TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

Burdens of stomach and esophageal cancer from 1990 to 2019 and projection to 2030 in China: Findings from the 2019 Global Burden of Disease Study.

Background: Stomach and esophageal cancer exhibit high morbidity and mortality rate in China, resulting in substantial disease burdens. It is imperative to identify the temporal trends of stomach and esophageal cancer from 1990 to 2019 and project future trends until 2030, which can provide valuable information for planning effective management and prevention strategies. Methods: We collected and analysed data from the Global Burden of Disease (GBD) between 1990 and 2019, including incidence, mortality, disability-adjusted life years (DALYs), age-standardised incidence rate (ASIR), mortality rate (ASMR) and DALYs rate. We also calculated and reported the proportion of mortality and DALYs attributable to risk factors by sex in China and different regions. The Bayesian age-period-cohort model was applied to project future trends until 2030. Results: The new cases, deaths and DALYs of stomach and esophageal cancer increased from 1990 to 2019. However, the ASIR, ASMR and age-standardised DALYs rates for stomach and esophageal cancer all decreased during the same period. These changes may be related to risks, such as smoking and diet. Furthermore, we utilised the projection model to estimate that the ASIR and ASMR of stomach and esophageal cancer among females will likely follow steady downward trends, while the ASMR of stomach cancer among males is expected to exhibit a significant decline. However, the ASIR of stomach and esophageal cancer and the ASMR of esophageal cancer among males are projected to display slight upward trends until 2030. Conclusions: The analysis of stomach and esophageal cancer trends in China from 1990 to 2030 reveals a general decline. However, it is crucial to acknowledge the persistent high burden of both cancers in the country. Adopting healthy lifestyle practices, including the reduction of tobacco and alcohol intake, avoidance of moldy foods and increased consumption of fresh fruits and vegetables can contribute to mitigating the risk of stomach and esophageal cancer. Significantly, the formulation and implementation of well-founded and efficacious public health policies are imperative for alleviating the disease burden in China.

A New Treatment Strategy for Spinal Metastasis: The "Systemic Conditions, Effectiveness of Systemic Treatment, Neurology, and Oncology" Decision Framework System.

BACKGROUND AND OBJECTIVES: Treating metastatic spinal tumors poses a significant challenge because there are currently no universally applied guidelines for managing spinal metastases. This study aims to propose a new decision framework for the 12-point epidural spinal cord compression grading system to treat patients with metastatic spinal tumors and investigate its clinical effectiveness in a multicenter analysis. METHODS: This study analyzed 940 patients with metastatic spinal tumors between December 2017 and March 2023. The study provided the clinical evidence for the systemic conditions, effectiveness of systemic treatment, neurology, and oncology (SENO) decision framework among spine metastases. The SENO decision framework was launched in January 2021 in our hospitals, classifying patients into 2 groups: The non-SENO group (n = 489) consisted of patients treated between December 2017 and January 2021, while the SENO group (n = 451) comprised patients treated from January 2021 to March 2023. RESULTS: Patients in the SENO group were more likely to receive minimally invasive surgery (67.85% vs 58.69%) and less chance of receiving spinal cord circular decompression surgery (14.41% vs 24.74%) than patients in the non-SENO group ( P < .001). Furthermore, patients in the SENO group experienced fewer perioperative complications (9.09% vs 15.34%, P = .004), incurred lower hospitalization costs ( P < .001), had shorter length of hospitalization ( P < .001), and received systematic treatments for tumors earlier ( P < .001). As a result, patients in the SENO group (329.00 [95% CI: 292.06-365.94] days) demonstrated significantly improved survival outcomes compared with those in the non-SENO group (279.00 [95% CI: 256.91-301.09], days) ( P < .001). At 3 months postdischarge, patients in the SENO group reported greater improvements in their quality of life, encompassing physical, social, emotional, and functional well-being, when compared with patients in the non-SENO group. CONCLUSION: The SENO decision framework is a promising approach for treating patients with metastatic spinal tumors.

Development of a novel 12-point grading system for evaluating epidural spinal cord compression and its clinical implications.

BACKGROUND CONTEXT: The assessment of epidural spinal cord compression (ESCC) plays a crucial role in clinical decision-making, yet the current grading system lacks reliability and requires improvements. PURPOSE: The study aims to develop a reliable grading system for evaluating ESCC and to investigate its association with the neurological status of patients. STUDY DESIGN/SETTING: A prospective cohort study. PATIENT SAMPLE: A total of 330 patients with metastatic spinal disease were included in the study. OUTCOME MEASURES: The main outcome was the neurological status evaluated using the American Spinal Injury Association (ASIA) scale. METHODS: We proposed a novel grading system, called the 12-point ESCC grading system, to evaluate ESCC based on findings from spinal magnetic resonance imaging (MRI). This new grading system consists of 12 grades, ranging from Grade 0 to 3, with higher grades indicating more severe ESCC. The detailed information about the sagittal image of the spine and the severity of spinal cord swelling was considered in this new grading system. The Spearman correlation analysis and logistic regression analysis were employed to investigate the correlation between the previous 6-point grading system and ASIA, as well as between the new 12-point ESCC grading system and ASIA. The prediction effectiveness was evaluated using the area under curve (AUC) analysis. RESULTS: Patients with higher grades in the 12-point ESCC grading system exhibited a higher likelihood of experiencing a worse neurological condition. Specifically, patients with grades 2a to 2d and 3a to 3d according to the new 12-point ESCC grading system were significantly associated with more complete paralysis (p<.001) compared with patients with grade 0. The Spearman correlation coefficient was 0.729 between the previous 6-point ESCC grading system and ASIS and 0.750 between the new 12-point ESCC grading system and ASIS. When categorizing ASIS into complete paralysis and other neurological statuses, the 6-point ESCC score yielded an AUC of 0.820, which increased to 0.860 with the new 12-point ESCC grading system. Furthermore, when ASIS was divided into normal and abnormal neurological statuses, the AUC increased from 0.889 to 0.906. Additionally, spinal cord swelling was significantly associated with more complete paralysis (p<.001) and abnormal neurological status (p<.001) based on the new 12-point ESCC grading system. CONCLUSIONS: The new 12-point ESCC grading system provides more detailed information and further improves the prediction effectiveness for evaluating neurological status compared with the previous 6-point ESCC grading system. In the new 12-point ESCC grading system, higher grades or the presence of spinal cord swelling are indicative of a worse neurological condition.

A Soft Sensor Model of Sintering Process Quality Index Based on Multi-Source Data Fusion.

In complex industrial processes such as sintering, key quality variables are difficult to measure online and it takes a long time to obtain quality variables through offline testing. Moreover, due to the limitations of testing frequency, quality variable data are too scarce. To solve this problem, this paper proposes a sintering quality prediction model based on multi-source data fusion and introduces video data collected by industrial cameras. Firstly, video information of the end of the sintering machine is obtained via the keyframe extraction method based on the feature height. Secondly, using the shallow layer feature construction method based on sinter stratification and the deep layer feature extraction method based on ResNet, the feature information of the image is extracted at multi-scale of the deep layer and the shallow layer. Then, combining industrial time series data, a sintering quality soft sensor model based on multi-source data fusion is proposed, which makes full use of multi-source data from various sources. The experimental results show that the method effectively improves the accuracy of the sinter quality prediction model.

Contrastive Learning-Based Embedder for the Representation of Tandem Mass Spectra.

Tandem mass spectrometry (MS/MS) shows great promise in the research of metabolomics, providing an abundance of information on compounds. Due to the rapid development of mass spectrometric techniques, a large number of MS/MS spectral data sets have been produced from different experimental environments. The massive data brings great challenges into the spectral analysis including compound identification and spectra clustering. The core challenge in MS/MS spectral analysis is how to describe a spectrum more quantitatively and effectively. Recently, emerging deep-learning-based technologies have brought new opportunities to handle this challenge in which high-quality descriptions of MS/MS spectra can be obtained. In this study, we propose a novel contrastive learning-based method for the representation of MS/MS spectra, called CLERMS, which is based on transformer architecture. Specifically, an optimized model architecture equipped with a sinusoidal embedder and a novel loss function composed of InfoNCE loss and MSE loss has been proposed for the attainment of good embedding from the peak information and the metadata. We evaluate our method using a GNPS data set, and the results demonstrate that the learned embedding can not only distinguish spectra from different compounds but also reveal the structural similarity between them. Additionally, the comparison between our method and other methods on the performance of compound identification and spectra clustering shows that our method can achieve significantly better results.

CARARIME: Interactive web server for comprehensive analysis of renal allograft rejection in immune microenvironment.

Background: Renal transplantation is a very effective treatment for renal failure patients following kidney transplant. However, the clinical benefit is restricted by the high incidence of organ rejection. Therefore, there exists a wealth of literature regarding the mechanism of renal transplant rejection, including a large library of expression data. In recent years, research has shown the immune microenvironment to play an important role in renal transplant rejection. Nephrology web analysis tools currently exist to address chronic nephropathy, renal tumors and children's kidneys, but no such tool exists that analyses the impact of immune microenvironment in renal transplantation rejection. Methods: To fill this gap, we have developed a web page analysis tool called Comprehensive Analysis of Renal Allograft Rerejction in Immune Microenvironment (CARARIME). Results: CARARIME analyzes the gene expression and immune microenvironment of published renal transplant rejection cohorts, including differential analysis (gene expression and immune cells), prognosis analysis (logistics regression, Univariable Cox Regression and Kaplan Meier), correlation analysis, enrichment analysis (GSEA and ssGSEA), and ROC analysis. Conclusions: Using this tool, researchers can easily analyze the immune microenvironment in the context of renal transplant rejection by clicking on the available options, helping to further the development of approaches to renal transplant rejection in the immune microenvironment field. CARARIME can be found in http://www.cararime.com.

Image-Based Differentiation of Benign and Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a dominant hereditary disease characterized by the mutation of the NF1 gene, affecting 1/3000 individuals worldwide. Most NF1 patients are predisposed to benign peripheral nerve sheath tumors (PNSTs), including cutaneous neurofibromas (CNFs) and plexiform neurofibromas (PNFs). However, 5%-10% of PNFs will ultimately develop into malignant peripheral nerve sheath tumors (MPNSTs), which have a poor prognosis. Early and reliable differentiation of benign and malignant tumors in NF1 patients is of great necessity. Pathological evaluation is the "gold standard" for a definite diagnosis, but the invasive nature of the biopsy procedure restricts it from applying as a screening tool during the decades-long follow-up of these patients. Non-invasive image-based diagnostic methods such as CT and MRI are often considered essential screening tools for multiple types of tumors. For NF1 patients' lifelong regular follow-ups, these radiological methods are currently used for tumor evaluation. However, no consensus was established on screening the malignant transformation of benign PNSTs. Moreover, novel technologies like radiogenomics and PET-MRI have not been well evaluated and fully adopted for NF1 patients. This review summarizes current studies of different imaging methods for differentiating benign and malignant tumors in NF1. Meanwhile, we discussed the prospects of the usage of new tools such as radiogenomics and PET-MRI to distinguish MPNST from benign PNSTs more precisely. Summarizing these findings will help clarify the directions of future studies in this area and ultimately contribute to the radiology images-based clinical screening of MPNST in NF1 patients and finally improve the overall survival rates of these patients.

Single cell sequencing coupled with bioinformatics reveals PHYH as a potential biomarker in kidney ischemia reperfusion injury.

Ischemia reperfusion injury(IRI) is an important factor affecting the early function and long-term survival of transplanted kidney. Single cell RNA sequencing (scRNA-seq) is a powerful method for investigating cell-specific transcriptome changes in the kidney. This study aimed to identify the significant cell type and potential biomarkers in IRI. First, we downloaded the IRI related scRNA dataset GSE139506 from the GEO database. Then, classification of cell type was characterized and proximal tubule cell (PTC) was identified as a significant cell type. The functional enrichment analysis indicated that PTC were related to kidney function and is significant in the ferroptosis of IRI. Analyses of three-dimensional structure and iron binding substructure of protein was carried out basing on SWISS-MODEL database. Finally, we constructed the murine model with IRI and verify the higher expression of PHYH in IRI by PCR, Western blot (WB) and Immunohistochemistry (IHC) experiments. In conclusion, this study provided novel insights on the cell-type-specific expression gene biomarker in IRI pathogenesis.

Dingxin Recipe IV attenuates atherosclerosis by regulating lipid metabolism through LXR-α/SREBP1 pathway and modulating the gut microbiota in ApoE-/- mice fed with HFD.

ETHNOPHARMACOLOGICAL RELEVANCE: Dingxin Recipe (DXR) is a traditional Chinese medicine formula that has been reported to be effective and safe treatment for cardiovascular diseases, such as arrhythmias, coronary heart disease. Dingxin Recipe IV (DXR IV) was further improved from the DXR according to the traditional use. However, the mechanism of DXR IV in atherosclerosis is unclear. AIM OF THE STUDY: This study aimed to illustrate whether DXR IV improve atherosclerosis through modulating the lipid metabolism and gut microbiota in atherosclerosis mice. MATERIALS AND METHODS: 40 male ApoE-/- mice were fed on HFD for 12 weeks and were then treated with DXR IV (1.8, 0.9, or 0.45 g/kg/d) for another 12 weeks. The decroation of DXR IV contains four traditional Chinese medicines: the dried rhizome of Coptis chinensis Franch. (15.09%), the root of Salvia miltiorrhiza Bunge (28.30%), the seed of Ziziphus jujuba Mill. (37.74%) and the fruiting body of Ganoderma lucidum (Leyss.ex Fr.) Karst. (18.87%). 8 male c57BL/6 mice fed a normal diet served as control group. The atherosclerotic plaque was quantified by oil-red O staining and masson trichrome staining. Mice feces were collected. The gut micobiota were detected by 16S rRNA gene sequencing and fecal metabolites were analyzed by 1H NMR spectroscopy. The effect of DXR IV on blood lipids (TG, TC, LDL-C, HDL-C) was investigated. The lipid metabolism related genes were determined by RT-qPCR and western blotting respectively. RESULTS: DXR IV exerted the anti-atherosclerosis effect by inhibiting the excessive cholesterol deposition in aorta and regulating the level of TG, TC, LDL-C and HDL-C. The composition of gut microbiota was changed. Interestingly, the relative abundance of Muribaculaceae and Ruminococcaceae increased after DXR IV administration, whereas the abundance of Erysipelotrichaceae decreased, which have been beneficial to lipid metabolism. Nine potential metabolic biomarkers, including acetate, butyrate, propionate, alanine, succinate, valerate, xylose, choline, glutamate, were identified, which were related to fatty acid metabolism. Further, the pathway of fatty acid was detected by the RT-qPCR and western blotting. Compared with model group, the level of LXR-α and SREBP1 decreased significantly in DXR IV group while LXR-ß, SREBP2 showed no statistical significance. It indicated that DXR IV modulated lipid metabolism by LXR-α/SREBP1 but not LXRß and SREBP2. CONCLUSIONS: DXR IV exhibits potential anti-atherosclerosis effect, which is closely related to lipid metabolism and the gut microbiota. This study may provide novel insights into the mechanism of DXR IV on atherosclerosis and a basis for promising clinical usage.

[Diagnostic Value of the Dual Source CT Dual Energy Pulmonary Perfusion Imaging for Pulmonary Embolism].

Objective To assess the diagnostic value of dual energy pulmonary perfusion imaging(DEPI)for pulmonary embolism.Methods The clinical data of 87 patients with suspected pulmonary embolism who had received DEPI between August 2017 and July 2018 in Jiaxing Second Hospital were retrospectively analyzed.With the findings of CT pulmonary angiography(CTPA)as the reference standard and with patients and pulmonary lobes as evaluation units,respectively,a diagnostic test was performed to calculate the diagnostic coincidence rate,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,positive likelihood ratio,negative likelihood ratio,and Kappa coefficient value for the diagnosis of DEPI and CTPA.Results The coincidence rate,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,positive likelihood ratio,and negative likelihood ratio were 85.06%,88.41%,72.22%,92.42%,61.90%,0.61,3.18,and 0.16,respectively,when applying the patients as evaluation units.When the pulmonary lobes were invoked as evaluation units,the above-mentioned indexes were 89.57%,76.80%,96.82%,93.20%,88.02%,0.74,24.15,and 0.24,respectively.The diagnostic results of DEPI and CTPA had a good and excellent consistency,respectively(Kappa value=0.571,0.765).Conclusions DEPI has high accuracy,sensitivity,and specificity in the detection of pulmonary embolism.The combination of DEPI with CTPA can simultaneously obtain the anatomical structure and functional information images,greatly improving the diagnostic accuracy for pulmonary embolism.Thus,it can be used as the preferred examination for patients with clinically suspected pulmonary embolism.

Comparison and Analysis of Geometric Correction Models of Spaceborne SAR.

Following the development of synthetic aperture radar (SAR), SAR images have become increasingly common. Many researchers have conducted large studies on geolocation models, but little work has been conducted on the available models for the geometric correction of SAR images of different terrain. To address the terrain issue, four different models were compared and are described in this paper: a rigorous range-doppler (RD) model, a rational polynomial coefficients (RPC) model, a revised polynomial (PM) model and an elevation derivation (EDM) model. The results of comparisons of the geolocation capabilities of the models show that a proper model for a SAR image of a specific terrain can be determined. A solution table was obtained to recommend a suitable model for users. Three TerraSAR-X images, two ALOS-PALSAR images and one Envisat-ASAR image were used for the experiment, including flat terrain and mountain terrain SAR images as well as two large area images. Geolocation accuracies of the models for different terrain SAR images were computed and analyzed. The comparisons of the models show that the RD model was accurate but was the least efficient; therefore, it is not the ideal model for real-time implementations. The RPC model is sufficiently accurate and efficient for the geometric correction of SAR images of flat terrain, whose precision is below 0.001 pixels. The EDM model is suitable for the geolocation of SAR images of mountainous terrain, and its precision can reach 0.007 pixels. Although the PM model does not produce results as precise as the other models, its efficiency is excellent and its potential should not be underestimated. With respect to the geometric correction of SAR images over large areas, the EDM model has higher accuracy under one pixel, whereas the RPC model consumes one third of the time of the EDM model.

Clinical report of intra-arterial interventional chemotherapy for synovial sarcoma on limbs.

OBJECTIVE: The efficiency of implantable intra-arterial interventional chemotherapy before the operation for synovial sarcoma on limbs was evaluated. MATERIALS AND METHODS: Drug delivery device (chemotherapy pumps) was implanted percutaneously for 36 patients, and the interventional chemotherapy was conducted for 3-4 cycles. The surgical resection was carried out after obvious improvement was observed by clinical and imaging examination. The evaluation standard for the efficiency of chemotherapy was tumor cell necrosis rate obtained from postoperative pathological test. RESULTS: The response rate (RR) of pain alleviation was 91% (32/36), and the RR of the changing of lesion imaging was 83% (30/36). Thirty cases received extensive tumor excision, and six cases received amputation because of poor response to tumor chemotherapy and local carcinelcosis. The postoperative pathological test showed 81% moderate and severe chemotherapy response (29/36). The average follow-up time was 39 months. There were three cases presenting with local tumor recurrence, and seven deaths due to pulmonary metastasis. CONCLUSION: Intra-arterial interventional chemotherapy before operation for synovial sarcoma can effectively control pain. After chemotherapy, the imaging performance significantly changed, and tumor cells were necrotized extensively. The pathological changes were obvious.

Combined effect of tnf-α polymorphisms and hypoxia on steroid-induced osteonecrosis of femoral head.

OBJECTIVE: Tumor necrosis factor (TNF)-α is a proinflammatory cytokine, some studies reported that TNF-α gene plays important role in the pathogenesis of SONFH. And the polymorphisms of TNF-α were presented as risk factors for steroid-induced osteonecrosis of the femoral head (SONFH). Meanwhile, various environment factors involve in the pathogenesis of SONFH. Our study aimed to investigate the interaction effect of TNF-α polymorphisms and hypoxia factor on SONFH. METHODS: 120 patients with SONFH and 100 healthy people, matched with the cases on age and sex, participated in this study. DNA was extracted from all participants. According to previous studies, genotyping of TNF-α polymorphisms (rs1800629, rs1799964 and rs1800630) was tested with the method of PCR-RDB (Reverse Dot Blot). Environmental factors were also chose. Logistic regression analysis was used to analyze the interaction between TNF-α polymorphisms and environment factors on SONFH. RESULTS: The polymorphisms of rs1800629 and rs1800630 were significantly associated with SONFH (OR: 3.70, 9.93). Patients with hypoxia history were found higher (65.00%) compared with the healthy controls (43.00%). For the person with hypoxic history, GG and AG+AA genotypes of rs1800629 could increase their risk to suffer SONFH (OR: 2.12, 3.78). If the patients with the variant genotypes of rs1800630 experienced hypoxia state, then the risk for SONFH increased 2.41 folds. CONCLUSION: We concluded that the onset of SONFH was influenced by TNF-α and hypoxia history. There existed strong interaction between TNF-α and hypoxia history.

[A modified porous tantalum implant technology for osteonecrosis of the femoral head: survival and prognostic evaluations of conversion into total hip arthroplasty].

OBJECTIVE: To assess the survival and prognostic significance of various demographic and radiographic parameters for conversion into total hip arthroplasty after treatment with a modified porous tantalum implant technology for early and intermediate stages of osteonecrosis of the femoral head (ONFH). METHODS: This study included 45 patients (59 hips) with Steinberg Stage I-IV A ONFH undergoing progressively core decompression, impaction bone grafting of 5 mm-composite bone filling material and inserting of a porous tantalum implant. Weight-bearing was forbidden within the first 3 months after implants. RESULTS: A total of 57 hips (44 patients) were available during a mean follow-up period of 44.8 (11-62) months. Their mean age was 43 (21-70) years. The mean Harris hip score significantly improved from 59.93 ± 2.80 preoperative to 77.84 ± 2.95 at the last follow-up (P < 0.001). Overall, 11 hips (19.30%) were converted into total hip arthroplasty. The overall survival rate was 72.49% at 60 months postoperatively. The Cox proportional hazard model revealed that bone marrow edema was an independent prognostic factor related with a conversion into total hip arthroplasty. CONCLUSION: Higher survival rates may be obtained from modified tantalum implant technology for early and intermediate stages of ONFH. And prognosis was poor for patients of ONFH with bone marrow edema.

Enhancement of radiosensitivity by 5-Aza-CdR through activation of G2/M checkpoint response and apoptosis in osteosarcoma cells.

Radiation resistance is a major problem preventing successful treatment. Therefore, identifying sensitizers is vitally important for radiotherapy success. Epigenetic events such as DNA methylation have been proposed to mediate the sensitivity of tumor therapy. In this study, we investigated the influence of demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on the radiosensitivity of human osteosarcoma cell lines. 5-Aza-CdR was capable of sensitizing three osteosarcoma cells to irradiation in a time-dependent manner, with the maximum effect attained by 48 h. Pretreatment with 5-Aza-CdR synchronized cells in G2/M phase of the cell cycle and enhanced irradiation-induced apoptosis compared with irradiation alone in SaOS2, HOS, and U2OS cells. Moreover, 5-Aza-CdR restored mRNA expressions of 14-3-3σ, CHK2, and DAPK-1 in the three cells, accompanied with demethylation of their promoters. These findings demonstrate that demethylation with 5-Aza-CdR increases radiosensitivity in some osteosarcoma cells through arresting cells at G2/M phase and increasing apoptosis, which is partly mediated by upregulation of 14-3-3σ, CHK2, and DAPK-1 genes, suggesting that 5-Aza-CdR may be a potential radiosensitizer to improve the therapy effect in osteosarcoma.

[Efficacies of bone-marrow-derived mononuclear cells with a hydroxylapatite composite in the treatment of osteonecrosis of the femoral head].

OBJECTIVE: To evaluate the efficacies of core decompression and implantation of concentrated autologous bone marrow containing mononuclear cells (BMMCs) with porous hydroxylapatite composite in the treatment of osteonecrosis of the femoral head. METHODS: A total of 35 patients with 57 osteonecrosis hips with ARCO stage I, stage II and stage IIIA disease were treated by BMMCs with a porous hydroxylapatite composite. The mean age at surgery was 39.4 (26-58) years and the mean period of follow-up 28 (12-40) months. In the control group, cell-free porous hydroxylapatite composite was implanted into 17 patients (27 hips) with osteonecrosis of the femoral head and the outcomes were compared. RESULTS: At the last follow-up, postoperative Harris hip scores significantly increased in both groups (P < 0.0001). The magnitude of increase was significantly greater in the BMMCs group compared with the control group (28.3% ± 0.9% vs 18.4% ± 1.7%, P < 0.01). Postoperative visual analog scale (VAS) scores significantly decreased in both groups (P < 0.01). The magnitude of decrease was significantly greater in the BMMCs group compared with the control group (-70.2% ± 2.1% vs -51.7% ± 2.9%, P < 0.001). The clinical success rate was significantly higher in the BMMCs group compared with the control group (75.4% vs 37.0%, P < 0.01). The radiological success rates were similar between the BMMCs and control groups (59.6% vs 40.7%, P = 0.1046). CONCLUSION: The combined regimen of core decompression and implantation of concentrated autologous BMMCs with porous hydroxylapatite composite appears to confer benefits in the treatment of in stages I-IIIA osteonecrosis of the femoral head.

Research on DNA methylation of human osteosarcoma cell MGMT and its relationship with cell resistance to alkylating agents.

The objective of this study was to explore the O(6)-methylguanine-DNA methyltransferase (MGMT) gene methylation status and its protein expression, as well as the effects of demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on MGMT gene expression and its resistance to alkylating agents, and to elucidate MGMT expression mechanism and significance in osteosarcoma. The human osteosarcoma cell lines Saos-2 and MG-63 were collected and treated with 5-Aza-CdR for 6 days. The cells not treated with 5-Aza-CdR were set as a negative control. The genomic DNA was extracted from the Saos-2 and MG-63 cells using methylation-specific PCR to detect the promoter CpG island methylation status of the MGMT gene. Cell sensitivity to alkylating agents before and after drug administration was detected by the MTT method. The variation in MGMT gene mRNA and protein was detected by reverse transcription PCR (RT-PCR) and Western blotting. The MGMT promoter gene of normal Saos-2 cells was methylated, with reduced MGMT mRNA and protein expression; the MGMT mRNA and protein expression of Saos-2 cells treated with 5-Aza-CdR was obviously enhanced, and its sensitivity to alkylating agents was reversed. Meanwhile, with promoter CpG island unmethylation of the MGMT gene, MGMT protein was expressed in the normal MG-63 cells and the MG-63 cells treated with 5-Aza-CdR, and both showed resistance to alkylating agents. The methylation status of the MGMT gene promoter in human osteosarcoma cells reflected the cells' ability to induce MGMT protein expression and can be used as a molecular marker to project the sensitivity of cancer tissues to alkylating agent drugs.

The significance of preoperative chemotherapy in evaluation of recurrent soft tissue liposarcoma necrosis.

To investigate the effect of preoperative induction chemotherapy on treatment of recurrent liposarcoma. 21 patients with recurrent liposarcoma received the treatment of preoperative intra-arterial chemotherapy and surgical resection. Intra-arterial chemotherapy was given by subcutaneous implantable drug delivery system with infusion of cisplatin and doxorubicin followed by caffeine. After treatment, patients were followed up for 39 months. The liposarcoma changes in CT imaging were observed in 18 cases and there were 15 cases with medium or severe pathological changes caused by chemotherapy. At the end of the postoperative follow-up of 39 months, liposarcoma reoccurred locally in 2 cases; pulmonary metastasis occurred in 1 case and death in 3 cases. Preoperative intra-arterial chemotherapy is effective for highly malignant tumors such as recurrent liposarcoma and the judgment of prognosis is based on the postoperative pathological changes of such tumor.