Biomechanical comparison of the therapeutic effect of a novel proximal femoral bionic intramedullary nail and traditional inverted triangle hollow screw on femoral neck fracture.

OBJECTIVE: A novel Proximal Femoral Bionic Nail (PFBN) has been developed by a research team for the treatment of femoral neck fractures. This study aims to compare the biomechanical properties of the innovative PFBN with those of the conventional Inverted Triangular Cannulated Screw (ITCS) fixation method through biomechanical testing. METHODS: Sixteen male femoral specimens preserved in formalin were selected, with the donors' age at death averaging 56.1 ± 6.3 years (range 47-64 years), and a mean age of 51.4 years. The femurs showed no visible damage and were examined by X-rays to exclude diseases affecting bone quality such as tumors, severe osteoporosis, and deformities. The 16 femoral specimens were randomly divided into an experimental group (n = 8) and a control group (n = 8). All femurs were prepared with Pauwels type III femoral neck fractures, fixed with PFBN in the experimental group and ITCS in the control group. Displacement and stress limits of each specimen were measured through cyclic compression tests and failure experiments, and vertical displacement and strain values under a 600 N vertical load were measured in all specimens through vertical compression tests. RESULTS: In the vertical compression test, the average displacement at the anterior head region of the femur was 0.362 mm for the PFBN group, significantly less than the 0.480 mm for the ITCS group (p < 0.001). At the fracture line area, the average displacement for the PFBN group was also lower than that of the ITCS group (0.196 mm vs. 0.324 mm, p < 0.001). The difference in displacement in the shaft area was smaller, but the average displacement for the PFBN group (0.049 mm) was still significantly less than that for the ITCS group (0.062 mm, p = 0.016). The situation was similar on the posterior side of the femur. The average displacements in the head area, fracture line area, and shaft area for the PFBN group were 0.300 mm, 0.168 mm, and 0.081 mm, respectively, while those for the ITCS group were 0.558 mm, 0.274 mm, and 0.041 mm, with significant differences in all areas (p < 0.001). The average strain in the anterior head area for the PFBN group was 4947 µm/m, significantly less than the 1540 µm/m for the ITCS group (p < 0.001). Likewise, in the fracture line and shaft areas, the average strains for the PFBN group were significantly less than those for the ITCS group (p < 0.05). In the posterior head area, the average strain for the PFBN group was 4861 µm/m, significantly less than the 1442 µm/m for the ITCS group (p < 0.001). The strain conditions in the fracture line and shaft areas also showed the PFBN group was superior to the ITCS group (p < 0.001). In cyclic loading experiments, the PFBN fixation showed smaller maximum displacement (1.269 mm vs. 1.808 mm, p < 0.001), indicating better stability. In the failure experiments, the maximum failure load that the PFBN-fixated fracture block could withstand was significantly higher than that for the ITCS fixation (1817 N vs. 1116 N, p < 0.001). CONCLUSION: The PFBN can meet the biomechanical requirements for internal fixation of femoral neck fractures. PFBN is superior in biomechanical stability compared to ITCS, particularly showing less displacement and higher failure resistance in cyclic load and failure experiments. While there are differences in strain performance in different regions between the two fixation methods, overall, PFBN provides superior stability.

A Controlled Variable Study of the Biomechanical Properties of the Proximal Femur before and after Cancellous Bone Removal.

OBJECTIVE: The biomechanical characteristics of proximal femoral trabeculae are closely related to the occurrence and treatment of proximal femoral fractures. Therefore, it is of great significance to study its biomechanical effects of cancellous bone in the proximal femur. This study examines the biomechanical effects of the cancellous bone in the proximal femur using a controlled variable method, which provide a foundation for further research into the mechanical properties of the proximal femur. METHODS: Seventeen proximal femoral specimens were selected to scan by quantitative computed tomography (QCT), and the gray values of nine regions were measure to evaluated bone mineral density (BMD) using Mimics software. Then, an intact femur was fixed simulating unilateral standing position. Vertical compression experiments were then performed again after removing cancellous bone in the femoral head, femoral neck, and intertrochanteric region, and data were recorded. According to the controlled variable method, the femoral head, femoral neck, and intertrochanteric trabeculae were sequentially removed based on the axial loading of the intact femur, and the displacement and strain changes of the femur samples under axial loading were recorded. Gom software was used to measure and record displacement and strain maps of the femoral surface. RESULTS: There was a statistically significant difference in anteroposterior displacement of cancellous bone destruction in the proximal femur (p < 0.001). Proximal femoral bone mass explained 77.5% of the strength variation, in addition proximal femoral strength was mainly affected by bone mass at the level of the upper outer, lower inner, lower greater trochanter, and lesser trochanter of the femoral head. The normal stress conduction of the proximal femur was destroyed after removing cancellous bone, the stress was concentrated in the femoral head and lateral femoral neck, and the femoral head showed a tendency to subside after destroying cancellous bone. CONCLUSION: The trabecular removal significantly altered the strain distribution and biomechanical strength of the proximal femur, demonstrating an important role in supporting and transforming bending moment under the vertical load. In addition, the strength of the proximal femur mainly depends on the bone density of the femoral head and intertrochanteric region.

Cross-site prognosis prediction for nasopharyngeal carcinoma from incomplete multi-modal data.

Accurate prognosis prediction for nasopharyngeal carcinoma based on magnetic resonance (MR) images assists in the guidance of treatment intensity, thus reducing the risk of recurrence and death. To reduce repeated labor and sufficiently explore domain knowledge, aggregating labeled/annotated data from external sites enables us to train an intelligent model for a clinical site with unlabeled data. However, this task suffers from the challenges of incomplete multi-modal examination data fusion and image data heterogeneity among sites. This paper proposes a cross-site survival analysis method for prognosis prediction of nasopharyngeal carcinoma from domain adaptation viewpoint. Utilizing a Cox model as the basic framework, our method equips it with a cross-attention based multi-modal fusion regularization. This regularization model effectively fuses the multi-modal information from multi-parametric MR images and clinical features onto a domain-adaptive space, despite the absence of some modalities. To enhance the feature discrimination, we also extend the contrastive learning technique to censored data cases. Compared with the conventional approaches which directly deploy a trained survival model in a new site, our method achieves superior prognosis prediction performance in cross-site validation experiments. These results highlight the key role of cross-site adaptability of our method and support its value in clinical practice.

Corydalis saxicolaBunting total alkaloid eliminates Porphyromonas gingivalis strain 33277 internalized into macrophages by inhibition of TLR2.

OBJECTIVE: This study aimed to investigate the impact of Corydalis Saxicola Bunting Total Alkaloid (CSBTA) on Porphyromonas gingivalis internalization within macrophages and explore the potential role of Toll-Like Receptor 2 (TLR2) in this process. METHODS: We established a P. gingivalis internalization model in macrophages by treating P. gingivalis-infected macrophages (MOI=100:1) with 200 µg/mL metronidazole and 300 µg/mL gentamicin for 1 h. Subsequently, the model was exposed to CSBTA at concentrations of 0.02 g/L or 1 µg/mL Pam3CSK4. After a 6 h treatment, cell lysis was performed with sterile water to quantify bacterial colonies. The mRNA expressions of TLR2 and interleukin-8 (IL-8) in macrophages were analyzed using RT-qPCR, while their protein levels were assessed via Western blot and ELISA respectively. RESULTS: P. gingivalis could internalize into macrophages and enhance the expression of TLR2 and IL-8. Activation of TLR2 by Pam3CSK4 contributed to P. gingivalis survival within macrophages and increased TLR2 and IL-8 expression. Conversely, 0.02 g/L CSBTA effectively cleared intracellular P. gingivalis, achieving a 90 % clearance rate after 6 h. Moreover, it downregulated the expression of TLR2 and IL-8 induced by P. gingivalis. However, the inhibitory effect of CSBTA on the internalized P. gingivalis model was attenuated by Pam3CSK4. CONCLUSION: CSBTA exhibited the ability to reduce the presence of live intracellular P. gingivalis and lower IL-8 expression in macrophages, possibly by modulating TLR2 activity.

The effects of CPET-guided cardiac rehabilitation on exercise tolerance in older persons with CHD after PCI.

Prescribing appropriate exercise is an important means to improve the safety and efficacy of cardiac rehabilitation. Improper exercise may induce an increased cardiovascular risk in older persons with coronary heart disease. Cardiopulmonary exercise testing (CPET)-guided cardiac rehabilitation could be helpful for providing clinical evidence for cardiac rehabilitation therapy in older persons after percutaneous coronary intervention (PCI). We retrospectively included older persons who underwent PCI and cardiac rehabilitation based on CPET at the Cardiac Rehabilitation Center of Peking University Third Hospital from January 2014 to December 2019. Patients' baseline and follow-up clinical data were collected. A total of 403 older persons after PCI were included in the study. The mean age was 80.5 ± 4.3. The mean follow-up time was 12 ± 2 months. During the follow-up period, no significant exercise-related adverse events occurred, and the peak oxygen uptake (VO2peak) increased compared with baseline (15.5 ± 3.8 ml/min/kg vs. 17.3 ± 4.1 ml/min/kg). Among the 90 patients (22.2%) without exercise habits at baseline who started regular exercise during follow-up, the improvement in VO2peak was most significant, at 3.2 ± 0.4 ml/min/kg. Cardiac rehabilitation based on CPET improved exercise habits and exercise tolerance in older persons with coronary heart disease after PCI.

Age-related Changes with the Trabecular Bone of Ward's Triangle and Neck-shaft Angle in the Proximal Femur: A Radiographic Study.

OBJECTIVE: The Ward triangle is an important area used clinically to diagnose and assess osteoporosis and its fracture risk in the proximal femur. The main objective of this study was to investigate the rules of development and maturation of the trabeculae of Ward's triangle to provide a basis for the prevention and treatment proximal femur fracture. METHODS: From January 2018 to December 2019, individuals from 4 months to 19 years old who underwent hip growth and development assessments at the Third Hospital of Hebei Medical University were selected retrospectively. The outpatient electronic medical record system was used to collect information such as age, gender, imaging images, and clinical diagnosis. The development score and maturity characteristics of the trabecular bone were analyzed using hip radiograph data. Correlation analysis was performed to identify the relationship among age, neck-shaft angle and development and maturity score of the trabecular bone. RESULTS: A total of 941 patients were enrolled in this study, including 539 males and 402 females. Primary compression trabeculae were all present at 1 year of age and matured at 7 years of age and older; primary tension trabeculae were all present at 4 years of age and matured at 18 years of age. Secondary compression trabeculae were present at 4 years of age and matured at 18 years of age. In addition, the neck-shaft angle progressively decreases from 4 months to 14 years of age but barely changes between 15 and 19 years of age. CONCLUSION: In short, the development and maturation of the trabeculae in the ward' triangle followed a specific temporal pattern that was related to the neck-shaft angle. Therefore, these findings can help us understand structure and mechanical characteristics of proximal femoral trabeculae, and improve our understanding of the mechanism and treatment of proximal femoral fractures.

Application of piezoelectric materials in the field of bone: a bibliometric analysis.

In the past 4 decades, many articles have reported on the effects of the piezoelectric effect on bone formation and the research progress of piezoelectric biomaterials in orthopedics. The purpose of this study is to comprehensively evaluate all existing research and latest developments in the field of bone piezoelectricity, and to explore potential research directions in this area. To assess the overall trend in this field over the past 40 years, this study comprehensively collected literature reviews in this field using a literature retrieval program, applied bibliometric methods and visual analysis using CiteSpace and R language, and identified and investigated publications based on publication year (1984-2022), type of literature, language, country, institution, author, journal, keywords, and citation counts. The results show that the most productive countries in this field are China, the United States, and Italy. The journal with the most publications in the field of bone piezoelectricity is the International Journal of Oral & Maxillofacial Implants, followed by Implant Dentistry. The most productive authors are Lanceros-Méndez S, followed by Sohn D.S. Further research on the results obtained leads to the conclusion that the research direction of this field mainly includes piezoelectric surgery, piezoelectric bone tissue engineering scaffold, manufacturing artificial cochleae for hearing loss patients, among which the piezoelectric bone tissue engineering scaffold is the main research direction in this field. The piezoelectric materials involved in this direction mainly include polyhydroxybutyrate valerate, PVDF, and BaTiO3.

Non­small cell lung cancer carrying PBRM1 mutation suggests an immunologically cold phenotype leading to immunotherapy failure even with high TMB.

High tumor mutation load (TMB-H, or TMB ≥ 10) has been approved by the U.S. FDA as a biomarker for pembrolizumab treatment of solid tumors, including non­small cell lung cancer (NSCLC). Patients with cancer who have immunotherapy-resistant gene mutations cannot achieve clinical benefits even in TMB-H. In this study, we aimed to identify gene mutations associated with immunotherapy resistance and further informed mechanisms in NSCLC. A combined cohort of 350 immune checkpoint blockade-treated patients from Memorial Sloan Kettering Cancer Center (MSKCC) was used to identify genes whose mutations could negatively influence immunotherapy efficacy. An external NSCLC cohort for which profession-free survival (PFS) data were available was used for independent validation. CIBERSORT algorithms were used to characterize tumor immune infiltrating patterns. Immunogenomic features were analysed in the TCGA NSCLC cohort. We observed that PBRM1 mutations independently and negatively influence immunotherapy efficacy. Survival analysis showed that the overall survival (OS) and PFS of patients with PBRM1 mutations (MT) were significantly shorter than the wild type (WT). Moreover, compared with PBRM1-WT/TMB-H group, OS was worse in the PBRM1-MT/TMB-H group. Notably, in patients with TMB-H/PBRM1-MT, it was equal to that in the low-TMB group. The CIBERSORT algorithm further confirmed that the immune infiltration abundance of CD8+ T cells and activated CD4+ memory T was significantly lower in the MT group. Immunogenomic differences were observed in terms of immune signatures, T-cell receptor repertoire, and immune-related genes between WT and MT groups. Nevertheless, we noticed an inverse relationship, given that MT tumors had a higher TMB than the WT group in MSKCC and TCGA cohort. In conclusion, our study revealed that NSCLC with PBRM1 mutation might be an immunologically cold phenotype and exhibited immunotherapy resistance. NSCLC with PBRM1 mutation might be misclassified as immunoresponsive based on TMB.

A Machine Learning Model to Predict Cardiovascular Events during Exercise Evaluation in Patients with Coronary Heart Disease.

OBJECTIVE: To develop and optimize a machine learning prediction model for cardiovascular events during exercise evaluation in patients with coronary heart disease (CHD). METHODS: 16,645 cases of cardiopulmonary exercise testing (CPET) conducted in patients with CHD from January 2016 to September 2019 were retrospectively included. Clinical data before testing and data during exercise were collected and analyzed. RESULTS: Cardiovascular events occurred during 505 CPETs (3.0%). No death was reported. Predictive accuracy of the model was evaluated by area under the curve (AUC). AUCs for the SVM, logistic regression, GBDT and XGBoost were 0.686, 0.778, 0.784, and 0.794 respectively. CONCLUSIONS: Machine learning methods (especially XGBoost) can effectively predict cardiovascular events during exercise evaluation in CHD patients. Cardiovascular events were associated with age, male, diabetes and duration of diabetes, myocardial infarction history, smoking history, hyperlipidemia history, hypertension history, oxygen uptake, and ventilation efficiency indicators.

Forkhead Box S1 mediates epithelial-mesenchymal transition through the Wnt/ß-catenin signaling pathway to regulate colorectal cancer progression.

BACKGROUND: Recent studies have shown that the fox family plays a vital role in tumorigenesis and progression. Forkhead Box S1 (FOXS1), as a newly identified subfamily of the FOX family, is overexpressed in certain types of malignant tumors and closely associated with patient's prognosis. However, the role and mechanism of the FOXS1 in colorectal cancer (CRC) remain unclear. METHOD: FOXS1 level in CRC tissues and cell lines was analyzed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) was used to detect the relationship between FOXS1 expression and clinicopathological features in 136 patients in our unit. The expression of FOXS1 was knocked down in CRC cells using small interfering RNA (siRNA) technology. Cell proliferation was assessed by CCK8 assay, colony formation, and 5-Ethynyl-20-deoxyuridine (EdU) incorporation assay. Flow cytometry detected apoptosis and wound healing, and Transwell assays determined cell migration and invasion. Western blotting was used to detect the levels of proteins associated with the Wnt/ß-catenin signaling pathway. Then, we used short hairpin RNA (shRNA) to knock down FOXS1 to see the effect of FOXS1 on the proliferation, migration, invasion, and metastasis of CRC cells in vivo. Finally, we investigated the impact of Wnt activator LiCl on the proliferation, migration, invasion, and metastasis of CRC cells after FOXS1 knockdown. RESULT: Compared to those in normal groups, FOXS1 overexpressed in CRC tissues and CRC cells (P < 0.05). Upregulation of FOXS1 association with poor prognosis of CRC patients. si-FOXS1 induced apoptosis and inhibited proliferation, migration, invasion, the epithelial-mesenchymal transition (EMT), and the Wnt/ß-catenin signaling pathway in vitro; sh-FOXS1 inhibited the volume and weight of subcutaneous xenografts and the number of lung metastases in vivo. LiCl, an activator of Wnt signaling, partially reversed the effect of FOXS1 overexpression on CRC cells. CONCLUSION: FOXS1 could function as an oncogene and promote CRC cell proliferation, migration, invasion and metastasis through the Wnt/ßcatenin signaling pathway, FOXS1 may be a potential target for CRC treatment.

Relative Prevalence and Associated Factors of Complex Regional Pain Syndrome Type I in Patients with Radial Head Fractures Treated with Open Reduction and Internal Fixation: A Cross-Sectional Study.

Objective: This cross-sectional study aimed to examine the incidence and associated factors of complex regional pain syndrome type I (CRPS I) in patients who underwent open reduction and internal fixation (ORIF) for radial head fractures. Methods: The study enrolled 601 radial head fracture patients treated with ORIF, 523 of which completed the 1-year follow-up. The incidence of CRPS I in those patients was assessed using the Budapest criteria. Patients were then divided into 2 groups: patients with CRPS I (n = 28) and patients without CRPS I (n = 495). The patients' demographic and clinical data before the operation were prospectively collected by our team. Independent t-tests and χ 2 tests were used as univariate analyses to compare the demographic and clinical data between the two groups. Meanwhile, multivariate regression analysis was conducted to identify the associated risk factors for CRPS I. Results: The incidence of CRPS I in patients with radial head fractures treated with ORIF was 5.5% during the first year following surgery. Significant differences were observed in age, gender, type of trauma, modified Mason Classification, and depressive personality disorders. The logistic regression analysis revealed that the female gender, modified Mason type III fractures, and depressive patients were significantly more likely to develop CRPS I (p=0.021, 0.023, and 0.025, respectively). Conclusions: The incidence of CRPS I among radial head fracture patients undergoing ORIF was 5.5%. In addition, early detection of CRPS I and providing adequate intervention will likely result in greater benefits for those patients.

Finite element analysis of biomechanical effects of residual varus/valgus malunion after femoral fracture on knee joint.

OBJECTIVE: Post-operative femoral shaft fractures are often accompanied by a residual varus/valgus deformity, which can result in osteoarthritis in severe cases. The purpose of this study was to investigate the biomechanical effects of residual varus/valgus deformities after middle and lower femoral fracture on the stress distribution and contact area of knee joint. METHODS: Thin-slice CT scanning of lower extremities and MRI imaging of knee joints were obtained from a healthy adult male to establish normal lower limb model (neutral position). Then, the models of 3°, 5°, and 10° of varus/valgus were established respectively by modifying middle and lower femur of normal model. To validate the modifying, a patient-specific model, whose BMI was same to former and had 10° of varus deformity of tibia, was built and simulated under the same boundary conditions. RESULT: The contact area and maximum stress of modified models were similar to those of patient-specific model. The contact area and maximum stress of medial tibial cartilage in normal neutral position were 244.36 mm2 and 0.64 MPa, while those of lateral were 196.25 mm2 and 0.76 MPa. From 10° of valgus neutral position to 10° of varus, the contact area and maximum stress of medial tibial cartilage increased, and the lateral gradually decreased. The contact area and maximum stress of medial meniscus in normal neutral position were 110.91 mm2 and 3.24 MPa, while those of lateral were 135.83 mm2 and 3.45 MPa. The maximum stress of medial tibia subchondral bone in normal neutral position was 1.47 MPa, while that of lateral was 0.65 MPa. The variation trend of medial/lateral meniscus and subchondral bone was consistent with that of tibial plateau cartilage in the contact area and maximum stress. CONCLUSION: This study suggested that varus/valgus deformity of femur had an obvious effect on the contact area and stress distribution of knee joint, providing biomechanical evidence and deepening understanding when performing orthopedic trauma surgery or surgical correction of the already existing varus/valgus deformity.

Ischemic Preconditioning Upregulates Decoy Receptors to Protect SH-SY5Y Cells from OGD Induced Cellular Damage by Inhibiting TRAIL Pathway and Agitating PI3K/Akt Pathway.

As ischemic preconditioning (IPC) represents a potential therapy against cerebral ischemia, the purpose of the present study is to explore the molecular mechanisms of ischemic preconditioning induced cerebral protective effect. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily, which induces apoptosis through binding to its death receptors (DR4 and DR5). When TRAIL binds to decoy receptors (DcR1 and DcR2), as DcRs lack intact cytoplasmic death domain, TRAIL fails to induce neuronal apoptosis. In the present study, we demonstrated that ischemic preconditioning upregulated DcR1 and DcR2, which subsequently inhibited oxygen glucose deprivation-induced cellular apoptosis. Then, we investigated the protective molecular mechanism of DcRs after ischemic preconditioning treatment. Results showed that DcR1 could competitively bind to TRAIL and partially inhibit TRAIL-induced cellular apoptosis. On the other hand, DcR2 could disturb DRs-associated death-inducing signaling complex formation (DISC), which further inhibited capase-8 activation. Besides, we also found that ischemic preconditioning activated IPC-induced Akt phosphorylation via regulating DcR2 level. Thus, ischemic preconditioning upregulated decoy receptors, which protected cells from oxygen glucose deprivation-induced cellular damage by inhibiting TRAIL-induced apoptosis and agitating PI3K/Akt pathway. Our data complemented the knowledge of neuroprotective mechanism of ischemic preconditioning and provided new evidence for supporting its clinical application.

The effects of atorvastatin and rosuvastatin on exercise tolerance in patients with coronary heart disease.

OBJECTIVES: This study was aimed to analyze the effects of atorvastatin and rosuvastatin and different lipid-lowering intensity treatments on exercise tolerance in patients with coronary heart disease (CHD). METHODS: A retrospective analysis was conducted in 549 patients with CHD who underwent cardiopulmonary exercise testing (CPET) from February 2014 to August 2018. The CPET results of patients taking different types and doses of statins were compared from baseline to follow-up. RESULTS: No significant difference was found in baseline VO2peak between the rosuvastatin group and the atorvastatin group. The VO2peak growth of the rosuvastatin group was significantly greater than that of the atorvastatin group after treatment [1.52 ± 4.03 ml/kg/min vs 0.90 ml/kg/min (-1.60, 3.45), p = 0.018]. Multivariate analysis showed that atorvastatin was a negative independent influencing factor of ΔVO2peak (B = -0.665, SE = 0.321, t = -2.070, p = 0.039, 95% CI: - 1.295~-0.034). There was no significant difference between the median intensity and high-intensity lipid-lowering groups in parameters of CPET. CONCLUSIONS: The exercise tolerance improvement was more considerable for patients with CHD taking rosuvastatin compared with those taking atorvastatin. The lipid-lowering intensity of statins was not independently associated with changes in exercise tolerance in patients with CHD.

Analysis of cyclin E co-expression genes reveals nuclear transcription factor Y subunit alpha is an oncogene in gastric cancer.

OBJECTIVE: To explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment. METHODS: The Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencing data were used to predict genes co-expressed with cyclin E. Co-expression genes predicted by cBioPortal online analysis with Pearson correlation coefficient ≥0.4 were analyzed by gene ontology (GO) enrichment annotation using the PANTHER online platform (Ver. 7). Interactions between proteins encoded by these genes were analyzed using the STRING online platform (Ver. 10.5) and Cytoscape software (Ver. 3.5.1). Genes displaying a high degree of connection were analyzed by transcription factor enrichment prediction using FunRich software (Ver. 3). The significant transcription factor and cyclin E expression levels and their impact on gastric cancer progression were analyzed by Western blotting and Kaplan-Meier survival curve analysis. RESULTS: After filtering the co-expression gene prediction results, 78 predicted genes that included 73 protein coding genes and 5 non-coding genes with Pearson correlation coefficient ≥0.4 were selected. The expressions of the genes were considered to be correlated with cyclin E expression. Among the 78 genes co-expressed with cyclin E, 19 genes at the central of the regulatory network associated with cyclin E were discovered. Nuclear transcription factor Y subunit alpha (NF-YA) was identified as a significant transcription factor associated with cyclin E co-expressing genes. Analysis of specimen donors' clinical records revealed that high expression of NF-YA tended to be associated with increased cyclin E expression. The expression of both was associated with progression of gastric cancer. Western blotting results showed that compared with normal tissues, NF-YA and cyclin E were highly expressed in tumor tissues (P < 0.001). Survival curve analysis clearly demonstrated relatively poor overall survival of gastric cancer patients with high cyclin E or high NF-YA expression level, compared to patients with low cyclin E or NF-YA expression (P < 0.05). CONCLUSIONS: NF-YA may promote gastric cancer progression by increasing the transcription of cyclin E and other cell cycle regulatory genes. NF-YA might be a potential therapeutically useful prognostic factor for gastric cancer.

The renal protect function of erythropoietin after release of bilateral ureteral obstruction in a rat model.

Congenital urinary tract obstruction is one of the most frequent malformations in fetuses or neonates, which usually causes profound impairment of renal function including reductions in both glomerular filtration rate (GFR) and tubular handling of water and solutes. Although obstruction can be released by surgical operation, the child will suffer from diuresis for sometime. It has been reported that erythropoietin (EPO) could prevent the down-regulation of aquaporin-2 (AQP2) and urinary-concentrating defects induced by renal ischemia/reperfusion (I/R) injury. However, whether EPO could promote the recovery of renal function and AQP2 expression after releasing of ureteral obstruction has not been reported yet. The purposes of the present study were to investigate the effects of EPO on renal function and AQP2 expression after release of bilateral ureteral obstruction (BUO-R) in rats. The results showed that EPO could promote interleukin (IL) 10 (IL-10) expression; inhibit tumor necrosis factor-α (TNF-α), IL-6, and inducible nitric oxide synthase (iNOS) expressions; reduce the fractional excretion of sodium (FENa) and plasma creatinine (CREA) and urea; and promote the recovery of water and salt handling and AQP2 expression in BUO-R rats, especially in the high dose of EPO-treated group rats. In conclusion, EPO could promote the recovery of renal function and AQP2 expression in BUO-R rats, which may partially associate with its anti-inflammation effect.

[Source Analysis and Environmental Health Risk Assessment of VOCs in Furniture Manufacturing].

Regarding furniture manufacturing, scholars have only studied the sources of VOCs in the spraying process, yet the main concern is the release of VOCs after the completion of the manufacturing process and its impact on indoor air quality. Therefore, in this study, the sources of VOCs for the entire process of furniture manufacturing were explored and probabilistic risk models were improved. Then, the carcinogenicity and non-carcinogenic health risks to workers at nine workstations in a furniture factory were evaluated via a Monte Carlo simulation method, and the sensitivity of each exposure parameter was analyzed. The results are as follows. The various types of paints, diluents, and curing agents used in the process of spraying primer paint and spraying surface paint release VOCs, such as benzene, toluene, xylene, styrene, butanone, cyclohexanone, butyl acetate, and ethyl acetate. The glue used in the leather pasting process, the glue process, and the viscose process generates VOCs, such as dichloromethane and ethyl acetate, and the paint remover used in the cleaning process emits dichloromethane. The carcinogenic risk at each station was more than 10-6. For benzene exposure, the probability of exceeding 10-6 was greater than 95% for all stations, excluding SWB, SWP, and CWP. The carcinogenicrisk of workers exposed to benzene was the highest at SWS, at 3.07×10-6±1.73×10-6, and the carcinogenicrisk of workers exposed to dichloromethane was the greatest at SWL, with a value of 5.14×10-6±2.70×10-6. The only non-carcinogenicrisk greater than 1 was to SWS workers. The parameters that had the greatest impact on the carcinogenic risk assessment were exposure day (ED), concentration (C), exposure time (ET), and exposure frequency (EF). In the non-carcinogenic risk assessment, the most influential variables were ED, ET, and EF. In addition, concentration also had a significant impact on the evaluation results.

Transplanted miR-219-overexpressing oligodendrocyte precursor cells promoted remyelination and improved functional recovery in a chronic demyelinated model.

Oligodendrocyte precursor cells (OPCs) have the ability to repair demyelinated lesions by maturing into myelin-producing oligodendrocytes. Recent evidence suggests that miR-219 helps regulate the differentiation of OPCs into oligodendrocytes. We performed oligodendrocyte differentiation studies using miR-219-overexpressing mouse embryonic stem cells (miR219-mESCs). The self-renewal and multiple differentiation properties of miR219-mESCs were analyzed by the expression of the stage-specific cell markers Nanog, Oct4, nestin, musashi1, GFAP, Tuj1 and O4. MiR-219 accelerated the differentiation of mESC-derived neural precursor cells (NPCs) into OPCs. We further transplanted OPCs derived from miR219-mESCs (miR219-OPCs) into cuprizone-induced chronically demyelinated mice to observe remyelination, which resulted in well-contained oligodendrocyte grafts that migrated along the corpus callosum and matured to express myelin basic protein (MBP). Ultrastructural studies further confirmed the presence of new myelin sheaths. Improved cognitive function in these mice was confirmed by behavioral tests. Importantly, the transplanted miR219-OPCs induced the proliferation of endogenous NPCs. In conclusion, these data demonstrate that miR-219 rapidly transforms mESCs into oligodendrocyte lineage cells and that the transplantation of miR219-OPCs not only promotes remyelination and improves cognitive function but also enhances the proliferation of host endogenous NPCs following chronic demyelination. These results support the potential of a therapeutic role for miR-219 in demyelinating diseases.

Decreased expression of SOX17 is associated with tumor progression and poor prognosis in breast cancer.

The SOX17 (SRY-related HMG-box) transcription factor is involved in a variety of biological processes and is related to the tumorigenesis and progression of multiple tumors. However, the clinical application of SOX17 for breast cancer prognosis is currently limited. The aim of this study was to investigate the clinicopathologic and prognostic significance of SOX17 expression in human breast cancer. qPCR and western blot assays were performed to measure the expression of SOX17 in breast cancer cell lines and 30 matched pairs of breast cancer and corresponding noncancerous tissues. A SOX17 overexpression cell model was used to examine changes in cell growth in vitro. Immunohistochemical analyses were performed to retrospectively examine the prognostic impact of SOX17 expression in 187 additional breast cancer patients. Our results showed that SOX17 expression was decreased at both the messenger RNA (mRNA) and protein levels in the breast cancer cell lines and tissues, and that SOX17 overexpression could strongly suppress cell growth in vitro. Furthermore, the lack of SOX17 protein expression was strongly correlated with higher tumor grade (P = 0.002), lymph node metastasis (P < 0.001), and tumor node metastasis (TNM) stage (P = 0.001) and had poorer disease-free survival (DFS) and overall survival (OS) compared to normal SOX17 expression (P = 0.002 and 0.001, respectively). Univariate and multivariate analyses indicated that lower SOX17 expression was an independent prognostic factor for DFS (P = 0.007; HR = 2.854; 95 % CI 1.326-6.147) and OS (P = 0.005; HR = 5.035; 95 % CI 1.648-15.385) for breast cancer. Our findings indicate that SOX17 expression is a useful prognostic biomarker for breast cancer.

Unusual early-stage pancreatic sarcomatoid carcinoma.

Sarcomatoid carcinoma of the pancreas (SCP) is a very rare pathological type of carcinoma that usually has a poor prognosis. Its pathogenesis has not been elucidated. We herein report a case of an early-stage SCP involving successful treatment and a good prognosis. The patient was a 48-year-old Chinese man with a 5-mo history of vague abdominal pain. Ultrasonography revealed a 93 mm × 94 mm × 75 mm mass of mixed echogenicity in the tail of the pancreas. Laboratory test results were within the normal range, with the exception of an obviously increased pretreatment neuron-specific enolase level. The plasma transforming growth factor (TGF)ß1 and interleukin-11 levels were obviously increased according to enzyme-linked immunosorbent assay. Microscopically, the excised tumor tissue comprised cancer cells and mesenchymal cells. Immunohistochemical analysis was positive for α-1-antichymotrypsin, pan-cytokeratin, cytokeratin 19, cytokeratin 8/18, and vimentin and negative for CD68 and lysozyme. The pathogenetic mechanism of this case shows that TGFß1 may regulate the epithelial-to-mesenchymal transition in SCP. With early eradication of the tumor and systemic therapy, this patient has been alive for more than 3 years without tumor recurrence or distant metastasis. This case is also the first to show that TGFß1 may regulate the epithelial-to-mesenchymal transition in early-stage SCP.