Clinical value of a differentiation prediction model for invasive lung adenocarcinoma / 中华肿瘤杂志

Objective: To investigate the value of predicting the degree of differentiation of pulmonary invasive adenocarcinoma (IAC) based on CT image radiomics model and the expression difference of immunohistochemical factors between different degrees of differentiation of lesions. Methods: The clinicopathological data of patients with pulmonary IAC confirmed by surgical pathology in the Affiliated Huai'an First People's Hospital to Nanjing Medical University from December 2017 to September 2018 were collected. High-throughput feature acquisition was performed for all outlined regions of interest, and prediction models were constructed after dimensionality reduction by the minimum absolute shrinkage operator. Receiver operating characteristic curve was used to assess the predictive efficacy of clinical characteristic model, radiomics model and individualized prediction model combined with both to identify the degree of pulmonary IAC differentiation, and immunohistochemical expressions of Ki-67, NapsinA and TTF-1 were compared between groups with different degrees of IAC differentiation using rank sum test. Results: A total of 396 high-throughput features were extracted from all IAC lesions, and 10 features with high generalization ability and correlation with the degree of IAC differentiation were screened. The mean radiomics score of poorly differentiated IAC in the training group (1.206) was higher than that of patients with high and medium differentiation (0.969, P=0.001), and the mean radiomics score of poorly differentiated IAC in the test group (1.545) was higher than that of patients with high and medium differentiation (-0.815, P<0.001). The differences in gender (P<0.001), pleural stretch sign (P=0.005), and burr sign (P=0.033) were statistically significant between patients in the well and poorly differentiated IAC groups. Multifactorial logistic regression analysis showed that gender and pleural stretch sign were related to the degree of IAC differentiation (P<0.05). The clinical feature model consisted of age, gender, pleural stretch sign, burr sign, tumor vessel sign, and vacuolar sign, and the individualized prediction model consisted of gender, pleural stretch sign, and radiomic score, and was represented by a nomogram. The Akaike information standard values of the radiomics model, clinical feature model and individualized prediction model were 54.756, 82.214 and 53.282, respectively. The individualized prediction model was most effective in identifying the degree of differentiation of pulmonary IAC, and the area under the curves (AUC) of the individualized prediction model in the training group and the test group were 0.92 (95% CI: 0.86-0.99) and 0.88 (95% CI: 0.74-1.00, respectively). The AUCs of the radiomics group model for predicting the degree of differentiation of pulmonary IAC in the training group and the test group were 0.91 (95% CI: 0.83-0.98) and 0.87 (95% CI: 0.72-1.00), respectively. The AUCs of the clinical characteristics model for predicting the degree of differentiation of pulmonary IACs in the training and test groups were 0.75 (95% CI: 0.63-0.86) and 0.76 (95% CI: 0.59-0.94), respectively. The expression level of Ki-67 in poorly differentiated IAC was higher than that in well-differentiated IAC (P<0.001). The expression levels of NapsinA, TTF-1 in poorly differentiated IAC were higher than those in well-differentiated IAC (P<0.05). Conclusions: Individualized prediction model consisted of gender, pleural stretch sign and radiomics score can discriminate the differentiation degree of IAC with the best performance in comparison with clinical feature model and radiomics model. Ki-67, NapsinA and TTF-1 express differently in different degrees of differentiation of IAC.

Zebularine induces apoptosis of esophageal cancer cells via demethylation SFRP2/Dkk3 to regulate Wnt/β-catenin signaling pathway / 药学学报

To explore the effect and mechanisms of demethylation drug zebularine on esophageal cancer cells apoptosis, ECA109 cells and KYSE170 cells were treated with zebularine at different concentrations (25, 50, 100, 200, and 400 μmol·L-1). The cell viability was measured by CCK-8. Flow cytometry was used to detect the cell apoptosis rate, Western blot was performed to determine the expression of apoptosis protein (Bcl-2, Bax, cleaved-caspase-3, and cleaved-PARP) and Wnt signal pathway molecules (β-catenin, cyclin D1, and c-Myc), real-time quantitative PCR was used to detect the expression level of negative regulatory genes of Wnt signaling pathway, methylation specific PCR (MSP) was used to detect the methylation status of secreted frizzled related protein 2 (SFRP2) and dickkopf 3 (Dkk3) genes. After knockdown of SFRP2 and Dkk3, the effect of zebularine on apoptosis was detected. The studies showed that zebularine could inhibit the activity of ECA109 and KYSE170 cells in a dose-dependent and time-dependent manner; zebularine could induce cell apoptosis, down-regulate the expression of Bcl-2 protein, up-regulate the expression of Bax, cleaved-caspase-3, and cleaved-PARP protein, and inhibit the expression of β-catenin, cyclin D1, and c-Myc protein (P < 0.05); the mRNA expression levels of Dkk3 and SFRP2 were significantly up-regulated by zebularine, while the methylation levels of SFRP2 and Dkk3 promoters were decreased; knockdown of SFRP2 and Dkk3 could reduce the apoptosis induced by zebularine. In summary, zebularine could reduce the methylation level of SFRP2 and Dkk3 gene promoter, promote the expression of SFRP2 and Dkk3 gene, and then induce the apoptosis of esophageal cancer cells by inhibiting Wnt/β-catenin signaling pathway.

Biomarkers enhance the long-term predictive ability of the KAMIR risk score in Chinese patients with ST-elevation myocardial infarction / 中华医学杂志(英文版)

BACKGROUND@#The Global Registry of Acute Coronary Events (GRACE) score is recommended by current ST-elevation myocardial infarction (STEMI) guidelines. But it has inherent defects. The present study aimed to investigate the more compatible risk stratification for Chinese patients with STEMI and to determine whether the addition of biomarkers to the Korea Acute Myocardial Infarction Registry (KAMIR) score could enhance its predictive value for long-term outcomes.@*METHODS@#A total of 1093 consecutive STEMI patients were included and followed up 48.2 months. Homocysteine, hypersensitive C-reactive protein (hs-CRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were detected. The KAMIR score and the GRACE score were calculated. The performance between the KAMIR and the GRACE was compared. The predictive power of the KAMIR alone and combined with biomarkers were assessed by the receiver-operating characteristic (ROC) curve.@*RESULTS@#The KAMIR demonstrated a better risk stratification and predictive ability than the GRACE (death: AUC = 0.802 vs. 0.721, P < 0.001; major adverse cardiovascular events (MACE): AUC = 0.683 vs. 0.656, P < 0.001). It showed that the biomarkers could independently predict death [homocysteine: HR = 1.019 (1.015-1.024), P < 0.001; hs-CRP: HR = 1.052 (1.000-1.104), P = 0.018; NT-pro BNP: HR = 1.142 (1.004-1.280), P = 0.021] and MACE [homocysteine: HR = 1.019 (1.015-1.024), P < 0.001; hs-CRP: HR = 1.012 (1.003-1.021), P = 0.020; NT-pro BNP: HR = 1.136 (1.104-1.168), P = 0.006]. When they were used in combination with the KAMIR, the area under the ROC curve (AUC) significantly increased for death [homocysteine: AUC = 0.802 vs. 0.890, Z = 5.982, P < 0.001; hs-CRP: AUC = 0.802 vs. 0.873, Z = 3.721, P < 0.001; NT-pro BNP: AUC = 0.802 vs. 0.871, Z = 2.187, P = 0.047; homocysteine, hs-CRP and NT-pro BNP: AUC = 0.802 vs. 0.940, Z = 6.177, P < 0.001] and MACE [homocysteine: AUC = 0.683 vs. 0.771, Z = 6.818, P < 0.001; hs-CRP: AUC = 0.683 vs. 0.712, Z = 2.022, P = 0.031; NT-pro BNP: AUC = 0.683 vs. 0.720, Z = 2.974, P = 0.003; homocysteine, hs-CRP and NT-pro BNP: AUC = 0.683 vs. 0.789, Z = 6.900, P < 0.001].@*CONCLUSION@#The KAMIR is better than the GRACE in risk stratification and prognosis prediction in Chinese STEMI patients. A combination of above-mentioned biomarkers can develop a more predominant prediction for long-term outcomes.

Safety and effect of transurethral holmium laser enucleation of the prostate versus bipolar transurethral plasmakinetic prostatectomy for benign prostatic hyperplasia: A meta-analysis / 中华男科学杂志

<p><b>Objective</b>To evaluate the safety and effect of transurethral holmium laser enucleation of the prostate (HoLEP) in comparison with bipolar transurethral plasmakinetic prostatectomy (TUPKP) in the treatment of benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>We searched the databases of PubMed, SCI, Ovid, The Cochrane Library, CNKI, CBM, VIP, and Wangfang Data for controlled clinical trials about HoLEP versus TUPKP in the treatment of BPH published up to April 2016. The studies were screened according to the inclusion and exclusion criteria, the data extracted, and their quality evaluated by 2 reviewers independently, followed by a meta-analysis using the RevMan 5.3 software.</p><p><b>RESULTS</b>A total of 7 studies were included, involving 2031 cases. In comparison with TUPKP, HoLEP showed significantly longer operation time (WMD = 24.61, 95% CI 11.88, 37.34, P lt; 0.001), shorter hospital stay (WMD =－1.91, 95% CI －3.74, －0.07, P = 0.04), shorter bladder irrigation time (WMD = －21.50, 95% CI －34.95, －8.06, P = 0.002), shorter catheter-indwelling time (WMD = －27.60, 95% CI －48.17, －7.03, P = 0.009), less hemoglobin loss (WMD = － 0.42, 95% CI －0.78, －0.07, P = 0.02); lower postvoid residual urine (PVR) at 3 months (WMD = －3.35, 95% CI －4.46, －2.23, P<0.001) and 6 months after surgery (WMD =－1.11, 95% CI －2.18, －0.05, P = 0.04); higher maximum urinary flow rate (Qmax) (WMD = 0.42, 95% CI 0.04, 0.80, P = 0.03) and fewer urinary tract irritation symptoms (OR =0.58, 95% CI 0.41, 0.81, P = 0.002) at 12 months after surgery. No statistically significant differences were found between the two groups in the volume of resected tissue, serum sodium reduction, urethral stricture, erectile dysfunction, retrograde ejaculation, or transient urinary incontinence (P>0.05), or in the improvement of the quality of life (QoL) at 1, 3 and 12 months, International Prostate Symptom Score (IPSS) at 1, 3, 6 and 12 months, Qmax at 1, 3 and 6 months, or International Index of Erectile Function-5 (IIEF-5) at 6 months after surgery (P>0.05).</p><p><b>CONCLUSIONS</b>HoLEP is preferred to TUPKP in clinical application for its advantages of higher Qmax at 12 months after surgery, lower PVR at 3 and 6 months, higher peri-operative safety, faster recovery, and fewer urinary tract irritation symptoms. However, for the quantity and quality limitations of the included publications, our findings are to be further supported by large-sample, multi-center, and high-quality prospective controlled clinical studies.</p>

Tea polyphenols reduces the apoptosis of spermatogenic cells in rats with experimental varicocele / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the effect of tea polyphenols (TP) on the apoptosis of germ cells in rats with experimental varicocele.</p><p><b>METHODS</b>Thirty-two adolescent male Wistar rats were randomly and equally divided into groups A (sham-operation), B (high-dose TP), C (low-dose TP), and D (experimental left varicocele). Experimental varicocele was induced by partial ligation of the left renal vein in the latter three groups of rats. The animals in groups A and D were fed with normal saline, while those in B and C with TP at 40 and 10 mg per kg per d, respectively, all for 4 weeks. Then, all the rats were sacrificed and the left testes harvested for determination of the expression of HIF-1, Bcl-2, Bax, CytC, and caspase-3 by immunohistochemistry and measurement of the apoptosis index (AI) of spermatogenic cells.</p><p><b>RESULTS</b>The expression of Bcl-2 was higher in groups B and C than in D but lower than in A (P < 0.05), and lower in C than in B (P < 0.05). However, the expressions of HIF-1, Bax, CytC, and caspase-3 were lower in groups B and C than in D but higher than in A (P < 0.05), and higher in C than in B (P < 0.05). The AI of spermatogenic cells was the lowest in group A, higher in D than in the other groups but lower in B than in C (P < 0.05).</p><p><b>CONCLUSION</b>TP can reduce the apoptosis of spermatogenic cells in a dose-dependent manner in varicocele rats.</p>

Isolation of gastric cancer stem cells based on colony morphology and detection of their sensitivity to 5-fluorouracil / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the sensitivity of gastric cancer stem cells (GCSCs) to 5-fluorouracil (5-FU), and to explore the cytological mechanism of drug-resistance of gastric cancer.</p><p><b>METHODS</b>Immunohistochemical staining was employed to examine expression of stem cell marker CD44 and drug-resistance protein thymidylate synthase (TS) in 71 cases with gastric cancer. Based on morphology of cell colonies derived from AGS gastric cell line, colonies consisting of GCSCs were isolated, and expression of CD44 and TS, as well as self-renewal capacity of GCSCs were detected. Sensitivity of GCSCs to 5-FU was examined through CCK-8 assay.</p><p><b>RESULTS</b>The positive rates of CD44 and TS were 59.2% (42/71) and 56.3% (40/71) in gastric cancer, and expression of CD44 was associated with that of TS (χ(2)=12.76, P<0.01; Kappa=0.41). Serial sections indicated that CD44+ cancer cells simultaneously expressed TS. AGS developed morphologically diverse colonies, and the GCSCs colonies exhibited a tight and regular shape, which were called holoclone. Holoclones expressed CD44 and TS strongly, possessing capacity of robust self-renewal and forming a lot of second passage clones after incubation. Subclones expressed CD44 and TS weakly, forming less second passage clones. Paraclones almost did not express CD44 and TS, forming no second passage clone after incubation. Affected by 5-Fu, three holoclones showed less growth inhibition compared with another colony type and wild-type AGS cells. Furthermore, IC50 of 5-FU for three holoclones was (113.43±5.81), (272.68±25.75) and (118.14±17.75) μmol/L respectively, which were significantly higher than that of one subcolony type [(16.97±1.01) μmol/L] and AGS cells [(27.52±0.59) μmol/L] (all P<0.05).</p><p><b>CONCLUSIONS</b>GCSCs possess lower sensitivity to 5-FU, and may play a critical role in drug-resistance of gastric cancer.</p>

Application of systems biology to the study of chronic kidney disease / 中华医学杂志(英文版)

Chronic kidney disease (CKD) is a major public health problem that affects about 10% of the general population. Current approaches to characterize the category and progression of CKD are normally based on renal histopathological results and clinical parameters. However, this information is not sufficient to predict CKD progression risk reliably or to guide preventive interventions. Nowadays, the appearance of systems biology has brought forward the concepts of "-omics" technologies, including genomics, transcriptomics, proteomics, and metabolomics. Systems biology, together with molecular analysis approaches such as microarray analysis, genome-wide association studies (GWAS), and serial analysis of gene expression (SAGE), has provided the framework for a comprehensive analysis of renal disease and serves as a starting point for generating novel molecular diagnostic tools for use in nephrology. In particular, analysis of urinary mRNA and protein levels is rapidly evolving as a non-invasive approach for CKD monitoring. All these systems biological molecular approaches are required for application of the concept of "personalized medicine" to progressive CKD, which will result in tailoring therapy for each patient, in contrast to the "one-size-fits-all" therapies currently in use.

Combination of docetaxel and capecitabine for the treatment of anthracycline-resistant advanced breast carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and toxicity of docetaxel and capecitabine combination in the treatment of anthracycline-resistant advanced breast carcinoma.</p><p><b>METHODS</b>Forty-three patients with anthracycline-resistant advanced breast carcinoma were treated with docetaxel combined with capecitabine between January 2002 and November 2004. Docetaxel was administered intravenously at a dose of 75 mg/m(2) on D1, and oral intake of capecitabine at a dose of 1600 mg/d on D1 to D14, every 21 days as a cycle. The median number of cycles was 4 (range, 4 approximately 6 cycles).</p><p><b>RESULTS</b>All the 43 patients had a mean follow-up of 15 months. The overall response rate was 62.8%, with a complete response rate of 20.9% and partial response rate of 44.2%. The median survival time was 15 months with a median time to progression of 7.5 months. The one-year and 2-year survival rates were 62.8% and 41.9%, respectively. The quality of life was improved in all patients. The major toxicity and adverse effects were gastrointestinal reaction and hematological toxicity.</p><p><b>CONCLUSION</b>The combination of docetaxel and capecitabine for the treatment of anthracycline-resistant advanced breast carcinoma is effective, safe and tolerable.</p>

Effect of arsenic trioxide on VEGF/R and MMP-2, 9 expressed in K562 cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of arsenic trioxide (As2 O3) on the level of VEGF, VEGFR and the activity of MMP-2, 9 in K562 cells.</p><p><b>METHODS</b>The inhibition ratio of K562 cell was detected by MTT assay, the level of VEGF by Enzyme-linked immunosorbent assay (ELISA), the expression ratio of VEGFR by flow cytometry (FCM), and the activity of MMP-2, 9 by gelatin zymography assay.</p><p><b>RESULTS</b>(1) The IC50 of K562 cells was (2.12 +/- 0.11) micromol/L. Proliferation of K562 cells was significantly inhibited at the concentration of 0.4 - 6.4 micromol/L As2 O3 (P < 0.05). (2) The expression of VEGF was slightly up-regulated by 0.05 micromol/L As2 O3 (P > 0.05) and prominently inhibited by 0.4 micromol/L and 3.2 micromol/L As2 O3 (P < 0.05). As2 O3 had no influence on VEGFR. (3) The activity of MMP-2 and 9 was partly inhibited by 0.05 micromol/L As2 O3 incubated 72 hours and by 0.4, 3.2 micromol/L, As2 O3. With the increase of As2 O3 concentration and the incubation time, the inhibited effect on MMP-2 and 9 was enhanced.</p><p><b>CONCLUSIONS</b>As2 O3 may down-regulate the expression of VEGF and inhibit the activity of MMP-2 and 9.</p>

Role of integrin-linked kinase in renal tubular epithelial-mesenchymal transition of mice with obstructive nephropathy / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of integrin-linked kinase (ILK) in kidneys of mice with unilateral ureteral obstruction and its relevance with the epithelial-mesenchymal transition.</p><p><b>METHODS</b>Mice were randomly divided into two groups, sham operation (C, n = 20) and unilateral ureteral obstruction (UUO, n = 40). The animals were sacrificed at day 1, 3, 7 and 14 respectively after the surgery. Tubulointerstitial fibrosis (TIF) was graded according to Masson staining. The protein level of ILK was examined by Western blot. Tissue/cytological expression for ILK, alpha-SMA and E-cadherin were investigated by immunohistochemistry. The mRNA levels of ILK, alpha-SMA and E-cadherin were analyzed by quantitative real-time PCR.</p><p><b>RESULTS</b>In the control animals (group C), weak staining for ILK was detected mainly in the podocytes. Significant increase of staining for ILK in the experimental mice (UUO group) was detected from day 1 onward (t = 16.5, P < 0.01), reaching the peak at day 7. The protein expression of E-cadherin was continuously down-regulated from day 3 onward after surgery (t = 21.0, P < 0.01), while expression for alpha-SMA was up-regulated. From day 1 to day 7, the protein expression of ILK was positively correlated with alpha-SMA (R = 0.88, P < 0.01), but negatively correlated with E-cadherin (R = -0.87, P < 0.01). The mRNA expression of ILK and alpha-SMA analyzed by real-time PCR increased from postoperative day 1 and 3 respectively, but the mRNA expression of E-cadherin decreased from day 3 onward.</p><p><b>CONCLUSION</b>Increasing expression of ILK occurs in the early phase of UUO mouse and may play an important role in the process of TIF through mediating the epithelial-mesenchymal transition.</p>

Involved-field three-dimensional conformal radiation treatment for stage III non-small-cell lung / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the feasibility of involved-field irradiation (IFI ) for stage III non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>From September 1997 to November 2001, 200 stage-III NSCLC patients were randomly divided into two groups-- IFI and ENI (elective node irradiation). The IFI group was irradiated by 3DCR to a dose of 68-74 Gy/34-37f/7-9 w including the primary tumor and the lymph nodes of > or = 10 mm in short axis. The ENI group was irradiated to a dose of 60-64 Gy/30-32f/6-7.5 w including the primary tumor, ipsilateral hilum, subcarinal and mediastinal lymph nodes, even the supraclavicular area when the lymph nodes of superior mediastinum were involved.</p><p><b>RESULTS</b>The overall response (CR + PR) rates were 90.0% in IFI group and 79.0% in ENI group. Radiation pneumonitis developed in 29.0% of the patients in ENI group and 17.0% in IFI group (P = 0.04). The 1-year primary tumor failure rate in IFI group (13.0%) was lower than that (23.0%) in ENI group. The 1-year involved nodal failure rate was 20.0% in ENI group and 10.0% in IFI group (P = 0.048). The 1-year elective node failure rate was 16.0% in ENI group versus 21.0% in IFI group (P = 0.39). The 1-, 2-and 3-year overall survival rate was 67.2% , 38.7% , 27.3% , respectively, in IFI group; versus 59.7% , 25.6% , 19.2% in ENI group, with a difference significant in the 2-year overall survival rate between IFI and ENI group (P = 0.048).</p><p><b>CONCLUSION</b>Involved-field 3D-CRT for stage-III non-small cell lung cancer is well tolerated. It does not increase the rate of lymph node failure in the elective node irradiation field, and may improve the survival due to dose escalation.</p>

Clinical value of positron emission tomography-CT for the diagnosis of postoperative recurrence and metastasis in the patients with esophageal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical value of the whole-body (18)F-fluoro-deoxy-D-glucose positron emission tomography with computerized tomography (PET-CT) for recurrence and distant metastasis after curative resection of the esophagus cancer.</p><p><b>METHODS</b>From June 2003 to June 2004, thirty-one patients with clinical or radiologic suspicion of recurrent disease underwent conventional diagnostic work-up, including a spiral CT scan, and a dedicated whole-body PET-CT. All cases were examined by pathology or followed-up for 6 months.</p><p><b>RESULTS</b>Among the 31 cases, recurrences were found in 23 patients, and 43 recurrent lesions were detected, including 14 perianastomotic lesions and 43 regional and distant lesions. For the diagnosis of recurrence, the accuracy, sensitivity and specificity of PET-CT were 97.7%, 100%, and 85.7%, while those of conventional CT were 77.3%, 61.7%, and 78.6% respectively. The sensitivity of PET-CT was significantly higher than that of conventional CT (100% vs 61.7%; chi (2)=4.161, P=0.041).</p><p><b>CONCLUSIONS</b>The sensitivity of PET-CT is higher than that of conventional CT. PET-CT will play an important role in the diagnosis of postoperative recurrence and metastasis of esophageal cancer.</p>

Interregulation of VEGF/R endostatin and MMP in the angiogenesis of hematologic malignancies--review / 中国实验血液学杂志

Some kinds of angiogenic correlation factors, e.g. VEGF/R, MMP, endo statin, are relative to the process of hematologic malignancies. The mechanisms of adjusting themselves and controlling mutually have been hot points of the academic research in last few years. Although the rapid progress has been made in studies of this field, it is still hard to come into a systematic theory now. This article introduces the last progress in the field of positive and negative regulatory factors of VEGF/R system in the angiogenesis of hematologic malignancies, the regulation of MMP and its relation with VEGF/R, the regulation of ES and its relation with VEGF/R and MMP.