Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway / 中国中药杂志

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1β, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(β-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1β, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and β-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1β, IL-6, CGRP, and NO in rat serum, increased VEGF and β-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and β-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1β. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing β-EP levels.

Clinical application of free/total PSA ratio in the diagnosis of prostate cancer in men over 50 years of age with total PSA levels of 2.0-25.0 ng ml-1 in Western China / 亚洲男科学杂志(英文版)

The goal of this study was to investigate the clinical application of free/total prostate-specific antigen (F/T PSA) ratio, considering the new broad serum total PSA (T-PSA) "gray zone" of 2.0-25.0 ng ml-1 in differential diagnosis of prostate cancer (PCa) and benign prostate diseases (BPD) in men over 50 years in Western China. A total of 1655 patients were included, 528 with PCa and 1127 with BPD. Serum T-PSA, free PSA (F-PSA), and F/T PSA ratio were analyzed. Receiver operating characteristic curves were used to assess the efficiency of PSA and F/T PSA ratio. There were 47.4% of cancer patients with T-PSA of 2.0-25.0 ng ml-1. When T-PSA was 2.0-4.0 ng ml-1, 4.0-10.0 ng ml-1, and 10.0-25.0 ng ml-1, the area under the curve (AUC) of F/T PSA ratio was 0.749, 0.769, and 0.761, respectively. The best AUC of F/T PSA ratio was 0.811 when T-PSA was 2.0-25.0 ng ml-1, with a specificity of 0.732, a sensitivity of 0.788, and an optimal cutoff value of 15.5%. The AUC of F/T PSA ratio in different age groups (50-59 years, 60-69 years, 70-79 years, and ≥80 years) was 0.767, 0.806, 0.815, and 0.833, respectively, and the best sensitivity (0.857) and specificity (0.802) were observed in patients over 80 years. The T-PSA trend was in accordance with the Gleason score, tumor node metastasis (TNM) stage, and American Joint Committee on Cancer prognosis group. Therefore, the F/T PSA ratio can facilitate the differential diagnosis of PCa and BPD in the broad T-PSA "gray zone". Serum T-PSA can be a Gleason score and prognostic indicator.

Psychological burden prediction based on demographic variables among infertile men with sexual dysfunction / 亚洲男科学杂志(英文版)

There has been increasing interest in the psycho-socio-relational and sexual disorders of infertility, as the risk of psychological burden among infertile men with sexual dysfunctions is significant. The purpose of this study was to develop and to validate a predictive model to estimate individual psychological burden among infertile men with sexual dysfunction and study the association between them. Comprehensive data were collected for infertile men (n = 480) who sought treatment for infertility in a reproductive medicine center between June 2012 and December 2013. Using independent predictors of psychological burden from the least absolute shrinkage and selection operator, univariable and multivariable analyses were developed into two models. Predictive accuracy was compared between the models. We explored the association between sexual dysfunction and psychological burden. A total of 480 patients were analyzed using 10-fold cross-validation. Independent predictors of psychological burden were incorporated into a model to measure anxiety (corrected-area under curve (AUC): 77.3%) and a model to measure depression (corrected-AUC: 70.2%). Anxiety and depression were both associated with erectile dysfunction (P < 0.05), with anxiety demonstrating the strongest association. Only anxiety was associated with premature ejaculation (P < 0.05). Premature ejaculation was not found to be associated with depression (P > 0.05). Predictive models for psychological burden among infertile men with sexual dysfunction are presented, and we found that there is an association between psychological burden and sexual dysfunction. According to the models, proper counseling and treatment of sexual dysfunction in infertile men may reduce the psychological burden, help attain natural pregnancy, and improve the quality of life.

Assessment of the Perioperative Risk of Different Operation Times on Renal Angiomyolipoma Patients with Rupture and Hemorrhage / 中山大学学报(医学科学版)

[Objective] To investigate the perioperative risk of different operation times on renal angiomyolipoma (AML) patients with rupture and hemorrhage.[Methods] From January 2006 to December 2016,AML patients with rupture and hemorrhage who receiving surgical treatment were recruited.According to the operation time,patients receiving surgery within 7 days after the hemorrhage were classified as short-term operation group.Patients receiving surgery exceeded 30 days after the hemorrhage were classified as long-term operation group.The general and perioperative data were compared between the two groups.[Results] There were no statistically significant differences in age,tumor size,clinical symptoms and operative methods between the two groups.However,as compared to the long-term operation group,the hemorrhage during surgery [(780±451) vs.(572±913) mL,P=0.029],the volume of transfused blood [(2600 ± 1733) vs.(820±582) mL,P=0.027],the nephrectomy rate (60.0％ vs.22.6％,P=0.027) were significantly increased in the short-term operation group.[Conclusions] A long-term operation group for AML patients with rupture and hemorrhage could have a lower perioperative risk.

Application value of procalcitonin and immune inflammatory factors for prediction of bacteraemia in patients with hematologic malignancy combined with febrile neutropenia / 中国实验血液学杂志

This study was purposed to evaluate the diagnostic value of procalcitonin (PCT), C-reactive protein, interleukin-6 (IL-6), serum amyloid A (SAA) for bacteremia in patients with hematologic malignancy combined with febrile neutropenia. The total of 297 patients with hematologic malignancy combined with febrile neutropenia were analyzed retrospectively from 1253 patients admitted to West China hospital of Sichuan University from March 2011 to October 2012. They were divided into sepsis group (n = 95) and non-sepsis group (n = 202) according to blood culture. The results showed that the levels of PCT, CRP, IL-6 and SAA in sepsis group were higher than those in non-sepsis group, and there was statistically significant difference between these two groups (P < 0.05). The PCT had an AUC value of 0.974 (P < 0.05), and obviously higher than that of CRP (AUC = 0.681, P < 0.05), IL-6 (AUC = 0.661, P < 0.05) and SAA (AUC = 0.605, P < 0.05). When PCT had cut-off value of 1.06 ng/ml, sensitivity of 95.8%, specificity of 92.1%, and the Youden indicator of 0.879, the negative and positive predictive values were 97.8% and 85.0% respectively, the negative and positive likelihood ratios were 0.05 and 12.5 respectively, and all significantly higher than that of CRP, IL-6 and SAA. It is concluded that for patients with hematologic malignancy combined with febrile neutropenia and bacterial infection, the diagnostic value of serum PCT is superior to that of immune inflammatory factors (CRP, IL-6 and SAA), the PCT can predict the bacterium infection, provide laboratory evidence for rational antimicrobial drug usage and mortality reduction.

Role of PI3K/Akt signaling in the protective effect of magnesium sulfate against ischemia-perfusion injury of small intestine in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The protective effects of magnesium sulfate against ischemia-reperfusion injury of the small intestine in Sprague-Dawley (SD) rats have been confirmed in our previous research. However, its exact mechanism is unclear. This study was to evaluate the role of PI3K/Akt signal pathway in the protective effect of magnesium sulfate against ischemia-reperfusion injury of the small intestine in SD rats.</p><p><b>METHODS</b>Rat model of intestinal ischemia-reperfusion injury was used. The SD rats were divided into four groups randomly: sham operation group, ischemia-reperfusion group, magnesium sulfate group and magnesium sulfate plus LY294002 (an inhibitor of PI3K) group. The pathological changes of intestinal mucosa were examined; the activity of diamine oxidase (DAO) in plasma, the plasma contents of malondialdehyde (MDA), and apoptosis rate of the intestinal mucosal cells were determined and compared. The expression of p-Akt was detected by Western blotting.</p><p><b>RESULTS</b>There were more evident pathological changes of the intestinal mucosa (higher Chiu's score, P < 0.05), enhanced DAO activity (P < 0.05), elevated contents of MDA (P < 0.05), higher apoptosis rate (P < 0.05), and lower level of p-Akt (P < 0.05) in the ischemia-reperfusion group compared with the sham operation group. There were less evident pathological changes of the intestinal mucosa (lower Chiu's score, P < 0.05), lower DAO activity (P < 0.05), lower contents of MDA (P < 0.05), and lower apoptosis rate (P < 0.05), but higher level of p-Akt (P < 0.05) in the magnesium sulfate group compared with the ischemia-reperfusion group. There were more evident pathological changes of the intestinal mucosa (higher Chiu's score, P < 0.05), higher contents of MDA (P < 0.05), higher DAO activity (P < 0.05) and higher apoptosis rate (P < 0.05), and lower level of p-Akt (P < 0.05) in the magnesium sulfate plus LY294002 group compared with the magnesium sulfate group.</p><p><b>CONCLUSIONS</b>Activation of PI3K/Akt signal pathway results in the reduction of cell apoptosis, which likely accounts for the protective effect of magnesium sulfate against intestinal ischemia-reperfusion injury.</p>

Comparison of the action of isolichenin and methanol extract of saffron on long-term potentiation in hippocampal dentate gyrus in vivo / 药学学报

Long-term potentiation (LTP) is thought as a generative mechanism underlying learning and memory via storing information in central nervous system. Electro-neurophysiological assay for LTP is generally used in screening the drugs that can facilitate learning and memory. By using in vivo LTP technique, isolichenin was found to facilitate LTP induction by a tetanic stimulation (20 pulses/100 Hz) in dentate gyrus. This tetanic stimulation by itself, however, cannot induce LTP. Previous study showed the reagent being able to facilitate LTP-induction, like methanol extract of saffron (MES), usually can antagonize the inhibiting effect of 30% ethanol on LTP induction (30 pulses/60 Hz). Isolichenin may also fall into such kind of drugs. Interestingly, comparatively study showed that isolichenin failed to antagonize the inhibiting effect of 30% ethanol on LTP induction (30 pulses/60 Hz). This result indicates a different unknown mechanism existing in the effect of isolichenin on LTP or memory formation.