Serum alpha-fetoprotein response as a preoperative prognostic indicator in unresectable hepatocellular carcinoma with salvage hepatectomy following conversion therapy: a multicenter retrospective study.

Background: This study evaluates the efficacy of alpha-fetoprotein (AFP) response as a surrogate marker for determining recurrence-free survival (RFS) in patients with unresectable hepatocellular carcinoma (uHCC) who undergo salvage hepatectomy following conversion therapy with tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody-based regimen. Methods: This multicenter retrospective study included 74 patients with uHCC and positive AFP (>20 ng/mL) at diagnosis, who underwent salvage hepatectomy after treatment with TKIs and anti-PD-1 antibody-based regimens. The association between AFP response-defined as a ≥ 80% decrease in final AFP levels before salvage hepatectomy from diagnosis-and RFS post-hepatectomy was investigated. Results: AFP responders demonstrated significantly better postoperative RFS compared to non-responders (P<0.001). The median RFS was not reached for AFP responders, with 1-year and 2-year RFS rates of 81.3% and 70.8%, respectively. In contrast, AFP non-responders had a median RFS of 7.43 months, with 1-year and 2-year RFS rates at 37.1% and 37.1%, respectively. Multivariate Cox regression analysis identified AFP response as an independent predictor of RFS. Integrating AFP response with radiologic tumor response facilitated further stratification of patients into distinct risk categories: those with radiologic remission experienced the most favorable RFS, followed by patients with partial response/stable disease and AFP response, and the least favorable RFS among patients with partial response/stable disease but without AFP response. Sensitivity analyses further confirmed the association between AFP response and improved RFS across various cutoff values and in patients with AFP ≥ 200 ng/mL at diagnosis (all P<0.05). Conclusion: The "20-80" rule based on AFP response could be helpful for clinicians to preoperatively stratify the risk of patients undergoing salvage hepatectomy, enabling identification and management of those unlikely to benefit from this procedure.

Targeting SHP2 reverses BRAF inhibitor tolerance in anaplastic thyroid carcinoma.

PURPOSE: To explore the possibility of a combination of dabrafenib and SHP2 inhibitor in the treatment of anaplastic thyroid carcinoma and to provide a new therapeutic strategy for the treatment of anaplastic thyroid cancer. PATIENTS AND METHODS: Firstly, a drug resistance model was established, and the expression levels of related RTK were detected by qPCR. Western blot was used to detect the protein expression levels of Akt and MAPK signaling pathways in the control group, single-drug group and two-drug combination group. The gene silencing of SHP2 was achieved by transfection of siRNA and verified by Western blot. CCK8 kit and clone formation assay were used to detect cell proliferation activity. In vivo model of mutant thyroid cancer cells was established by subcutaneous injection of mice and then divided into four groups. Tumor diameter was measured every two days. Immunohistochemistry was used to evaluate the expression of p-ERK, p-AKT and Ki67 in mouse tumors. RESULTS: In this study, dabrafenib-resistant ATC cells were first constructed, and the response of RTKs in drug-resistant cells was upregulated to activate Akt and MER/ERK pathways. The activation of Akt and MEK/ERK pathways in the combination group was significantly inhibited, and the proliferation ability of tumor cells was significantly reduced compared with Dabrafenib, SHP099 group and DMSO group. To verify that SHP099 was not off-target, we also silenced SHP2 expression by transfection with siRNA and obtained the same results. Finally, by building a mouse drug resistance model, we confirmed that dabrafenib and SHP099 can also play a powerful anti-cancer effect in vivo. CONCLUSION: The SHP2 inhibitor SHP099 can effectively reverse the drug resistance of dabrafenib through inhibiting the reactivated RAS signaling pathway in anaplastic thyroid cancer.The combination of dabrafenib with SHP2 inhibitor has shown significant tumor suppressive effects for dabrafenib-resistant cells and it may be a new therapeutic strategy with longer lasting therapeutic benefits.

Progress of MRI Radiomics in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third leading cause of cancer-related death. Although the diagnostic scheme of HCC is currently undergoing refinement, the prognosis of HCC is still not satisfactory. In addition to certain factors, such as tumor size and number and vascular invasion displayed on traditional imaging, some histopathological features and gene expression parameters are also important for the prognosis of HCC patients. However, most parameters are based on postoperative pathological examinations, which cannot help with preoperative decision-making. As a new field, radiomics extracts high-throughput imaging data from different types of images to build models and predict clinical outcomes noninvasively before surgery, rendering it a powerful aid for making personalized treatment decisions preoperatively. OBJECTIVE: This study reviewed the workflow of radiomics and the research progress on magnetic resonance imaging (MRI) radiomics in the diagnosis and treatment of HCC. METHODS: A literature review was conducted by searching PubMed for search of relevant peer-reviewed articles published from May 2017 to June 2021.The search keywords included HCC, MRI, radiomics, deep learning, artificial intelligence, machine learning, neural network, texture analysis, diagnosis, histopathology, microvascular invasion, surgical resection, radiofrequency, recurrence, relapse, transarterial chemoembolization, targeted therapy, immunotherapy, therapeutic response, and prognosis. RESULTS: Radiomics features on MRI can be used as biomarkers to determine the differential diagnosis, histological grade, microvascular invasion status, gene expression status, local and systemic therapeutic responses, and prognosis of HCC patients. CONCLUSION: Radiomics is a promising new imaging method. MRI radiomics has high application value in the diagnosis and treatment of HCC.

A study of the correlations between IVIM-DWI parameters and the histologic differentiation of hepatocellular carcinoma.

The present study aimed to investigate the value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) in the preoperative prediction of the histologic differentiation of hepatocellular carcinoma (HCC). Seventy HCC patients were scanned with a 3.0 T magnetic resonance scanner. The values of apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*), and the fraction of the fast apparent diffusion coefficient (f) were measured. Analysis of variance was used to compare the differences in parameters between groups with different degrees of histologic differentiation. p < 0.05 was considered statistically significant. Receiver operating characteristic (ROC) curves were used to analyse the efficacy of IVIM-DWI parameters for predicting the histologic differentiation of HCC. The ADC and D values for well, moderately and poorly differentiated HCC were 1.35 ± 0.17 × 10-3 mm2/s, 1.16 ± 0.17 × 10-3 mm2/s, 0.98 ± 0.21 × 10-3 mm2/s, and 1.06 ± 0.15 × 10-3 mm2/s, 0.88 ± 0.16 × 10-3 mm2/s, 0.76 ± 0.18 × 10-3 mm2/s, respectively, and all differences were significant. The D* and f values of the three groups were 32.87 ± 14.70 × 10-3 mm2/s, 41.68 ± 17.90 × 10-3 mm2/s, 34.54 ± 18.60 × 10-3 mm2/s and 0.22 ± 0.07, 0.23 ± 0.08, 0.18 ± 0.07, respectively, with no significant difference. When the cut-off values of ADC and D were 1.25 × 10-3 mm2/s and 0.97 × 10-3 mm2/s, respectively, their diagnostic sensitivities and specificities for distinguishing well differentiated HCC from moderately differentiated and poorly differentiated HCC were 73.3%, 85.5%, 86.7%, and 78.2%, and their areas under the ROC curve were 0.821 and 0.841, respectively. ADC and D values can be used preoperatively to predict the degree of histologic differentiation in HCC, and the D value has better diagnostic value.

Adjuvant transarterial chemoembolization following radical resection for intrahepatic cholangiocarcinoma: A multi-center retrospective study.

Background and Aims: The prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection is far from satisfactory, but the effect of postoperative transarterial chemoembolization (p-TACE) remains controversial. This multi-center retrospective study was to evaluate the clinical value of p-TACE and identify the selected patients who would benefit from p-TACE. Methods: Data of ICC patients who underwent radical resection with/without p-TACE therapy was obtained from 12 hepatobiliary centers in China between Jan 2014 and Jan 2017. Overall survival (OS) was set as the primary endpoint, which was analyzed by the Kaplan-Meier method before and after propensity score matching (PSM). Subgroup analysis was conducted based on the established staging system and survival risk stratification. Results: A total of 335 patients were enrolled in this study, including 39 patients in the p-TACE group and 296 patients in the non-TACE group. Median OS in the p-TACE group was longer than that in the non-TACE group (63.0 months vs. 18.0 months, P=0.041), which was confirmed after 1:1 PSM (P=0.009). According to the 8th TNM staging system, patients with stage II and stage III stage would be benefited from p-TACE (P=0.021). Subgroup analysis stratified by risk factors showed that p-TACE could only benefit patients with risk factors <2 (P=0.027). Conclusion: Patients with ICC should be recommended to receive p-TACE following radical resection, especially for those with stage II, stage III or risk factors <2. However, the conclusion deserved further validation.

A Correlative Study Between IVIM-DWI Parameters and the Expression Levels of Ang-2 and TKT in Hepatocellular Carcinoma.

BACKGROUND: Noninvasive evaluation of the expression of angiopoietin-2 (Ang-2) and transketolase (TKT) in hepatocellular carcinoma (HCC) is of great significance for the clinical development of individualized treatment plans. However, the correlation between intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and the expression of Ang-2 and TKT has not been reported. We sought to investigate the correlations between IVIM-DWI parameters and Ang-2 and TKT expression levels in HCCs. METHODS: Conventional non-enhanced magnetic resonance imaging (MRI) and IVIM-DWI and dynamic contrast MRI were performed for 61 patients with HCC before surgical treatment. Various IVIM-DWI parameters, such as apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*) and fraction of fast apparent diffusion coefficient (f), were calculated using Function-MADC software. Expression levels of Ang-2 and TKT in HCC were detected via immunohistochemical staining and classified into two grades. Independent sample t tests were used to compare differences in parameters between the two groups. The Spearman rank correlation test was used to analyze the correlations between IVIM-DWI parameters and Ang-2 and TKT expression levels in HCCs. RESULTS: The D* and f values were significantly higher in the high Ang-2 group than in the low Ang-2 group; there were no obvious between-group differences in ADC and D. Ang-2 expression was positively correlated with D* and f but not with ADC and D. The ADC and D values were significantly lower in the high TKT group than in the low TKT group, whereas the between-group differences for D* and f were not significant. TKT expression was negatively correlated with ADC and D but not with D* and f. CONCLUSIONS: IVIM-DWI can be used to evaluate Ang-2 and TKT expression in HCC.

[Clinical Characteristics of Peripheral Hemogram and DNMT3A Gene Mutation in Patients with Primary AML Treated by FLT3-ITD-mt and FLT3-ITD-wt].

OBJECTIVE: To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed or refractory peripheral T-cell lymphoma(PTCL). METHODS: The clinical data of 6 patients with relapsed or refractory PTCL undergoing allo-HSCT from Sep. 2014 to Sep. 2018 in the department of hematology, aerospace center hospital were retrospectively analyzed. Complications and disease-free survival after HSCT were observed. RESULTS: All the patients could well tolerate the conditioning regimen and acquired hematopoietic recon-struction. Following up till December 2018, with a median time of 11.5 months (1-51); acute GVHD developed in 2 cases and chronic GVHD developed in 5 cases, Among 6 cases one case died of viral pheumonia and the other 5 patients remained disease-free survival. The longest disease-free survival time has reached 51 months. CONCLUSION: allo-HSCT is a safe and effective method for relapsed or refractory peripheral T-cell lymphoma, which can be chosen as salvage treatment method for patients with primary resistance. Optimization of the conditioning regimen may result in better efficacy of allo-HSCT.

Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/ß-catenin feedback loop.

RNA-binding motif protein 5 (RBM5) acts as a tumor suppressor in various human cancers and presents with several important characteristics, such as the potentiation of apoptosis, inhibition of the cell cycle, and alternative splicing of Fas and caspase-2 precursor mRNA. However, its role in bladder urothelial carcinoma (BUC) remains unknown. In this study, we found that RBM5 expression was significantly down-regulated in BUC tissues when compared with the adjacent nontumor tissues. The down-regulation of RBM5 activates ß-catenin, which binds to the T-cell factor/lymphocyte enhancer factor element of the miR-432-5p promoter and elevates the expression of miR-432-5p in bladder cancer cells. The up-regulated miR-432-5p directly targets 3'-UTR and depresses RBM5 expression. Thus, RBM5-miR-432-5p-ß-catenin forms a feedback loop in regulating bladder cancer cell apoptosis. Our findings provide evidence that the regulatory feedback loop among RBM5, miR-432-5p, and Wnt-ß-catenin is responsible for the progress of bladder cancer cells.-Zhang, Y.-P., Liu, K.-L., Wang, Y.-X., Yang, Z., Han, Z.-W., Lu, B.-S., Qi, J.-C., Yin, Y.-W., Teng, Z.-H., Chang, X.-L., Li, J.-D., Xin, H., Li, W. Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/ß-catenin feedback loop.

[Change of Neutrophils/ Lymphocyte Ratio in Patients with DLBCL before and after CHOP or R-CHOP Chemotherapy and Its Effect on Survival of Patients].

OBJECTIVE: To analyze the change of neutrophil/lymphocyte ratio (NLR) in patients with diffuse large B cell lymphoma (DLBCL) patients before and after CHOP or R-CHOP chemotherapy and its effect on survival of patients. METHODS: Clinical data of 60 patients with DLBCL were collected and were retrospectively analyzed. According to median NLR, 60 patients were divided into the group L in 33 cases (NLR< 2.27) and group H in 27 cases (NLR≥ 2.27). The curative effect and survival rate by using CHOP or R-CHOP after chemotherapy were compared between the two groups. RESULTS: In the group H, the total effective rate after chemotherapy (55.56%) was significantly lower than that of group L (87.88%), which showed that the difference were statistically significant (P<0.05); the cumulative survival rate of 1,2,3 years in the group H (70.37%, 59.26%, 37.04%) were significantly lower than that in the group L (93.94%, 87.88%, 60.61%) (P<0.05). The NLR≥ 2.27 before chemotherapy was the factor influencing the prognosis of patients with DLBCL (P<0.05). CONCLUSION: The NLR≥ 2.27 before chemotherapy may be used as a factor influencing the prognosis of patients with DLBCL, and the high NLR may indicate poor clinical efficacy and worse prognosis.

Silencing of miR-193a-5p increases the chemosensitivity of prostate cancer cells to docetaxel.

BACKGROUND: Docetaxel-based chemotherapy failure in advanced prostate carcinoma has partly been attributed to the resistance of prostate cancer (PC) cells to docetaxel-induced apoptosis. Hence, there is an urgent need to identify mechanisms of docetaxel chemoresistance and to develop new combination therapies. METHODS: miR-193a-5p level was evaluated by qPCR in prostate tissues and cell lines, and its expression in the tissues was also examined by in situ hybridization. PC cell line (PC3 cell) was transfected with miR-193a-5p mimic or its inhibitor, and then cell apoptosis and the expression of its downstream genes Bach2 and HO-1 were detected by TUNEL staining and Western blotting. Luciferase reporter assay was used to detect the effect of miR-193a-5p and Bach2 on HO-1 expression. Xenograft animal model was used to test the effect of miR-193a-5p and docetaxel on PC3 xenograft growth. RESULTS: miR-193a-5p was upregulated in PC tissues and PC cell lines, with significant suppression of PC3 cell apoptosis induced by oxidative stress. Mechanistically, miR-193a-5p suppressed the expression of Bach2, a repressor of the HO-1 gene, by directly targeting the Bach2 mRNA 3'-UTR. Docetaxel treatment modestly decreased Bach2 expression and increased HO-1 level in PC3 cells, whereas a modest increase of HO-1 facilitated docetaxel-induced apoptosis. Notably, docetaxel-induced miR-193a-5p upregulation, which in turn inhibits Bach2 expression and thus relieves Bach2 repression of HO-1 expression, partly counteracted docetaxel-induced apoptosis, as evidenced by the increased Bcl-2 and decreased Bax expression. Accordingly, silencing of miR-193a-5p enhanced sensitization of PC3 cells to docetaxel-induced apoptosis. Finally, depletion of miR-193a-5p significantly reduced PC xenograft growth in vivo. CONCLUSIONS: Silencing of miR-193a-5p or blockade of the miR-193a-5p-Bach2-HO-1 pathway may be a novel therapeutic approach for castration-resistant PC.

Sweroside eradicated leukemia cells and attenuated pathogenic processes in mice by inducing apoptosis.

Acute myeloid leukemia (AML), characterized by extremely heterogeneous molecular and biologic abnormalities, is an aggressive hematologic malignancy, hampering the research and development of effective targeted treatment modalities. Sweroside (SWE), an iridoid glycoside, is isolated from Lonicera japonIca. It has diverse biological activities, but little is known in human leukemia. Here, our study showed the potential of sweroside as an effective agent against human leukemia using in vitro and in vivo approaches. Sweroside treatment obviously reduced the cell viability in human leukemia cell lines and primary human leukemia cells. S and G2/M cell-cycle arrest were induced by sweroside, associated with the down-regulation of Cyclin D1, cyclin-dependent kinase 4 (CDK4), CDC2 and CDC25 as well as the up-regulation of p53 and p21. In addition, apoptosis was highly induced by sweroside both in vitro and in vivo through enhancement of cleaved Caspase-3 and poly (ADP-ribosyl) transferase (PARP). Consistently, anti-apoptotic molecule of B cell CLL/lymphoma 2 (Bcl-2) was impeded by sweroside, while pro-apoptotic signal of Bcl-2-associated X protein (Bax) was elevated. In vivo, HL-60-bearing tumor growth was considerably inhibited by sweroside, which was related to proliferation suppression and apoptosis induction. Our study highlighted the therapeutic potential of sweroside, and provided new insights into the molecular mechanism of sweroside chemosensitization in human leukemia.

[Abnormal Expression and Clinical Significance of B Lymphocyte Stimulating Factor in B Cell-derived Malignant Hematologic Diseases].

OBJECTIVE: To explore the expression and clinical significance of B cell lymphocyte stimulating factor (BLyS) in B cell-derived malignant hematological diseases. METHODS: Fifty-seven cases of newly diagnosed B cell-derived hematologic malignancies were admitted and treated in our hospital from March 2015 to 2016 July. including 17 cases of multiple myeloma(MM) (A group) and 40 cases of B cell non-Hodgkin's lymphoma(B-NHL) (B group), 30 healthy volunteers were enrolled in control group(C group). The BLyS level in peripheral blood of A,B and C groups was detected by ELISA kit; for patient with hematologic malignancies, the BLyS level was detected again after chemotherapy and was compared with level before chemotherapy. RESULTS: The BLyS level in patients with B cell-derived hematologic malignancies significantly increased, as compared with healthy volanteers(P<0.05). After chemotherapy, the BLyS level in patients all significantly dicreased (P<0.05); the BLyS level in peripheral blood of DLBCL and FL patients was significantly higher than that in patients with B-NHL of other types(P<0.05); the BLyS level in peripheral blood of patients at III-IV stage was significantly higher than that in patients at I-II stage. CONCLUSION: The BLyS expression in B cell derived hematologic malignancies significantly increases, moreover the its expression level in B-NHL patients at different stages and histologic types is different, suggesting that detection of BLyS expression level in patients in vivo possesses a certain guiding role for diagnosis, staging and treatment of B cell-derived hematologic malignancies.

[Efficacy of alpha-lipoic acid combined with tamoxifen citrate in the treatment of oligoasthenospermia].

OBJECTIVE: To investigate the effect of alpha-lipoic acid (α-LA) combined with tamoxifen citrate (TC) in the treatment of oligoasthenospermia. METHODS: From June to November 2016, we treated 60 patients with oligoasthenospermia in our Department of Andrology, 30 (the trial group) with oral α-LA (0.6 g, qd) + TC (20 mg, qd) and the other 30 (the control group) with oral L-carnitine (1g, bid) + TC (20 mg, qd). Before and after 3 months of medication, we examined the semen parameters of the patients and the levels of their seminal oxidative stress biomarkers, including methylenedioxyamphetamine (MDA) and total antioxidant capacity (TAC) in the seminal plasma. We also compared the pregnancy rate and adverse reactions between the two groups. RESULTS: Totally, 57 of the patients completed the treatment, 28 in the trial group and 29 in the control. Compared with the baseline, the patients of the trial group showed significant improvement after 3 months of medication in the semen volume (ï¼»2.50 ± 0.71ï¼½ vs ï¼»3.37 ± 0.70ï¼½ ml, P <0.05), sperm concentration (ï¼»12.00 ± 1.65ï¼½ vs ï¼»19.34 ± 2.04ï¼½ ×106/ml, P <0.05), percentage of progressively motile sperm (PMS) (ï¼»18.01 ± 3.01ï¼½% vs ï¼»35.41 ± 6.49ï¼½%, P<0.05), MDA level (ï¼»14.96 ± 2.76ï¼½ vs ï¼»10.04 ± 1.04ï¼½ nmol/ml, P <0.05), and TAC in the seminal plasma (ï¼»9.83 ± 1.02ï¼½ vs ï¼»12.25 ± 1.11ï¼½ U/ml, P <0.05), and so did the controls in the semen volume (ï¼»2.76 ± 0.67ï¼½ vs ï¼»3.36 ± 0.93ï¼½ ml, P <0.05), sperm concentration (ï¼»11.47 ± 1.10ï¼½ vs ï¼»17.77 ± 3.56ï¼½ ×106/ml, P <0.05), percentage of PMS (ï¼»19.22 ± 1.41ï¼½ vs ï¼»36.01 ± 5.22ï¼½ %, P <0.05), MDA level (ï¼»14.66 ± 2.75ï¼½ vs ï¼»10.14 ± 1.01ï¼½ nmol/ml, P <0.05), and TAC in the seminal plasma (ï¼»9.84 ± 0.90ï¼½ vs ï¼»11.14 ± 0.84ï¼½ U/ml, P <0.05). There were no statistically significant differences in the above post-medication parameters between the trial and control groups (P >0.05) except in TAC, which was markedly more improved in the former than in the latter (P <0.05), nor in the percentage of morphologically normal sperm before and after treatment in either of the two groups (P >0.05). After 3 months of treatment, 3 pregnancies were achieved in the trial group and 1 in the control (10.7% vs 3.45%, P >0.05). No obvious adverse events occurred during the treatment. CONCLUSIONS: Alpha-lipoic acid combined with tamoxifen citrate can evidently improve semen parameters in oligoasthenospermia patients by relieving oxidative stress injury.

[Situation and Characteristics of Air Pollutants Emission from Crematories in Beijing, China].

Hazardous Air Pollutants (HAPs) such as exhaust particulate matter (PM), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen oxide (NOx), mercury (Hg) and polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-furans ( PCDD/Fs) are emitted by the process of cremation and the burning of oblation. Risks to health posed by emissions of hazardous air pollutants from crematories are emerging concerns. Through field investigation and data collection, we obtained the related activity levels and monitored the concentrations of air pollutants from typical cremators, so as to better understand the current pollutants emission levels for crematory. Using the emission factor method, we calculated the emission inventory of HAPs for crematory of Beijing in 2012 and quantified the range of uncertainty. Using atmospheric diffusion model ADMS, we evaluated the influence of crematories on the surrounding environment, and identified the characteristics of air pollution. The results showed that: for the cremators installed with flue gas purification system, the emission concentration of exhaust PM was rather low, and the CO emission concentration fluctuated greatly. However, relative high emission concentrations of PCDD/Fs were detected mainly due to insufficient combustion. Exhaust PM, CO, SO2, NOx, Hg and PCDD/Fs emitted by crematory of Beijing in 2012 were estimated at about 11. 5 tons, 41.25 tons, 2.34 tons, 7.65 tons, 13.76 kg and 0.88 g, respectively; According to the results of dispersion model simulation, the concentration contributions of exhaust PM, CO, SO2, NOx, Hg, PCDD/Fs from crematories were 0.05947 microg x m(-3), 0.2009 microg x m(-3) and 0.0126 microg x m(-3), 0.03667 microg x m(-3) and 0.06247 microg x m(-3), 0.004213 microg x m(-3), respectively.

[Combined transgenic inhibition of CaMKII and Ik1 on cardiac remodeling].

This study was aimed to establish an experimental mouse model of combined transgenic inhibition of both multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and inward rectifier potassium current (Ik1), and to observe whether the specific inhibition of both CaMKII and Ik1 can bring about any effects on cardiac remodeling. Mice were divided into 4 groups: wild type (WT), CaMKII inhibited (AC3-I), Ik1 inhibited (Kir2.1-AAA) and combined inhibition of both CaMKII and Ik1 (AC3-I+Kir2.1-AAA). Mice in each group received electrocardiogram (ECG) and echocardiography examination. ECG in the condition of isoproterenol (ISO) injection was also checked. The whole cell patch clamp technique was used to measure Ik1 and the transient outward potassium current (Ito) from enzymatically isolated myocytes of left ventricle. In the condition of basal status, no significant changes of heart rate, PR interval and QRS interval were observed. No mouse showed ventricular arrhythmias in all of the 4 groups. After ISO injection, each group presented no significant ventricular arrhythmias either. The indexes measured by M-mode (motion-mode) and two-dimensional echocardiography had no significant differences among the four groups. Ik1 in AC3-I group was significantly higher than those in other three groups (P < 0.01) because of the results brought about by CaMKII inhibition. Among the latter three groups, both Kir2.1-AAA group and AC3-I+Kir2.1-AAA group had a significant reduced Ik1 compared with that of WT group, which was due to the Ik1 inhibition (P < 0.01). Ito in AC3-I group was higher than that of the other three groups (P < 0.01), but there were no significant differences in Ito among WT, Kir2.1-AAA and AC3-I+Kir2.1-AAA groups. Thus, combined transgenic myocardial CaMKII and Ik1 inhibition eliminated the up-regulation of Ik1 in CaMKII inhibited mice, and had no effects on cardiac remodeling including heart structure and function as well as arrhythmias at the basic and ISO conditions. The results of this study may provide a basis for the further investigation of combined inhibition of CaMKII and Ik1 in pathogenic cardiac remodeling.

[Correlation analysis of VEGF and PTEN expression in gingival carcinoma].

PURPOSE: To study the expression of vascular endothelial growth factor (VEGF) and phosphatase and tensin homolog (PTEN) in gingival carcinoma and their correlation in order to provide reference for clinical treatment. METHODS: Sixty-six gingival cancer patients were determined by pathological examination, among which 31 were well-differentiated, 20 were moderately differentiated and 15 were poorly differentiated. 15 adjacent normal tissues were chosen as control group. The expression of VEGF and PTEN was examined by immunohistochemical method. Correlation analysis was performed with SPSS13.0 software package. RESULTS: The positive rate of PTEN in control group was significantly higher than other groups (P<0.05). The expression of VEGF in poorly differentiated group was significantly higher than other groups (P<0.05). Correlation analysis showed that the expression of VEGF was positively correlated to recurrence and lymph node metastasis (P<0.05); PTEN was negatively correlated to recurrence and lymph node metastasis (P<0.05); VEGF and PTEN in gingival carcinoma was negatively correlated (P<0.05). CONCLUSIONS: The increased expression of VEGF and decreased expression of PTEN in gingival carcinoma may play a mutual role in the development of gingival cancer.

MicroRNA-23a expression in paraffin-embedded specimen correlates with overall survival of diffuse large B-cell lymphoma.

It has been demonstrated that aberrant expression of microRNAs (miRNAs) is strongly associated with carcinogenesis. Recently, specific miRNAs may serve as potential biomarkers for the diagnosis and prognosis of various types of tumor. MiR-23a is known to play important role in the development of cancers and deregulated in various hematological malignancies. The aim of the present study is to explore miR-23a as potential diagnostic and/or prognostic marker of diffuse large B-cell lymphoma (DLBCL). We compared the expression level of miR-23a in DLBCL patients (n = 104) and reactive lymph nodes as controls (n = 28) from formalin-fixed, paraffin-embedded tissues using quantitative reverse transcription-polymerase chain reaction. The expression level of miR-23a was significantly higher in DLBCL patients than in controls (P = 0.001). No significant association was observed between the miR-23a expression level and clinical features such as age, gender, Ann Arbor stage, performance status, lactate dehydrogenase, extranodal sites and International Prognostic Index score (IPI). Kaplan-Meier analysis showed that higher expression level of miR-23a was significantly associated with a poor overall survival (OS) in DLBCL patients (log-rank test, P = 0.029), and multivariable Cox regression revealed the expression of miR-23a (adjusted P = 0.034) and IPI (adjusted P = 0.021) was independently associated with OS. To our knowledge, we provide here the first evidence that miR-23a may represent a diagnostic and prognostic marker for DLBCL. DLBCL patients with a high expression level of miR-23a had a shorter OS than patients with a lower expression level. Further investigation of the changes may be of prognostic significance in clinical practice.

Role of polymorphisms in BCL-2 and BAX genes in modulating the risk of developing non-Hodgkin lymphoma.

The aim of this study was to investigate whether polymorphisms of - 938C/A and Thr43Ala in the BCL-2 gene and G - 248A in the BAX gene are associated with the risk of developing non-Hodgkin lymphoma (NHL). We genotyped polymorphisms of - 938C/A and Thr43Ala in the BCL-2 gene and G-248A in the BAX gene among 424 patients with NHL and 446 controls. We found that the - 938AA genotype of the BCL2 gene was significantly associated with the risk of developing NHL (p < 0.001) and this genotype was associated with advanced stage (p = 0.01). Meanwhile, individuals having - 248AG + AA genotypes were significantly associated with an increased risk of NHL (p = 0.01), and these genotypes were associated with larger tumor size (p = 0.02). The present study demonstrated that the - 938AA genotype of the BCL-2 gene and - 248AG + AA genotype of the BAX gene may be susceptible genotypes for NHL. There appeared to be an impact of the BCL2 - 938AA genotype on advanced stage and - 248AG + AA genotypes on tumor size in NHL.

[Application and benefit evaluation of tiered health risk assessment approach on site contaminated by benzene].

The procedures of implementing tiered health risk assessment approach were introduced in detail, and took a large-scale site polluted by benzene in Beijing as an example, the difference on the remediation target of benzene in soil, as well as the corresponding soil remediation volume and costs, were compared. The results indicate that the benzene concentration in soil within 1.5 m in depth and the one below should be remediated to 0.26 mg x kg(-1) and 0.15 mg x kg(-1), respectively, in order to keep the cumulative carcinogenic health risk below 1 x 10(-6) based on tiered II assessment. However, according to tiered III assessment result, which is based on the benzene in soil gas within the contaminated areas in the investigated site, the soil in the corresponding depth should only be remediated to 2.6 mg x kg(-1) and 1.5 mg x kg(-1), respectively. That means the soil remediation volume delimited on tiered III assessment result is less than the one on tiered II by 139 537 m3 and the corresponding remediation costs will be reduced by 57 million Yuan, meaning the enormous economic benefits compared to the costs (around 100 thousands Yuan) spent to carry out tiered III assessment in the site.

[Study of Ag-containing on casting cobalt chromium alloy on the surface structure and the cell toxicity in vitro].

OBJECTIVE: To detect cobalt chromium alloy antimicrobial coating silver of the surface structure and the cell toxicity in order to provide a theoretical basis for clinical application. METHODS: Plasma spraying technique was adopted to prepare cobalt chromium alloy antimicrobial coating silver. Scanning electron microscopy, energy dispersive analysis and X-ray diffraction analysis were used to evaluate the surface properties. The methyl thiazolyl tetrazolium and flow cytometry method was adopted to test the L929 cell proliferation and the influence of the cell cycle. RESULTS: The surface of the coating was uniform and compact, combined perfectly with substrate material. The content of the surface was mainly Ag, Cr and a small amount of Ag(2)O, Cr(2)O(3). After cobalt chromium alloy was cultured in leach liquor for 1, 2 and 3 days, the statistical result showed that there was no significant different between the three groups. The cytotoxic level of negative control group was level 0 at each time point and that of other groups was level 1 at each time point. There was no significant difference between cobalt chromium alloy and cobalt chromium alloy antimicrobial coating silver in cell toxicity (P > 0.05). There was no statistical significance of the influence on cell cycle between cobalt chromium alloy with Ag coating [the G2's rate of cell cycle was (8.23 ± 0.39)%] and cobalt chromium alloy group [the G2's rate of cell cycle was (8.70 ± 0.46)%] (P > 0.05). CONCLUSIONS: The surface of the coating was stable and there was no significant difference between cobalt chromium alloy widely used in clinic and cobalt chromium alloy with Ag coating of the influence on proliferation of L929 cell and cell cycle, the cell compatibility of cobalt chromium with Ag coating is well.