Search

Active and passive anti-Aβ immunotherapies have successfully been used for the prevention and treatment of Alzheimer's disease animal models. However, clinical use of these immunotherapies is not effective, because the vaccination is administered too late. At 1 month of age, 100 μL of Aβ3-10-KLH peptide (vaccine, 2 μg/μL) was subcutaneously injected into the neck of an amyloid precursor protein/presenilin-1/tau transgenic (3×Tg-AD) mouse model. Aβ3-10-KLH peptide was re-injected at 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5 months of age. Serum levels of Aβ antibody were detected by enzyme-linked immunosorbent assay, while spatial learning and memory ability were evaluated by Morris water maze. Immunohistochemistry was used to detect total tau with HT7 and phosphorylated tau with AT8 (phosphorylation sites Ser202 and Thr205) and AT180 (phosphorylation site Thr231) antibodies in the hippocampus. In addition, western blot analysis was used to quantify AT8 and AT180 expression in the hippocampus. The results showed that after vaccine injection, mice produced high levels of Aβ antibody, cognitive function was significantly improved, and total tau and phosphorylated tau levels were significantly reduced. These findings suggest that early active immunization with Aβ3-10-KLH vaccine can greatly reduce tau phosphorylation, thereby mitigating the cognitive decline of 3×Tg-AD mice. This study was approved by the Animal Ethics Committee of China Medical University, China (approval No. 103-316) on April 2, 2016.

Background Diffuse large B-cell lymphoma (DLBCL) is a common subtype of non-Hodgkin’s lymphoma (NHL). We assessed serum biomarkers to identify patients with DLBCL and healthy controls, as well as prognosis-related paired pre- and post-R-CHOP therapy effect of patients with DLBCL. Methods Serum samples from 329 DLBCL patients and 100 healthy controls were collected in this study, as well as 72 samples from additional DLBCL patients with paired pre- and post-R-CHOP therapy (n=36). All serum samples were pretreated and detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Serum biomarkers were discriminated between DLBCL patients and healthy controls, as well as between DLBCL patients with prognosis-related paired pre- and post-R-CHOP therapy, and identified by Veristrat Identification Platform 1.0, Bioyong Explore 1.0 and mMass software. Results Two peaks, m/z values of 15,140.74 and 15,885.43, were significantly different from all peaks among the DLBCL patients and healthy controls (P

Purpose Despite selection based on human epidermal growth factor receptor 2 (HER2) overexpression, not all HER2-positive patients benefit from trastuzumab therapy. Recent reports indicate that trastuzumab treatment failure may be associated with immune system dysfunction. We examined the prognostic relevance of the absolute lymphocyte count (ALC) in patients with HER2-positive metastatic breast cancer (MBC) who received trastuzumab combined with chemotherapy. Methods Baseline ALC and neutrophil-to-lymphocyte ratio (NLR) data from trastuzumab-treated patients with MBC were studied retrospectively, and associations between baseline ALC and clinical characteristics evaluated. Kaplan-Meier analysis and the Cox regression hazard model were applied to assess effects on outcomes. Results Of a total of 68 patients, 19.1% (13/68) had baseline ALCs ≤ 1 G/L. Baseline lymphopenia was correlated with increased lactate dehydrogenase (LDH) and higher NLR. In univariate analysis, higher alkaline phosphatase (ALP) was associated with inferior overall survival (OS) (P = 0.001); higher LDH was associated with inferior progression-free survival (PFS) (P = 0.045) and OS (P = 0.010). We did not observe any differences in objective response rate or disease control rate between patients with lymphopenia and those with normal ALC. Importantly, patients with baseline lymphopenia had inferior PFS (0.60 years vs 1.17 years, P = 0.000009) and OS (1.88 years vs 3.80 years, P = 0.0003). In multivariable analysis, significance of ALCs was retained for lymphopenia (PFS: P = 0.0005; OS: P = 0.016). Conclusion Our data indicate that baseline ALC value of ≤1 G/L is a predictor of poor outcomes, but not of response, in patients with MBC treated with trastuzumab.

Simple Summary Chemotherapy is the standard treatment for advanced upper urinary tract urothelial carcinoma (UTUC), and shock wave treatment is a common strategy for upper urinary tract stones. We explored the mechanism of the combination therapy of low-energy shock waves (LESWs) and cisplatin for UTUC in vitro, in vivo, and in patient-derived organoid (PDO) models. Histopathological examination showed more deteriorated cell arrangement and oedema in the combination treatment group than in the cisplatin only group. Immunohistochemical analysis revealed reduced expression of proliferation markers, increased expression of apoptosis markers, and increased cisplatin infiltration in the combination treatment group. Western blotting revealed decreased cisplatin efflux and membranous protein levels after shock wave application. Moreover, LESW improved the cytotoxicity of cisplatin in the preclinical PDO model of UTUC. Our findings showed that LESW enhanced the antitumour efficacy of cisplatin in UTUC. Hence, combination therapy could have promising applications for locally advanced UTUC in clinical settings. Abstract Upper urinary tract urothelial carcinoma (UTUC) is a relatively rare cancer with a poor prognosis if diagnosed at an advanced stage. Although cisplatin-based chemotherapy is a common treatment strategy, it has a limited response rate. Shock wave lithotripsy is a common treatment for upper urinary tract stones. Low-energy shock waves (LESWs) temporarily increase tissue permeability and enhance drug penetration to the targeted tissue. However, no study has investigated the efficacy of the combination of shock wave lithotripsy and chemotherapy in UTUC. Hence, in this study, we aimed to identify the potential application of the combination of LESW and chemotherapy in UTUC. We evaluated the synergistic effects of LESW and cisplatin in vitro, in vivo, and in patient-derived organoid (PDO) models. Compared with cisplatin alone, the combination treatment caused more significant tumour suppression in vitro and in animal models, without increased toxicity. Histological examination showed that compared with animals treated with cisplatin alone, those who received the combination treatment showed more deteriorated cell arrangement and cell oedema. Moreover, LESW improved the cytotoxicity of cisplatin in the preclinical PDO model of UTUC. Thus, LESW combined with cisplatin is a potential new antitumour strategy for improving the treatment response in locally advanced UTUC.

Ribosome-binding protein 1 (RRBP1) is a potential oncogene in several cancer types. However, the correlation between RRBP1 expression and the prognosis of patients with upper tract urothelial carcinoma (UTUC) remains unclear. In this study, we identified that RRBP1 is associated with carcinogenesis and metastasis in UTUC using a methylation profiling microarray. High correlations between RRBP1 and cancer stages, nodal metastasis status, molecular subtypes, and prognosis in bladder urothelial cancer (BLCA) were found. Aberrant DNA methylation in the gene body region of RRBP1 was determined in UTUC tissues by methylation-specific PCR. RRBP1 expression was significantly increased in UTUC tissues and cell lines, as determined by real-time PCR and immunohistochemistry. RRBP1 depletion significantly reduced BFTC909 cell growth induced by specific shRNA. On the other hand, molecular subtype analysis showed that the expression of RRBP1 was associated with genes related to cell proliferation, epithelial–mesenchymal transition, and basal markers. A patient-derived organoid model was established to analyze patients’ responses to different drugs. The expression of RRBP1 was related to chemoresistance. Taken together, these results provide the first evidence that RRBP1 gene body hypomethylation predicts RRBP1 high expression in UTUC. The data highlight the importance of RRBP1 in UTUC malignancy and chemotherapeutic tolerance.

Background: Bone marrow metastasis occurs in lung adenocarcinoma patients with a poor prognosis due to the late course and lack of definitive treatments, although reports on this are limited. This study analyzed the clinical manifestation, laboratory examination, treatment, and prognosis of patients with lung adenocarcinoma with bone marrow metastasis. Methods: All patients were confirmed to have bone marrow infiltration by bone marrow aspiration. The clinical data of 12 patients with lung adenocarcinoma with bone marrow metastasis were analyzed retrospectively. The prognostic factors were analyzed by Kaplan-Meier statistics. Results: The common biomarker abnormalities in 12 patients were elevated carcinoembryonic antigen in 12 cases (100%), elevated lactate dehydrogenase in 9 cases (75%), increased alkaline phosphatase and anemia in 8 cases each (66.7%), and thrombocytopenia in 4 cases (33.3%). After diagnosis of bone marrow metastasis, 5 patients were treated with platinum-based chemotherapy, 3 patients received chemotherapy and targeted drug tyrosine kinase inhibitor (TKI) therapy, 2 patients received simple TKI therapy, and 2 patients received only best supportive care (BSC) therapy. The median duration of survival after the diagnosis of bone marrow involvement was 422 days. The survival time of patients receiving TKI therapy after bone marrow metastasis was significantly better than that of patients receiving only BSC and chemotherapy (χ2=4.636, P=0.031). Conclusions: The survival period of patients with lung adenocarcinoma with bone marrow metastasis is short, and targeted drug TKI treatment can prolong the survival time for patients with EGFR mutation–carrying lung adenocarcinoma with bone marrow metastasis.

The long noncoding RNA (lncRNA) H19 has been described to participate in the metastasis of various tumors. Nevertheless, whether H19 promotes or impedes tongue squamous cell carcinoma (TSCC) cell migration and invasion remains controversial. Here we found that the expression of H19 was elevated in TSCC tissues compared with adjacent normal tissues. Moreover, we demonstrated that the expression of H19 was higher in metastasized tumors compared with unmetastasized tumors. Consistently, TSCC cells express higher levels of H19 than human squamous cells. Subsequently, depletion of H19 impaired the migration and invasion abilities of TSCC cells. Mechanistically, we demonstrated that H19 functions as a competing endogenous RNA (ceRNA) to sponge miRNA let-7a, leading to an increase in a let-7a target, the key regulator of tumor metastasis HMGA2, which is enriched in TSCC tissues and cell lines. Intriguingly, inhibition of let-7a significantly rescued the short hairpin H19 (shH19)-induced decrease in TSCC migration and invasion. These findings revealed that the H19/let-7a/HMGA2/EMT axis plays a critical role in the regulation of TSCC migration and invasion, which may provide a new therapeutic target for TSCC.

PurposeTo assess the association of tumor architecture with cancer recurrence, metastasis, and cancer-specific survival (CSS) in patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC) in Taiwan.Materials and MethodsData were collected from 857 patients treated with RNU between January 2005 and August 2016 in our hospital. Pathologic slides were reviewed by genitourinary pathologists. Propensity score weighting was performed for data analysis.ResultsSessile growth pattern was observed in 212 patients (24.7%). Tumor architecture exhibited a significant association with bladder cancer history, chronic kidney disease (CKD), tumor stage, lymph node status, histological grade, lymphovascular invasion, concomitant carcinoma in situ, and the variant type [standardized mean difference (SMD) > 0.1 for all variables before weighting]. In the propensity score analysis, 424 papillary and sessile tumor architecture were analyzed to balance the baseline characteristics between the groups. Tumor architecture was an independent predictor of metastatic disease and CSS (p = 0.033 and p = 0.002, respectively). However, the associations of tumor architecture with bladder and contralateral recurrence were nonsignificant (p = 0.956 and p = 0.844, respectively).ConclusionsTumor architecture of UTUC after RNU is associated with established features of aggressive disease and predictors of metastasis and CSS. Assessment of tumor architecture may help identify patients who could benefit from close follow-up or early administration of systemic therapy after RNU. Tumor architecture should be included in UTUC staging after further confirmation.

Yi-Qun Che,1 Yue Zhang,1 Kai-Ping Ou,2 Di Wang,3 Di Shen,1 Hui-Ying Liu,4 Yang Luo5 1Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 2Department of Medical Oncology, Beijing Chaoyang District Sanhuan Cancer Hospital, Beijing 100122, People’s Republic of China; 3State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China; 4Department of Clinical Laboratory, Jinzhou Central Hospital, Jinzhou 121000, Liaoning Province, People’s Republic of China; 5Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of ChinaCorrespondence: Yang LuoDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. No.17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, People’s Republic of ChinaTel/Fax + 86-10-87788820Email luoyang@cicams.ac.cnBackground: To evaluate whether the depth of response (DepRe) and early tumor shrinkage (ETS) are predictive factors of clinical outcomes in HER2-positive metastatic breast cancer (mBC) patients treated with trastuzumab.Methods: We performed a retrospective study of 100 HER2-positive mBC patients who received trastuzumab combined with chemotherapy as first-line treatment. ETS and DepRe were calculated. We employed Youden’s index to determine the optimal cutoff value of ETS and DepRe for predicting progression-free survival (PFS) and overall survival (OS). We used Kaplan–Meier analysis, Log-rank tests, and Cox proportional hazards regression models to evaluate the impacts of ETS and DepRe on clinical outcomes.Results: The optimal cutoff values were 30% for ETS and 40% for DepRe; ETS and DepRe were observed in 51.0% (51/100) and in 56.0% (56/100) of patients, respectively. Both ETS≥ 30% and DepRe≥ 40% were significant tumor-size metrics for predicting PFS (ETS: median 1.43 vs 0.69 years, hazard ratio [HR] = 0.384; 95% confidence interval [CI]: 0.245 to 0.601; P=0.000030; DepRe: median 1.43 vs 0.59 years, HR = 0.390; 95% CI: 0.250 to 0.609; P=0.0000034), but only DepRe≥ 40% was a significant predictor for OS (median 4.02 vs 3.07 years, HR = 0.484; 95% CI: 0.255 to 0.919; P = 0.027). Multivariate analyses also identified DepRe as an independent prognostic factor for PFS (HR = 0.52; 95% CI: 0.29 to 0.93; P = 0.028) and OS (HR=0.37; 95% CI:0.15 to 0.90; P = 0.029).Conclusion: ETS≥ 30% and DepRe≥ 40% were significant predictors of better clinical outcomes in mBC patients treated with first-line trastuzumab-based chemotherapy. Further validation in prospective trials with larger patient populations is needed.Keywords: depth of response, early tumor shrinkage, metastatic breast cancer, trastuzumab, survival

Background S100A14 is a member of the S100 calcium-binding protein family that exerts important phenotypic effects on cell proliferation, apoptosis, differentiation, and motility. However, the functional role and potential clinical significance of S100A14 in lung adenocarcinoma has not yet been clarified. Methods We analyzed genomic alterations of S100A14 using The Cancer Genome Atlas lung adenocarcinoma genomic dataset. S100A14 displayed significant copy number amplification in lung adenocarcinoma. We detected S100A14 expression in lung adenocarcinoma and analyzed the correlation between S100A14 expression and clinicopathological characteristics. Results Immunohistochemical analysis showed that S100A14 expression was obviously upregulated in lung adenocarcinoma tissues compared to matched normal counterparts. Statistical analysis revealed that S100A14 expression strongly correlated with poor differentiation, metastasis, stage, smoking, and EGFR mutation. Furthermore, our data indicated that S100A14 serum levels were higher in lung adenocarcinoma patients than healthy controls. Intriguingly, S100A14 serum levels were related to distant metastasis (P = 0.028). High S100A14 expression was significantly associated with overall (P = 0.0016) and post progression (P = 0.039) survival. In addition, we investigated the biological functions of S100A14 in lung adenocarcinoma cell lines. The results demonstrated that S100A14 promoted cell migration and invasion of SPCA1 and Glc-82 cells. Conclusions S100A14 increases the motility of lung adenocarcinoma cells, and might be a diagnostic and prognostic serum biomarker and potential therapeutic target for lung adenocarcinoma.

A microwave processing technology was applied to degrade saponins from the stems and leaves of Panax notoginseng. Six transformation products (1–6), named 20(S)-ginsenoside Rg3 (1), 20(R)-ginsenoside Rg3 (2), notoginsenoside SFt3 (3), ginsenoside Rk1 (4), ginsenoside Rg5 (5), and 20(S)-ginsenoside Rh2 (6) were isolated and identified from a microwave processed extract of the stems and leaves of P. notoginseng (MEL). This transformation method was also applied for producing the minor ginsenosides in flowers, seeds and pedicels of P. notoginseng. The extract and compounds 1–6 in MEL were evaluated in vitro for anticancer and anticoagulant activities. The results showed that the MEL extract and transformation products had outstanding inhibitory activities against human cervical cancer Hela and lung cancer A549 cells. The strongest inhibitory effect was observed for 20(S)-Rh2 (6) with an IC50 value of 8.23 μM in Hela cells. Moreover, the results showed that the MEL significantly prolonged prothrombin time in a concentration-dependent manner. The anticoagulant effect of the MEL improved with the increased contents of Rk1, Rg5, and SFt3.

Preserving renal function and controlling oncological outcomes are pertinent when managing renal neoplasms. Cryoablation is the recommended treatment only for clinical T1a stage renal tumour. Here, we compared the outcomes of robot-assisted laparoscopic partial nephrectomy (RaPN) and laparoscopic cryoablation (LCA) in the treatment of patients with localised T1-T2 renal tumours. Overall, 86 patients who received RaPN and 78 patients underwent LCA were included in this study. The intraoperative, postoperative, and oncological outcomes in the LCA group were non-inferior to the RaPN group. Moreover, LCA demonstrated shorter operative time (267.45 ± 104.53 min vs. 138.56 ± 45.28 min, p &lt, 0.001), lower blood loss (300.56 ± 360.73 mL vs. 30.73 ± 50.31 mL, p &lt, 0.001), and slight renal function deterioration because of the reduced invasiveness, without compromising on the oncological outcomes.

The objective of this experiment was to investigate the effects of exogenous glutathione (GSH) on tomato (Solanum lycopersicum L. cv. Zhongshu No. 4) seedlings under NaCl stress (100 mM), particularly the effects on (1) redox status, (2) antioxidative metabolism, and (3) the gene expression and activity of five enzymes related to GSH synthesis and metabolism. Salt stress resulted in an oxidative burst in tomato seedling leaves, as evidenced by increases in hydrogen peroxide (H2O2), malondialdehyde (MDA), and superoxide radical (O2 −). Salt stress also reduced leaf GSH level and GSH redox homeostasis, whereas application of GSH reversed the negative effects of salt stress. Furthermore, application of GSH increased the transcript levels and activities of enzymes related to GSH synthesis and metabolism, including gamma-glutamylcysteine synthetase (γ-ECS), glutathione synthetase (GS), glutathione-S-transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GR). Application of GSH also enhanced the activities of antioxidant enzymes such as superoxidase dismutase (SOD), peroxidase (POD), catalase (CAT) and the enzymes involved in the ascorbate-glutathione cycle, and the contents of GSH and the ratios of reduced and oxidized glutathione (GSH/GSSG) in the salt-stressed plants or salt-stress plants treated with buthionine sulfoximine (BSO, inhibitor of GSH synthesis key enzyme gamma-glutamylcysteine synthetase). Taken together, our findings demonstrate that exogenous GSH application increases resistance to salt-induced oxidative stress by enhancing the antioxidant defense system, and regulating GSH synthesis and metabolism to maintain cellular redox homeostasis.

Collagen triple helix repeat containing 1 (CTHRC1) is a gene that has been associated with tumor progression in human prostate cancer (PC). The tumor immune microenvironment has been linked with disease outcome in PC. In the present study, the correlation between CTHRC1 with PC recurrence and the tumor immunological microenvironment was investigated. Using the data supplied by the Tumor Immune Estimation Resource (TIMER), the expression of CTHRC1, programmed cell death protein 1 (PD‑1), and programmed cell death 1 ligand 1 (PD‑L1) were analyzed. Immunohistochemical staining of CTHRC1, PD‑1 and PD‑L1 was performed using a tissue microarray construction of prostate adenocarcinoma (PRAD) specimens. In PRAD, an association was reported between the CTHRC1 expression and the disease free survival (DFS) rate (P=0.022). Overexpression of CTHRC1 was correlated with increased levels of PD‑1 (R=0.272, P=0.021) and PD‑L1 (R=0.298, P=0.016), elevated levels of infiltrating B cells (P=9.51e‑11), CD4+ cells (P=1.51e‑11), macrophages (P=8.25e‑5), neutrophils (P=2.17e‑9) and dendritic cells (P=3.13e‑13). Bioinformatics analysis revealed that CTHRC1 was correlated with the expression levels of matrix metalloproteinase‑9, mucin 1 and solute carrier organic anion transporter family member 2B1 genes, which exert an influence in PRAD. The occurrence of this condition is most likely to be associated with regulation of the tumor microenvironment. Taken together, we demonstrated that the prognosis and immunity of PC are closely linked to CTHRC1 upregulation. Furthermore, these results suggest that the immune function of PC may be suppressed by CTHRC1‑targeting therapy.

Background: Circulating tumor cells (CTCs) with an epithelial-mesenchymal transition phenotype in peripheral blood may be a useful marker of carcinomas with poor prognosis. The aim of this study was to determine the prognostic significance of CTCs expressing Krüppel-like factor 8 (KLF8) and vimentin in pancreatic cancer (PC). Methods: CTCs were isolated by immunomagnetic separation from the peripheral blood of 40 PC patients before undergoing surgical resection. Immunocytochemistry was performed to identify KLF8+ and vimentin+ CTCs. The associations between CTCs and time to recurrence (TTR), clinicopathologic factors, and survival were assessed. Univariate and multivariate analyzes were performed to identify risk factors. Results: Patients with CTCs ( n = 30) had a higher relapse rate compared to those without ( n = 10) (70.0% vs 20.0%; P < 0.01). The proportion of KLF8+/vimentin+ CTCs to total CTCs was inversely related to TTR ( r = −0.646; P < 0.01); TTR was reduced in patients with > 50% of CTCs identified as KLF8+/vimentin+ ( P < 0.01). Independent risk factors for recurrence were perineural invasion and > 50% KLF8+/vimentin+ CTCs (both P < 0.05). Conclusion: Poor prognosis can be predicted in PC patients when > 50% of CTCs are positive for KLF8 and vimentin.

In the original publication, Prof. Lin-Nei Hsu’s institution was incorrectly published as ‘Tainan Municipal An-Nan Hospital’ in affiliation 4. The correct affiliation should read as ‘Department of Urology, An-Nan Hospital, China Medical University, Tainan, Taiwan’.

BackgroundAnti-thymocyte globulin (ATG) as induction therapy in renal transplantation is facing the dilemma of reducing the incidence of acute rejection (AR) and delayed graft function (DGF) or increasing risks of infection and malignancy. The purpose of this study was to delineate the safety and efficiency of the optimal ATG dosage.MethodsWe retrospectively evaluated 91 deceased donor kidney transplant recipients (KTRs) in our institution between March 2011 and January 2019. The patients were classified into three groups based on induction therapy: (1) Group 1: modest-dose ATG (three mg/kg) intraoperatively (N= 21); (2) Group 2: low-dose ATG (1–1.5 mg/kg) intraoperatively (N= 23); (3) Group 3: basiliximab 20 mg both on day 0 and 4 (N= 47). In Groups 1 and 2, all patients received a daily low-dose program (1–1.5 mg/kg each day) with target dosage of six mg/kg. Induction therapy was combined with standard immunosuppressive regimen consisting of calcineurin inhibitors, mycophenolate/the mammalian target of rapamycin inhibitors and corticosteroids.ResultsThere was no significant difference in patient characteristics among groups. The outcomes of infection rate, biopsy-proven acute rejection, post-transplant diabetes mellitus, graft survival, and patient survival were similar among groups. Compared to the daily low-dose ATG regimen, the intraoperative modest-dose regimen did not cause more dose interruption and hence was more likely to reach the target ATG dosage. The intraoperative modest-dose regimen also seemed to reduce the rate of DGF.DiscussionIn recent years, a trend of using a “lower” dose of ATG has seemed to emerge. Our results suggest intraoperative modest-dose ATG followed by daily low-dose ATG regimen was safe and effective in cadaveric renal transplantations for preventing DGF, AR, and graft loss.

Preserving renal function and controlling oncological outcomes are pertinent while managing renal tumours. We compared outcomes of percutaneous cryoablation (PCA) and retroperitoneoscopic cryoablation (RCA) in patients with renal neoplasms. We identified 108 patients with renal tumours at two medical centres, where 63 patients received PCA and 45 patients underwent RCA from August 2009 to July 2015, and they were followed up until February 2017. We compared preoperative and postoperative parameters, namely gender, systemic diseases, age, American Society of Anesthesiologists score, body mass index (BMI), haemoglobin, the estimated glomerular filtration rate, tumour size, operative time, tumour type, Clavien–Dindo classification of surgical complications, and tumour recurrence, by using an independent sample t test, Pearson’s Chi-square test, Fisher’s exact test, a Mann–Whitney test, and a generalised linear model. Based on baseline characteristics, we found that the patients in the PCA group were older and had higher BMI than those in the RCA group, whereas the patients in the RCA group had more comorbidities than those in the PCA group. Retroperitoneoscopic and percutaneous methods had similar operative times, blood transfusion rates, postoperative fever episodes, and complication rates for either minor or major complications. However, the percutaneous method was associated with a shorter length of stay. No patient experienced deterioration in renal function until 2 years after both procedures. Impaired renal function was found in both groups in the 3-year follow-up. In both groups, tumour recurrence was significant for tumours > 4 cm. Our results confirm that both cryoablation methods (PCA and RCA) are safe and effective for renal cell carcinoma. Favourable oncological control was achieved in both groups if the renal tumour size was ≤ 4 cm.

Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is a common subtype of non-Hodgkin’s lymphoma and is very likely to infiltrate the bone marrow. Over 30% of patients are converted to relapsed/refractory DLBCL after first-line rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, with a poor prognosis. Our aim was to identify molecular markers that might be utilized to predict relapsed/refractory ABC-DLBCL patients. Hence, we collected bone marrow aspirate smears from 202 patients with ABC-DLBCL and detected expression of bone marrow molecular marker proteins by immunocytochemistry. Signal transducer and activator of transcription (Stat)3, nuclear factor (NF)-κB p65, Syk, Bruton’s tyrosine kinase (BTK), and Bcl2 proteins were strongly expressed in bone marrow aspirate smears of ABC-DLBCL patients. The same smear could present positive expression of multiple proteins simultaneously. Positive combinations of protein expression were associated with resistance. The most significant finding was that the Stat3+NF-κB+ group developed resistance, which was significantly higher than that of the Stat3-NF-κB-group (80 vs. 14%). There was a significant difference in two-year relapse-free survival between protein-positive and protein-negative combinations of Stat3-NF-κB (P = 0.005), Bcl2-Stat3 (P = 0.009), Bcl2-Pax5 (P = 0.003), and BTK-Syk (P < 0.001). Thus, we detected key molecules in multiple signaling pathways in bone marrow aspirate smears. At the same time, the results provide further clinical evidence of ABC-DLBCL drug-resistant molecules and provide a theoretical basis for rational second-line treatment after drug resistance.

Nasopharyngeal carcinoma (NPC) has the highest incidence of all types of head and neck cancer in China. The present study aimed to investigate the association between the expression of programmed death ligand 1 (PD-L1) in NPC tissues and clinicopathological features, as well the outcomes for NPC patients. In addition, the association between tissue expression of PD-L1 and immune components in peripheral blood was assessed. The expression of PD-L1 was determined by immunohistochemistry, while immune indexes were determined by ELISA and flow cytometry. The positive expression rate of PD-L1 in NPC patients was 29.2%, and the PD-L1 expression levels were associated with distant metastasis (P=0.010) and the T-stage of the primary tumor (P=0.032). The expression of PD-L1 was associated with the distant metastasis-free survival of NPC patients (P=0.006). In addition, a statistically significant association of PD-L1 expression with Epstein-Barr virus viral capsid antigen IgA (EBV VCA-IgA; P=0.046) and with CD3-CD19+ cells (P=0.014) was identified. These results indicated that PD-L1 may be a potential prognostic biomarker for NPC patients, and that EBV VCA-IgA and CD3-CD19+ cells may be useful for predicting PD-L1 expression when its levels cannot be detected due to the lack of a tumor tissue sample.

We evaluated the effects of Bio-Oss® (a natural bone substitute derived from the mineral portion of bovine bone) on delayed osseointegration of implants. The bilateral third and fourth mandibular premolars of 4 adult, healthy, male and female dogs were extracted. We randomly selected 2 extraction sockets in each dog to be filled with Bio-Oss® (the experimental group); the other 2 extraction sockets, which were not treated, served as controls. Dental implants were inserted into the alveolar bone of the experimental group and the control group 3 months after insertion of the Bio-Oss®. The osteogenic activity in the bone around the implants was assessed by evaluating the histological morphology and estimating histomorphometric variables at 3 and 6 months after delayed implantation. After 3 months, Goldner's trichrome staining analysis showed that the rate of content between the bone and the implant and the mineralised area of bone around the implant were significantly higher in the experimental group (76%(9%) and 69.5% (9.6%), respectively) than those in the control group (56.1% (8.2%) and 52.8% (7.3%), respectively, p=0.003 and 0.000). However, the 2 groups did not differ significantly at 6 months. Fluorescence microscopy showed that the mean rates of mineralisation of the bony tissue around the implant in the experimental group at months 3 and 6 were 6.8 (0.4) μm and 8.4 (0.8) μm, respectively, which were significantly higher than those in the control group (p=0.000 and 0.03). These data indicate that putting Bio-Oss® into the extraction sockets can promote osseointegration after delayed implantation, and may be a promising option for clinical use.

Tomato (Lycopersicon esculentum Miller) cv. Jiahe No. 9 (a salinity-resistant cultivar) and cv. Shuangfeng 87-5 (a salinity-sensitive cultivar) were used as experimental materials to investigate the effects of exogenous selenium (Na2SeO3 0.05 mM) on plant growth, chlorophyll fluorescence, photosynthetic rate, and antioxidative metabolism of chloroplasts in tomato seedlings under NaCl (100 mM) stress. Salt stress significantly inhibited plant growth, net photosynthetic rate (Pn), maximum quantum yield of PSII (Fv/Fm), actual photochemical efficiency of PSII (ΦPSII), photochemical quenching coefficient (qP), and non-photochemical quenching coefficient (qN) of both cultivars, whereas application of Se reversed the negative effects of salt stress. Furthermore, application of Se significantly decreased the levels of hydrogen peroxide (H2O2) and malondialdehyde. Application of Se increased the activities of superoxidase dismutase, glutathione reductase, dehydroascorbate reductase, monodehydroascorbate reductase, glutathione peroxidase, and thioredoxin reductase, and the contents of ascorbate, glutathione (GSH) and NADPH, and the ratios of GSH/GSSH, AsA/DHA, and NADPH/ NADP+ in the salt-stressed chloroplasts of both cultivars. These results suggest that Se alleviates salt-induced oxidative stress through regulating the antioxidant defense systems in the chloroplasts of tomato seedlings, which is associated with the improvement of the photochemical efficiency of PSII, thereby maintaining higher photosynthetic rates. In addition, the salt tolerance of Jiahe No. 9 is closely related with high reactive oxygen species scavenging activity and reducing power levels in the chloroplasts.

To investigate the association between nocturia and erectile dysfunction, androgen deficiency, overactive bladder and systemic diseases in men with type 2 diabetic mellitus.A self-administered questionnaire containing overactive bladder symptom score and sexual health inventory for men was obtained from subjects with type 2 diabetic mellitus. Nocturia and severe nocturia were defined as rising ≥2 or ≥3 per night to void, respectively. Patient characteristics and diabetes-related complications to risk of nocturia were evaluated.Of 632 consecutive subjects, 56.0 and 24.2 % reported having nocturia and severe nocturia, respectively. After adjustment of age, diabetic mellitus duration, and overactive bladder, the presence of erectile dysfunction, stroke, hypertension, and higher serum creatinine level was associated with nocturia and severe nocturia. The patients with the lowest quartile of testosterone level (2.21 ± 0.51 ng/mL) had higher prevalence of nocturia (65.1 %) and severe nocturia (32.9 %) than the sum of the other three quartiles. The patients with severe nocturia had threefold higher mortality than the other group after 3.5-year follow-up.The presence of nocturia was associated with erectile dysfunction, systemic vascular events, higher mortality, and indicated poor health in male with type 2 diabetic mellitus.

As an attractive technique for the improvement of biomaterials, Plasma immersion ion implantation (PIII) has been applied to modifying the titanium material for dental implant application. The present study investigated the cytocompatibility and early osseointegration of fluoride-ion-implanted titanium (F-Ti) surface and implants, both characterizing in their composition of titanium oxide and titanium fluoride. The cytocompatibility of F-Ti was evaluated in vitro by using scanning electron microscope, Cell Counting Kit-8 assay, alkaline phosphatase activity assay, and quantitative real-time polymerase chain reaction. The results showed that the F-Ti weakened the effects that Porphyromonas gingivalis exerted on the MG-63 cells in terms of morphology, proliferation, differentiation, and genetic expression when MG-63 cells and Porphyromonas gingivalis were co-cultured on the surface of F-Ti. Meanwhile, the osteogenic activity of F-Ti implants was assessed in vivo via evaluating the histological morphology and estimating histomorphometric parameters. The analysis of toluidine blue staining indicated that the new bone was more mature in subjects with F-Ti group, which exhibited the Haversian system, and the mean bone-implant contact value of F-Ti group was slightly higher than that of cp-Ti group (p>0.05). Fluorescence bands were wider and brighter in the F-Ti group, and the intensity of fluorochromes deposited at the sites of mineralized bone formation was significantly higher for F-Ti surfaces than for cp-Ti surfaces, within the 2nd, 3rd and 4th weeks (p

To detect the accuracy of measurement results with Z300P portable formaldehyde analyzer, and provide scientific data for detecting formaldehyde concentration in the air using instrument instead of chemical method, the different formaldehyde concentration was detected by phenol reagent and acetyl acetone which are the national standard method for the formaldehyde concentrations determination in indoor air and their precision test and linear analysis were done. At the same time, the formaldehyde of low, medium and high concentrations of in different indoor field was detected with Z300P portable formaldehyde analyzer, then significant difference test among the results was done. The average relative standard deviation of measurement results through phenol reagent and acetyl acetone national standard method was less than 5%, there is a good linear relationship (r> 0.997).There was no significant difference (P> 0.05) indifferent formaldehyde concentrations results through phenol reagent with acetyl acetone method. But there was a significant difference (P

A 10-hydroxycamptothecin-encapsulated magnetic nanovehicle (HEMN) was fabricated by coencapsulating Fe(3)O(4) nanoparticles and 10-hydroxycamptothecin (HCPT) into a micelle core self-assembled from the amphiphilic copolymer methoxy-poly(ethylene glycol)-poly(d,l-lactide-co-glycolide) through a facile dialysis method. A satisfactory drug-loading content of (9.03 ± 0.67) % and a relatively high encapsulation efficiency of (53.52 ± 6.46) % were achieved. In vitro drug release was performed by membrane dialysis and a pH-dependent release behavior was observed. In comparison with free HCPT dissolved in dimethylsulfoxide, HEMNs showed a greatly improved in vitro antitumor efficacy against three different human cancer cell lines-HeLa, A549, and HepG2-and lower IC(50) values were measured. The mechanism of cell death was investigated, and it was clearly demonstrated that the apoptosis process was triggered. An in vitro wound-healing assay and a transwell assay indicated that HEMNs exerted much stronger activity in inhibiting HeLa cell migration. The cellular uptake of HEMNs in a desired area can be significantly enhanced by an external magnetic field. These results demonstrate HCPT-encapsulated magnetic nanovehicles might have important potential in clinical applications for inhibiting tumor metastasis and for targeted drug delivery.