Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract: a randomized clinical trial.

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

Differentiation of Meningiomas and Gliomas by Amide Proton Transfer Imaging: A Preliminary Study of Brain Tumour Infiltration.

Background: Gliomas are more malignant and invasive than meningiomas. Objective: To distinguish meningiomas from low-grade/high-grade gliomas (LGGs/HGGs) using amide proton transfer imaging (APT) combined with conventional magnetic resonance imaging (MRI) and to explore the application of APT in evaluating brain tumour invasiveness. Materials and Methods: The imaging data of 50 brain tumors confirmed by pathology in patients who underwent APT scanning in our centre were retrospectively analysed. Of these tumors, 25 were meningiomas, 10 were LGGs, and 15 were HGGs. The extent of the tumour-induced range was measured on APT images, T2-weighted imaging (T2WI), and MRI enhancement; additionally, and the degree of enhancement was graded. Ratios (RAPT/T2 and RAPT/E) were obtained by dividing the range of changes observed by APT by the range of changes observed via T2WI and MR enhancement, respectively, and APTmean values were measured. The Mann-Whitney U test was used to compare the above measured values with the pathological results obtained for gliomas and meningiomas, the Kruskal-Wallis test was used to compare LGGs, HGGs and meningiomas, and Dunn's test was used for pairwise comparisons. In addition, receiver operating characteristic (ROC) curves were drawn. Results: The Mann-Whitney U test showed that APTmean (p=0.005), RAPT/T2 (p<0.001), and RAPT/E (p<0.001) values were statistically significant in the identification of meningioma and glioma. The Kruskal-Wallis test showed that the parameters APTmean, RAPT/T2, RAPT/E and the degree of enhancement are statistically significant. Dunn's test revealed that RAPT/T2 (p=0.004) and RAPT/E (p=0.008) could be used for the identification of LGGs and meningiomas. APTmean (p<0.001), RAPT/T2 (p<0.001), and RAPT/E (p<0.001) could be used for the identification of HGGs and meningiomas. APTmean (p<0.001) was statistically significant in the comparison of LGGs and HGGs. ROC curves showed that RAPT/T2 (area under the curve (AUC)=0.947) and RAPT/E (AUC=0.919) could be used to distinguish gliomas from meningiomas. Conclusion: APT can be used for the differential diagnosis of meningioma and glioma, but APTmean values can only be used for the differential diagnosis of HGGs and meningiomas or HGGs and LGGs. Gliomas exhibit more obvious changes than meningiomas in APT images of brain tissue; this outcome may be caused by brain infiltration.

Establishment of the concurrent experimental model of osteoporosis combined with Alzheimer's disease in rat and the dual-effects of echinacoside and acteoside from Cistanche tubulosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche tubulosa is a precious traditional Chinese medicine that has been widely used in the treatment of osteoporosis and Alzheimer's disease. Echinacoside and acteoside are the main active constituents in Cistanche tubulosa that have the pharmacological activities with research value. It has been reported that echinacoside and acteoside could improve the learning and memory ability, promote the proliferation and differentiation of osteoblast. AIM OF STUDY: Echinacoside and acteoside from Cistanche tubulosa have shown significant activities of anti-osteoporosis and anti-Alzheimer's disease, while these effects have not been studied concurrently in a rat model. The aim of this study was to establish and verify the model of osteoporosis combined with Alzheimer's disease in rat, and to investigate the double effects of echinacoside and acteoside on this concurrent model. MATERIALS AND METHODS: Three model groups of ovariectomy (OVX), sham surgery with D-galactose and AlCl3 (D), ovariectomy with D-galactose and AlCl3 (OVX + D) were set at the same time. The rats in drug treatment groups were ovariectomized. While conducting the intraperitoneal injection of D-galactose and intragastric administration of AlCl3 in the rats of drug treatment groups, the rats were orally administered echinacoside (90 mg/kg/d), acteoside (90 mg/kg/d) and the positive control drugs of estradiol valerate (0.6 mg/kg/d), donepezil HCl (0.8 mg/kg/d), respectively. After the drug treatment of 8 weeks, Morris Water Maze (MWM) test for 6 days was firstly performed. The rats were then sacrificed to harvest the blood, uteri, femora, tibiae and brain tissues. The serum was used for biochemical tests. The uteri were used for histomorphometry. The right femora were used for Micro-CT and histomorphometry, respectively. The right tibiae were used for biomechanical test. The hippocampus collected on ice box was used for biochemical tests. The brain collected by perfusion was used for histomorphometry. RESULTS: Compared with Sham group, OVX + D group could significantly reduce the learning and memory ability by causing oxidative damage, impairing neurons in hippocampus and affecting the hydrolysis and synthesis of acetylcholine. Meanwhile, the activities of BALP and TRAP in OVX + D group increased significantly (P < 0.001) as compared to Sham group. In addition, compared with Sham group, the mean bone mineral density obviously decreased (P < 0.05), the trabecular bone mass and microarchitecture were also destroyed significantly in OVX + D group. Furthermore, the maximum load and maximum stress significantly reduced (P < 0.01) and the energy absorption also decreased greatly as compared to Sham group. After administrated with echinacoside and acteoside, the typical pathological features of osteoporosis and Alzheimer's disease were ameliorated. CONCLUSIONS: The model of osteoporosis combined with Alzheimer's disease in rat was feasible and successfully established. Echinacoside and acteoside also showed some significant effects on this concurrent model, and they could be potential candidates from Cistanche tubulosa with double effects for further study.

Anterior insular cortex mediates hyperalgesia induced by chronic pancreatitis in rats.

Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. This study was designed to examine the role of anterior insular cortex (aIC) in the pathogenesis of hyperalgesia in a rat model of CP. CP was induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). Abdomen hyperalgesia and anxiety were assessed by von Frey filament and open field tests, respectively. Two weeks after surgery, the activation of aIC was indicated by FOS immunohistochemical staining and electrophysiological recordings. Expressions of VGluT1, NMDAR subunit NR2B and AMPAR subunit GluR1 were analyzed by immunoblottings. The regulatory roles of aIC in hyperalgesia and pain-related anxiety were detected via pharmacological approach and chemogenetics in CP rats. Our results showed that TNBS treatment resulted in long-term hyperalgesia and anxiety-like behavior in rats. CP rats exhibited increased FOS expression and potentiated excitatory synaptic transmission within aIC. CP rats also showed up-regulated expression of VGluT1, and increased membrane trafficking and phosphorylation of NR2B and GluR1 within aIC. Blocking excitatory synaptic transmission significantly attenuated abdomen mechanical hyperalgesia. Specifically inhibiting the excitability of insular pyramidal cells reduced both abdomen hyperalgesia and pain-related anxiety. In conclusion, our findings emphasize a key role for aIC in hyperalgesia and anxiety of painful CP, providing a novel insight into cortical modulation of painful CP and shedding light on aIC as a potential target for neuromodulation interventions in the treatment of CP.

[Expression of G-protein coupled estrogen receptor in the testis of the male mouse with kidney yin or kidney yang deficiency and its impact on the reproductive function of the mouse].

OBJECTIVE: To investigate the expression of the G-protein coupled estrogen receptor (GPER) in the testis of the male mouse with kidney yin or kidney yang deficiency and its influence on the reproductive function of the mouse. METHODS: We randomized 30 six-week-old male Kunming mice into three groups of equal number: kidney yang deficiency, kidney yin deficiency, and normal control, and established the models of kidney yang deficiency and kidney yin deficiency by peritoneal injection of hydrocortisone at 50 mg/kg for 5 days and 25 mg/kg for 10 days, respectively. We observed the behavioral changes of the mice using the elevated plus-maze, exhaustive swimming and field experiment, examined the semen quality with the automatic sperm quality analyzer, calculated the average number of the offspring, measured the serum testosterone (T) and estradiol (E2) levels and T/E2 ratio by Roche electrochemiluminescence assay, and determined the localization and expression of GPER in the testis by immunohistochemistry and immunofluorescence staining. RESULTS: Compared with the mice with kidney yin deficiency, those with kidney yang deficiency showed remarkably fewer entries into the open arm and central area (P <0.05) and shorter time of exhaustive swimming (P <0.05), but no statistically significant difference in the time spent in the open arm or the central area (P >0.05); the latter group also exhibited significant decreases in the epididymal sperm count (ï¼»7.27 ± 1.30ï¼½ vs ï¼»3.05 ± 1.06ï¼½ ×108/g, P <0.01), sperm motility (ï¼»54.15 ± 13.52ï¼½ vs ï¼»51.57 ± 8.75ï¼½ %, P <0.01) and average number of the offspring (6.46 vs 4.33, P <0.05), a slight increase in the rate of morphologically abnormal sperm (ï¼»13.42 ± 2.32ï¼½ vs ï¼»15.39 ± 2.48ï¼½ %, P >0.05), and markedly reduced serum T (ï¼»24.96 ± 6.18ï¼½ vs ï¼»16.72 ± 5.92ï¼½ ng/dl,P <0.05), E2 (ï¼»19.81 ± 4.01ï¼½ vs ï¼»15.24 ± 1.11ï¼½ pg/ml,P <0.05) and T/E2 ratio (1.41 vs 1.25, P <0.05). The expression of GPER was found in the cytoplasm of the Leydig cells, negative in the nuclei and cell membrane, significantly higher in the kidney yang than in the kidney yin deficiency group (P <0.05). CONCLUSIONS: The numbers of sperm and offspring decreased while the percentage of morphologically abnormal sperm increased in both the kidney yang and kidney yin deficiency mice, even more significantly in the former, which might be associated with the up-regulated expression of GPER in the testis of the mouse with kidney yang deficiency and consequently the reduced serum T level and T/E2 ratio.

Antihypertensive drugs use and the risk of prostate cancer: a meta-analysis of 21 observational studies.

BACKGROUND: Due to the lack of strong evidence to identify the relationship between antihypertensive drugs use and the risk of prostate cancer, it was needed to do a systematic review to go into the subject. METHODS: We systematically searched PubMed, Web of Science and Embase to identify studies published, through May 2015. Two evaluators independently reviewed and selected articles involving the subject. We used the Newcastle-Ottawa Scale (NOS) to assess the quality of the studies. All extracted results to evaluate the relationship between antihypertensive drugs usage and prostate cancer risk were pool-analysed using Stata 12.0 software. RESULTS: A total of 12 cohort and 9 case-control studies were ultimately included in our review. Most of the studies were evaluated to be of high quality. There was no significant relationship between angiotensin converting enzyme inhibitors (ACEI) usage and the risk of prostate cancer (RR 1.07, 95% CI 0.96-1.20), according to the total pool-analysed. Use of angiotensin receptor blocker (ARB) was not associated with the risk of prostate cancer (RR 1.09, 95% CI 0.97-1.21), while use of CCB may well increase prostate cancer risk based on the total pool-analysed (RR 1.08, 95% CI 1-1.16). Moreover, subgroup analysis suggested that use of CCB clearly increased prostate cancer risk (RR 1.10, 95% CI 1.04-1.16) in terms of case-control studies. There was also no significant relationship between use of diuretic (RR 1.09, 95% CI 0.95-1.25) or antiadrenergic agents (RR 1.22, 95% CI 0.76-1.96) and prostate cancer risk. CONCLUSIONS: There is no significant relationship between the use of antihypertensive drugs (ACEI, ARB, beta-blockers and diuretics) and prostate cancer risk, but CCB may well increase prostate cancer risk, according to existing observational studies.

Aqueous proinflammatory cytokines in acute primary angle-closure eyes.

AIM: To evaluate changes of proinflammatory cytokines in aqueous humor of patients with acute primary angle-closure (APAC) and age-related cataracts. METHODS: Twenty eyes of 20 APAC patients and 15 eyes of 15 age-related cataract patients were included in this cross-sectional study. Aqueous humor samples were collected prospectively. The levels of 20 proinflammatory cytokines were evaluated in the aqueous humor of the APAC and cataract patients using the multiplex bead immunoassay technique. Clinical data were collected for correlation analysis. RESULTS: Seven of the 20 proinflammatory cytokines included in the magnetic bead panel were detectable in both APAC eyes and cataract eyes: interleukin (IL)-10, IL-12, IL-15, IL-21, IL-6, chemokine (C-C motif) ligand 20, and tumor necrosis factor alpha (TNF-α). IL-27 was only detectable in APAC eyes. Compared with the cataract eyes, the APAC eyes had significantly elevated concentrations of IL-12 (P=0.036), IL-15 (P=0.001), IL-6 (P=0.012), and IL-27 (only detectable in APAC eyes). Age was positively correlated with IL-12 (P=0.022) and IL-6 (P=0.037), and time elapsed between APAC onset and aqueous humor samples collection was positively correlated with IL-15 (P=0.037), IL-27 (P=0.040), and TNF-α (P=0.042). CONCLUSION: Several proinflammatory cytokines including IL-12, IL-15, IL-6 and IL-27, were elevated in the APAC eyes and may be implicated in its pathologic mechanism.

[Protective effect of Icariin against TGF-ß1-induced injury of rat Leydig cells].

OBJECTIVE: To study the effect of Icariin on rat Leydig cells with TGF-ß1-induced injury. METHODS: We determined the optimal concentration of Icariin for protecting primarily cultured Leydig cells against TGF-ß1-induced injury by methyl thiazolyl tetrazolium assay. We detected the effects of Icariin on the secretion of estradiol (E2) and activity of aromatase in the injured Leydig cells by radioimmunoassay and Tritium water release experiment and its effect on the gap junctional intercellular communication (GJIC) between the Leydig cells by fluorescence distribution after photobleaching. RESULTS: Different concentrations of Icariin showed different degrees of protective effect on the TGF-ß1-treated Leydig cells, the effect observed at 20 µg/ml and at its optimum at 160 µg/ml. After treatment of the injured Leydig cells with Icariin at 160 µg/ml, significant improvement was observed in the E2 secretion and aromatase activity (P<0.01) as well as in the GJIC between the Leydig cells (P<0.01). CONCLUSIONS: Icariin can effectively protect rat Leydig cells against TGF-ß1-induced injury, which is largely attributed to its effects of increasing E2 synthesis, enhancing aromatase activity, and improving GJIC between Leydig cells.

Characterization of transferrin receptor-dependent GaC-Tf-FeN transport in human leukemic HL60 cells.

BACKGROUND: Understanding the uptake of GaC-Tf-FeN by cells will provide key insights into studies on transferrin-mediated drug delivery. METHODS: The mechanism of GaC-Tf-FeN transporting into and out of HL60 cells has been investigated by comparing transports between GaC-Tf-FeN and apoTf by means of 125I-labeled transferrin. RESULTS: An association constant for GaC-Tf-FeN was 2 times that for apoTf. GaC-Tf-FeN and apoTf of cell surface-bound displayed similar kinetics during the uptake, but the release rates of internalized GaC-Tf-FeN and apoTf from cells were different which showed characteristic disparate. The release continued to occur during the incubation of GaC-Tf-FeN in the presence of nonradioactive apoTf. Neither NaN3 nor NH4Cl could completely block internalization of GaC-Tf-FeN, but they prevented the release of GaC-Tf-FeN from the cells. Excess cold unlabeled apoTf could overcome the block in the release due to NH4Cl but not NaN3. The binding and internalization of GaC-Tf-FeN could be competitively inhibited by nonradioactive apoTf. It implies that both bind to the same receptor on the membrane and the localization of GaC-Tf-FeN resembles that of apoTf inside cells. Pretreated cells with pronase abolished the binding of GaC-Tf-FeN significantly. CONCLUSION: On the basis of these findings, we proposed the "transferrin receptor" for the mechanism of GaC-Tf-FeN transport by HL60 cells.

Relationship between cholecystolithiasis and polypoid gallbladder.

OBJECTIVE: To study the relationship between cholecystolithiasis and polypoid gallbladder (PLG), 260 patients with polypoid gallbladder were investigated. The patients were divided into 2 groups: group A (PLG combined with cholecystolithiasis) and group B (without cholecystolithiasis). The clinical pathological characteristics were analyzed. The intestinal epithelium metaplasia and atypical hyperplasia of the gallbladder mucosa were observed under light microscope. RESULTS: Intestinal epithelium metaplasia and atypical hyperplasia of gallbladder mucosa were found in 47 of the 260 cases. The pathological lesions included 16 gallbladder carcinoma, 11 adenomatosis polyp, 5 myoadenoma, 7 cholesterol polyp, 4 inflammatory polyp and 4 adenomatosis hyperplasia, which occurred in 26 and 21 patients in group A and group B, i.e. 44.0% and 10.3% respectively. The difference between group A and group B was statistically significant (P<0.01). CONCLUSION: Cholecystolithiasis and the succeeding inflammatory reaction is a risk-factor for the polypoid gallbladder to develop tumour.