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.

[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.

[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.

The Correlation of Centromere Protein Q with Diagnosis and Prognosis in Hepatocellular Carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is one of the major types of liver cancer. Previous studies have shown that the centromere protein family is associated with malignant biological behaviors such as HCC proliferation. As a member of the centromere protein family, centromere protein Q (CENPQ) is closely associated with immunotherapy and immune cell infiltration in various tumors. However, the role and mechanism of CENPQ in HCC remain unclear. Methods: Multiple public databases and RT-qPCR were used to study the expression of CENPQ in HCC. Based on TCGA data, the correlation between CENPQ and clinicopathological characteristics and prognosis of HCC patients was analyzed, and its diagnostic value was evaluated. The potential biological functions of CENPQ in HCC were explored by functional enrichment analysis of differentially expressed genes. The distribution of tumor-infiltrating immune cell types was assessed using single-sample GSEA, and immune checkpoint gene expression was analyzed using Spearman correlation. Subsequently, loss-of-function experiments were performed to determine the function of CENPQ on the cell cycle and proliferation of HCC cells in vitro. Results: CENPQ was found highly expressed in HCC and correlated with weight, BMI, age, AFP, T stage, pathologic stage, histologic grade, and prothrombin time (all p < 0.05). ROC and Kaplan-Meier analyses indicated that CENPQ may be potentially used as a diagnostic marker for HCC (AUC = 0.881), and its upregulation is associated with decreased OS (p = 0.002), DSS (p < 0.001), and PFI (p = 0.002). Functional enrichment analysis revealed an association of CENPQ with biological processes such as immune cell infiltration, cell cycle, and hippo-merlin signaling deregulation in HCC. Furthermore, knockdown of CENPQ manifested in HCC cells with G0/1 phase cycle arrest and decreased proliferative capacity. Conclusion: CENPQ expression was higher in HCC tissues than in normal liver tissues. It was significantly associated with poor prognosis, immune cell infiltration, cell cycle, and proliferation. Therefore, CENPQ may become a promising prognostic biomarker for HCC patients.

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.

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.

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.

[Comparison of the metastatic characteristics of HCCLM3 cells and SMCC-7721 cells in nude mice model].

OBJECTIVE: To compare the metastatic characteristics of HCCLM3 cells and SMCC-7721 cells in nude mice model. METHODS: Nude mice were divided into two groups (n = 8, each), mice were transplanted with HCCLM3 cells (group A) and SMMC-7721 cells (group B). Tumor size, metastasis rate and other clinical parameters were compared between the two groups. Statistical analysis was performed with the help of SPSS 16.0 for Windows computer software (SPSS, Inc., Chicago, IL). P values of less than 0.05 were considered statistically significant. RESULTS: Intrahepatic metastases rate was 100% (8 / 8), mean intrahepatic primary tumor volume was (6954+/-1945) mm(3) in group A, Intrahepatic metastases rate was 62.5% (5/8), and mean intrahepatic primary tumor volume was (6034+/-2035) mm(3) in the group B. There was no statistical difference in the primary liver tumor size and intrahepatic metastases rate (P = 0.20; t = 6.38, P = 0.37, respectively). The numbers of intrahepatic metastases and the involved lobes, and the volume of tumor were 4.5 (median), 3, and 975 mm(3) (median) respectively, in group A, and these were 1 (median), 1 and 274 mm(3) (median) respectively in group B. The difference between two groups was statistically significant (Z values, -2.818, -2.289, and -1.975, respectively).The rate of lung metastasis and other organ metastasis in the A group was significantly higher than that in group B (P less than 0.001, P less than 0.041, respectively). CONCLUSION: HCCLM3 cells have higher metastatic potential than SMMC-7721 cells in nude mice.

[Different prognostic factors are associated with early and late intrahepatic recurrence following curative hepatectomy for patients with hepatocellular carcinoma].

OBJECTIVE: To investigate prognostic factors related to early and late intrahepatic recurrences after curative hepatectomy for patients with hepatocellular carcinoma (HCC). METHODS: A retrospective review was conducted on medical records of patients with HCC treated by curative hepatectomy from January 2002 to January 2009. Clinicopathologic data were evaluated for their possible association with postoperative intrahepatic recurrence in univariate and multivariate analysis using Cox proportional hazard model. Recurrence time calculated by Kaplan-Meier method was compared using Log-rank test. Receiver operator characteristic curve (ROC) analysis with calculation of the area under the curve (AUC), sensitivity, and specificity where appropriated and risk stratification were applied to assess predictive ability of prognostic factors. RESULTS: All 101 patients underwent curative hepatectomy. During follow-up period, 75 patients developed postoperative intrahepatic recurrence, among whom, 63 experienced early recurrence (84.0%) and the remaining had late recurrence (16.0%). The 1-, 2-, 3-and 5-year cumulative recurrent rates were 48.5% (49/101), 62.4% (63/101), 70.3% (71/101) and 74.3% (75/101), respectively. Multivariate analysis identified that tumor residual resectional margin, increased BCLC staging and severity of concomitant liver cirrhosis as independent prognostic factors predicting early recurrence while age ≥ 60 years and presence of tumor capsule predicting late recurrence. Cutoff point values (PI ≥ 2.798) predicted early recurrence with AUC 0.897 (95%CI = 0.829 - 0.965), sensitivity 76.6%and specificity 88.9% calculated from ROC. Median recurrent time of early recurrence and late recurrence reached statistically difference after risk stratification, 20.2 months vs. 4.4 months (χ(2) = 29.198, P = 0.000), 46.6 months vs. 28.6 months (Log-rank test, χ(2) = 8.479, P = 0.004), respectively. CONCLUSIONS: Postoperative recurrence for HCC after curative hepatectomy should be differentiated as early recurrence and late recurrence, since each is associated with different risk factors, indicating possible different mechanism responsible for postoperative recurrence. Risk stratification can be used for prediction of different type of recurrence.

[L-carnitine: safe and effective for asthenozoospermia].

OBJECTIVE: One of the important reasons for male infertility is asthenozoospermia, for which there is no specific cure for the time being. The authors explored the clinical effect of L-carnitine for infertile males with asthenozoospermia. METHODS: A total of 135 patients with asthenozoospermia were randomly divided into Groups A (n = 68) and B (n = 67), the former treated with L-carnitine (2 g/d) and vitamin E, while the latter with vitamin E only, both for 3 months. All the patients received semen analyses before and after the treatment, and were observed for adverse effects. The pregnancy rates of their wives were recorded. RESULTS: Group A showed a significantly increased percentage of forward motile sperm after the treatment (45.4% +/- 11.1%) as compared with pretreatment (28.6% +/- 9.2%) (P < 0.01), but no statistically significant differences were found in sperm density and the percentage of the sperm of normal morphology (P > 0.05). The rate of pregnancy was significantly higher in Group A (31.1%) than in B (3.8%) after the treatment (P < 0.01). No adverse events were found during the treatment. CONCLUSION: L-carnitine, capable of significantly improving sperm motility and raising the rate of pregnancy, is a safe and effective therapeutic option for asthenozoospermia.

[Antibiotic-loaded cement articulating spacer made by a self-made mold system in the treatment of the infected hip replacement].

OBJECTIVES: To summarize the experience and lessons of the using of antibiotic-loaded cement articulating spacer made by a self-made mold system for the treatment of the infected hip replacement, and to evaluate its efficiency and role in the two-stage revision of infected total hip arthroplasty (THA). METHODS: The patients with infected THA treated with two-stage revision protocol from August 2005 to December 2009 were reviewed. All of the 127 patients were debridement thoroughly and followed by implantation of an antibiotic-loaded cement articulated spacer made by a self-made mold system; Two-stage revisions were not followed until the infection were controlled. Among of them, 106 patients, 107 hips were gotten fully followed up. Evaluations were made for the efficiency of infection control, convenience of making, implanting and removing of the spacers, occurrence of complications, the deal of the special circumstances, the function and satisfaction of the patients. RESULTS: The 107 hips were gotten an average of 34.3 months' (3 - 55 months) follow-up. The infection control rate was 96.3% after the first-stage surgery, the infection control rate was 94.4% at last follow-up after two-stage revisions. The breakage rate of the spacer was 4.7%, dislocation rate was 2.8%, removal of the spacers with difficulty were seen in 15 patients (14.0%). The satisfactory rate of the patients was 93.5%. CONCLUSIONS: Antibiotic-loaded cement articulating spacer made by a self-made mold system is an effective methods for the two-stage revision of the infected hip replacement, characterized by simple, good reproducible, high rates of infection control, better joint function after surgeries, high rate of patients satisfaction and other advantages. And it can decrease the complications, such as the breakage, spacer dislocation of hip joint and difficulty in removal of spacer at the second stage revision. Using of metallic internal fixation or allograft bone combined with spacer does not affect the results of infection controlling.

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.

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.

[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.

[A comparative study of the role of two femoral shortening techniques in total hip arthroplasty on patients with Crowe's IV congenital dislocated hips].

OBJECTIVE: To compare proximal femoral resection with transverse subtrochanteric osteotomy in the treatment of Crowe's IV congenital dislocated hip (CDH) with total hip arthroplasty (THA). METHODS: Thirty-six primary hip arthroplasties were performed in patients with Crowe grade IV CDH from April 2003 to October 2007. These patients were divided into two groups, one for proximal femoral resection (n = 20) and another for subtrochanteric osteotomy (n = 16). The leg length discrepancy, rotation center height and Harris score were measured pre- and post-operation to compare the two methods of osteotomy. RESULTS: All surgeries were successfully performed. The average leg discrepancy was 0.6 cm (range from 0 to 1.5 cm) for subtrochanteric osteotomy group and 0.3 cm (range from -1.0 to 1.5 cm) for proximal femoral resection group, there was no significant difference between them (P > 0.05). There were also no statistically significant difference between the two groups in other index. The complication rates were much higher in the proximal femoral resection group. At the latest follow up, the Harris score of subtrochanteric osteotomy group was 90 +/- 6, and the proximal femoral resection group was 83 +/- 8. There was statistical difference between the two groups (P < 0.05). CONCLUSIONS: Although both the femoral shortening techniques can restore the leg length of Crowe IV CDH, the subtrochanteric osteotomy technique has advantage of avoiding the potential complications in the high riding patients (high dislocation > 4 cm).

[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.

[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.

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.

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.