The antihyperuricemia activity of Astragali Radix through regulating the expression of uric acid transporters via PI3K/Akt signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix (AR) is the dry root of the leguminous plants Astragalus membranaceus (Fisch) Beg. var. mongholicus (Beg) Hsiao, and Astragalus membranaceus (Fisch) Bge., being used as a medicinal and edible resource. AR is used in traditional Chinese medicine prescriptions to treat hyperuricemia, but this particular effect is rarely reported, and the associated mechanism of action is still need to be elucidated. AIM OF THE STUDY: To research the uric acid (UA)-lowering activity and mechanism of AR and the representative compounds through the constructed hyperuricemia mouse and cellular models. MATERIALS AND METHODS: In our study, the chemical profile of AR was analysed by UHPLC-QE-MS, as well as the mechanism of action of AR and the representative compounds on hyperuricemia was studied through the constructed hyperuricemia mouse and cellular models. RESULTS: The main compounds in AR were terpenoids, flavonoids and alkaloids. Mice group treated with the highest AR dosage showed significantly lower (p < 0.0001) serum uric acid (208 ± 9 µmol/L) than the control group (317 ± 11 µmol/L). Furthermore, UA increased in a dose-dependence manner in urine and faeces. Serum creatinine and blood urea nitrogen standards, as well as xanthine oxidase in mice liver, decreased (p < 0.05) in all cases, indicating that AR could relieve acute hyperuricemia. UA reabsorption protein (URAT1 and GLUT9) was down-regulated in AR administration groups, while the secretory protein (ABCG2) was up-regulated, indicating that AR could promote the excretion of UA by regulating UA transporters via PI3K/Akt signalling pathway. CONCLUSION: This study validated the activity, and revealed the mechanism of AR in reducing UA, which provided experimental and clinical basis for the treatment of hyperuricemia with it.

Tumor-Associated Inflammation: The Tumor-Promoting Immunity in the Early Stages of Tumorigenesis.

Tumorigenesis is a multistage progressive oncogenic process caused by alterations in the structure and expression level of multiple genes. Normal cells are continuously endowed with new capabilities in this evolution, leading to subsequent tumor formation. Immune cells are the most important components of inflammation, which is closely associated with tumorigenesis. There is a broad consensus in cancer research that inflammation and immune response facilitate tumor progression, infiltration, and metastasis via different mechanisms; however, their protumor effects are equally important in tumorigenesis at earlier stages. Previous studies have demonstrated that during the early stages of tumorigenesis, certain immune cells can promote the formation and proliferation of premalignant cells by inducing DNA damage and repair inhibition, releasing trophic/supporting signals, promoting immune escape, and activating inflammasomes, as well as enhance the characteristics of cancer stem cells. In this review, we focus on the potential mechanisms by which immune cells can promote tumor initiation and promotion in the early stages of tumorigenesis; furthermore, we discuss the interaction of the inflammatory environment and protumor immune cells with premalignant cells and cancer stem cells, as well as the possibility of early intervention in tumor formation by targeting these cellular mechanisms.

A promising Prognostic risk model for advanced renal cell carcinoma (RCC) with immune-related genes.

BACKGROUND: Renal cell carcinoma (RCC) is a third most common tumor of the urinary system. Nowadays, Immunotherapy is a hot topic in the treatment of solid tumors, especially for those tumors with pre-activated immune state. METHODS: In this study, we downloaded genomic and clinical data of RCC samples from The Cancer Genome Atlas (TCGA) database. Four immune-related genetic signatures were used to predict the prognosis of RCC by Cox regression analysis. Then we established a prognostic risk model consisting of the genes most related to prognosis from four signatures to value prognosis of the RCC samples via Kaplan-Meier (KM) survival analysis. An independent data from International Cancer Genome Consortium (ICGC) database were used to test the predictive stability of the model. Furthermore, we performed landscape analysis to assess the difference of gene mutant in the RCC samples from TCGA. Finally, we explored the correlation between the selected genes and the level of tumor immune infiltration via Tumor Immune Estimation Resource (TIMER) platform. RESULTS: We used four genetic signatures to construct prognostic risk models respectively and found that each of the models could divide the RCC samples into high- and low-risk groups with significantly different prognosis, especially in advanced RCC. A comprehensive prognostic risk model was constructed by 8 candidate genes from four signatures (HLA-B, HLA-A, HLA-DRA, IDO1, TAGAP, CIITA, PRF1 and CD8B) dividing the advanced RCC samples from TCGA database into high-risk and low-risk groups with a significant difference in cancer-specific survival (CSS). The stability of the model was verified by independent data from ICGC database. And the classification efficiency of the model was stable for the samples from different subgroups. Landscape analysis showed that mutation ratios of some genes were different between two risk groups. In addition, the expression levels of the selected genes were significantly correlated with the infiltration degree of immune cells in the advanced RCC. CONCLUSIONS: Sum up, eight immune-related genes were screened in our study to construct prognostic risk model with great predictive value for the prognosis of advanced RCC, and the genes were associated with infiltrating immune cells in tumors which have potential to conduct personalized treatment for advanced RCC.

CERS6-AS1 promotes cell proliferation and represses cell apoptosis in pancreatic cancer via miR-195-5p/WIPI2 axis.

Pancreatic cancer (PC) is a lethal malignancy that threatens human health. Long noncoding RNAs (lncRNAs) act as important mediators in PC development. Our study aimed to investigate the function and mechanism of lncRNA ceramide synthase 6 antisense RNA 1 (CERS6-AS1) in PC. As shown by RT-qPCR, CERS6-AS1 was significantly upregulated in PC cells and tissues. Silencing CERS6-AS1 suppressed PC cell viability and proliferation while enhancing cell apoptosis according to colony formation assays, EdU assays, and flow cytometry analyses. Mechanistically, CERS6-AS1 interacted with miR-195-5p to elevate the expression level of the WD repeat domain phosphoinositide interacting 2 (WIPI2), which is a downstream target gene of miR-195-5p in PC. Moreover, miR-195-5p expression was negatively associated with CERS6-AS1 expression (or WIPI2 expression) in PC tissues. Rescue assays revealed that WIPI2 overexpression rescued the effects of CERS6-AS1 deficiency on cell viability, proliferation, and apoptosis. In summary, CERS6-AS1 facilitates PC cell proliferation while inhibiting PC cell apoptosis by upregulating WIPI2 via miR-195-5p. This study might provide promising insight into the role of CERS6-AS1 in PC development.

The association between abnormal serum magnesium levels and prognosis of elderly patients with community-acquired pneumonia.

To investigate the association between abnormal serum magnesium levels and the prognosis of elderly patients with community-acquired pneumonia (CAP). Methods: A retrospective study was conducted on 1381 elderly patients with CAP in the First Hospital of Qinhuangdao between January 2015 and December 2018. Serum magnesium concentrations in the range of 0.75-1.25 mmol/L were defined as normal. Patients were assigned into normal, hypomagnesemia, and hypermagnesemia groups. The primary outcome was in-hospital mortality, indicating whether a patient died at the time of discharge from the hospital. The percentages of respiratory failure and mechanical ventilation were 18.6% and 10.6 % in the normal group, 29% and 16.5 % in the hypomagnesemia, and 42.9% and 35.7% in the hypermagnesemia groups. The occurrence of shock was 8.5% and 4.5% in the hypomagnesemia group and the normal group. The percentages of the length of stay at ICU were 14.9%, 18.8%, and 57.1% in the hypomagnesemia, normal, and hypermagnesemia groups. The in-hospital mortality rate was 5.3%, 9.1%, and 35.7% in the normal, hypomagnesemia, and hypermagnesemia groups, respectively. The results of univariate analysis showed that the in-hospital mortality in the hypomagnesemia group was 1.790 (95% confidence interval (CI): 1.009∼3.176, P=0.046) times higher than that in the normal group; in the hypermagnesemia group, it was 9.947 (95% CI: 3.238-30.556, P<0.001) times higher than that in the normal group. The results of multivariate logistic regression analysis showed that after adjusting for gender, age, diabetes, heart failure, cerebrovascular disease, cancer, estimated glomerular filtration rate (eGFR), glucose, and CURB-65 score, in the hypomagnesemia group, the in-hospital mortality was 1.746 (95% confidence interval (CI): 0.956∼3.186, P=0.070) times higher than that in the normal group, and 5.689 (95% CI: 1.583- 20.446, P=0.008) times higher in the hypermagnesemia group than that in the normal group. Abnormal serum magnesium levels are strongly associated with in-hospital mortality in elderly patients with CAP. The measurement of serum magnesium levels in elderly patients with CAP at admission may assist clinicians to determine the prognosis of such patients.

The Effects of Type 2 Diabetes and Postoperative Pneumonia on the Mortality in Inpatients with Surgery.

OBJECTIVE: The aim of the study was to explore the relationship between type 2 diabetes (T2DM) and postoperative pneumonia, and the effects of T2DM and postoperative pneumonia on the mortality in inpatients with surgery. METHODS: A retrospective study was conducted on 43,174 inpatients with surgery in The First Hospital of Qinhuangdao. These patients were divided into four groups according to T2DM and postoperative pneumonia, Group A subjects without T2DM and postoperative pneumonia, Group B subjects with T2DM only, Group C subjects with postoperative pneumonia only and Group D subjects with T2DM and postoperative pneumonia. In-hospital mortality was collected. RESULTS: The incidences of postoperative pneumonia were higher in patients with T2DM than patients without T2DM (T2DM 3.2% vs Non-diabetes 1.7%, χ 2=36.219, P<0.001). The mortalities were 0.3% in Group A, 0.3% in Group B, 4.6% in Group C and 8.6% in Group D. In multiple logistic regression analysis, adjusted for sex, age, emergency admissions, coronary heart disease, heart failure, chronic kidney disease, hypoproteinemia, stroke and transient ischemic attack, the mortalities of Group C and Group D were 4.515 (95% CI: 2.779～7.336, P<0.001) times and 8.468 (95% CI: 3.567～20.099, P<0.001) times than the mortality of Group A. CONCLUSION: T2DM is susceptible to postoperative pneumonia. The mortality increased in patients with postoperative pneumonia. When patients with T2DM and postoperative pneumonia at the same time, the mortality increased further. In T2DM patients with postoperative pneumonia, perioperative management should be improved for patient safety.

The Association between Metabolic Syndrome and Morbid Events in Type 2 Diabetes after a 7-Year Community Management: Beijing Community Diabetes Study 17.

BACKGROUND: To examine the association between morbid events and metabolic syndrome (MS) in patients with type 2 diabetes mellitus (T2DM). METHODS: A prospective, longitudinal, multicenter study was conducted at 13 community health centers associated with Beijing Tongren Hospital. From 2008 to 2015, there have been 3,525 T2DM patients being managed based on the Chinese guideline for T2DM. The morbid events included macrovascular events, diabetic kidney disease, ophthalmologic events, cancer, and all-cause death. RESULTS: At baseline, there were 2,708 people with MS and 817 without MS. After a seven-year management, there were 351 (12.96%) events in MS people and 74 (9.06%) events in people without MS (p = 0.003). The prevalence of macrovascular events (6.06%) was much higher in MS people than in people without MS (3.79%, p = 0.013). Cox regression analysis showed an association between MS and morbid events even after adjusting for confounding variables (adjusted hazard ratio = 1.44). MS was also associated with macrovascular events (adjusted hazard ratio = 1.96). The occurrence of morbid events and macrovascular events was increased when the numbers of metabolic abnormalities were 1, 2, 3, and 4 (p < 0.001). There was no continuously statistically significant difference in the cumulative prevalence of morbid events between patients with MS and patients without MS during the first five years. However, after six or seven years, the cumulative prevalence of morbid events in patients with MS was continuously significantly higher than that in patients without MS (11.00% vs. 8.20%, 12.96% vs. 9.06%, p < 0.05). CONCLUSIONS: T2DM with MS had higher incidence of morbid events, especially cardiovascular events, even after integrated management. The occurrence of morbid and macrovascular events increased as the number of metabolic abnormalities increased. MS was associated with increased risk of morbid events by 44% and macrovascular events by 96%. It would take at least six years to observe the association between MS and morbid events in T2DM.

Retraction: Activation of endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance of human small cell lung cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

[This retracts the article DOI: 10.18632/oncotarget.12718.].

Comparison of the clinical application value of mo-targeted X-ray, color doppler ultrasound and MRI in preoperative comprehensive evaluation of breast cancer.

OBJECTIVE: To investigate the clinical application value of the Mo-targeted X-ray examination, color Doppler ultrasound and magnetic resonance imaging (MRI) in the diagnosis and preoperative comprehensive evaluation of breast cancer. METHODS: Among 170 breast cancer patients, they underwent Mo-targeted X-ray examination, color Doppler ultrasound and MRI before surgery to evaluate the lesions in breast, axillary lymph nodes and the availability of breast-conserving surgery. RESULTS: The detection rates using color Doppler ultrasound examination and MRI were higher than that in the Mo-targeted X-ray examination, which were 90%, 94% and 82%, respectively (P < 0.01 or 0.05). With the result of pathological examination as the golden criteria, we found that specificities of Mo-targeted X-ray examination, color Doppler ultrasound examination and MRI in evaluating the metastasis in axillary lymph nodes were similar (85.11%, 77.66% and 79.79%; P > 0.05). Before surgery, the sensitivities and accuracies of the color Doppler ultrasound examination and MRI were higher than those using the Mo-targeted X-ray examination, which were 73.21%, 82.14%, and 28.57%, 76.00%, 80.67% and 64.00% (P < 0.01 or 0.05). Before surgery, the accuracy rate of MRI in evaluating the breast-conserving surgery was higher than those of Mo-targeted X-ray examination and color Doppler ultrasound (92.00%, 83.33% and 84.67%; P < 0.05). CONCLUSION: Combined application of Mo-targeted X-ray examination, color Doppler ultrasound and MRI shows a higher accuracy in diagnosis of breast cancer and evaluation of axillary lymph node metastasis, which is conducive to the selection of surgical methods.

Exosomal CCL2 from Tubular Epithelial Cells Is Critical for Albumin-Induced Tubulointerstitial Inflammation.

Albuminuria is a key instigator of tubulointerstitial inflammation associated with CKD, but the mechanism through which filtered albumin propagates renal injury remains unclear. In this study, we explored the role in this process of exosome mRNA released from tubular epithelial cells (TECs). Compared with control mice, acute and chronic kidney injury models had more exosomes containing inflammatory cytokine mRNA, particularly the chemokine CCL2, in kidneys and urine. In vitro stimulation of TECs with BSA recapitulated this finding. Notably, the internalization of purified TEC exosomes by cultured macrophages increased if TECs were exposed to BSA. Macrophage internalization of exosomes from BSA-treated TECs led to an enhanced inflammatory response and macrophage migration, but CCL2 silencing in TECs prevented these effects. Using a GFP-CCL2 fusion mRNA construct, we observed direct transfer of CCL2 mRNA from TEC exosomes to macrophages. Mice subjected to tail vein injection of purified BSA-treated TEC exosomes developed tubular injury with renal inflammatory cell infiltration. However, injection of exosomes from BSA-treated CCL2-deficient TECs induced less severe kidney inflammation. Finally, in patients with IgA nephropathy, the increase of proteinuria correlated with augmented urinary excretion of exosomes with exaggerated expression of CCL2 mRNA. Moreover, the level of CCL2 mRNA in urinary exosomes correlated closely with levels of renal interstitial macrophage infiltration in these patients. Our studies demonstrate that the increasing release of exosomes that transfer CCL2 mRNA from TECs to macrophages constitutes a critical mechanism of albumin-induced tubulointerstitial inflammation.

One pot simultaneous preparation of both enantiomer of ß-amino alcohol and vicinal diol via cascade biocatalysis.

OBJECTIVES: To investigate the efficiency of a new cascade biocatalysis system for the conversion of R, S-ß-amino alcohols to enantiopure vicinal diol and ß-amino alcohol. RESULTS: An efficient cascade biocatalysis was achieved by combination of a transaminase, a carbonyl reductase and a cofactor regeneration system. An ee value of > 99% for 2-amino-2-phenylethanol and 1-phenyl-1, 2-ethanediol were simultaneously obtained with 50% conversion from R, S-2-amino-2-phenylethanol. The generality of the cascade biocatalysis was further demonstrated with the whole-cell approaches to convert 10-60 mM R, S-ß-amino alcohol to (R)- and (S)-diol and (R)- and (S)-ß-amino alcohol in 90-99% ee with 50-52% conversion. Preparative biotransformation was demonstrated at a 50 ml scale with mixed recombinant cells to give both (R)- and (S)-2-amino-2-phenylethanol and (R)- and (S)-1-phenyl-1, 2-ethanediol in > 99% ee and 40-42% isolated yield from racemic 2-amino-2-phenylethanol. CONCLUSIONS: This cascade biocatalysis system provides a new practical method for the simultaneous synthesis of optically pure vicinal diol and an ß-amino alcohol.

Activation of endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance of human small cell lung cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: This study aims to investigate the effects of endoplasmic reticulum stress (ERS) on autophagy, apoptosis and chemoresistance of human small cell lung cancer (SCLC) cells via the PI3K/AKT/mTOR signaling pathway. RESULTS: The expressions of ERS-related proteins (PEAK, eIF2α and CHOP) up-regulated, autophagy-related proteins (LC3, LC3-II and Beclin1) and apoptosis-related proteins (Bax and procaspase-3) down-regulated in NCI-H446 and H69 cells after tunicamycin treatment for 24 h. Compared with the blank group, the tunicamycin, BEZ235 and tunicamycin + BEZ235 groups exhibited decreased expressions of p-PI3K, p-AKT and p-mTOR, and increased expressions of autophagy-related proteins (LC3, LC3-II and Beclin1) and apoptosis proteins (Bax and procaspase-3), and the most obvious changes were observed in the tunicamycin + BEZ235 group. MATERIALS AND METHODS: CCK-8 assay was applied to select the best cell line from five SCLC cell lines (NCI-H446, H69, H526, H146 and H209). Finally, NCI-H446 and H69 cells were selected for further experiments. NCI-H446/CDDP and H69/CDDP were selected and divided into the blank group, tunicamycin (an ESR inducer) group, BEZ235 (inhibitors of PI3K/AKT/mTOR pathway) group and tunicamycin + BEZ235 group. Cell apoptosis was detected by flow cytometry. Autophagy was observed by fluorescence microscopy and flow cytometry. Western blotting was used to detect the expressions of ERS-related proteins, autophagy-related proteins, apoptosis-related proteins and PI3K/AKT/mTOR pathway-related proteins. CONCLUSIONS: Our findings provide evidence that the activation of ERS could promote autophagy and apoptosis and reverse chemoresistance of human SCLC cells by inhibiting the PI3K/AKT/mTOR pathway.

C-C Motif Chemokine 5 Attenuates Angiotensin II-Dependent Kidney Injury by Limiting Renal Macrophage Infiltration.

Inappropriate activation of the renin angiotensin system (RAS) is a key contributor to the pathogenesis of essential hypertension. During RAS activation, infiltration of immune cells into the kidney exacerbates hypertension and renal injury. However, the mechanisms underpinning the accumulation of mononuclear cells in the kidney after RAS stimulation remain unclear. C-C motif chemokine 5 (CCL5) drives recruitment of macrophages and T lymphocytes into injured tissues, and we have found that RAS activation induces CCL5 expression in the kidney during the pathogenesis of hypertension and renal fibrosis. We therefore evaluated the contribution of CCL5 to renal damage and fibrosis in hypertensive and normotensive models of RAS stimulation. Surprisingly, during angiotensin II-induced hypertension, CCL5-deficient (knockout, KO) mice exhibited markedly augmented kidney damage, macrophage infiltration, and expression of proinflammatory macrophage cytokines compared with wild-type controls. When subjected to the normotensive unilateral ureteral obstruction model of endogenous RAS activation, CCL5 KO mice similarly developed more severe renal fibrosis and greater accumulation of macrophages in the kidney, congruent with enhanced renal expression of the macrophage chemokine CCL2. In turn, pharmacologic inhibition of CCL2 abrogated the differences between CCL5 KO and wild-type mice in kidney fibrosis and macrophage infiltration after unilateral ureteral obstruction. These data indicate that CCL5 paradoxically limits macrophage accumulation in the injured kidney during RAS activation by constraining the proinflammatory actions of CCL2.

High IFIT1 expression predicts improved clinical outcome, and IFIT1 along with MGMT more accurately predicts prognosis in newly diagnosed glioblastoma.

Interferon-induced protein with tetratricopeptide repeat 1 (IFIT1) plays a key role in growth suppression and apoptosis promotion in cancer cells. Interferon was reported to induce the expression of IFIT1 and inhibit the expression of O-6-methylguanine-DNA methyltransferase (MGMT).This study aimed to investigate the expression of IFIT1, the correlation between IFIT1 and MGMT, and their impact on the clinical outcome in newly diagnosed glioblastoma. The expression of IFIT1 and MGMT and their correlation were investigated in the tumor tissues from 70 patients with newly diagnosed glioblastoma. The effects on progression-free survival and overall survival were evaluated. Of 70 cases, 57 (81.4%) tissue samples showed high expression of IFIT1 by immunostaining. The χ(2) test indicated that the expression of IFIT1 and MGMT was negatively correlated (r = -0.288, P = .016). Univariate and multivariate analyses confirmed high IFIT1 expression as a favorable prognostic indicator for progression-free survival (P = .005 and .017) and overall survival (P = .001 and .001), respectively. Patients with 2 favorable factors (high IFIT1 and low MGMT) had an improved prognosis as compared with others. The results demonstrated significantly increased expression of IFIT1 in newly diagnosed glioblastoma tissue. The negative correlation between IFIT1 and MGMT expression may be triggered by interferon. High IFIT1 can be a predictive biomarker of favorable clinical outcome, and IFIT1 along with MGMT more accurately predicts prognosis in newly diagnosed glioblastoma.

The vascular delta-like ligand-4 (DLL4)-Notch4 signaling correlates with angiogenesis in primary glioblastoma: an immunohistochemical study.

Delta-like ligand-4 (DLL4)-Notch signaling is known to play a pivotal role in the regulation of tumor angiogenesis. We had previously found that DLL4 was overexpressed, while Notch1 receptor, which binds to DLL4 during angiogenesis, was absent in the majority of human primary glioblastomas. Thus, DLL4-Notch signaling pathway in the regulation of tumor angiogenesis in primary glioblastoma remains unknown. Tumor tissues from 70 patients with primary glioblastoma were analyzed by immunohistochemistry for expression of components of DLL4-Notch signaling, vascular endothelial growth factor (VEGF), and microvessel density (MVD). Immunohistochemistry results showed that the positive staining of DLL4 and Notch4 was primarily distributed in tumor vascular endothelial cells but rarely detected in tumor cells. However, VEGF, hairy/enhancer of split-1 (HES1; a target gene of Notch signaling), and Notch1-3 expression was seen in both tumor vascular endothelial cells and tumor cells. Univariate analysis showed that the expression levels of VEGF and DLL4, HES1, and Notch4 in tumor endothelial cells were significantly associated with MVD in primary glioblastoma (P < 0.001). Binary logistic regression analysis showed that high expression levels of DLL4, HES1, and Notch4 in tumor endothelial cells were associated with a decrease of MVD in primary glioblastoma, while MVD increased with elevated VEGF expression in contrast. In addition, DLL4, Notch4, and HES1 expression were positively correlated in tumor vascular endothelial cells (P < 0.05). We conclude that the vascular DLL4-Notch4 signaling and VEGF signaling complementing each other plays an important role in the progression of tumor angiogenesis in primary glioblastoma. Graphical abstract A, positive staining of DLL4 in human kidney; B, positive staining of VEGF in human breast cancer; C, positive staining of CD34 in human lung cancer; D, positive staining of HES1 in human breast cancer; E-H, positive staining of Notch1-4: E-F in human lung cancer; G-H in human kidney.

[Safety and effect of transurethral holmium laser enucleation of the prostate versus bipolar transurethral plasmakinetic prostatectomy for benign prostatic hyperplasia: A meta-analysis].

OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

[Tea polyphenols reduces the apoptosis of spermatogenic cells in rats with experimental varicocele].

OBJECTIVE: To study the effect of tea polyphenols (TP) on the apoptosis of germ cells in rats with experimental varicocele. METHODS: 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. RESULTS: 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). CONCLUSION: TP can reduce the apoptosis of spermatogenic cells in a dose-dependent manner in varicocele rats.

Peritumoral edema shown by MRI predicts poor clinical outcome in glioblastoma.

BACKGROUND: Magnetic resonance imaging (MRI) plays an irreplaceable role in the preoperative diagnosis of glioma, and its imaging features are the base of making treatment decisions in patients with glioma, but it is still controversial whether peritumoral edema shown by MRI from preoperative routine scans are associated with patient survival. The aim of this study was to assess the prognostic value of preoperative MRI features in patients with glioblastoma. METHODS: A retrospective review of 87 patients with newly diagnosed supratentorial glioblastoma was performed using medical records and MRI data from routine scans. The Kaplan-Meier method and COX proportional hazard model were applied to evaluate the prognostic impact on overall survival of pretreatment MRI features (including peritumoral edema, edema shape, necrosis, cyst, enhancement, tumor crosses midline, edema crosses midline, and tumor size). RESULTS: In addition to patient age, Karnofsky performance status (KPS) and postoperative chemoradiotherapy, peritumoral edema extent and necrosis on preoperative MRI were independent prognostic indicator for poor survival. Furthermore, patients with two unfavorable conditions (major edema and necrosis) had a shorter overall survival compared with the remainder. CONCLUSIONS: Our data confirm that peritumoral edema extent and necrosis are helpful for predicting poor clinical outcome in glioblastoma. These features were easy to determine from routine MRI scans postoperatively and therefore could provide a certain instructive significance for clinical activities.