Effects of external environment on promoter methylation of PIK3R5 and related pathway regulation in steroid-induced femoral head necrosis.

BACKGROUND: Steroid-induced Avascular Necrosis of the Femoral Head (SANFH) is a condition characterized by the necrosis of the femoral head caused by long-term or high-dose hormone usage. Studies have shown that the PI3K/AKT pathway plays a crucial regulatory role in the development of SANFH. The aim of this study is to determine how external environmental factors induce changes in endogenous hormone levels, how these changes lead to steroid-induced femoral head necrosis, and the interrelationship between the changes in PIK3R5 promoter methylation levels and the regulation of the associated signaling pathways. METHODS: Femoral head samples underwent molecular sequencing analysis. Candidate genes were screened by differential gene analysis and functional enrichment analysis.Methylation level of candidate gene PIK3R5 was verified by methylation-specific PCR(MS-PCR). SANFH model was constructed in New Zealand white rabbits, and the model results were verified by magnetic resonance imaging (MRI) and haematoxylin-eosin (HE) staining.The expression of PIK3R5, PI3K and AKT in rabbit models and human specimens was verified by real-time fluorescence quantitative PCR(RT-qPCR) and Western Blot(WB), respectively. RESULTS: Human femoral head sequencing results indicate distinct differences in the methylation level and mRNA expression of PIK3R5 in SANFH. MS-PCR results showed the methylation level of SANFH patients was significantly higher than that of the control group (P < 0.01). The RT-qPCR results showed that PIK3R5 and PI3K expression levels in the SANFH group were lower than those in the control group (P < 0.05), and the WB experiment results were consistent with the RT-qPCR results. The MRI and HE staining results showed that the rabbit model of SANFH was successfully constructed, and the results of RT-qPCR and WB were consistent with the results of human tissues. CONCLUSION: During the occurrence and development of SANFH, PIK3R5 gene regulates the PI3K/AKT pathway through methylation modification, promotes the oxidative stress response of cells, and accelerates the disease process.

Exosome-mediated miR-144-3p promotes ferroptosis to inhibit osteosarcoma proliferation, migration, and invasion through regulating ZEB1.

BACKGROUND: Osteosarcoma (OS) is the most prevalent orthopedic malignancy with a dismal prognosis. The high iron absorption rate in OS cells of patients suggests that ferroptosis may be related to the progression of OS, but its potential molecular regulatory role is still unclear. Based on the ability to couple with exosomes for targeted delivery of signals, exosome-derived micro ribonucleic acids (miRNAs) can potentially serve as diagnostic biomarkers for OS. METHODS: We identified ferroptosis-related miRNAs and messenger ribonucleic acids(mRNAs) in OS using bioinformatics analysis and performed survival analysis. Then we measured miRNA expression levels through exosome microarray sequencing, and used RT-qPCR and IHC to verify the expression level of miR-144-3p and ZEB1. Stable gene expression cell lines were fabricated for in vitro experiments. Cell viability, migration and invasion were determined by CCK-8 and transwell experiment. Use the corresponding reagent kit to detect GSH/GSSG ratio, Fe2+ level, MDA level and ROS level, and measure the expression levels of GPX4, ACSL4 and xCT through RT-qPCR and WB. We also constructed nude mice model for in vivo experiments. Finally, the stability of the miRNA/mRNA axis was verified through functional rescue experiments. RESULTS: Low expression of miR-144-3p and high expression of ZEB1 in OS cell lines and tissues was observed. Overexpression of miR-144-3p can promote ferroptosis, reduce the survival ability of OS cells, and prevent the progression of OS. In addition, overexpression of miR-144-3p can downregulate the expression of ZEB1 in cell lines and nude mice. Knockdown of miR-144-3p has the opposite effect. The functional rescue experiment validated that miR-144-3p can regulate downstream ZEB1, and participates in the occurrence and development of OS by interfering with redox homeostasis and iron metabolism. CONCLUSIONS: MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of OS cells.

Consensus Clustering and Survival-Related Genes of Cuproptosis in Cutaneous Melanoma.

As a highly malignant tumor, the morbidity and mortality of cutaneous melanoma (CM) are increasing year by year. A novel type of cell death connected to mitochondrial metabolism is called cuproptosis. Cuproptosis regulates tumor biological behavior. Thus, genes controlling cuproptosis could be a promising candidate bioindicator for cancer therapy. Datasets of CM patients were obtained from the public database that includes clinical information and RNA-seq data. We divided CM patients into three different subgroups by unsupervised clustering method and explored the differences in functional pathways among the three subgroups by GSVA to prove the possible potential mechanism of copper death-related genes in the formation and development of CM. Secondly, we used differential analysis and Cox regression analysis to find the differential genes related to prognosis, constructed the CRG score, found the critical score for dividing high and low CRG score groups, and then analyzed the prognosis and immune infiltration of high and low CRG score groups. The results show a great correlation between OS and CRG scores. Compared with patients with high CRG scores, patients with low CRG scores have a significantly higher survival rate. In a word, copper sagging plays a certain role in the progress of CM.

Verification of Ferroptosis Subcluster-Associated Genes Related to Osteosarcoma and Exploration of Immune Targeted Therapy.

Background: Despite tremendous advances in treating osteosarcoma (OS), the survival rates of patients have failed to improve dramatically over the past decades. Ferroptosis, a newly discovered iron-dependent type of regulated cell death, is implicated in tumors, and its features in OS remain unascertained. We designed to determine the involvement of ferroptosis subcluster-related modular genes in OS progression and prognosis. Methods: The OS-related datasets retrieved from GEO and TARGET database were clustered for identifying molecular subclusters with different ferroptosis-related genes (FRGs) expression patterns. Weighted gene coexpression network analysis (WGCNA) was applied to identify modular genes from FRG subclusters. The least absolute shrinkage and selection operator (LASSO) algorithm and multivariable Cox regression analysis were adopted to develop the prognostic model. Potential mechanisms of development and prognosis in OS were explored by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Then, a comprehensive analysis was conducted for immune checkpoint markers and assessment of predictive power to drug response. The protein expression levels of the three ferroptosis subcluster-related modular genes were verified by immunohistochemistry. Results: Two independent subclusters presenting diverse expression profiles of FRGs were obtained, with significantly different survival states. Ferroptosis subcluster-related modular genes were screened with WGCNA, and the GESA results showed that ferroptosis subcluster-related modular genes could affect the cellular energy metabolism, thus influencing the development and prognosis of osteosarcoma. A prognostic model was established by incorporating three ferroptosis subcluster-related modular genes (LRRC1, ACO2, and CTNNBIP1) and a nomogram by integrating clinical features, and they were evaluated for the predictive power on OS prognosis. The 20 immune checkpoint-related genes confirmed the insensitivity to tumor immunotherapy in high-risk patients. IC50s of Axitinib and Cytarabine suggested a higher sensitivity to the targeted drug. Finally, the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry were consistent with bioinformatics analysis. Conclusion: Ferroptosis are closely associated with the OS prognosis. The risk-scoring model incorporating three ferroptosis subcluster-related modular genes has shown outstanding advantages in predicting patient prognosis.

Prognostic Model and Immune Infiltration of Ferroptosis Subcluster-Related Modular Genes in Gastric Cancer.

Background: Gastric cancer (GC) is one of the gastrointestinal tumors with the highest mortality rate. The number of GC patients is still high. As a way of iron-dependent programmed cell death, ferroptosis activates lipid peroxidation and accumulates large reactive oxygen species. The role of ferroptosis in GC prognosis was underrepresented. The objective was to investigate the role of ferroptosis-related genes (FRGs) in the prognosis and development of GC. Methods: Datasets of GC patients were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database that include clinical information and RNA seq data. Through nonnegative matrix factorization (NMF) clustering, we identified and unsupervised cluster analysis of the expression matrix of FRGs. And we constructed the co-expression network between genes and clinical characteristics by consensus weighted gene co-expression network analysis (WGCNA). The prognostic model was constructed by univariate and multivariate regression analysis. The potential mechanisms of development and prognosis in GC were explored by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene ontology (GO), tumor immune microenvironment (TIME), and tumor mutation burden (TMB). Results: Two molecular subclusters with different expression patterns of FRGs were identified, which have significantly different survival states. Ferroptosis subcluster-related modular genes were identified by WGCNA. Based on 8 ferroptosis subcluster-related modular genes (collagen triple helix repeat containing 1 (CTHRC1), podoplanin (PDPN), procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2), glutamine-fructose-6-phosphate transaminase 2 (GFPT2), ATP-binding cassette subfamily A member 1 (ABCA1), G protein-coupled receptor 176 (GPR176), serpin family E member 1 (SERPINE1), dual specificity phosphatase 1 (DUSP1)) and clinicopathological features, a nomogram was constructed and validated for their predictive efficiency on GC prognosis. Through receiver operating characteristic (ROC) analysis, the results showed that the area under the curve (AUC) of 1-, 3-, and 5-year survival were 0.721, 0.747, and 0.803, respectively, indicating that the risk-scoring model we constructed had good prognosis efficacy in GC. The degree of immune infiltration in high-risk group was largely higher than low-risk group. It indicated that the immune cells have a good response in high-risk group of GC. The TMB of high-risk group was higher, which could generate more mutations and was more conducive to the body's resistance to the development of cancer. Conclusion: The risk-scoring model based on 8 ferroptosis subcluster-related modular genes has shown outstanding advantages in predicting patient prognosis. The interaction of ferroptosis in GC development may provide new insights into exploring molecular mechanisms and targeted therapies for GC patients.

Identification of Monocyte-Associated Genes Related to the Instability of Atherosclerosis Plaque.

Background: Atherosclerotic plaque instability is a common cause of stroke and ischemic infarction, and identification of monocyte-associated genes has become a prominent feature in cardiovascular research as a contributing/predictive marker. Methods: Whole genome sequencing data were downloaded from GSE159677, GSE41571, GSE120521, and GSE118481. Single-cell sequencing data analysis was conducted to cluster molecular subtypes of atherosclerotic plaques and identify specific genes. Differentially expressed genes (DEGs) between normal subjects and patients with unstable atheromatous plaques were screened. Weighted gene coexpression network analysis (WGCNA) was performed to find key module genes. In addition, GO and KEGG enrichment analyses explored potential biological signaling pathways to generate protein interaction (PPI) networks. GSEA and GSVA demonstrated activations in plaque instability subtypes. Results: 239 monocyte-associated genes were identified based on bulk and single-cell RNA-sequencing, followed by the recognition of 1221 atherosclerotic plaque-associated DEGs from the pooled matrix. GO and KEGG analyses suggested that DEGs might be related to inflammation response and the PI3K-Akt signaling pathway. Eight no-grey modules were obtained through WGCNA analysis, and the turquoise module has the highest correlation with unstable plaque (R 2 = 0.40), which contained 1323 module genes. After fetching the intersecting genes, CXCL3, FPR1, GK, and LST1 were obtained that were significantly associated with plaque instability, which had an intense specific interaction. Monocyte-associated genes associated with atherosclerotic plaque instability have certain diagnostic significance and are generally overexpressed in this patient population. In addition, 11 overlapping coexpressed genes (CEG) might also activated multiple pathways regulating inflammatory responses, platelet activation, and hypoxia-inducible factors. GSVA showed that the corresponding pathways were significantly activated in high expression samples. Conclusions: Overexpression of CXCL3, GK, FPR1, and LST1 was advanced recognition and intervention factors for unstable plaques, which might become targets for atherosclerosis rupture prevention. We also analyzed the potential mechanisms of CEG from inflammatory and oxidative stress pathways.

Identification of Ferroptosis-Associated Long Noncoding RNA Prognostic Model and Tumor Immune Microenvironment in Thyroid Cancer.

Background: Thyroid cancer (TC) is a rapidly increasing incidence of endocrine malignancies, occupying 3% of new cancer incidence, of which 10% has a heterogeneous prognosis. Ferroptosis is a form of cell death distinct from apoptosis, which involves antitumor drug-related research. Long noncoding RNAs (lncRNAs) could affect cancer prognosis by regulating the ferroptosis; thus, ferroptosis-associated lncRNAs are emerging as prospective biomarkers for cancer therapy and prognosis. However, the prognostic factors of ferroptosis-associated lncRNAs in this solid tumor and their mechanisms remain unknown. Methods: The TC lncRNA data were extracted from RNA sequencing files of The Cancer Genome Atlas (TCGA). Then, we performed a two-cluster analysis and grouped 502 patients with TC in a 7 : 3 ratio. Both the least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis were conducted to create and validate the ferroptosis-associated lncRNA prognostic model (Ferr-LPM). Based on the median Ferr-LPM-based risk score (LPM_score) of the training cohort, we categorized patients into high and low LPM_score groups, which were then subjected to prognostic correlation and difference analysis. We also created a nomogram and assessed its predictive ability. Furthermore, immune-related mechanisms were investigated by analyzing the tumor immune microenvironment (TIME) and applying algorithms such as CIBERSROT. Results: We built a highly accurate nomogram to promote the clinical applicability of Ferr-LPM. The area under the receiver operating characteristic curve (AUC-ROC) reached above 0.9. Survival analysis suggested that when the Ferr-LPM score was higher, the overall survival (OS) of patients within this group was shorter. Meanwhile, we found a strong association between Ferr-LPM and TIME. Interestingly, the LPM_score was inversely proportional to the tumor purity but positively related to immune checkpoint blockade (ICB) response. Conclusion: We constructed a novel ferroptosis-associated lncRNA nomogram that could highly predict the prognosis of TC patients. Ferroptosis-associated lncRNAs might possess potential functions in regulating TIME, and lncRNAs provide TC patients with new prognostic biomarkers and therapeutic targets.

Identification of Potential Therapeutic Target Genes in Osteoarthritis.

Objective: Osteoarthritis (OA), also known as joint failure, is characterized by joint pain and, in severe cases, can lead to loss of joint function in patients. Immune-related genes and immune cell infiltration play a crucial role in OA development. We used bioinformatics approaches to detect potential diagnostic markers and available drugs for OA while initially exploring the immune mechanisms of OA. Methods: The training set GSE55235 and validation set GSE51588 and GSE55457 were obtained from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified by the limma package. Gene set enrichment analysis (GSEA) was performed on the GSE55235 dataset using the cluster profiler package. At the same time, DEGs were analyzed by gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, protein-protein interaction (PPI) analysis was performed on the common DEGs of the three datasets using the STRING database. Proteins with direct linkage were identified as hub genes, and the relation of hub genes was subsequently analyzed using the GOSemSim package. Hub genes' expression profiles and diagnostic capabilities (ROC curves) were analyzed and validated using three datasets. In addition, we performed RT-qPCR to validate the levels of hub genes. The immune microenvironment was analyzed using the CIBERSORT package, and the relationship between hub genes and immune cells was evaluated. In addition, we used a linkage map (CMAP) database to identify available drug candidates. Finally, the GSEA of hub genes was used to decipher the potential pathways corresponding to hub genes. Results: Three hub genes (CX3CR1, MYC, and TLR7) were identified. CX3CR1 and TLR7 were highly expressed in patients with OA, whereas the expression of MYC was low. The results of RT-qPCR validation were consistent with those obtained using datasets. Among these genes, CX3CR1 and TLR7 can be used as diagnostic markers. It was found that CX3CR1, MYC, and TLR7 affect the immune microenvironment of OA via different immune cells. In addition, we identified a potential drug for the treatment of OA. Altogether, CX3CR1, MYC, and TLR7 affect the immune response of OA through multiple pathways. Conclusion: CX3CR1, MYC, and TLR7 are associated with various immune cells and are the potential diagnostic markers and therapeutic targets for OA.

Predicting the Risk of Diabetic Foot Ulcers From Diabetics With Dysmetabolism: A Retrospective Clinical Trial.

Background: Diabetic foot ulcer (DFU) in patients with type 2 diabetes mellitus (T2D) often leads to amputation. Early intervention to prevent DFU is urgently necessary. So far, there have been no studies on predictive models associated with DFU risk factors. Our study aimed to quantify the predictive risk value of DFU, promote health education, and further develop behavioral interventions to reduce the incidence of DFU. Methods: Data from 973 consecutive patients with T2D was collected from two hospitals. Patients from the Guangxi Medical University First Affiliated Hospital formed the training cohort (n = 853), and those from the Wuming Hospital of Guangxi Medical University formed the validation cohort (n = 120). Independent variable grouping analysis and multivariate logistic regression analysis were used to determine the risk factors of DFUs. The prediction model was established according to the related risk factors. In addition, the accuracy of the model was evaluated by specificity, sensitivity, predictive value, and predictive likelihood ratio. Results: In total, 369 of the 853 patients (43.3%) and 60 of the 120 (50.0%) were diagnosed with DFUs in the two hospitals. The factors associated with DFU were old age, male gender, lower body mass index (BMI), longer duration of diabetes, history of foot disease, cardiac insufficiency, no use of oral hypoglycemic agent (OHA), high white blood cell count, high platelet count, low hemoglobin level, low lymphocyte absolute value, and high postprandial blood glucose. After incorporating these 12 factors, the nomogram drawn achieved good concordance indexes of 0.89 [95% confidence interval (CI): 0.87 to 0.91] in the training cohort and 0.84 (95% CI: 0.77 to 0.91) in the validation cohort in predicting DFUs and had well-fitted calibration curves. Patients who had a nomogram score of ≥180 were considered to have a low risk of DFU, whereas those having ≥180 were at high risk. Conclusions: A nomogram was constructed by combining 12 identified risk factors of DFU. These 12 risk factors are easily available in hospitalized patients, so the prediction of DFU in hospitalized patients with T2D has potential clinical significance. The model provides a reliable prediction of the risk of DFU in patients with T2D.

MAIP1-Related Tumor Immune Infiltration: As a Potential Prognostic Biomarker for Esophageal Cancer.

Background: Esophageal cancer (EC), a common malignant tumor of digestive tract, is also one of the most deadly cancers. Accumulating studies have shown that the initiating and progressing multiple human diseases were closely related to the expression of MAIP. However, the specific roles and mechanisms of MAIP1 in EC remain incompletely defined. Purpose: This study aims to determine the clinical significance of MAIP1 in EC and explores its potential molecular mechanisms regulating tumor immune infiltration. Methods: We obtained RNA-seq datasets and corresponding clinical data for EC patients from the Cancer Genome Atlas (TCGA) database via the UCSC Xena browser to extract MAIP1 expression and plot survival curves to determine their prognosis. Based on the differential expression of MAIP1, EC patients were divided into high and low group to investigate the mechanism of MAIP1 in EC. In addition, the single sample gene set enrichment analysis (ssGSEA) quantified the expression of various immune cell signature marker genes and assessed the degree of immune infiltration in EC. Results: In the TCGA-EC cohort, the overexpression of MAIP1 was observed in tumor tissues compared to normal tissues (p = 0.0038). Overall survival analysis showed that EC patients with the overexpression of MAIP1 presented a lower overall survival and worse prognosis (p = 0.004). Enrichment analysis revealed that the differential genes (DEGs) between high and low group are involved in biological functions such as extracellular matrix and organization extracellular structure. The results of ssGSEA showed that DCs, iDCs, macrophages, mast cells, and NK cells were significantly different in MAIP1high and MAIP1low groups, and all showed high expression in the MAIP1low group. Conclusion: We proposed that MAIP1 overexpression was associated with poor prognosis and tumor immune infiltration in EC. At present, there are few MAIP1-related tumor immune infiltration studies in EC, and further investigation is needed.

Application of modified Matutes score containing CD200 in diagnosis of chronic lymphocytic leukemia / 中南大学学报(医学版)

OBJECTIVES@#Immunophenotyping technique is a powerful tool for the diagnosis and differential diagnosis of chronic lymphocytic leukemia (CLL) and other B-cell chronic lymphoproliferative diseases (B-CLPD). CD200 is strongly expressed in CLL. This study aims to analyze the clinical value of modified Matutes score (MMS) containing CD200 in the diagnosis of CLL.@*METHODS@#We retrospectively analyzed 103 B-CLPD patients diagnosed from January 2020 to July 2021, including 64 CLL patients, 11 follicular lymphoma (FL) patients, 14 mantle cell lymphoma (MCL) patients, 6 marginal zone lymphoma (MZL) patients, 1 hairy cell leukemia (HCL) patient, and 7 lymphoplasmic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) patients. The expression of CD markers between the CLL group and the non-CLL group was compared, and the sensitivity, specificity, and clinical consistency of MMS and Royal Marsden Hospital (RMH) immunophenotyping score system were analyzed.@*RESULTS@#There were significant differences in the expressions of CD5, CD23, FMC7, CD22, CD79b, CD200, and sIg between the CLL group and the non-CLL group (χ2 values were 37.42, 54.98, 30.71, 11.67, 55.26, 68.48, and 17.88, respectively, all P<0.01). When the RMH immunophenotyping score≥4, the sensitivity was 79.7%, and the specificity was 100%. When the MMS≥3, the sensitivity was 95.3%, and the specificity was 100%. The Kappa coefficient of RMH immunophenotyping system was 0.677, and the Kappa coefficient of MMS system was 0.860.@*CONCLUSIONS@#The MMS system containing CD200 has better sensitivity and same specificity compared with RMH immunophenotyping system, and MMS system may be more useful in the diagnosis of CLL.

Trace Element Analysis by PIYE and ICP-AES of Raw Material and Ancient Serpentine Artifacts from China.

This work mainly talks about serpentine mineral with the aim to explore the possible raw materials sources of ancient serpentine artifacts by trace element content analysis. The major and trace elements of serpentine samples from several typical deposits in China were nondestructively determined by external-beam proton-induced X-ray emission (PIXE). For comparison, trace element concentrations were destructively measured by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The results showed the trend of the trace element contents of serpentine jade obtained by the two methods have preferably coherence, which indicate that the nondestructive technique of PIXE can be applied to trace element analysis of serpentine. The relationship between trace element contents and serpentine formation mechanism was discussed. The difference of the trace elements contents in these serpentine minerals is obvious. It can be used to distinguish the different kinds of serpentine formed by different mechanisms. A low amount of Ni and almost no Cr and Co were found in type I serpentine group mineral, whereas significant amounts of Cr, Co and Ni were found in Type II serpentine group mineral. The chemical composition of 18 ancient serpentine artifacts were analyzed by PIXE, they were unearthed from 14 sites and tombs in provinces of Zhejing, Jiangsu, Henan, Anhui and Hubei and dated from Neolithic Age to the Warring States Period (4585 BC­231 BC). By comparing the trace element contents between ancient serpentine artifacts and two kinds of serpentine samples, the provenance of ancient serpentine artifacts were preliminarily inferred. It is beneficial to try to explore the possible raw material of ancient serpentine artifacts based on the relationship between the trace element contents and serpentine formation mechanism in this article.

Effect of dexmedetomidine hydrochloride on H2O2-induced oxidative stress and inflammatory response in Kupffer cells / 中南大学学报(医学版)

OBJECTIVE@#To evaluate whether dexmedetomidine hydrochloride, an α(2)-adrenergic receptor agonist, can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells.
@*METHODS@#H(2)O(2)-induced oxidative damage model of Kupffer cell was established. Kupffer cells were pre-conditioned by dexmedetomidine hydrochloride or Yohimbine for 24 h. MTT colorimetry was used to demonstrate the survival rate of Kupffer cells. The levels of lactate dehydrogenase (LDH), malonaldehyde (MDA) and TNF-α in the culture medium were assessed by corresponding kits.
@*RESULTS@#Dexmedetomidine hydrochloride protected Kupffer cells from H(2)O(2)-induced oxidative damage, showing an increase in the cell survival rate while a decrease in LDH, MDA and TNF-α release in the culture supernatant. Yohimbine, an α(2)-adrenergic receptor antagonist, completely neutralized the protective effect of Dexmedetomidine hydrochloride on Kupffer cells. Yohimbine itself had no effect on H(2)O(2)-induced oxidative damage and inflammatory response.
@*CONCLUSION@#Dexmedetomidine hydrochloride can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells through activation of α(2)-adrenergic receptors.

[The Non-Destructive Analysis of Some Ancient Jade Artifacts Unearthed from Henan Province by a Variety of Optical Techniques].

A total of 14 pieces of ancient jade artifact unearthed from Henan Province were non-destructively analyzed by means of a portable X-ray fluorescence spectrometer (pXRF), laser Raman spectroscopy (portable and mobile) and optical coherence tomography (OCT) technology, comprehensively. The raw materials of ancient jade artifacts could be determined accurately through the combination of pXRF and portable Raman spectrometer in a short time. With the advantages of small size and easy-operation, these two instruments are suitable to in situ non-destructive analysis of ancient jade artifacts. The results of the pXRF shows that these ancient jade artifacts can be divided into 6 categories such as rich in Si Al K, rich in Ca, rich in Si Ca, rich in Si Mg, rich in Si, rich in Ca P. Their main phases have been successfully identified by the portable Raman spectrometer. In the lab, the mobile confocal laser Raman spectrometer, which help us find the Raman vibration peak of [OH] in the tremolite jade, is used to make up the disadvantages of the portable Raman spectrometer such as lower spectral resolution, lower accuracy and narrower measuring range. We can use the OCT to analyze the transparency, fiber fineness and inclusion etc. of the jade artifacts. The confocal laser Raman spectroscopy combined with OCT is used to analyze 2 containing inclusion of tremolite jade samples. OCT image can visually display the distribution characteristics of the inclusion in these 2 samples. Confocal laser Raman spectroscopy can accurately locate the sample surface of inclusion, then we can observe the micro morphology and analyze its phase. The results show that the black inclusion is graphite. This work is very significant to study the geographical origin of jade. Through the study we find, the use of pXRF, laser Raman spectroscopy (portable and mobile) and OCT can be achieved on the identification and analysis of cultural relic's phase composition and texture feature and meet the basic requirements of field archaeological work analysis.

[Application of calibration curve method and partial least squares regression analysis to quantitative analysis of nephrite samples using XRF].

The authors tried to find a method for quantitative analysis using pXRF without solid bulk stone/jade reference samples. 24 nephrite samples were selected, 17 samples were calibration samples and the other 7 are test samples. All the nephrite samples were analyzed by Proton induced X-ray emission spectroscopy (PIXE) quantitatively. Based on the PIXE results of calibration samples, calibration curves were created for the interested components/elements and used to analyze the test samples quantitatively; then, the qualitative spectrum of all nephrite samples were obtained by pXRF. According to the PIXE results and qualitative spectrum of calibration samples, partial least square method (PLS) was used for quantitative analysis of test samples. Finally, the results of test samples obtained by calibration method, PLS method and PIXE were compared to each other. The accuracy of calibration curve method and PLS method was estimated. The result indicates that the PLS method is the alternate method for quantitative analysis of stone/jade samples.

[A study on the relationship between the composition and spectral feature parameters in chlorite].

In order to explore the intrinsic relationship of mineral spectral characteristics and its composition, and provide the basis for the detection of mineral micro information by using hyperspectral technology, based on the thinsection analysis, the authors identified the minerals characteristics and mineral assemblages in rock samples, delineated typical chlorite minerals and divided the occurrence characteristics of chlorite. The authors measured chemical composition of 146 typical chlorite mineral particles by using electron probe micro analysis technology, and calculated the relevant chemical parameters of n(Al(IV)), n(Al(VI)), n(Fe), n(Mg), and n(Fe)/n(Fe + Mg) ratio. In addition we analysed the rock and mineral spectra, and extracted chlorite characteristic spectral parameters. The relationship between the spectra feature parameters and the main crystal chemical parameters in chlorite was analyzed. The study indicated that the diagnostic spectral wavelength of chlorites moved to long wavelength. The results have important guiding significance for identifying the alteration and rock forming mineral species, composition and structure characteristics by usinghyperspectral remote sensing technology.

The anti-apoptotic effect of cytoplasmic alpha-fetoprotein in hepatoma cells induced by all-trans retinoic acid involves activation of the PI3K/AKT signaling pathway / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the effect of alpha-fetoprotein (AFP) on transduction of the PI3K/ AKT signal in hepatocellular carcinoma cells and the role played by AFP in resistance to cytotoxicity of all-trans retinoic acid (ATRA).</p><p><b>METHODS</b>The effects of ATRA of human liver cancer cells was assessed using the BEL-7402 cell line with the MTT assay (to evaluate proliferation), microscopy (to evaluate morphology), flow cytometry (to evaluate apoptosis), laser confocal microscopy and coimmunoprecipitation (co-IP; to evaluate co-localization and interaction of AFP with PTEN), Western blotting (to evaluate expression of phosphorylated-protein kinase B (pAKT) and Src, and RNA interference (RNAi)-mediated knockdown of AFP. Finally, application of the PI3K-specific inhibitor Ly294002 was used to monitor the influence of AFP in transduction of the PI3K signal pathway.</p><p><b>RESULTS</b>The human hepatoma cell line BEL-7402 were resistant to ATRA cytotoxicity. PTEN and AFP co-localized in the cytoplasm, and co-IP indicated that AFP interacts with PTEN in BEL-7402 cells.RNAi knockdown of AFP expression led to reduced growth of BEL-7402 cells.BEL-7402 cells transfected with AFP-short interfering (si)RNA vectors showed enhanced sensitivity to ATRA and reduced expression of pAKT(Ser473) and Src; Ly294002 reduced the role of AFP in stimulating expression of pAKT(Ser473) and Src.</p><p><b>CONCLUSION</b>AFP can activate transduction of the PI3K/AKT signal, and expression of AFP in hepatoma cells is a pivotal event for resisting ATRA-induced apoptosis.</p>

p42/p44 mitogen-activated protein kinases inhibit atrial natriuretic peptide mRNA transcription in gp130-mediated hypertrophic ventricular myocytes

OBJECTIVE@#To understand the role of ANP mRNA transcription regulation in gp130-mediated cardiomyocyte hypertrophy, and the involved mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK, also called p42/p44 MAPK) signaling pathway.@*METHODS@#Isolated neonatal ventricular myocytes were treated with different concentrations of CT-1 (10(-9), 10(-8)and 10(-7)mol/L). MTT was used to analyze the viability and RT-PCR was used to detect ANP mRNA levels in cardiomyocyte. To inhibit p42/p44 MAPK activity in hypertrophic cardiomyocytes, the cells were pretreated with a specific MEK1 inhibitor.@*RESULTS@#CT-1 significantly induced ANP mRNA expression and the viability of cardiomyocytes in a dose- and time-dependent manner. Furthermore, blocking p42/p44 MAPK activity by the special MEK1 inhibitor upregulated the ANP mRNA.@*CONCLUSIONS@#p42/p44 MAPK have an important role in suppressing ANP mRNA transcription and cell activity in gp130-mediated hypertrophic ventricular myocytes.

[Coloration mechanism and chromaticity of Xiuyan Jade of China].

The coloration mechanism of Xiuyan Jade was studied with the chemical composition, valance and coordination states of transition metal ions. The result of inductively-coupled plasma atom emission spectrometer (ICP-AES) indicated that there are little other transition metal elements except for iron and manganese. Electron paramagnetic resonance (EPR) revealed that Fe3+ ions locate at both octahedral sites and tetrahedral sites. Optical absorption spectrum (OAS) showed the presence of Fe2+ and Fe3+ ions. Moreover, depending on the results of OAS, Fe2+ ions determine the green color of Xiuyan Jade, while the coexistence of Fe3+ and Fe2+ ions introduces the yellow color of Xiuyan Jade. The chromaticity coordinate was calculated according to diffuse reflectance spectrum. The result demonstrated that chromaticity coordinates can be used to quantitatively distinguish Xiuyan Jade with similar color, which can provide a scientific reference for the evaluation of the value of Xiuyan Jade.

[Influence of cations on the laser Raman spectra of silicate glasses].

Na2O(K2O)-CaO(MgO)-SiO2, Na2O(K2O)-Al2O3-SiO2, Na2O(K2O)-B2O3-SiO2, Na2O(K2O)-PbO-SiO2 and PbO-BaO-SiO2 glass systems were investigated using laser Raman spectroscopic technique. The modification of short-range structure of glass caused by network modifier cations will influence Raman signature. Alkali and alkali-earth ions can weaken the bridging oxygen bond, thus lower the frequency of Si-O(b)-Si anti-symmetric stretching vibration. When coordina ted by oxygen ions, B3+ can form [BO4] tetrahedron and enter the silicon-oxygen network, but this effect had little impact on the frequency of Raman peaks located in the high-frequency region. Al3+ can also be coordinated by oxygen ions to form [AlO4] tetrahedron. [AlO4] will increase the disorder degree of network while entering network. Ba2+ can increase the density of electron cloud along the Si-O(nb) bond when it bonds with non-bridging oxygen, which will lead to a higher peak intensity of O-Si-O stretching vibration. The Raman peaks of alkli- and alkali-earth silicate glasses are mainly distributed in the region of 400 - 1 200 cm(-1), while in the spectrum of Na2O(K2O)-PbO-SiO2 glass system a 131 cm(-1) peak existed. The authors assigned it to the Pb-O symmetric stretching vibration. Some of the samples were produced in the laboratory according to the average compositions of ancient glasses, so this research is very significant to discriminating ancient silicate glasses of different systems by Laser Raman spectroscopic technique.