Effect of bisphosphonate on bone microstructure, mechanical strength in osteoporotic rats by ovariectomy.

BACKGROUND: Bisphosphonate (BP) can treat osteoporosis and prevent osteoporotic fractures in clinical. However, the effect of BP on microstructure and mechanical properties of cortical and trabecular bone has been taken little attention, separately. METHODS: In this study, BP was used to intervene in ovariectomized female SD rats. The femoral micro-CT images were used to measure the structural parameters and reconstruct the 3D models in volume of interest. The structural parameters of cortical and trabecular bone were measured, and the mechanical properties were predicted using micro-finite element analysis. RESULTS: There was almost no significant difference in the morphological structure parameters and mechanical properties of cortical bone between normal, ovariectomized (sham-OVX) and BP intervention groups. However, BP could significantly improve bone volume fraction (BV/TV) and trabecular separation (Tb.SP) in inter-femoral condyles (IT) (sham-OVX vs. BP, p < 0.001), and had no significant effect on BV/TV in medial and lateral femoral condyles (MT, LT). Similarly, BPs could significantly affect the effective modulus in IT (sham-OVX vs. BP, p < 0.001), and had no significant difference in MT and LT. In addition, the structural parameters and effective modulus showed a good linear correlation. CONCLUSION: In a short time, the effects of BP intervention and osteoporosis on cortical bone were not obvious. The effects of BP on trabecular bone in non-main weight-bearing area (IT) were valuable, while for osteoporosis, the main weight-bearing area (MT, LT) may improve the structural quality and mechanical strength of trabecular bone through exercise compensation.

Improved PAA algorithm for breast mass detection in mammograms.

Mammography screening is instrumental in the early detection and diagnosis of breast cancer by identifying masses in mammograms. With the rapid development of deep learning, numerous deep learning-based object detection algorithms have been explored for mass detection studies. However, these methods often yield a high false positive rate per image (FPPI) while achieving a high true positive rate (TPR). To maintain a higher TPR while also ensuring lower FPPI, we improved the Probability Anchor Assignment (PAA) algorithm to enhance the detection capability for mammographic characteristics with our previous work. We considered three dimensions: the backbone network, feature fusion module, and dense detection heads. The final experiment showed the effectiveness of the proposed method, and the TPR/FPPI values of the final improved PAA algorithm were 0.96/0.56 on the INbreast datasets. Compared to other methods, our method stands distinguished with its effectiveness in addressing the imbalance between positive and negative classes in cases of single lesion detection.

Deciphering programmed cell death mechanisms in osteosarcoma for prognostic modeling.

Osteosarcoma (OS), known for its high recurrence and metastasis rates, poses a significant challenge in oncology. Our research investigates the role of programmed cell death (PCD) genes in OS and develops a prognostic model using advanced bioinformatics. We analyzed single-cell sequencing data from the Gene Expression Omnibus (GEO) database to identify subpopulations, distinguish malignant from non-malignant cells, assess cell cycle phases, and map PCD gene distribution. Additionally, we applied consistency clustering to bulk sequencing data from GEO and TARGET (Therapeutically Applicable Research to Generate Effective Treatments) databases, facilitating survival analysis across clusters with the Kaplan-Meier method. We calculated PCD scores for each cluster using the Single-sample Gene Set Enrichment Analysis (ssGSEA), which enabled a detailed examination of PCD-related gene expression and pathway scores. Our study also explored drug sensitivity differences and conducted comprehensive immune cell infiltration analyses using various algorithms. We identified differentially expressed genes, leading to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses that provided insights into relevant biological processes and pathways. The prognostic model, based on five pivotal genes (BAMBI, TMCC2, NOX4, DKK1, and CBS), was developed using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and validated in the TARGET-OS and GSE16091 datasets, showing significant predictive accuracy. This research enhances our understanding of PCD in OS and supports the development of effective treatments.

Return to flight duty (RTFD) after posterior lumbar spine surgery for symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) in Chinese military pilots.

BACKGROUND: Symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) present significant challenges for military pilots, which may result in grounding if not effectively managed. Surgical treatment for LDH and LIS may offer a pathway to return to flight duty (RTFD), but recent data on this crucial topic is lacking. This study seeks to address this gap by investigating the RTFD outcomes among Chinese military pilots who have undergone lumbar spine surgery for symptomatic LDH and LIS. METHODS: A retrospective review was conducted on active-duty military pilots who underwent isolated decompressive or fusion procedures at an authorized military medical center from March 1, 2007, to March 1, 2023. The analysis utilized descriptive statistics to examine demographic, occupational, surgical, and outcome data, with a particular focus on preoperative flight status, recommended clearance by spine surgeons, and actual RTFD outcomes and time. RESULTS: Among the identified cases of active-duty military pilots with LDH or LIS treated by lumbar surgery (n = 24), 70.8% (17 of 24) consistently maintained RTFD status without encountering surgical complications or medical issues during the follow-up period. Of the seven pilots who did not RTFD, one retired within a year of surgery, two had anterior cruciate ligament injuries, three had residual radicular symptoms, and one had chronic low back pain. Excluding pilots who retired and did not RTFD for reasons unrelated to their lumbar conditions, the RTFD rate stood at 81.0% (17 of 21). The median time for recommended clearance by spine surgeons was 143.0 days (inter-quartile range, 116.5-196.0), while the median duration for actual RTFD attainment was 221.0 days (inter-quartile range, 182.0-300.0). The median follow-up post-lumbar surgery was 1.7 years (inter-quartile range, 0.4-2.9). CONCLUSION: Most military pilots diagnosed with symptomatic LDH and LIS can continue their careers and regain active-duty flight status following lumbar spine surgery, as reflected by the high RTFD rate. Lumbar spine surgery can successfully alleviate the physical constraints associated with spinal conditions, facilitating the return of military pilots to their demanding profession.

Necrotizing apoptosis-related genes prognosis and treatment effect analysis of osteosarcoma in children.

BACKGROUND: Immune cell homeostasis plays a crucial role in cancer research and therapeutic response. While chemotherapy and immunotherapy hold promise in treating osteosarcoma (OS), identifying patients who are likely to respond would significantly improve clinical practices. Necroptosis, a fundamental mechanism mediating chemotherapy and immunotherapy efficacy, offers valuable insights. In this context, subtypes based on necroptosis-related genes have been established to predict the response of OS patients to immunotherapy and chemotherapy. METHODS: We conducted a high-throughput screening test to identify necroptosis-associated genes that regulate the development of osteosarcoma. Subsequently, the ConsensusClusterPlus package was employed to classify OS patients into subtypes, enabling comparisons of prognosis and clinical information between these subtypes. Patients from the TARGET-OS and GSE21257 datasets were stratified into high-risk and low-risk groups, and their prognoses were compared. Additionally, we assessed the accuracy of the Risk Scoring Model in predicting prognosis, identified independent prognostic factors and explored potential chemotherapeutic agents and immunotherapy drugs. RESULTS: Through the intersection of expression profiles from the TARGET-OS and GSE21257 datasets, we have identified a total of 92 genes associated with necroptosis. Based on differences in the expression of these genes, patients were divided into three subtypes, and we investigated the differences in tumor-infiltrating immune cells, immune-related pathways, and prognosis among these subtypes. Our nomogram effectively differentiated subtypes with distinct responses to chemotherapy and immunotherapy. The established signature demonstrated superior prediction ability compared with single clinical indicators. CONCLUSIONS: This pioneering study unveils the prognostic role of necroptosis-related genes in OS patients, providing a promising alternative for prognostic prediction in clinical disease management. Moreover, our findings highlight the significance of immune cell homeostasis in cancer research and therapeutic response, underscoring its relevance in advancing current treatment strategies.

Meta-analysis of the role of neutrophil to lymphocyte ratio in neonatal sepsis.

INTRODUCTION: The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, measures innate-adaptive immune system balance. In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the diagnostic role of NLR in neonatal sepsis. METHODS: PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 14, 2022. RESULTS: Thirty studies, including 2328 neonates with sepsis and 1800 neonates in the control group, were included in our meta-analysis. The results indicated that NLR is higher in neonates with sepsis compared to healthy controls (SMD = 1.81, 95% CI = 1.14-2.48, P-value < 0.001) in either prospective (SMD = 2.38, 95% CI = 1.40-3.35, P-value < 0.001) or retrospective studies (SMD = 0.87, 95% CI = 0.63-1.12, P-value < 0.001) with a pooled sensitivity of 79% (95% CI = 62-90%), and a pooled specificity of 91% (95% CI = 73-97%). Also, we found that NLR is higher in neonates with sepsis compared to those who were suspected of sepsis but eventually had negative blood cultures (SMD =1.99, 95% CI = 0.76-3.22, P-value = 0.002) with a pooled sensitivity of 0.79% (95% CI = 0.69-0.86%), and a pooled specificity of 73% (95% CI = 54-85%). In addition, neonates with sepsis had elevated levels of NLR compared to other ICU admitted neonates (SMD = 0.73, 95% CI = 0.63-0.84, P < 0.001). The pooled sensitivity was 0.65 (95% CI, 0.55-0.80), and the pooled specificity was 0.80 (95% CI, 0.68-0.88). CONCLUSION: Our findings support NLR as a promising biomarker that can be readily integrated into clinical settings to aid in diagnosing neonatal sepsis. As evidenced by our results, restoring balance to the innate and adaptive immune system may serve as attractive therapeutic targets. Theoretically, a reduction in NLR values could be used to measure therapeutic efficacy, reflecting the restoration of balance within these systems.

[Development and Research Progress of 3D Printing Technology in Orthopedic Medical Devices].

With the characteristics of fast prototyping and personalized manufacturing, 3D-printing (three-dimensional printing) is an emerging technology with promising applications for orthopedic medical devices. It can complete the process of medical devices with complex shape which can not be completed by conventional fabrication process. At present, a variety of orthopedic medical devices manufactured by 3D printing technology, has been approved for marketing, and their use has been proved to be beneficial. 3D bioprinting in this area has also made a few breakthroughs. However, many challenges still remain to be addressed as well. In this study, the research status, as well as the development of the 3D-printing technology in the field of orthopedic medical devices is elaborated.

[Meteorological Formation Mechanisms and Potential Sources of an Ozone Pollution Process in Winter of 2022 in Guangdong Province].

Meteorological conditions play an important role in seasonal ozone variations. In order to understand the meteorological formation mechanisms of ozone pollution in Guangdong Province in winter, the moderate ozone pollution process in Guangdong Province from January 3-6, 2022 was selected for comparison with that in autumn (high pollution season) of 2015 to 2021. The research was based on ground and vertical sounding data and reanalysis data of air quality and meteorological elements. Eight cities exceeded the standard during the pollution process, among which Zhaoqing showed moderate pollution (219 µg·m-3) on January 4th. The average O3-8h concentration in Guangdong Province was 123 µg·m-3, which was 21% higher than that in historical autumn. However, its scope of pollution was less than the historical pollution processes in autumn. Lower wind speed, longer sunshine hours, and airflow reflux effect under local circulation were the most important ground-level meteorological conditions for the ozone pollution process, whereas lower temperature might be an important reason for its small scope of pollution. Vertical detection analysis showed that the combined effect of low-level temperature inversion layer, stronger downdraft, and lower wind speed kept the NO2 concentrations at a high level, and further induced a higher increment of ozone concentration in the morning (34.2 µg·m-3 higher than that in the non-pollution period). The downward transport of ozone in the residual layer aggravated the ozone pollution on January 4th. The accumulation of ozone and its precursors was an important factor of the aggravation of ozone pollution the following day. Airflow trajectory analysis revealed that the ground-level ozone was affected by horizontal transport and vertical mixing of pollutants. Potential sources at 10 m were mainly distributed in the coastal areas from Fujian to Guangdong, and the scope of potential sources was concentrated in Guangdong as the height increased. Airflow backward trajectories at different heights during the ozone process passed over the areas of potential sources in Guangdong, which indicated that the local emissions in Guangdong had a greater impact on the ozone pollution process.

Electrochemical Performance of Corn Waste Derived Carbon Electrodes Based on the Intrinsic Biomass Properties.

The exploration of cost-effective and sustainable biomass-derived carbon materials as electrodes for energy conversion and storage has gained extensive attention in recent research studies. However, the selection of the biomass and the electrochemical performance regulation of the derived biochar, as well as their interrelationship still remain challenging for practical application. Herein, corn wastes with high carbon content (>40%), corn cob and corn silk, were selected as precursors for the preparation of high value-added and high yield carbon materials via a modified synthetic process. Uniquely, this work put emphasis on the theoretical and experimental investigations of how the biomass properties influence the composition and nanostructure regulation, the electrolyte ion adsorption free energy, and the electrical conductivity of the derived carbon materials as well as their electrochemical performance optimization. Owing to the favorable specific surface area, the hierarchical porous structure, and the diverse elemental distribution, corn cob and corn silk derived carbon materials (CBC and SBC) present great potential as promising electrodes for alkaline aqueous zinc batteries and supercapacitors. The assembled CBC//Zn and SBC//Zn zinc batteries deliver high energy densities of 63.0 Wh kg-1 and 39.1 Wh kg-1 at a power density of 575 W kg-1, with excellent cycling performance of 91.1% and 84.3% capacitance retention after 10,000 cycles. As for the assembled symmetric supercapacitors, high energy densities of 14.9 Wh kg-1 and 13.6 Wh kg-1, and superior long-term cycling stability of 99.3% and 96.6% capacitance retention after 20,000 cycles could be achieved. This study highlights the advantages of utilizing corn cob and corn silk as carbon sources on the designed synthesis of carbon electrodes, and presents a meaningful perspective in the investigation of biomass-derived carbon materials and their potential applications in rechargeable devices.

Intensified glycemic control by HbA1c for patients with coronary heart disease and Type 2 diabetes: a review of findings and conclusions.

The occurrence and development of coronary heart disease (CHD) are closely linked to fluctuations in blood glucose levels. While the efficacy of intensified treatment guided by HbA1c levels remains uncertain for individuals with diabetes and CHD, this review summarizes the findings and conclusions regarding HbA1c in the context of CHD. Our review showed a curvilinear correlation between regulated level of HbA1c and therapeutic effectiveness of intensified glycemic control among patients with type 2 diabetes and coronary heart disease. It is necessary to optimize the dynamic monitoring indicators of HbA1c, combine genetic profiles, haptoglobin phenotypes for example and select more suitable hypoglycemic drugs to establish more appropriate glucose-controlling guideline for patients with CHD at different stage of diabetes.

Delicate Design of ZnS@In2S3 Core-Shell Structures with Modulated Photocatalytic Performance under Simulated Sunlight Irradiation.

ZnS@In2S3 core-shell structures with high photocatalytic activity have been delicately designed and synthesized. The unique structure and synergistic effects of the composites have an important influence on the improvement of photocatalytic activity. The photocatalytic activity has been studied by photodegrading individual eosin B (EB) and the mixture solution consisting of eosin B and rhodamine B (EB-RhB) in the presence of hydrogen peroxide (H2O2) under simulated sunlight irradiation. The results show that all of the photocatalysts with different contents of In2S3 exhibit enhanced catalytic activity compared to pure ZnS for the degradation of EB and EB-RhB solution. When the theoretical molar ratio of ZnS to In2S3 was 1:0.5, the composite presents the highest photocatalytic efficiency, which could eliminate more than 98% of EB and 94% of EB-RhB. At the same time, after five cycles of photocatalytic tests, the photocatalytic efficiency could be about 96% for the degradation of the EB solution, and relatively high photocatalytic activity could also be obtained for the degradation of the EB-RhB mixed solution. This work has proposed a facile synthetic process to realize the controlled preparation of core-shell ZnS@In2S3 composites with effectively modulated structures and compositions, and the composites have also proved to be high-efficiency photocatalysts for the disposal of complicated pollutants.

Attitudes and willingness to pay for clean heating by typical households: a case study of rural areas in Yongcheng City, Henan Province, China.

Understanding households' attitudes and willingness to pay (WTP) for clean heating can provide a scientific basis for decision-makers to assess the potential to develop clean heating, choose heating methods, and formulate subsidy standards in the region. In this paper, the double-bounded dichotomous contingent valuation method-modified by the spike model-was used to better estimate the actual WTP of households through a sample survey of 456 households in rural areas of Yongcheng City, China, in 2021. The factors influencing attitudes and WTP were examined to reveal mechanisms of accepting clean heating. The results showed that 94.96% of households were willing to pay for clean heating. The annual WTP was 1071 yuan per household, more than eight times the current heating cost. Factors that affect clean heating attitudes do not necessarily affect the WTP. Specifically, gender, length of time spent living at home, and family income had significant influences on WTP, whereas the educational level, adaptive perceptions in relation to environmental perceptions, and the recognition variables for gender equality in energy consumption had a significant impact on attitudes. It is worth noting that elderly people and females were identified as vulnerable groups in the implementation of clean heating.

Designing and validating a comparison card method for quantification of glenoid bone defect.

To design and investigate a comparison card to evaluate the glenoid bone defect compared with Sugaya method. 33 patients with bony Bankart lesions were included. The comparison card and Sugaya method were performed on two occasions by three participants. The intra-group correlation coefficient (ICC) analysis and the inter-group correlation coefficient analysis of two measurements was performed. The concordance of the two methods was assessed using Bland-Altman analysis. Firstly, the percentage of defect measured by Sugaya method was 10.32 ± 8.38, and the comparison card method was 10.26 ± 8.41, 10.15 ± 8.23, and 10.62 ± 8.48, separately. There was no statistically significant difference (P > 0.05). The second measurement showed it was 10.37 ± 8.39 for Sugaya method, and 10.23 ± 8.37, 10.15 ± 8.35, 10.54 ± 8.49 for the comparison card, without a statistically significant difference (P > 0.05). For the comparison card, the intra- and inter-observer ICC values were all > 0.75. In the first measurement, Bland-Altman analysis demonstrated agreement between the two methods (bias, -0.03; SD, 0.48; - 0.97- 0.91; 95% CI, - 0.1999- 0.1413). Agreement was also found between them (bias, 0.07; SD, 0.61; - 1.13- 1.26; 95% CI, - 0.1509- 0.2812) in the second measurement. The comparison card method has similar accuracy with Sugaya method, which is of great reliability and convenience.

Limb-Bud and Heart (LBH) Upregulation in Cardiomyocytes under Hypoxia Promotes the Activation of Cardiac Fibroblasts via Exosome Secretion.

The activation of cardiac fibroblasts (CFs) after myocardial infarction (MI) is essential for post-MI infarct healing, during which the regulation of transforming growth factor beta1 (TGF-ß1) signaling is predominant. We have demonstrated that TGF-ß1-mediated upregulation of LBH contributes to post-MI CF activation via modulating αB-crystallin (CRYAB), after being upregulated by TGF-ß1. In this study, the effect of LBH-CRYAB signaling on the cardiac microenvironment via exosome communication and the corresponding mechanisms were investigated. The upregulation of LBH and CRYAB was verified in both cardiomyocytes (CMs) and CFs in hypoxic, post-MI peri-infarct tissues. CM-derived exosomes were isolated and identified, and LBH distribution was elevated in exosomes derived from LBH-upregulated CMs under hypoxia. Treatment with LBH+ exosomes promoted cellular proliferation, differentiation, and epithelial-mesenchymal transition-like processes in CFs. Additionally, in primary LBHKO CFs, western blotting showed that LBH knockout partially inhibited TGF-ß1-induced CF activation, while LBH-CRYAB signaling affected TGF-ß1 expression and secretion through a positive feedback loop. The administration of a Smad3 phosphorylation inhibitor to LBHKO CFs under TGF-ß1 stimulation indicated that Smad3 phosphorylation partially accounted for TGF-ß1-induced LBH upregulation. In conclusion, LBH upregulation in CMs in post-MI peri-infarct areas correlated with a hypoxic cardiac microenvironment and led to elevated exosomal LBH levels, promoting the activation of recipient CFs, which brings new insights into the studies and therapeutic strategies of post-MI cardiac repair.

GABPB1-AS1 Promotes the Development of Osteosarcoma by Targeting SP1 and Activating the Wnt/ß-Catenin Pathway.

In this study, the role of GABPB1-AS1 in osteosarcoma (OS) was analyzed. The expression of GABPB1-AS1 in different OS cell lines U2OS, HOS, MG63, and hFOB1.19 was detected. SiRNA GABPB1-AS1 was transfected with U2OS and HOS cell lines. The effects of GABPB1-AS1 silencing on proliferation, clonal formation, and migration of U2OS and HOS were detected by CCK-8 method, plate cloning method, and Transwell chamber. Western blot analysis was used to detect the protein levels of SP1, Wnt, ß-catenin, c-Myc, and SOX2 in osteosarcoma cells. The binding relationship between GABPB1-AS1 and miR-199a-3p in OS cells was detected by a dual-luciferase reporter gene assay. Results showed that GABPB1-AS1 was higher in OS cells than that in hFOB1.19. Silencing GABPB1-AS1 inhibited the proliferation, clonal formation, migration, and epithelial-mesenchymal transformation of U2OS and HOS. There was a binding relationship between GABPB1-AS1 and miR-199a-3p in OS cells. GABPB1-AS1 mediated osteosarcoma cells via the SP1/Wnt/ß-catenin signaling pathway. This study suggested that GABPB1-AS1 plays a carcinogenic role in OS through the SP1/Wnt/ß-catenin signaling pathway through competitive binding and inhibition of miR-199a-3p.

A DNA-Methylation-Driven Genes Based Prognostic Signature Reveals Immune Microenvironment in Pancreatic Cancer.

Pancreatic cancer (PACA), which is characterized by an immunosuppressive nature, remains one of the deadliest malignancies worldwide. Aberrant DNA methylation (DNAm) reportedly influences tumor immune microenvironment. Here, we evaluated the role of DNA methylation driven genes (MDGs) in PACA through integrative analyses of epigenomic, transcriptomic, genomic and clinicopathological data obtained from TCGA, ICGC, ArrayExpress and GEO databases. Thereafter, we established a four-MDG signature, comprising GPRC5A, SOWAHC, S100A14, and ARNTL2. High signature risk-scores were associated with poor histologic grades and late TNM stages. Survival analyses showed the signature had a significant predictive effect on OS. WGCNA revealed that the signature may be associated with immune system, while high risk-scores might reflect immune dysregulation. Furthermore, GSEA and GSVA revealed significant enrichment of p53 pathway and mismatch repair pathways in high risk-score subgroups. Immune infiltration analysis showed that CD8+ T cells were more abundant in low score subgroups, while M0 macrophages exhibited an opposite trend. Moreover, negative regulatory genes of cancer-immunity cycle (CIC) illustrated that immunosuppressors TGFB1, VEGFA, and CD274 (PDL1) were all positively correlated with risk-scores. Furthermore, the four signature genes were negatively correlated with CD8+ lymphocytes, but positively associated with myeloid derived suppressor cells (MDSC). Conversely, specimens with high risk-scores exhibited heavier tumor mutation burdens (TMB) and might show better responses to some chemotherapy and targeted drugs, which would benefit stratification of PACA patients. On the other hand, we investigated the corresponding proteins of the four MDGs using paraffin-embedded PACA samples collected from patients who underwent radical surgery in our center and found that all these four proteins were elevated in cancerous tissues and might serve as prognostic markers for PACA patients, high expression levels indicated poor prognosis. In conclusion, we successfully established a four-MDG-based prognostic signature for PACA patients. We envisage that this signature will help in evaluation of intratumoral immune texture and enable identification of novel stratification biomarkers for precision therapies.

α-Mangostin protects lipopolysaccharide-stimulated nucleus pulposus cells against NLRP3 inflammasome-mediated apoptosis via the NF-κB pathway.

Intervertebral disc degeneration (IDD) is a common and chronic inflammatory disorder. α-Mangostin exhibits a novel biological function against inflammation in various inflammatory diseases. Here, we aimed to explore the role of α-mangostin in IDD using an in vitro cell model. Human nucleus pulposus cells (NPCs) were exposed to lipopolysaccharide (LPS) to induce inflammatory injury. Cell viability of NPCs was determined by CCK-8 assay. ELISA was performed to examine the production of interleukin (IL)-1ß and IL-18. Apoptotic cell death in NPCs was detected by TUNEL staining. The expression levels of apoptotic-associated proteins were detected by western blotting. Nuclear factor-kappa B (NF-κB) activation was examined by determining the expression levels of p-p65, p65, and nuclear p65. Results showed that treatment with α-mangostin improved the viability of LPS-treated NPCs. α-Mangostin treatment also inhibited the LPS-induced increase in expression levels of NLRP3, ASC and pro-caspase-1, as well as the production of IL-1ß and IL-18 in NPCs. Moreover, treatment with α-mangostin or NLRP3 inhibitor (MCC950) significantly decreased apoptotic cell death in NPCs, as compared with treatment with LPS. In addition, the expression levels of cleaved caspase-3 and Bax were decreased, while Bcl-2 expression was increased in α-mangostin- or MCC950-treated NPCs. Treatment with α-mangostin also suppressed LPS-induced increase of p-p65/p65 and nuclear p65 levels. Moreover, inhibition of NF-κB by PDTC aggravated the inhibitory effects of α-mangostin on NLRP3 inflammasome activation and apoptosis in LPS-induced NPCs. These findings suggested that α-mangostin exerted a protective effect on NLRP3 inflammasome-mediated apoptosis in LPS-induced NPCs through regulating NF-κB signaling.

[Comparative study between 3D guide plate assisted and free-hand insertion of anterior cervical transpedicular screw].

OBJECTIVE: To compare accuracy of anterior cervical pedicle screws between assist of rapid prototyping 3D guide plate and free-hand insertion, and evaluate the safety of two methods. METHODS: Eight adult cervical cadaver specimens after formaldehyde immersion, including 4 males and 4 females, aged 32 to 65(40.3±5.6) years old. After X-ray examination to exclude bone damage and deformity, 4 of them (3D guide plate group) randomly selected were for CT scan to obtain DICOM format data, and the data was imported into Mimics software for model, designed the ideal entry point and nail path for anterior cervicaltranspedicular screw (ATPS). After obtaining the personalized guide plate of the nail channel, it was exported as STL data, and the individual guide plate was printed by rapid prototyping and 3D printing technology. In turn, with the assistance of 3D guide plates, one-to-one personalized ATPS screws were placed on the four lower cervical cadaver specimens. Another 4 (free-hand group) lower cervical cadaver specimens were implanted with ATPS screws using free-hand technique. All specimens were performed CT thin-layer scanning and three-dimensional reconstruction after operation. The Tomasino method was used to evaluate the safety of the screws on the CT cross-sectional and sagittal images, to determine whether there was a cortical puncture of the lower and inner edges of the pedicle. According to the CT rating results, gradeⅠandⅡwere safe, and grade Ⅲ- Ⅴ were dangerous.And the accuracy of screws was recorded and analyzed between two groups. RESULTS: Two screws were inserted in each segment from C3 to C7 in 8 adult cadavers. A total of 80 screws were inserted, 40 in the 3D guide plate group, and 40 in the free-hand group. The Tomasino screw rating method was used to evaluate the safety of screw, 21 screws were gradeⅠ, 14 screws were gradeⅡ, 3 screws were grade Ⅲ, 1 screw was grade Ⅳ, 2 screws were grade Ⅴ in 3D guide plate group, while 14 screws were gradeⅠ, 8 screws were gradeⅡ, 8 screws were grade Ⅲ, 6 screws were grade Ⅳ, 2 screws were grade Ⅴ in free-hand group. The safety rate of 3D guide plate group was 87.5%, and 55.0% of the free hand group (χ2=8.7, P=0.003). CONCLUSION: The 3D printing rapid prototyping guide plate assisted insertion of the anterior cervical pedicle screw can significantly improve the accuracy and safety, and provide a theoretical basis for further clinical application.

Limb-bud and Heart (LBH) mediates proliferation, fibroblast-to-myofibroblast transition and EMT-like processes in cardiac fibroblasts.

Cardiac fibrosis is an important pathological change after myocardial infarction (MI). Its progression is essential for post-MI infarct healing, during which transforming growth factor beta1 (TGF-ß1) plays a critical role. Limb-bud and Heart (LBH), a newly discovered target gene of TGF-ß1, was shown to promote normal cardiogenesis. αB-crystallin (CRYAB), an LBH-interacting protein, was demonstrated to be involved in TGF-ß1-induced fibrosis. The roles and molecular mechanisms of LBH and CRYAB during cardiac fibrosis remain largely unexplored. In this study, we investigated the alterations of LBH and CRYAB expression in mouse cardiac tissue after MI. LBH and CRYAB were upregulated in activated cardiac fibroblasts (CFs), while in vitro TGF-ß1 stimulation induced the upregulation of LBH, CRYAB, and fibrogenic genes in primary CFs of neonatal rats. The results of the ectopic expression of LBH proved that LBH accelerated CF proliferation under hypoxia, mediated the expression of CRYAB and fibrogenic genes, and promoted epithelial-mesenchymal transition (EMT)-like processes in rat CFs, while subsequent CRYAB silencing reversed the effects induced by elevated LBH expression. We also verified the protein-protein interaction (PPI) between LBH and CRYAB in fibroblasts. In summary, our work demonstrated that LBH promotes the proliferation of CFs, mediates TGF-ß1-induced fibroblast-to-myofibroblast transition and EMT-like processes through CRYAB upregulation, jointly functioning in post-MI infarct healing. These findings suggest that LBH could be a promising potential target for the study of cardiac repair and cardiac fibrosis.