Impact of shift work on dementia: a systematic review and dose-response meta-analysis.

OBJECTIVES: Although shift work has been reported as having a link to dementia, evidence remains inconsistent, and a comprehensive dose-response meta-analysis of the association is still lacking. We therefore conducted this meta-analysis to explore the association between shift work and the risk of dementia. STUDY DESIGN: Systematic review and dose-response meta-analysis. METHODS: PubMed, Embase, and Web of Science databases were systematically searched. Fixed or random-effects models were used to estimate the summary relative risks (RRs) and 95% confidence intervals (95% CIs). Generalized least squares regression was used to estimate dose-response associations, and restricted cubic splines were used to examine possible linear or non-linear associations. RESULTS: Five articles (10 studies) with 72,999 participants and 23,067 cases were eventually included in the meta-analysis. The summary RRs and 95% CIs of dementia risk with shift work and night shift work versus daytime work were 1.13 (95% CI: 1.05-1.21, I2 = 46.70%) and 1.13 (95% CI: 1.03-1.24, I2 = 9.20%), respectively. The risk of dementia increased by 1% (RR = 1.01, 95% CI: 1.01-1.02, I2 = 41.3%) with each 1-year increase in the duration of shift work. We found a non-linear dose-response association between the duration of shift work and the risk of dementia (Pnon-linearity = 0.006). Though the shape of the curve was steeper with the duration of shift work <7 years, the increase was more gradual after 7 years. CONCLUSION: Our findings suggest that shift work may be a risk factor for future dementia and that controlling the length of shift work is a feasible measure that may contribute to prevent dementia.

[Effects of 4'-O-methylochnaflavone on endothelial dysfunction induced by palmitic acid in rat cavernous endothelial cells].

OBJECTIVE: To investigate the effect of biflavonoid 4'-O-methylochnaflavone (MF) on palmitic acid-induced endothelial dysfunction in rat cavernous endothelial cells (RCECs). METHODS: The isolated RCECs were commercially available and randomly divided into four groups: normal+BSA group (NC group), palmitic acid (PA) group, MF group, and icariside Ⅱ (ICA Ⅱ) group. The protein expression levels of protein kinase B (PKB/AKT) and endothelial nitric oxide synthase (eNOS) in each group were evaluated via Western blotting. The differences in the intracellular nitric oxide of RCECs treated by MF or ICA Ⅱ were detected by DAF-FM DA that served as a nitric oxide fluorescent probe. Effects of MF and ICA Ⅱ on cell proliferation of PA-stimulated RCECs were determined via CCK-8 assay. RESULTS: The content of nitric oxide in RCECs was significantly increased after the treatment of MF and ICA Ⅱ in comparison with the NC group (P < 0.05). Moreover, compared with ICA Ⅱ group, MF demonstrated a more obvious effect in promoting nitric oxide production (P < 0.05). Compared with the NC group, the expression levels of eNOS and AKT in the PA group were significantly decreased, indicating that a model for simulating the high-fat environment in vitro was successfully constructed (P < 0.05). Meanwhile, the intervention of MF and ICA Ⅱ could effectively increase the expression of eNOS and AKT, suggesting that MF and ICA Ⅱ could promote the recovery of endothelial dysfunction caused by high levels of free fatty acids (P < 0.05). The results of CCK-8 assays showed that PA could significantly reduce the proli-feration ability of RCECs (P < 0.05). Furthermore, the decreased cell viability induced by PA was significantly elevated by treatment with ICA Ⅱ and MF (P < 0.05). CONCLUSION: In RCECs, MF and ICA Ⅱ could effectively increase the content of nitric oxide. The down-regulation of the expression of proteins associated with the AKT/eNOS pathway after PA treatment revealed that this pathway was involved in the development of endothelial dysfunction, which could be effectively reversed by MF and ICA Ⅱ. In addition, the cell proliferation ability was significantly decreased following PA treatment, but MF and ICA Ⅱ could restore the above changes. Overall, biflavonoid MF has an obvious repairing effect on PA-stimulated endothelial dysfunction.

Study for the binding affinity of thyroid hormone receptors based on machine learning algorithm.

Long-term exposure of exogenous compounds to thyroid hormone receptors (TRs) may lead to thyroid dysfunction. Quantitative structure-activity relationship (QSAR) is expected to predicting the binding affinity of compounds to TR. In this work, two comprehensive and large datasets for TRα and TRß were collected and investigated. Five machine learning models were established to predict the pIC50 of compounds. Meanwhile, the reliability of the models was ensured by a variety of evaluation parameters. The results showed that the support vector regression model exhibited the best robustness and external prediction ability (r2train = 0.77, r2test = 0.78 for TRα, r2train = 0.78, r2test = 0.80 for TRß). We have proposed an appropriate mechanism for explaining the TR binding affinity of a compound. The molecular volume, mass, and aromaticity affected the activity of TRα. Molecular weight, electrical properties and molecular hydrophilicity played a significant role in the binding affinity of compounds to TRß. We also characterized the application domain of the model. Finally, the obtained models were utilized to predict the TR binding affinities of 109 compounds from the list of endocrine disruptors. Therefore, this model is expected to be an effective tool for alerting the effects of exogenous compounds on the thyroid system.

[Effect of China Children's Asthma Action Plan on exercise in school-age children with bronchial asthma].

Objective: To investigate the effect of China Children's Asthma Action Plan (CCAAP) on the exercise status of school-age children with asthma. Methods: We included 400 school-age asthmatic children as research objects from CCAAP asthma management platform of the Affiliated Hospital of Qingdao University during March 1, 2018 to February 28, 2021 by simple random sampling method. The questionnaires of basic information and international physical activity were applied through WeChat or face to face investigation to collect the basic information and exercise status of the object. There were 346 valid questionnaires included in the study to compare the differences in exercise status and incidence of exercise-related asthma-like symptoms between the good and poor CCAAP application groups. Results: There were 232 (67.05%) and 114 (32.95%) cases in good and poor CCAAP application group, respectively. Age, female proportion and BMI of good CCAAP application group were (8±2) years, 47.0% (109/232) and (19.79±2.32) kg/m2, respectively, no statistic difference comparing to poor CCAAP application group [(8±2) years, 46.5% (53/114) and (19.87±2.43) kg/m2, respectively] (all P values>0.05). In good CCAAP application group, 30.18% (70/232) achieved the standard of moderate (high) intensity exercise per day, no statistic difference comparing to poor CCAAP application group [29.82% (34/112)] (P=0.947); 31.90% (74/232) participated in high-intensity exercise per week, higher than that of poor CCAAP application group [17.54% (20/112)] (P=0.005); incidence of exercise-related asthma-like symptoms was 19.83% (46/232), lower than that of poor CCAAP application group [29.82% (34/112)] (P=0.038). Conclusion: CCAAP promotes the exercise of school-age children with asthma.

[Evaluation of the efficacy of Chinese Children's Asthma Action Plan on the long-term management of children with asthma at home].

Objective: During the COVID-19 pandemic, the electronic "questionnaire star" was employed to investigate the general situation, medication situation and pandemic impact of children diagnosed with asthma in our hospital and enrolled in the electronic platform of the Chinese Children's Asthma Action Plan (CCAAP). The internet technology and big data were used to grasp the trend and asthma control of children who had been at home for a long time due to the pandemic, so as to facilitate the management. Methods: By random cluster sampling survey method, according to the needs and medication adherence score, the electronic "questionnaire star" was designed to conduct a survey among children (0 to 14 years old) who diagnosed with asthma and joined the CCAAP on the basis of bronchial asthma medication adherence scale. Finally, the results of electronic questionnaire survey were analyzed. Results: A total of 423 questionnaires were sent out, 422 of which were valid, with an effective response rate of 99.7%. The results of questionnaire survey showed that 296 cases were male, accounting for 70.1%, and 126 cases were female, accounting for 29.9%, with an average age of (5.4±2.6) years old. The average age of males and females was (5.3±2.6) and (5.4±2.6) years old, respectively. There were more children aged ≥5 years than children who were younger than 5 years. Additionally, 13.95% of the parents thought that the pandemic had more than moderate impact on children with asthma, and 76.12% of the children were in the green zone and had no asthma attack. The proportion of green zone inhaled drugs (79.8%) was higher than yellow zone and red zone (49.8%). After using the CCAAP platform, the dissatisfaction rate was only 1.42%. Moreover, 71.87% of the children's medical expenses decreased, and the proportion of frequent use and intermittent use of antibiotics reduced, however, the proportion of occasional use and never use of antibiotics increased significantly (all P<0.05). The average score of drug compliance was 4.56, and the more frequently the platform was used, the higher the score of medication compliance was (P<0.05). Conclusions: After using CCAAP management with the aid of internet technology, children with asthma who had been isolated at home for a long time were less affected by COVID-19, with high medication compliance, generally lower medical expenses, significantly reduced use of antibiotics, and high satisfaction. This management mode provides a new idea for internet medicine.

Using artificial intelligence algorithms to identify existing knowledge within the back pain literature.

PURPOSE: Artificial intelligence algorithms can now identify hidden data patterns within the scientific literature. In 2019, these algorithms identified a thermoelectric material within the pre-2009 chemistry literature; years before its discovery in 2012. This approach inspired us to apply this algorithm to the back pain literature as the cause of back pain remains unknown in 90% of cases. METHODS: We created a subset of all PubMed abstracts containing "back" and "pain" and then trained the Word2vec algorithm to predict word proximity. We then identified word pairings having high vector proximities between three spinal domains: anatomy, pathology and treatment. We plotted both between-domain and within-domain proximities then used the highest proximity pairs as ground truths in analogy testing to identify known associations (e.g., Canal is to Stenosis as Multifidus is to ?) RESULTS: We found  50,038 abstracts resulting in 27,984 unique words and 108,252 instances of "back pain". Ground truth pairings ranged in proximity from 0.86 to 0.70. Plotting revealed unique proximity representations between the three spine domains. From analogy testing, we identified 13 known word associations (pars_interarticularis is to stress_reaction as nerve_root is to compression). CONCLUSIONS: Artificial intelligence algorithms can successfully extract complex concepts from back pain literature. While use of AI algorithms to discover potentially unknown word associations requires future validation, our results provide investigators with a novel tool to generate new hypotheses regarding the origins of LBP and other spine related topics. To encourage use of these tools, we have created a free web-based app for investigator-driven queries.

Chitinase-like protein YKL-40 regulates human bronchial epithelial cells proliferation, apoptosis, and migration through TGF-ß1/Smads pathway.

In order to study the effects of chitinase-like protein YKL-40 on proliferation, apoptosis, and migration of human bronchial epithelial cell line (BEAS-2B), and the underlying mechanisms, we cultured BEAS-2B alone or with different concentrations of YKL-40. thiazolyl blue tetrazolium bromide (MTT) assay was used to examine the cell proliferation. Annexin V-fluorescein isothiocyanate isomer (FITC)/propidium iodide staining and scratch assay were performed to test the cell apoptosis and migration. The concentrations of transforming growth factor-ß1 (TGF-ß1), Smad3, Smad7, alpha-smooth muscle actin (α-SMA), interleukin-4 (IL-4), IL-6, and IL-8 in the cell culture supernatant were detected by enzyme-linked immunosorbent assay. The messenger RNA and protein levels of YKL-40, TGF-ß1, Smad3, Smad7, and α-SMA were detected by reverse transcription polymerase chain reaction and Western blot. BEAS-2B cells cultured with different concentrations of YKL-40 showed significantly higher cell proliferation and migration and inflammatory cytokines compared with that of control group, while the cell apoptosis was significantly lower than that of control group (p < 0.05). In addition, BEAS-2B cells cultured with YKL-40 had increased TGF-ß1, Smad3, Smad7, and α-SMA levels in the supernatant, compared with that of BEAS-2B cells cultured alone (p < 0.05). Furthermore, LY364947, as TGF-ß1/Smads signaling pathway inhibitor, decreased cell proliferation and migration ability and enhanced cell apoptosis of BEAS-2B cells compared with control group (p < 0.05). However, YKL-40 administration reversed the effect of LY364947 on the biological behavior of BEAS-2B cells. YKL-40 could affect the biological behaviors of BEAS-2B cells, which might be related to the TGF-ß1/Smads pathway.

[Influence of five-in-one management mode on disease prevention and control of school children with asthma].

Objective: To investigate the influence of five-in-one management mode(standardized asthma treatment, asthma diary, peak expiratory flow (PEF) monitoring, reasonable diet and physical exercise) on disease prevention and control of school children with asthma. Methods: From April to October 2018, 70 children with asthma in clinical remission were selected from Affiliated Hospital of Qingdao University using randomized controlled study design. These children were randomly divided into study group and control group, with 35 cases in each group. In the study group, 5 cases were lost to follow-up, and 30 cases were actually enrolled. In the control group, 6 cases were lost to follow-up, and 29 cases were actually enrolled. Children in the control group received routine medication and regular outpatient consultation, and children in the study group received the five-in-one asthma management model. In the first time of seeing a doctor, after 3 months and 6 months of follow-up, asthma control test score, medication compliance index score and lung function index (forced expiratory volume in 1 second (FEV1), PEF were evaluated respectively.Parental satisfaction, asthma acute episodes, weight, height and biochemical index were recorded during the 6 months of follow-up. Pulmonary function index, asthma control score and body mass index of overweight children with asthma were compared with t-test, medication compliance was compared with chi-square test, and the rank sum test was used for the comparison of the number of emergency visits of asthma attacks and parents' satisfaction. Results: A total of 59 children with asthma were included, among them 30 were in the study group (8.1±1.5) years old and 29 in the control group (9.2±1.1) years old. After 3 months of follow-up, FEV1, PEF, asthma control score in the study group were (86.3±1.5)%, (83.3±2.4)%, (24.7±2.6) points respectively; and in the control group, FEV1, PEF, asthma control score were (84.4±2.5)%, (82.2±1.9)%, (21.1±1.3) points respectively. The indicators in the study group were higher than those in the control group (t=3.62, 1.97, 6.64, P<0.05). After 6 months of follow-up, FEV1, PEF, asthma control score in the study group were (88.4±2.3)%, (85.4±2.2)%, (26.8±1.8) points respectively; and in the control group, FEV1, PEF, asthma control score were (85.5±1.9)%, (83.2±1.7)%, (22.5±1.4) points respectively. The indicators in the study group were significantly higher than those in the control group (t=5.34, 4.24, 10.41, P<0.05). During the 6-month follow up, the number of emergency visits of asthma attacks in the study group and in the control group were 0.42(0.36, 0.51) and 0.92(0.72, 1.27) respectively. The indicator in the study group was significantly lower than that in the control group (Z=3.21, P<0.05). After 3 months of follow-up, the proportions of children with good compliance in the study group and control group were 67% (20/30) and 62% (18/29), the proportions of poor compliance were 27% (8/30) and 34% (10/29), the proportions of non-compliance were 7% (2/30) and 7% (2/29). There were no statistically significant differences (χ(2)=0.14, 0.43, 0.00, P=0.71, 0.51, 0.97). After 6 months of follow-up, the proportions of children with good compliance in the study group and control group were 87% (26/30) and 69% (20/29), the proportion of poor compliance were 10% (3/30) and 28% (8/29), the proportion of non-compliance were 3% (1/30) and 7% (2/29), There were no statistically significant differences (χ(2)=2.70, 3.00, 0.39, P=0.10, 0.08, 0.53). After 6 months of follow-up, the number of great satisfaction, satisfaction and dissatisfaction in the study group were 20, 10 and 0 respectively, the satisfaction rate was 100%, meanwhile those indicators in the control group were 4, 15 and 10 respectively, the satisfaction rate was 66%, The indicator in the study group was significantly higher than that in the control group (Z=4.60, P<0.05). Conclusions: The application of "five-in-one" asthma management model (standardized asthma treatment, asthma diary, PEF monitoring, reasonable diet and physical exercise) for school-age children with asthma can significantly improve lung function, as well as reduce the number of acute asthma attacks. It has a high parent satisfaction, therefore it should be recommended for clinical implementation.

Therapeutic effect of ginsenoside Rg1 on mastitis experimentally induced by lipopolysaccharide in lactating goats.

Escherichia coli is a cause of subclinical and clinical mastitis in dairy cattle and goats, and sometimes causes severe clinical disease that may result in death of the animal. Previous investigation showed that ginsenoside Rg1 extracted from Panax ginseng C.A. Meyer (Araliaceae) has an anti-inflammatory effect on the sepsis induced by E. coli lipopolysaccharide via competitive binding to toll-like receptor 4. We hypothesized that intravenous injection of Rg1 had therapeutic effect on mastitis experimentally induced by intramammary infusion of lipopolysaccharide in lactating goats. In this study, 9 lactating goats were randomly assigned to 1 of the 3 groups: (1) lipopolysaccharide intramammary infusion + saline intravenous injection, (2) lipopolysaccharide intramammary infusion + Rg1 intravenous injection, and (3) saline intramammary administration + saline intravenous injection. Because no adverse clinical signs were observed after intramammary infusion of saline and intravenous injection of Rg1 in a preliminary experiment, and available qualified goats were limited in this study, this treatment was not included in this study. One udder half of each goat received intramammary infusion of lipopolysaccharide (50 µg/kg of body weight; groups 1 and 2) or saline solution (group 3), and the other half was infused with 2 mL of saline solution at h 0. Afterward, intravenous injections of saline solution (groups 1 and 3) or Rg1 (2.5 mg/kg of body weight; group 2) were administered at h 2 and 4 post-lipopolysaccharide challenge. Blood and milk samples were collected 3, 6, 9, 12, 15, 18, 21, 24, 48, and 72 h post-lipopolysaccharide challenge, and clinical signs were monitored hourly after lipopolysaccharide challenge within the first 10 h and at the same time points as blood samples. The results showed that Rg1 treatment downregulated rectal temperature, udder skin temperature, udder girth, milk somatic cell count, and N-acetyl-ß-d-glucosaminidase and upregulated milk production, lactose, and recovered blood components, such as white blood cells, neutrophils, lymphocytes, total proteins, albumin, and globulin. Considering the positive therapeutic effect on lipopolysaccharide-induced mastitis in goats presented in this study as well as the anti-inflammatory activity found previously, the botanical Rg1 deserves further study as a therapeutic agent in the treatment of E. coli mastitis in dairy animals.

Identification of critical microRNAs in gastrointestinal stromal tumor patients treated with Imatinib.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Imatinib mesylate was considered to be a breakthrough drug in clinical treatment of GIST, but GIST patients showed resistance against it. We aimed to identify critical microRNAs (miRNAs) related to imatinib resistance in imatinib-treated GIST patients. Microarray datasets under the accession number of GSE63159 and GSE45901 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed miRNAs (DEMs) that are related to imatinib resistance were identified. GO function and KEGG pathway enrichment analyses were performed, and lncRNA-miRNA-target gene regulatory networks were constructed. Finally, the critical miRNAs and their target genes that are related to imatinib resistance or sensitivity were identified. In total, 20 DEMs in the GSE63159 dataset (7 significantly up-regulated and 13 down-regulated) and 23 DEMs in the GSE45901 dataset (8 up-regulated and 15 down-regulated) were identified. In lncRNA-miRNA-target gene regulatory networks, five critical miRNAs and 109 target genes were identified. GO function and KEGG pathway enrichment analysis showed that the target genes of DEMs were mainly involved in several signaling pathways, such as focal adhesion and the GnRH signaling pathway. Among the five miRNAs, the overexpression of hsa-miR-28-5p and hsa-miR-125a-5p had significant correlation to imatinib resistance or imatinib sensitivity in GIST patients. Hsa-miR-28-5p and hsa-miR-125a-5p may be involved in the development and progression of GIST, and they may be able to serve as prognostic markers for imatinib-response in GIST patients.

Exosomes derived from mesenchymal stem cells exert therapeutic effect in a rat model of cavernous nerves injury.

Postradical prostatectomy erectile dysfunction (pRP-ED) is a major health issue. There has been a shortage of an effective treatment method until now. In this study, a total of 48 adult male Sprague-Dawley (SD) rats were randomly equally divided into four groups, including group 1-sham surgery with cavernous nerve exposure plus vehicle, group 2-bilateral cavernous nerve injury (BCNI) plus vehicle, group 3-BCNI plus adipose-derived mesenchymal stem cells (ADSCs)-derived exosomes (ADSC-Exo), and group 4-BCNI plus bone marrow-derived mesenchymal stem cell (BMSCs)-derived exosomes (BMSC-Exo). Twenty-one days following surgery, erectile function was measured before tissue harvest. Histologic and Western blot analyses were then performed. Exosomes were capable of internalization into human umbilical vein endothelial cells (HUVEC) in vitro and could be detected in the corpus cavernosum in vivo. The nNOS expression in the penile dorsal nerves (DN) and major pelvic ganglion (MPG), protein level of neurofilament in the DN, endothelial markers vWF, alpha smooth muscle actin (α-SMA), the ratio of smooth muscle to collagen content were obviously lower in BCNI group compared with the sham group, while ADSC-Exo and BMSC-Exo groups resulted in significant restoration of the above histopathological changes. Moreover, BCNI treated with ADSC-Exo or BMSC-Exo had significantly higher mean intracavernous pressure/mean arterial pressure ratio compared with BCNI group. The results demonstrated that both ADSC-Exo and BMSC-Exo treatment could significantly alleviate pathological changes and improve the erectile function in BCNI-related rats. Exosomes derived from ADSCs and BMSCs may be a potential agent for pRP-ED treatment.

A Knowledge Base Completion Model Based on Path Feature Learning.

Large-scale knowledge bases, as the foundations for promoting the development of artificial intelligence, have attracted increasing attention in recent years. These knowledge bases contain billions of facts in triple format; yet, they suffer from sparse relations between entities. Researchers proposed the path ranking algorithm (PRA) to solve this fatal problem. To improve the scalability of knowledge inference, PRA exploits random walks to find Horn clauses with chain structures to predict new relations given existing facts. This method can be regarded as a statistical classification issue for statistical relational learning (SRL). However, large-scale knowledge base completion demands superior accuracy and scalability. In this paper, we propose the path feature learning model (PFLM) to achieve this urgent task. More precisely, we define a two-stage model: the first stage aims to learn path features from the existing knowledge base and extra parsed corpus; the second stage uses these path features to predict new relations. The experimental results demonstrate that the PFLM can learn meaningful features and can achieve significant and consistent improvements compared with previous work.

[Modulation of umbilical cord blood mesenchymal stem cells on Treg cells in the patients with aplastic anemia].

Objective: To research the modulation of Umbilical cord blood mesenchymal stem cells on the number and function of Treg cells in the patients with aplastic anemia, as well as the expression of LFA-1 on Treg cells. Methods: A total of 20 newly diagnosed NSAA patients were collected from May 2015 to Jun 2016 in Department of Hematopathy, General Hospital of Jinan Military, and 10 healthy volunteers were recruited as controls. Separation of the patients and controls with peripheral blood mononuclear cells were divided into two groups, including PBMCs culture alone, PBMCs co-culture with UC-MSCs, application of flow cytometry detect respectively the proportion of the Treg cells and the expression of LFA-1 on Treg cells under different culture conditions. The Treg cells and CD4(+) CD25(-)T lymphocyte were separated by magnetic cell sorting (MACS) system, CFSE label CD4(+) CD25(-)T lymphocyte, comparing the inhibitive function of Treg cells on CD4(+) CD25(-)T lymphocyte with or without co-culture with UC-MSCs. Results: The intensity of fluorescence expression of LFA-1 on T lymphocyte in aplastic anemia increased obviously((71.4±10.1)vs(52.5±8.7) , P=0.002), but the LFA-1 expressed on Treg cells had no significant difference(P=0.199). After co-cultured with UC-MSCs, the proportion of LFA-1 on Treg cells in aplastic anemia reduced greatly ((20.96±1.76)% vs(44.26±1.19)%, P=0.012), at the same time, UC-MSCs increased the proportion of Treg cells obviously ((5.33±1.14)%vs(1.94±0.65)%, P=0.003), but the effect of Treg cells on the mean frquency of dividing CD4(+) CD25(-)T lymphocyte had no significant difference with or without co-culture with UC-MSCs(P=0.290). Conclusions: The intensity of fluorescence expression of LFA-1 on lymphocyte in aplastic anemia increases obviously, indicating the possible pathogenesis of AA. UC-MSCs inhibit the expression of LFA-1 on Treg cells and enhance the proportion of Treg cells, but UC-MSCs doesn't directly improve the immunosuppression of single Treg cells.

Effect of icariin in combination with daily sildenafil on penile atrophy and erectile dysfunction in a rat model of bilateral cavernous nerves injury.

The commonly utilized phosphodiesterase type 5 inhibitors do not lead to satisfactory penile erection after radical prostatectomy mainly because of insufficient nitric oxide drive from the damaged cavernous nerves. The aim of this study was to assess the efficacy and mechanisms of icariin in combination with daily sildenafil on neurogenic erectile dysfunction and penile atrophy in a rat model of bilateral cavernous nerves injury. Sixty male Sprague-Dawley rats injected with 5-ethynyl-2-deoxyuridine (50 mg/kg) at postnatal day 1 for the purpose of tracking endogenous stem cells in penis. Forty-eight rats of bilateral cavernous nerves injury were randomized equally into gavage feeding of vehicle, sildenafil (10 mg/kg), icariin (1.5 mg/kg) and sildenafil + icariin, respectively. Twelve sham-operated rats served as control. The intracavernous pressure and mean arterial pressure was measured and mid-penile cross sections were histologically examined 5 weeks after surgery. Western blotting of cavernous tissue protein was also performed. Animals treated with sildenafil + icariin had significantly higher mean intracavernous pressure/mean arterial pressure ratio relative to other rats with bilateral cavernous nerves injury (p < 0.05). The circumference and mean cross-sectional area of the paired corpus cavernosum were effectively preserved in the sildenafil + icariin. Treatment with sildenafil + icariin significantly increased the cavernous cyclic guanosine monophosphate concentration compared with the icariin group (p < 0.05). In addition, the numbers of neuronal nitric oxide synthase-positive nerves and 5-ethynyl-2-deoxyuridine-positive cells co-expressing S100 in the icariin-treated groups were greater compared with the bilateral cavernous nerves injury control group (p < 0.05). These data suggest that the combined use of icariin and daily sildenafil holds promise as a potential therapy for neurogenic erectile dysfunction in the future. The underlying mechanisms appears to involve two aspects: (i) icariin promotes differentiation of endogenous stem cells to Schwann cells, which help to repair the damaged neural pathway for erection; (ii) on this basis, sildenafil can further improve penile engorgement through the cyclic guanosine monophosphate-dependent smooth muscle relaxation.

[Feasibility study of transplantation of penile corpus cavernosum and major pelvic ganglion in renal subserous region].

OBJECTIVE: To study the feasibility of transplantation of normal rat penile corpus cavernosum and major pelvic ganglion (MPG) into the renal subserous region of a Nu/Nu mouse based on allograft technology. METHODS: Penile corpus cavernosum and MPG, harvested from Sprague-Dawley (SD) rats under sterile condition, were transplanted underneath the kidney capsule of Nu/Nu mice through the microsurgery instruments and surgery microscope. The histopathologic changes and cellular proliferation in the transplanted penile corpus cavernosum and MPG were then analyzed at the end of 1week and 4 weeks after transplantation. Histological staining and immunohistochemical staining were used to evaluate the main outcome measures. RESULTS: After 1 week, the tissue morphology of the transplanted corpus cavernosum underneath the kidney capsule of Nu/Nu mice was consistent with normal penile corpus cavernosum, and blood could be observed in the penis cavernous sinus of the graft; after 4 weeks, the mophorlogy of the tranplanted corpus cavernosum near the kidney was consistent with normal penile corpus cavernosum, while fibrosis was noteworthy in the graft away from the kidney, but blood could still be seen in the penis cavernous sinus. After 1 week, the tissue morphology of the transplanted MPG was consistent with normal MPG, multiple islet-like cell clusters could be seen in the transplanted MPG in the renal subserous region, and angiogenesis could be observed near the kidney; after 4 weeks, a network of blood vessels was clearly visible away from the kidney, and islet-like cell clusters were still clearly observed in the transplanted MPG. In addition, ki67 positive cells were observed in the transplanted penile corpus cavernosum and MPG after 4 weeks of transplantation, which indicated that there was still cell proliferation activity in the grafts. CONCLUSION: The transplanted corpus cavernosum and MPG underneath the kidney capsule of Nu/Nu mice could survive at least 4 weeks. Moreover, the inner structure of the transplanted corpus cavernosum and MPG was close to the normal tissue. The underlining mechanism may be related to the local microenvironment underneath the kidney capsule of Nu/Nu mice and the neovascularization in the transplanted grafts.

The association of DLG5 polymorphisms with inflammatory bowel disease: a meta-analysis of 25 studies.

OBJECTIVE: The aim of this study was to explore the association of polymorphisms in DLG5 gene (G113A, C4136A and e26) with inflammatory bowel disease (IBD) risk. MATERIALS AND METHODS: A total of 25 studies involved 26583 subjects were pooled for analysis. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. RESULTS: For G113A variant, a significant association was observed with CD risk in children (A vs. G: OR = 0.745, 95% CI = 0.569-0.977) and high quality studies (A vs. G: OR = 0.913, 95% CI = 0.850-0.981). Additionally, the results of genotype-phenotype analysis suggested G113A variant was associated with colonic involvement in CD. However, in overall population, the results indicated G113A variant was not associated with CD or UC. We also provided evidence that C4136A polymorphism had different effects on CD risk between Europeans (AA vs. CC: OR = 3.239, 95% CI = 1.149-9.136) and Asians (AA vs. CC: OR = 0.511, 95% CI = 0.299-0.873). For UC, patients with AA genotype of C4136A variant had a significantly increased UC risk (AA vs. CC: OR = 3.877, 95% CI = 1.168-12.867). Finally, no association was detected with G113A or e26 polymorphism in CD or UC patients. CONCLUSIONS: This meta-analysis indicated G113A variant may be significantly associated with CD risk in children and colonic involvement.

Nanoscale precipitates strengthened lanthanum-bearing Mg-3Sn-1Mn alloys through continuous rheo-rolling.

We elucidate the effect of lanthanum (La) on the microstructure and mechanical properties of Mg-3Sn-1Mn-xLa (wt.%) alloy plates processed through continuous rheo-rolling for the first time. At x = 0.2 wt.%, La dissolved completely in the α-Mg matrix. As the La content was increased to 0.6 wt.%, a new plate-shaped three-phase compound composed of La5Sn3, Mg2Sn and Mg17La2 phases was formed with an average length of 380 ± 10 nm and an average width of 110 ± 5 nm. This compound had a pinning effect on the α-Mg grain boundary and on dislocations. With further increase in La-content to 1.0 wt.%, the length of the plate-shaped compound increased to an average length of 560 ± 10 nm, while the width was reduced to 90 ± 5 nm. The particle size of Mg2Sn decreased from 100 nm to 50 nm with increase in La-content from 0.2 to 1.4 wt.%. At La content of 1.0 wt.%, the tensile strength and elongation of the alloy was maximum, with 29% and 32% increase, respectively, compared to the Mg-3Sn-1Mn (wt.%) alloy, and 37% and 89% increase, in comparison to the Mg-3Sn-1Mn-0.87 Ce (wt.%) alloy.

[Effect of thermo-sensitive Matrigel on minimization of thermal injury to the nearby structures in radiofrequency ablation of subcapsular hepatic tumors in a rat model].

OBJECTIVE: To evaluate the effect and safety of using thermo-sensitive Matrigel as artificial ascites on minimizing thermal injury to the nearby structures in a rat model of radiofrequency (RF) ablation of the liver. METHODS: In this research, the morphological characterization of Matrigel was observed at different temperatures in vitro. In vivo study was conducted by using 42 SD rats in Matrigel, Saline and control groups of 14 rats each. Artificial ascites with 10 ml of Matrigel or saline was produced under ultrasound guidance before RF in the experimental groups. Using a 0.7 cm exposed 17 G RF electrode for 5 minutes (90 ± 2) ℃, 41 hepatic ablations was performed abutting the diaphragm, abdominal wall and stomach. The 41 rats were sacrificed at 24 h, and necropsy was performed.Gross and histopathologic examinations were performed to compare the frequency and extent of thermal injury to the nearby organs.The animal status was followed up to achieve long term safety evaluation of Matrigel. RESULTS: Matrigel was in liquid formation at 0-4 ℃, but was not moving in vials at temperature 37 ℃ in 1 min, presenting gel formation.In vivo experiment, the artificial fluid thickness of Matrigel in site was significant larger than that of saline group, especially at 5 min of ablation ((8.1 ± 1.1) mm vs (2.4 ± 0.8)mm, P<0.01). Thermal injury to the nearby structures was found in 12 of 13 cases in control group, 8 of 14 cases (P=0.037) in saline group, and 1 of 14 cases (P<0.01) in Matrigel group. The sizes of the ablation zone of the liver did not differ among the three groups. There was no difference in the incidence of operation related complications among the three groups. There was no significant difference in body weight and health related parameters between Matrigel and saline group during 60 days of follow up. CONCLUSIONS: Using thermo-sensitive Matrigel as artificial ascites may be a safe and useful technique and help to further reduce the frequency and severity of collateral thermal injury to the nearby structures compare to conventional saline, during RF ablation of subcapsular hepatic tumors.

Misfolding Ectodomain Mutations of the Lutropin Receptor Increase Efficacy of Hormone Stimulation.

We demonstrate 2 novel mutations of the LHCGR, each homozygous, in a 46,XY patient with severe Leydig cell hypoplasia. One is a mutation in the signal peptide (p.Gln18_Leu19ins9; referred to here as SP) that results in an alteration of the coding sequence of the N terminus of the mature mutant receptor. The other mutation (p.G71R) is also within the ectodomain. Similar to many other inactivating mutations, the cell surface expression of recombinant human LHR(SP,G71R) is greatly reduced due to intracellular retention. However, we made the unusual discovery that the intrinsic efficacy for agonist-stimulated cAMP in the reduced numbers of receptors on the cell surface was greatly increased relative to the same low number of cell surface wild-type receptor. Remarkably, this appears to be a general attribute of misfolding mutations in the ectodomains, but not serpentine domains, of the gonadotropin receptors. These findings suggest that there must be a common, shared mechanism by which disparate mutations in the ectodomain that cause misfolding and therefore reduced cell surface expression concomitantly confer increased agonist efficacy to those receptor mutants on the cell surface. Our data further suggest that, due to their increased agonist efficacy, extremely small changes in cell surface expression of misfolded ectodomain mutants cause larger than expected alterations in the cellular response to agonist. Therefore, for inactivating LHCGR mutations causing ectodomain misfolding, the numbers of cell surface mutant receptors on fetal Leydig cells of 46,XY individuals exert a more exquisite effect on the relative severity of the clinical phenotypes than already appreciated.

[Feasibility study of transplantation of penile corpus cavernosum and major pelvic ganglion in renal subserous region].

OBJECTIVE: To study the feasibility of transplantation of normal rat penile corpus cavernosum and major pelvic ganglion (MPG) into the renal subserous region of a Nu/Nu mouse based on allograft technology. METHODS: Penile corpus cavernosum and MPG, harvested from Sprague-Dawley (SD) rats under sterile condition, were transplanted underneath the kidney capsule of Nu/Nu mice through the microsurgery instruments and surgery microscope. The histopathologic changes and cellular proliferation in the transplanted penile corpus cavernosum and MPG were then analyzed at the end of 1week and 4 weeks after transplantation. Histological staining and immunohistochemical staining were used to evaluate the main outcome measures. RESULTS: After 1 week, the tissue morphology of the transplanted corpus cavernosum underneath the kidney capsule of Nu/Nu mice was consistent with normal penile corpus cavernosum, and blood could be observed in the penis cavernous sinus of the graft; after 4 weeks, the mophorlogy of the tranplanted corpus cavernosum near the kidney was consistent with normal penile corpus cavernosum, while fibrosis was noteworthy in the graft away from the kidney, but blood could still be seen in the penis cavernous sinus. After 1 week, the tissue morphology of the transplanted MPG was consistent with normal MPG, multiple islet-like cell clusters could be seen in the transplanted MPG in the renal subserous region, and angiogenesis could be observed near the kidney; after 4 weeks, a network of blood vessels was clearly visible away from the kidney, and islet-like cell clusters were still clearly observed in the transplanted MPG. In addition, ki67 positive cells were observed in the transplanted penile corpus cavernosum and MPG after 4 weeks of transplantation, which indicated that there was still cell proliferation activity in the grafts. CONCLUSION: The transplanted corpus cavernosum and MPG underneath the kidney capsule of Nu/Nu mice could survive at least 4 weeks. Moreover, the inner structure of the transplanted corpus cavernosum and MPG was close to the normal tissue. The underlining mechanism may be related to the local microenvironment underneath the kidney capsule of Nu/Nu mice and the neovascularization in the transplanted grafts.