glucose tolerance(NGT).General information of the subjects were recorded,blood biochemical and insulin indexes were measured,body composition was measured by dual-energy X-ray absorptiometry,and insulin resistance index(HOMA-IR)and islet cell sensitivity index(HOMA-β)were calculated.Fatty liver and pancreatic fat deposition were detected by ultrasound.Both the T2DM group and NGT group were further divided into two subgroups according to the pancreatic fat deposition.Differences in general demographic information,biochemical and body fat indices among the groups were compared.Multivariate logistic regression was used to analyze the influencing factors of pancreatic fat deposition.Results In the NGT group,the subgroup with pancreatic fat deposition showed higher levels of age,waist circumference,waist-to-hip ratio(WHR),body mass index(BMI),fasting insulin levels(FINS),2-hour postprandial insulin levels(2 h INS),triglycerides(TG),uric acid(UA),alanine aminotransferase(ALT),fatty liver prevalence,abdominal fat percentage,and abdomen-to-hip ratio(AHR),compared with the subgroup without pancreatic fat deposition.High-density lipoprotein cholesterol(HDL-C)and limb fat percentage were lower in the subgroup with pancreatic fat deposition.In the T2DM group,the subgroup with pancreatic fat deposition showed higher levels of waist circumference,BMI,FINS,2 h INS,TG,UA,ALT,aspartate aminotransferase(AST),fatty liver prevalence,and abdominal fat percentage,compared with the subgroup without pancreatic fat deposition,with statistically significant differences(P<0.05).The HOMA-IR and HOMA-β in both NGT and T2DM groups with pancreatic fat deposition were significantly higher than those in the groups without pancreatic fat deposition.The prevalence of insulin resistance also significantly increased,with statistically significant differences(P<0.05).The results of multivariate logistic regression analysis showed that HDL-C,HOMA-β,abdominal fat percentage,age and fatty liver were the influencing factors for pancreatic fat deposition in NGT.Conclusion Elderly individuals with abdominal obesity and fatty liver are more prone to developing pancreatic fat deposition,which can affect islet function and aggravate the insulin resistance.

Objective To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation(LDH)by finite element analysis.Methods Lumbar CT image of a 48-year-old female patient with LDH(heighted 163 cm,weighted 53 kg)was collected.Mimics 20.0,Geomagic Studio,Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments.Compression techniques under horizon-tal position,30° forward bending and 10° backward extension were simulated respectively.After applying the pressure,the ef-fects of compression techniques under different positions on stress,strain and displacement of various tissues of intervertebral disc and nerve root were observed.Results L4,5 segment finite element model was successfully established,and the model was validated.When compression manipulation was performed on the horizontal position,30° flexion and 10° extension,the annular stress were 0.732,5.929,1.286 MPa,the nucleus pulposus stress were 0.190,1.527,0.295 MPa,and the annular strain were 0.097,0.922 and 0.424,the strain sizes of nucleus pulposus were 0.153,1.222 and 0.282,respectively.The overall displace-ment distance of intervertebral disc on Y direction were-3.707,-18.990,-4.171 mm,and displacement distance of nerve root on Y direction were+7.836,+5.341,+3.859 mm,respectively.The relative displacement distances of nerve root and interverte-bral disc on Y direction were 11.543,24.331 and 8.030 mm,respectively.Conclusion Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend,by increasing the distance between herniated interverte-bral disc and nerve root,to reduce symptoms of nerve compression,to achieve purpose of treatment for patients with LDH,in which the compression manipulation is more effective when the forward flexion is 30°.

Objective To evaluate and compare the success rate and short-term clinical prognosis of transfemoral transcatheter aortic valve replacement(TF-TAVR)for patients with pure aortic regurgitation(PAR)of different annulus sizes.Methods This study is a single center retrospective study,selecting symptomatic PAR patients who received TF-TAVR treatment at Zhongshan Hospital Fudan University from September 2019 to September 2023.Based on preoperative CT results,all patients were divided into three groups:Group A(aortic annulus circumference＜80 mm),Group B(80 mm≤aortic annulus circumference＜85 mm),and Group C(aortic annulus circumference&ge; 85 mm).The primary endpoint was success rate and 30d all-cause mortality,while the secondary endpoint was TAVR related complications.Results A total of 61 PAR patients were included in this study,including 27 in Group A,21 in Group B,and 13 in Group C.The overall success rate is 82.0％,and the 30 d all-cause mortality rate is 3.3％.The success rate of Group C patients was significantly lower(P=0.012),with higher rates of conversion to surgery and valve-in-valve implantation(P=0.022 and P=0.040).In terms of secondary endpoint events,there were no significant differences among the three groups in major bleeding events,major vascular complications,stroke,myocardial infarction,newly developed atrial fibrillation,implantation of new pacemakers,coronary artery occlusion,and postoperative moderate to severe perivalvular leakage(all P＞0.05).Conclusions The circumference of the aortic valve annulus is a key factor affecting the success rate of TF-TAVR in PAR,and PAR patients with an aortic valve annulus circumference less than 85mm may be more suitable for TF-TAVR.

OBJECTIVE: To explore the clinical effect of Kirschner wire intramedullary fixation in the treatment of both-bone forearm fractures in children of high altitude area. METHODS: From August 2020 to December 2021, 19 children were treated with Kirschner wire intramedullary fixation including 11 males and 8 females, aged from 4 to 13 years old with an average of (8.16±2.71) years old. The course of disease was 1 to 10 days, with a mean of (4.11±2.51) d. First, close reduction was performed. If the reduction was unsuccessful, limited open reduction was performed, followed by Kirschner wire intramedullary fixation of the radius and ulna. The fracture healing was evaluated by X-ray after operation, and the curative effect was evaluated by Anderson forearm function score standard. RESULTS: The wound healed well after operation, 2 cases had clinical manifestations of needle tail irritation after operation, and the symptoms disappeared after removing the internal fixation. The average follow-up time was(7.68±3.50) months (3 to 14 months). X-ray showed that all fracture healing in follow-up, Anderson forearm function score showed excellent in 16 cases, good in 2 cases and fair in 1 case at the final follow-up. CONCLUSION Children with fractures in plateau areas often have delayed medical treatment, lack of medical conditions and insufficient compliance. Based on these characteristics, Kirschner wire intramedullary fixation for the treatment of children's double forearm fractures has the advantages of small injury and rapid recovery. It is a kind of operation method that can be popularized.
Male ; Female ; Humans ; Child ; Child, Preschool ; Adolescent ; Bone Wires ; Forearm ; Altitude ; Treatment Outcome ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods* ; Radius Fractures/surgery* ; Fracture Fixation, Intramedullary/methods*

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Astragalus polysaccharide(APS), one of the main active components of Astragali Radix, plays an anti-tumor effect by regulating the inflammatory microenvironment of tumors. Exosomes are small extracellular vesicles with a diameter ranging from 50 to 200 nm and carry several biological components from parental cells such as nucleic acids and proteins. When combined with recipient cells, they play an important role in intercellular communication and immune response. In this study, exosomes released from H460 cells at the inflammatory state or with APS addition activated by Toll-like receptor 4(TLR4) were extracted by ultracentrifugation and characterized by Western blot, transmission electron microscopy, and nanoparticle tracking analysis. The exosomal proteins derived from H460 cells in the three groups were further analyzed by label-free proteomics, and 897, 800, and 911 proteins were identified in the three groups(Con, LPS, and APS groups), 88% of which belonged to the ExoCarta exosome protein database. Difference statistical analysis showed that the expression of 111 proteins was changed in the LPS group and the APS group(P<0.05). The biological information analysis of the differential proteins was carried out. The molecular functions, biological processes, and signaling pathways related to the differential proteins mainly involved viral processes, protein binding, and bacterial invasion of proteasome and epithelial cells. Key differential proteins mainly included plasminogen activator inhibitor-1, laminin α5, laminin α1, and CD44, indicating that tumor cells underwent systemic changes in different states and were reflected in exosomes in the inflammatory microenvironment. The analysis results also suggested that APS might affect the inflammatory microenvironment through the TLR4/MyD88/NF-κB signaling pathway or the regulation of the extracellular matrix. This study is conducive to a better understanding of the mechanism of tumor development in the inflammatory state and the exploration of the anti-inflammatory effect of APS at the exosome level.
Humans ; Exosomes/metabolism* ; Proteomics ; Toll-Like Receptor 4/metabolism* ; Lipopolysaccharides ; Astragalus Plant/chemistry* ; Lung Neoplasms/metabolism* ; Polysaccharides/metabolism* ; Tumor Microenvironment

ObjectiveTo observe the effect of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis on high-fat diet-induced apolipoprotein E gene knockout （ApoE^-/-） mice， and explore its mechanism of treating atherosclerosis by regulating intestinal flora. MethodThirty-two 8-week-old male ApoE^-/- mice were randomly divided into model group， rosuvastatin group （10 mg·kg^-1）， high-， low-dose groups of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis （75， 25 mg·kg^-1）， with 8 mice in each group. Eight C57BL/6 mice were used as blank group. After 8 weeks of continuous administration， blood was taken to determine the blood lipid level. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of related indexes in serum of mice. Hematoxylin-eosin （HE） staining was used to observe the formation of aortic plaque in mice. Cecal contents were collected and 16S rRNA amplicon sequencing was used to detect intestinal flora. ResultCompared with the blank group， the plaque area of the model group was significantly increased with inflammatory infiltration， the contents of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， inflammatory factors and inducible nitric oxide synthase （iNOS） were increased， while the content of high-density lipoprotein cholesterol （HDL-C） was decreased. Compared with the model group， rosuvastatin group and high- and low-dose groups of ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis could improve the deposition of aortic plaque， reduce the contents of TG， TC， LDL-C， inflammatory factors and iNOS， and increase the content of HDL-C. Compared with the blank group， the relative abundances of Firmicutes and Proteobacteria in the model group increased， while the relative abundance of Bacteroidetes decreased. Alpha and Beta diversity analysis showed that samples of each group could be significantly isolated， and the total number and abundance of intestinal flora species in the model group were low. Compared with the model group， ethyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis could increase the relative abundance of beneficial bacteria and decrease the relative abundance of pathogenic bacteria. ConclusionEthyl acetate extract of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis was mainly composed of flavonoids， which can treat atherosclerosis by regulating the intestinal flora and improve the pathological changes in the aorta of ApoE^-/- mice induced by high-fat diet. The mechanism may be related to its ability to reduce the level of inflammatory factors， improve antioxidant capacity and repair the disorder of intestinal flora structure.

The increasing incidence of obesity and diabetes has made diabetic kidney disease （DKD） the main cause of chronic kidney disease and end-stage renal disease. Despite current pharmacological interventions for blood glucose control and renin-angiotensin system inhibition， the risk of kidney disease progression and complications remains high. At present， the pathogenesis of DKD has been clarified to be related to chronic inflammatory response， oxidative stress， glucose and lipid metabolism disorders， and hemodynamic abnormalities. According to recent studies， the programmed cell deaths （PCD） of renal intrinsic cells such as pyroptosis and necroptosis play a key role in the occurrence and development of DKD. Pyroptosis and necroptosis， the two newly discovered routes of PCD， can protect the hosts from being invaded by microbial pathogens， but their dysregulation is associated with multiple autoimmunity and autoinflammatory responses. Pyroptosis and necroptosis are closely interlinked and cross-regulated. Different from apoptosis， these two cellular suicide mechanisms cause membrane rupture and release of cell contents through their respective gasdermin D （GSDMD） and mixed lineage kinase domain-like protein （MLKL）， with damage-associated molecular patterns （DAMPs） and inflammatory cytokines like interleukin-1β （IL-1β） involved to trigger inflammation， and chronic inflammatory responses are key factors leading to the progression of DKD. Traditional Chinese medicine （TCM） has long been employed for the prevention and treatment of DKD and the resulting clinical outcomes are remarkable. TCM has been proved to exert a protective effect against DKD by affecting the expression of nucleotide oligomerization domain-like receptor protein 3 （NLRP3） inflammasome， receptor-interacting protein kinase 3 （RIPK3）， and MLKL. This paper reviewed the relationship of pyroptosis and necroptosis with DKD and its intervention with TCM.

Objective: To investigate the efficacy and safety of a new cervical artificial disc prosthesis in the treatment of cervical degenerative diseases. Methods: The clinical data of 18 patients with single-level cervical degenerative diseases who underwent three dimensional printed anatomical bionic cervical disc replacement at Department of Spinal Surgery,Honghui Hospital,Xi'an Jiaotong University from May 2019 to July 2020 were analyzed retrospectively. There were 7 males and 11 females,aged (45±8) years old(range:28 to 58 years).The surgical segment was located at C_3－4 level in 2 cases, C_4－5 level in 5 cases, C_5－6 level in 9 cases, and C_6－7 level in 2 cases.The clinical and radiographic outcomes were recorded and compared at preoperative,postoperative times of one month and twelve months.The clinical assessments contained Japanese orthopedic association (JOA) score,neck disability index (NDI) and visual analogue scale (VAS).Imaging assessments included range of motion (ROM) of cervical spine, prosthesis subsidence and prosthesis anteroposterior migration.Repeated measurement variance analysis was used for comparison between groups,and paired t test was used for pairwise comparison. Results: All patients underwent the operation successfully and were followed up for more than 12 months.Compared with preoperative score,the JOA score,NDI and VAS were significantly improved after surgery (all P<0.01).There was no significant difference in postoperative ROM compared with 1-and 12-month preoperative ROM (t=1.570,P=0.135;t=1.744,P=0.099). The prosthesis subsidence was (0.29±0.13) mm (range: 0.18 to 0.50 mm) at 12-month postoperatively.The migration of prosthesis at 12-months postoperatively were (0.71±0.20) mm (range: 0.44 to 1.08 mm).There was no prosthesis subsidence or migration>2 mm at 12-month postoperatively. Conclusion: Three dimensional printed anatomical biomimetic cervical artificial disc replacement has a good early clinical effect in the treatment of cervical degenerative diseases, good mobility can be obtained while maintaining stability.
Adult ; Biomimetics ; Cervical Vertebrae/surgery* ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc/surgery* ; Intervertebral Disc Degeneration/surgery* ; Male ; Middle Aged ; Range of Motion, Articular ; Retrospective Studies ; Total Disc Replacement/methods* ; Treatment Outcome