The Plasma Concentration of Ticagrelor and Aspirin as a Predictor of Bleeding Complications in Chinese Acute Coronary Syndrome Patients With Dual Antiplatelet Therapy: A Prospective Observational Study.

PURPOSE: This study evaluated the association among the plasma concentration of ticagrelor, ARC124910XX, aspirin, and salicylic acid with the risk of recent bleeding in patients with the acute coronary syndrome. To this end, we developed an accurate model to predict bleeding. METHODS: A total of 84 patients included in this study cohort between May 2021 and November 2021. The risk factors were identified by univariate and multivariate analyses, and statistically significant risk factors identified in the multivariate analysis were included in the nomogram. We used the calibration curve and the receiver operating characteristic curve to verify the accuracy of the prediction model. RESULTS: Multivariable logistic analysis showed that ticagrelor concentration (odds ratio [OR]: 2.47, 95% confidence interval [CI], 1.51-4.75, P = 0.002), ST-segment elevation acute myocardial infarction (OR: 32.2, 95% CI, 2.37-780, P = 0.016), and lipid-lowering drugs (OR: 11.52, 95% CI, 1.91-110, P = 0.015) were positively correlated with bleeding. However, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (OR: 0.04, 95% CI, 0.004-0.213, P < 0.001) was negatively correlated with bleeding. The receiver operating characteristic curve analysis showed that ticagrelor concentration and these factors together predict the occurrence of bleeding (area under receiver operating characteristic curve = 0.945, 95% CI, 0.896-0.994) and that ticagrelor concentration >694.90 ng/mL is the threshold of bleeding concentration (area under receiver operating characteristic curve = 0.696, 95% CI, 0.558-0.834). CONCLUSION: In patients with acute coronary syndrome treated with dual antiplatelet therapy, ticagrelor concentration >694.90 ng/mL was an independent risk factor for bleeding (OR: 2.47, 95% CI, 1.51-4.75, P = 0.002), but ARC124910XX and salicylic acid concentration did not affect bleeding risk ( P > 0.05).

Ultrasonic optic disc height combined with the optic nerve sheath diameter as a promising non-invasive marker of elevated intracranial pressure.

Background/aim: Patients with elevated intracranial pressure (ICP) tend to have optic disc edema and a thicker optic nerve sheath diameter (ONSD). However, the cut-off value of the optic disc height (ODH) for evaluating elevated ICP is not clear. This study was conducted to evaluate ultrasonic ODH and to investigate the reliability of ODH and ONSD for elevated ICP. Methods: Patients suspected of having increased ICP and who underwent a lumbar puncture were recruited. ODH and ONSD were measured before lumbar puncture. Patients were divided according to elevated and normal ICP. We analyzed the correlations between ODH, ONSD, and ICP. ODH and ONSD cut-off points for the identification of elevated ICP were determined and compared. Results: There were a total of 107 patients recruited for this study, 55 patients with elevated ICP and 52 with normal ICP. Both ODH and ONSD in the elevated ICP group were higher than in the normal group [ODH: median 0.81 (range 0.60-1.06) mm vs. 0.40 [0-0.60] mm, p < 0.001; ONSD: 5.01 ± 0.37 mm vs. 4.20 ± 0.38 mm, p < 0.001]. ICP was positively correlated with ODH (r = 0.613; p < 0.001) and ONSD (r = 0.792; p < 0.001). The cut-off values of ODH and ONSD for evaluating elevated ICP were 0.63 mm and 4.68 mm, respectively, with 73% and 84% sensitivity and 83% and 94% specificity, respectively. ODH combined with ONSD showed the highest value under the receiver operating characteristic curve of 0.965 with a sensitivity of 93% and a specificity of 92%. Conclusion: Ultrasonic ODH combined with ONSD may help monitor elevated ICP non-invasively.

Markers of Iron Metabolism and Stroke Risk: Cross-Sectional and Longitudinal Findings from the China Health and Nutrition Survey (CHNS).

BACKGROUND: The association of iron metabolism or status with the stroke risk remains unclear. We aimed to examine the associations between markers of iron metabolism or status and stroke risk using data from the China Health and Nutrition Survey (CHNS). METHODS: Overall, 8589 in the CHNS in 2009, and 7290 participants between 2009 and 2015 were included in the cross-sectional and longitudinal analyses, respectively. Markers included hemoglobin, ferritin (FET), transferrin (TRF), soluble transferrin receptor (sTRF-R), and ratio of sTRF-R/log FET (sTfR-F index). Multivariable logistic regression and Cox proportional hazards models were used to analyze the associations between those markers and risk of stroke. Age, gender, high-sensitivity CRP (hsCRP), body mass index (BMI), current smoking, drinking status, diabetes and hypertension were included as potential confounding factors. RESULTS: We observed longitudinal associations of hemoglobin (HR: 1.54, 95% CI: 1.15 - 2.06, P = 0.004), and sTfR-F index (HR: 0.68, 95% CI: 0.46 - 0.99, P = 0.044) with stroke risk among the participants whose BMI ≤ 23 kg/m2. In addition, FET levels were significantly associated with stroke risk among female (HR: 1.45, 95% CI: 1.00 - 2.09, P = 0.049) after a median of 6.1 years follow-up. Hemoglobin, FET, TRF, sTRF-R, and sTfR-F index were not associated with the risk of stroke in overall analyses. CONCLUSION: FET among female, hemoglobin and sTfR-F index among those BMI ≤ 23 kg/m2 may be contributing factors for stroke.

Ultrasonic optic nerve sheath diameter could improve the prognosis of acute ischemic stroke in the intensive care unit.

Objectives: Stroke patients with high intracranial pressure (ICP) may have poor prognosis. Non-invasive ultrasonic optic nerve sheath diameter (ONSD) could evaluate increased ICP. To investigate whether ONSD is valuable for prognosis of patients with acute ischemic stroke (AIS). Methods: AIS receiving intensive care were recruited with the Glasgow Coma Scale (GCS) score. Patients in group A underwent ultrasonic ONSD to assess ICP voluntarily, whereas group B without ONSD. Patients were followed up at discharge and once a week for 3 months with Glasgow Outcome Scale (GOS) score (four to five scores indicated good prognosis and one to three scores indicated poor prognosis). Results: Forty-nine patients were included. GCS scores did not differ significantly between groups A (26 patients) and B (8 ± 3 vs. 7 ± 3, p < 0.05). In group A, ONSD was 5.01 ± 0.48 mm, which correlated with GCS score (p < 0.05). At discharge, the GOS score was higher in group A than in group B (3.35 ± 1.35 vs. 2.57 ± 1.121, p = 0.034). The proportion of patients with a good prognosis was higher in group A than in group B (46.2% vs. 13.0%, p = 0.006). At discharge and after 3 months of follow-up, ONSD at admission was correlated with the GOS score in group A (r = -0.648 [p < 0.05] and -0.731 [p < 0.05], respectively). After 3 months of follow-up, the GOS score was higher in group A than group B (3.00 ± 1.673 vs. 2.04 ± 1.430, p < 0.05). The proportion of patients with a good prognosis was higher in group A than in group B (46.2% vs. 21.2%, p = 0.039). The Kaplan-Meier curve showed a higher rate of good prognosis in group A than in group B. ONSD (p < 0.05) was an independent predictor of poor prognosis. Conclusion: Non-invasive ultrasonic ONSD could be useful in improving the prognosis of patients with AIS receiving intensive care.

Determination of pharmacokinetic parameters of vitamin K1 in rats after an intravenous infusion.

Pharmacokinetic parameters of vitamin K1 have a large range of values in different literature. The aim of this study was to determine the pharmacokinetic parameters of vitamin K1 following post-constant speed intravenous infusion (PCSII) to provide rational pharmacokinetic parameters of vitamin K1 and compare these with results of noncompartmental analysis following intravenous injection (IV). After 15 hours intravenous infusion of vitamin K1 in rats, the logarithmic concentration-time curve of vitamin K1 was fit to a linear equation following PCSII (R2  = 0.9599 ± 0.0096). Then, half-time (T1/2 ), apparent volume of distribution (Vd ), and clearance rate (CL) were estimated successively. T1/2 of vitamin K1 was 4.07 ± 0.41 hour, CL was 89.47 ± 3.60 mL/h, and Vd was 525.38 ± 54.45 mL in rats following PCSII. There was no significant difference in pharmacokinetic parameters of vitamin K1 among different sampling times. For noncompartmental analysis, T1/2 and mean residence time (MRTINF ) for a sampling duration of 6h were shorter than those of 12 hours or 24 hours sampling duration following IV (P < .05, P < .01). In addition, T1/2 of vitamin K1 was obviously different from MRT-equated half-time (T1/2,MRT )(P < .05). Vd and CL of vitamin K1 following PCSII were larger than those following IV based on noncompartmental analysis (P < .01). The results demonstrated that drug distribution in the body was balanced and the Napierian logarithmic concentration-time curve of vitamin K1 fit to a linear equation following PCSII. Vitamin K1 has a long T1/2 and a relatively large Vd following PCSII.

Synthesis of Epoxides from Alkyl Bromides and Alcohols with in Situ Generation of Dimethyl Sulfonium Ylide in DMSO Oxidations.

Direct conversion of the readily available alkyl bromides and alcohols to value-added epoxides using dimethyl sulfoxide (DMSO) under mild reaction conditions has been developed. Benzyl and allyl bromides, and activated and unactivated alcohols all proceeded smoothly to give epoxides in high to excellent yield. Dimethyl sulfide, generated by DMSO oxidations, was in situ elaborated to form the substituted dimethyl sulfonium ylide species that participates in the Corey-Chaykovsky epoxidation in a domino and one-pot fashion, respectively.

miR-200c-3p Suppresses the Proliferative, Migratory, and Invasive Capacities of Nephroblastoma Cells via Targeting FRS2.

Objectives: miR-200c-3p has been shown to serve as a tumor suppressor in various tumor types. However, the biological function of miR-200c-3p in nephroblastoma remains unknown. This study aims to investigate the biological function and regulatory mechanisms of miR-200c-3p in nephroblastoma development. Methods: The expression of miR-200c-3p in nephroblastoma tissues and cells was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of miR-200c-3p on the proliferation and cell cycle of SK-NEP-1 nephroblastoma cell line were evaluated by CCK-8 assay, colony formation assay, and flow cytometry. The effects of miR-200c-3p on the migratory and invasive capacities of SK-NEP-1 cells were measured by wound healing assay and transwell assay. The ability of miR-200c-3p to target fibroblast growth factor receptor substrate 2 (FRS2) was detected by quantitative PCR, western blot, and luciferase reporter assay. Results: The expression of miR-200c-3p was significantly downregulated in nephroblastoma tissues and cells compared with that in normal renal tissues and cells. miR-200c-3p inhibited the proliferative, migratory, and invasive capacities of nephroblastoma cells by targeting FRS2. Conclusions: miR-200c-3p suppresses the malignant behaviors of nephroblastoma cells by downregulating the expression of FRS2.

Manipulation of Light Signal Transduction Factors as a Means of Modifying Steroidal Glycoalkaloids Accumulation in Tomato Leaves.

Steroidal glycoalkaloids (SGAs) are cholesterol-derived specialized metabolites produced by Solanaceous plant species. They contribute to pathogen defense but are considered as anti-nutritional compounds and toxic to humans. Although the genes involved in the SGA biosynthetic pathway have been successfully cloned and identified, transcription factors regulating this pathway are still poorly understood. We report that silencing tomato light signal transduction transcription factors ELONGATED HYPOCOTYL 5 (SlHY5) and PHYTOCHROME INTERACTING FACTOR3 (SlPIF3), by virus-induced gene silencing (VIGS), altered glycoalkaloids levels in tomato leaves compared to control plant. Electrophoretic mobility shift assay (EMSA) and Chromatin immunoprecipitation (ChIP) analysis confirmed that SlHY5 and SlPIF3 bind to the promoter of target genes of GLYCOALKALOID METABOLISM (GAME1, GAME4, GAME17), affecting the steady-state concentrations of transcripts coding for SGA pathway enzymes. The results indicate that light-signaling transcription factors HY5 and PIF3 regulate the abundance of SGAs by modulating the transcript levels of these GAME genes. This insight into the regulation of SGA biosynthesis can be used for manipulating the level of these metabolites in crops.

Asymmetric Formal Synthesis of (-)-Cephalotaxine via Palladium-Catalyzed Enantioselective Tsuji Allylation.

Asymmetric synthesis of the pentacyclic alkaloid (-)-cephalotaxine was accomplished via palladium-catalyzed enantioselective Tsuji allylation for construction of the aza-containing tetrasubstituted stereogenic center (95% yield, 93% ee). The allyl enol carbonate precursor was prepared from Hanaoka's ketone intermediate, which was formed by a novel formic acid promoted ring-expansion reaction.

The role of phytochromes in regulating biosynthesis of sterol glycoalkaloid in eggplant leaves.

Glycoalkaloids are toxic compounds that are synthesized by many Solanum species. Glycoalkaloid biosynthesis is influenced by plant genetic and environmental conditions. Although many studies have shown that light is an important factor affecting glycoalkaloid biosynthesis, the specific mechanism is currently unknown. Chlorophyll and carotenoid biosynthesis depend on light signal transduction and share some intermediate metabolites with the glycoalkaloid biosynthetic pathway. Here, we used virus-induced gene silencing to silence genes encoding phytoene desaturase (PDS) and magnesium chelatase (CHLI and CHLH) to reduce chlorophyll and carotenoid levels in eggplant leaves. Quantification of carotenoid and chlorophyll levels is analyzed by LC/PDA/APCI/MS and semipolar metabolite profiling by LC/HESI/MS. Notably, the resulting lines showed decreases in glycoalkaloid production. We further found that the expression of some genes involved in the production of glycoalkaloids and other metabolites were suppressed in these silenced lines. Our results indicate that photosynthetic pigment accumulation affects steroidal glycoalkaloid biosynthesis in eggplant leaves. This finding lays the foundation for reducing the levels of endogenous antinutritional compounds in crops.

TRIB3 inhibits proliferation and promotes osteogenesis in hBMSCs by regulating the ERK1/2 signaling pathway.

Osteogenic differentiation in human bone marrow-derived mesenchymal stem cells (hBMSCs) is regulated by various factors, including bone morphogenetic proteins (BMPs), Notch, growth hormones and mitogen-activated protein kinases (MAPKs). Tribbles homolog 3 (TRIB3), a pseudokinase, plays an important role in cancer cells and adipocytes. However, TRIB3 function in osteogenic differentiation is unknown, although it is involved in regulating signaling pathways associated with osteogenic differentiation. Here, we found that TRIB3 was highly expressed during osteogenic differentiation in hBMSCs. Inhibition of focal adhesion kinase (FAK) or phosphatidylinositol 3-kinase (PI3K) resulted in a significant decrease in TRIB3 expression, and expression of TRIB3 was restored by increasing insulin-like growth factor-1 (IGF-1) via activating phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling. TRIB3 knock-down enhanced proliferation and decreased osteogenic differentiation at the middle stage of differentiation, and these effects were reversed by inhibiting the activation of extracellular signal-regulated kinase (ERK)-1/2. In conclusion, TRIB3 plays an important role in proliferation and osteogenic differentiation by regulating ERK1/2 activity at the middle stage of differentiation, and expression of TRIB3 is regulated by FAK in a PI3K/AKT-dependent manner.

Application and progress of high-throughput sequencing technologies in the research of hereditary hearing loss.

Hearing loss (HL) is the most common birth defect. Elucidating the genetic basis of hereditary deafness can not only assist diagnosis, provide the basis for genetic counseling and the prevention of deafness, but also bring a deeper understanding of the disease pathogenesis. In the genomic era, high-throughput sequencing technologies, represented by whole genome sequencing (WGS), whole exome sequencing (WES) or target region sequencing, have been widely used in the studies of hereditary HL. Here, we summarize the application and progress of WES and target region sequencing in the research of causative genes and clinical molecular diagnosis of hereditary HL, hoping to be helpful for the development and improvement of clinical genetic diagnosis of deafness in China.

Cytotoxic activity of a synthetic deoxypodophyllotoxin derivative with an opened D-ring.

Podophyllotoxin and its synthetic derivatives are valuable medicinal agents that have antitumor, insecticidal, and antifungal properties. We previously synthesized a deoxypodophyllotoxin derivative with an opened D-ring (DPD) exhibiting potent insecticidal activity. This article was firstly performed to identify the cytotoxicity of DPD toward human cancer cell lines (SGC7901, HeLa, and A549) and normal cell line (HEK293T) using MTT assay. DPD showed potent cytotoxicity against human cancer lines (HeLa and A549) and less cytotoxicity against normal cell lines HEK293T. DPD could also induce the cell cycle arrest at G2/M phase in HeLa cells and significantly increase the phosphorylation (Tyr 15) of CDC2 leading to inactivation of CDC2. The effects of DPD on cellular microtubule networks were detected using immunofluorescence technique in HeLa cells. The immunofluorescence results showed DPD influenced the arrangement and organization of cellular microtubule networks in HeLa cells. Microtubules are long, hollow cylinders made up of polymerized tubulin dimers. Total microtubules were separated after DPD treatment. Western blot results showed that the free polymerized tubulin dimers were obviously increased after DPD treatment. DPD may be a good drug candidate with the therapeutic potential to human cancer by affecting microtubule polymerization.

[Characteristics of Nitrogen and Phosphorus Losses in Longhong Ravine Basin of Westlake in Rainstorm Runoff].

In order to understand the non-point source pollution status in Longhong ravine basin of Westlake, the characteristics of nutrient losses in runoff was investigated during three rainstorms in one year. The results showed that long duration rainstorm event generally formed several runoff peaks, and the time of its lag behind the peaks of rain intensity was dependent on the distribution of heavy rainfall. The first flush was related to the antecedent rainfall, and the less rainfall in the earlier period, the more total phosphorus (TP) and ammonia (NH4+ -N) in runoff was washed off. During the recession of runoff, more subsurface runoff would result in a concentration peak of total nitrogen (TN) and nitrogen (NO3- -N) . The event mean concentration (EMC) of runoff nitrogen had a negative correlation with rainfall, rainfall duration, maximum rain intensity and average rain intensity except for antecedent rainfall, whereas the change in TP EMC showed the opposite trend. The transport fluxes of nutrients increased with an elevation in runoffs, and Pearson analysis showed that the transport fluxes of TN and NO3- -N had good correlations with runoff depth. The average transport fluxes of TP, TN, NH4+ -N and NO3- -N were 34.10, 1195.55, 1006.62 and 52.38 g x hm(-2), respectively, and NO3- -N was the main nitrogen form and accounted for 84% of TN.

Genetic Correction of Induced Pluripotent Stem Cells From a Deaf Patient With MYO7A Mutation Results in Morphologic and Functional Recovery of the Derived Hair Cell-Like Cells.

UNLABELLED: The genetic correction of induced pluripotent stem cells (iPSCs) induced from somatic cells of patients with sensorineural hearing loss (caused by hereditary factors) is a promising method for its treatment. The correction of gene mutations in iPSCs could restore the normal function of cells and provide a rich source of cells for transplantation. In the present study, iPSCs were generated from a deaf patient with compound heterozygous MYO7A mutations (c.1184G>A and c.4118C>T; P-iPSCs), the asymptomatic father of the patient (MYO7A c.1184G>A mutation; CF-iPSCs), and a normal donor (MYO7A(WT/WT); C-iPSCs). One of MYO7A mutation sites (c.4118C>T) in the P-iPSCs was corrected using CRISPR/Cas9. The corrected iPSCs (CP-iPSCs) retained cell pluripotency and normal karyotypes. Hair cell-like cells induced from CP-iPSCs showed restored organization of stereocilia-like protrusions; moreover, the electrophysiological function of these cells was similar to that of cells induced from C-iPSCs and CF-iPSCs. These results might facilitate the development of iPSC-based gene therapy for genetic disorders. SIGNIFICANCE: Induced pluripotent stem cells (iPSCs) were generated from a deaf patient with compound heterozygous MYO7A mutations (c.1184G>A and c.4118C>T). One of the MYO7A mutation sites (c.4118C>T) in the iPSCs was corrected using CRISPR/Cas9. The genetic correction of MYO7A mutation resulted in morphologic and functional recovery of hair cell-like cells derived from iPSCs. These findings confirm the hypothesis that MYO7A plays an important role in the assembly of stereocilia into stereociliary bundles. Thus, the present study might provide further insight into the pathogenesis of sensorineural hearing loss and facilitate the development of therapeutic strategies against monogenic disease through the genetic repair of patient-specific iPSCs.

[Quantitative Analysis of Heave Mental Ion Based on Portable NIR Spectrometer].

By virtue of the characters of rapid analysis and simple pretreatment, near infrared reflectance spectroscopy technique is widely used in agriculture, medicine, environment, petrochemical and other fields. To satisfy the rapid on-site identification and analysis, portable near-infrared spectrometers have gained more and more attention. Because near infrared reflectance spectroscopy technique also is a green tool for multi-component analysis, the paper aims at investigating the feasibility for simultaneous quantitative analysis of various heavy metal ions in dilute solution using portable near infrared spectrometer. First, amino modified polymerized starch was used as adsorbent to enrich nickel ions and copper ions in diluted solution. Then, the diffuse reflectance spectra of amino modified polymerized starch samples were measured directly by portable near-infrared spectrometer. Furthermore, with the help of spectral preprocessing methods and partial least-squares regression, quantitative models were built from the near infrared diffuse reflectance spectra of amino modified polymerized starch enriched with heavy metal ions and reference concentrations. At last, the stability of the models was proved through cross validation and external validation. The results show that nickel ions and copper ions in diluted solution can be efficiently enriched by amino modified polymerized starch in the presence of other interfering ions. The adsorption rates for nickel ions and copper ions are 99.5% and 99.8%, respectively. Two robust models can be achieved after spectra processing and partial least squares regression. The spectra processing methods contains Continuous wavelet transform and multiplicative scatter correction combined with Savitzky-Golay. The obtained corresponding correlation coefficients of the two robust models are 0.981 9 and 0.965 4, respectively. Thus, simultaneous quantitative analysis of nickel ions and copper ions in the mixed diluted solution was achieved, and the detectable concentrations of nickel ions and copper ions are both as low as 3.0 mg·L(-1). The method not only improves the sensitivity of near infrared reflectance spectroscopy technique, but also demonstrates the feasibility for simultaneous quantitative determination of various heavy metal ions by using portable near infrared spectrometer. Moreover, the method may be a useful exploration to further broaden the application of near infrared reflectance spectroscopy technique.

[Primary neuroendocrine tumor of the testis: clinicopathological study of 7 cases].

OBJECTIVE: To investigate the clinicopathologic characteristics, diagnosis, differential diagnosis and treatment of primary neuroendocrine tumor (NET) of the testis. METHODS: Using light microscopy and immunohistochemistry, we studied 7 cases of primary NET of the testis, reviewed relevant literature, and analyzed the clinical manifestations, histomorphologic and immunohistochemical characteristics, treatment and prognosis of the tumor. RESULTS: The 7 male patients, at the mean age of 40.6 years, all presented with testicular painless masses, none accompanied with carcinoid syndrome. Histologically, the uniform tumor cells were arranged in trabecular, island, solid and/or flake structures and locally in a tubulo glandular pattern, round and polygonal in shape, with a small amount of lipid vacuoles in the eosinophilic cytoplasm. The cells had round nuclei with fine chromatin and rarely identified mitosis. Immunohistochemical staining showed that the tumor cells were positive for Syn, CgA, NSE and CK, with a Ki-67 positive rate of < 2%. CONCLUSION: Primary NET of the testis is a rare and low-grade malignancy. Early diagnosis and surgical resection are essential for good prognosis. Immunohistochemistry helps its diagnosis and differential diagnosis from other metastatic neuroendocrine carcinoma, teratomas with carcinoid, seminoma, and Sertoli cell tumor.

The correlation between morphology and the expression of TGF-ß signaling pathway proteins and epithelial-mesenchymal transition-related proteins in synovial sarcomas.

Synovial sarcoma (SS) is a malignant tumor of soft tissue and is noted for late local recurrence and metastasis. Aberrant epithelial-mesenchymal transition (EMT) has been implicated in the pathogenesis of diverse human malignancies. Immunohistochemical techniques were used to assess EMT-related proteins (E-cadherin, N-cadherin, ß-catenin, Snail, and Slug) and the TGF-ß1 pathway (TGF-ß1 and Smad2/3) proteins expression in different histological subtypes and epithelial mesenchymal compositions of SS. The expression of cell-surface (E-cadherin) and cytoskeletal proteins (ß-catenin) were higher significantly in biphasic SSs (BSSs) (70.4%, 51.9%) than MFSSs (both for 10%). Among monophasic fibrous SSs (MFSSs) samples, E-cadherin protein expression was negatively correlated with expression Snail, Slug, TGF-ß1, and Smad2/3. The expression levels of Snail and Smad2/3 were correlated with the pTNM stage (I-II vs. III-IV; P=0.047, P=0.021) and TGF-ß1 exhibited a tendency toward a positive correlation with pTNM stage (I-II vs. III-IV; P=0.052), but did not correlate with the histological grade (p>0.05). Interestingly, our data showed that expression of E-cadherin protein correlated with greater survival in SS patients. Overexpression of Snail, and TGF-ß1 is associated with suppressed expression of E-cadherin in MFSSs, which supports the hypothesis that the MFSS subtype may have developed via neoplastic EMT.

[Expression of homeobox gene HOXA9 in childhood acute leukemia, and its clinical significance].

OBJECTIVE: To investigate the expression of homeobox gene HOXA9 in the bone marrow mononuclear cells of children with acute leukemia (AL) and its clinical significance. METHODS: Forty-six children with AL were divided into acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) groups. Fifteen children with idiopathic thrombocytopenic purpura were selected as a control group. The mRNA expression of HOXA9 was measured by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: HOXA9 expression was detected in 63% of the 52 bone marrow samples from 46 AL children. The positive HOXA9 expression rate in the AML group was significantly higher than in the ALL and control groups (86% vs 35% and 13%; P<0.05). The mRNA expression of HOXA9 in the AML group was significantly higher than in the ALL and control groups (P<0.05). Among the children with AML, those with M5 AML had the highest HOXA9 mRNA level, followed by children with M4 AML and children with M1 and/or M2 AML, but HOXA9 expression was not detected in children with M3 AML. The high-risk subgroup of AML children had relatively high levels of HOXA9 expression. In the children with AML, the initial treatment subgroup had significantly higher positive HOXA9 expression rate and HOXA9 mRNA levels than in the remission subgroup and control group (P<0.05), but there were no significant differences between the latter two groups (P>0.05). The non-remission subgroup had significantly higher HOXA9 expression than the remission subgroup and control group (P<0.05). CONCLUSIONS: High expression of HOXA9 is associated with the occurrence of AL, and its expression level is significantly higher in children with AML than in those with ALL. There is a positive correlation between the expression level of HOXA9 and the risk of childhood leukemia, and high expression of HOXA9 suggests poor prognosis. Therefore, HOXA9 can be used as one of the indices in the diagnosis, treatment and prognosis prediction of childhood AL.