Sleep characteristics before assisted reproductive technology treatment predict reproductive outcomes: a prospective cohort study of Chinese infertile women.

Sleep disorders affect mental and physical health. Infertile women undergoing assisted reproductive technology (ART) treatment are prone to sleep disorders. Sleep condition, its influencing factors, and the association between sleep condition and ART treatment outcomes before treatment have not been explored within a population with a large sample size. Therefore, we investigated the sleep characteristics of 1002 Chinese infertile women before ovulation induction and investigated the influencing factors (negative and positive psychological factors, demographics, and fertility characteristics). We also examined whether sleep conditions before treatment predicted reproductive outcomes. We found that 24.1% of participants reported poor sleep quality. Women with primary infertility reported poorer sleep than women with secondary infertility. Negative psychological factors, including depression, anxiety, and perceived stress were associated with poor sleep, whereas positive affect was linked with good sleep. Adverse sleep characteristics, including poor subjective sleep quality, sleep disturbances, and poor sleep efficiency, decreased the quantity and quality of oocytes retrieved, fertilization rates, and clinical pregnancy rates. This study indicates that before ART treatment, a large number of females with infertility suffer from sleep problems, which are affected by psychological factors and infertility type, and unhealthy sleep characteristics may impair treatment outcomes. Our findings highlight the importance of screening and treatment for sleep disorders before the enrollment of ART treatment in infertile women.

Extracellular vesicles, hyperadhesive von willebrand factor, and outcomes of gastric cancer: a clinical observational study.

Von Willebrand factor (VWF) is an adhesive ligand critical for maintaining hemostasis. However, it has also been increasingly recognized for its role in cancer development because it has been shown to mediate the adhesion of cancer cells to endothelial cells, promote the epithelial-mesenchymal transition, and enhance angiogenesis. We have previously shown that gastric cancer cells synthesize VWF, which mediates the interaction between the cancer and endothelial cells to promote cancer growth. Here, we report results from a clinical observational study that demonstrate the association of VWF in plasma and on the surface of extracellular vesicles (EVs) with the pathological characteristics of gastric cancer. We found that patients with gastric cancer had elevated and intrinsically hyperadhesive VWF in their peripheral blood samples. VWF was detected on the surface of EVs from cancer cells, platelets, and endothelial cells. Higher levels of these VWF-bound EVs were associated with cancer aggression and poor clinical outcomes for patients. These findings suggest that VWF+ EVs from different cell types serve collectively as a new class of biomarkers for the outcome assessment of gastric cancer patients.

Gastric cancer cell-derived extracellular vesicles disrupt endothelial integrity and promote metastasis.

The endothelium is the critical barrier that controls transendothelial communications. Blood vessels in cancer tissue are poorly developed and highly permeable. However, it is poorly understood how circulating cancer cells released through these "leaky" vessels break the intact vasculature of remote organs to metastasize. We investigated the roles of cancer cell-derived extracellular vesicles (CEVs) in regulating cancer metastasis by analyzing samples from gastric cancer patients, performing in vitro experiments, and studying mouse models. We made several novel observations. First, the rate of metastasis was closely associated with plasma levels of CEVs in patients with gastric cancer. Second, cultured endothelial cells endocytosed CEVs, resulting in cytoskeletal rearrangement, low expression of the junction proteins cadherin and CD31, and forming large intercellular gaps to allow the transendothelial migration of cancer cells. The dynamin inhibitor Dynasore prevented these CEV-induced changes of endothelial cells by blocking CEVs endocytosis. Third, CEVs disrupted the endothelial barrier of cancer-bearing mice to promote cancer metastasis. Finally, lactadherin promoted the clearance of circulating CEVs to reduce metastasis. These results demonstrate the essential role of CEVs in promoting the metastasis of gastric cancer.

Does using outpatient room air for bleomycin foam preparation increase the risk of infection?

OBJECTIVE: To evaluate whether the risk of infections is increased with the use of air from outpatient rooms to prepare bleomycin foam. METHODS: Settling plates were adopted to collect bacteria from outpatient room air, operating theatre air, human serum albumin, bleomycin solution and bleomycin foam prepared with both outpatient room and operating theatre air. The plates were placed in an incubator at 37°C for 48 h, and the number of bacterial colonies was recorded using colony-forming units. The results were analysed by the t-test. A retrospective study was then performed to evaluate the outpatient safety of bleomycin foam. RESULTS: The number of colony-forming units in the bleomycin foam produced using both operating and outpatient room air was very low, with no statistic difference. No infection cases were reported in clinical evaluation. CONCLUSION: Using the air from outpatient treatment rooms for bleomycin foam preparation does not increase the risk of infections.

Identifying the Most Stable State of a Foam Sclerosant for Foam Sclerotherapy.

BACKGROUND: Foam sclerotherapy is an effective treatment strategy for vascular malformations, and its sclerosing power depends on foam stability. Twenty quick passages have been widely used as an indicator of the most stable state of sclerosants, but the universality of their effectiveness has not been proven yet. OBJECTIVE: We aimed to identify simple and objective indicators of the most stable state of commonly used sclerosants and provide practitioners with suggestions to judge when foam producing is completed in sclerotherapy. MATERIALS AND METHODS: The universality of the effectiveness of 20 passages was tested by producing bleomycin foam with different passages. Further study was performed by testing modified bleomycin, polidocanol, and sodium tetradecylsulfate foam. RESULTS: The bleomycin foam became denser as passages were added, and the sound of each passage became almost silent after 40 passages. The almost silent sound can be an indicator of foam stability for most sclerosants. It has a different application range compared with 20 quick passages. CONCLUSION: We suggest that practitioners choose a different indicator depending on the foam used.

Effects of adatom and gas molecule adsorption on the physical properties of tellurene: a first principles investigation.

Tellurene is a new member of the two-dimensional (2D) materials' family, whose existence has been recently confirmed by first principles calculation and experimental work. Tellurene is also the first 2D mono-elemental material of group-VI predicted by scientists, and investigations of its basic properties are still in their infancy. In this study, we use first principles calculation based on density functional theory to investigate the adsorption of nineteen typical adatoms (Li, Na, K, Ca, Fe, Co, Ni, Cu, Zn, Ag, Au, Pd, Pt, B, N, O, Si, Cl, and Al), and five typical gas molecules (H2, O2, H2O, NO2, and NH3) on α-phase as well as ß-phase tellurene sheets. Our calculations shows that most adatoms are chemisorbed on tellurene sheets with large adsorption energies. Moreover, some of the adatoms are observed to give rise to distinct structural deformations and even local reconstructions. We report that a variety of electronic states are induced by the adatoms, which implies that different electronic structures can be engineered by the adsorption of adatoms. In fact, n-type doping, p-type doping, half-metal, and spin-gapless semiconductor features can be acquired by doping adatoms on tellurene sheets. Our calculations also show that the five gas molecules are all physisorbed on tellurene sheets, and no splitting behaviors are observed. Therefore, the adsorption of the five gas molecules has a weak effect on the electronic properties of tellurene. To conclude, our results indicate that adatom engineering may be used to greatly expand the potential applications of 2D tellurene.

Cancer cell-derived von Willebrand factor enhanced metastasis of gastric adenocarcinoma.

Cancer prognosis is poor for patients with blood-borne metastasis. Platelets are known to assist cancer cells in transmigrating through the endothelium, but ligands for the platelet-mediated cancer metastasis remain poorly defined. von Willebrand factor (vWF) is a major platelet ligand that has been widely used as a biomarker in cancer and associated inflammation. However, its functional role in cancer growth and metastasis is largely unknown. Here we report that gastric cancer cells from patients and cells from two well-established gastric cancer lines express vWF and secrete it into the circulation, upon which it rapidly becomes cell-bound to mediate cancer-cell aggregation and interaction with platelets and endothelial cells. The vWF-mediated homotypic and heterotypic cell-cell interactions promote the pulmonary graft of vWF-overexpressing gastric cancer BGC823 cells in a mouse model. The metastasis-promoting activity of vWF was blocked by antibodies against vWF and its platelet receptor GP Ibα. It was also reduced by an inhibitory siRNA that suppresses vWF expression. These findings demonstrate a causal role of cancer-cell-derived vWF in mediating gastric cancer metastasis and identify vWF as a new therapeutic target.

Effect of Qingfei Mixture () on pediatric mycoplasma pneumoniae pneumonia with phlegm heat obstructing Fei (Lung) syndrome.

OBJECTIVE: To explore the effect and mechanism of Qingfei Mixture (), a Chinese medicine, in treating mycoplasma pneumonia (MP) in MP patients and rat model METHODS: A total of 46 MP children with phlegm heat obstructing Fei (Lung) syndrome were randomly assigned to two groups by the method of random number table, with 23 children in each group. The control group was treated with intravenous infusion of azithromycin; the treatment group received intravenous infusion of azithromycin and oral administration of Qingfei Mixture. The treatment course was 7 days. Major symptoms and minor symptoms were observed and scored before and after treatments. A rat model of MP was also established. A total of 120 wistar rats were randomly divided into 5 groups: a normal group, infection group, Qingfei Mixture treatment group, azithromycin treatment group, and Qingfei Mixture + azithromycin treatment group. Each group contained 24 rats, from which every 6 were euthanatized 1, 3, 7 and 14 days after infection. MP DNA in pulmonary tissue homogenates was detected using real-time fluorescence quantitative polymerase chain reaction. Pathology was assessed after hematoxylin (HE) staining and lung tissue pathology scores were determined in pulmonary tissue. Transmission electron microscopic detection and electronic image analysis were performed on lung tissue 3 days after infection. Interleukin (IL)-17 was detected in serum using enzymelinked immunosorbent assay (ELISA) 7 days after infection. RESULTS: In the clinical study, both control and the treatment group showed improved results on removing symptoms of phlegm heat syndrome compared to the control group (P<0.05). In animal experiments, On the 7th day after MP infection, as detected by electron microscopy, the pulmonary capillary basement membranes of the azithromycin + Qingfei Mixture treatment group were much thinner than those of the azithromycin or Qingfei mixture treatment groups (P<0.05). The level of serum IL-17 in the azithromycin + Qingfei Mixture treatment group was lower than that in the azithromycin or Qingfei Mixture groups (P<0.01). CONCLUSION: Both Qingfei Mixture and azithromycin have therapeutic effects on mycoplasma pneumoniae pneumonia, but the combination of both agents had the greatest effect.

MicroRNA-27a Negatively Modulates the Inflammatory Response in Lipopolysaccharide-Stimulated Microglia by Targeting TLR4 and IRAK4.

microRNA, a family of small non-coding RNA, plays significant roles in regulating gene expression, mainly via binding to the 3'-untranslated region of target genes. Although the role of miRNA in regulating neuroinflammation via the innate immune pathway has been studied, its role in the production of inflammatory mediators during microglial activation is poorly understood. In this study, we investigated the effect of miR-27a on lipopolysaccharide (LPS)-induced microglial inflammation. miR-27a expression was found to be rapidly decreased in microglia by real-time polymerase chain reaction (real-time PCR) after LPS stimulation. Over-expression of miR-27a significantly decreased the production of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), whereas knockdown of miR-27a increased the expression of these inflammatory factors. We also demonstrated by loss- and gain-of-function studies that miR-27a directly suppressed the expression of toll-like receptor 4 (TLR4) and interleukin-1 receptor-associated kinase 4 (IRAK4)-a pivotal adaptor kinase in the TLR4/MyD88 signaling pathway-by directly binding their 3'-UTRs: knocking down TLR4 or IRAK4 in microglia significantly decreased TLR4 or IRAK4 expression and inhibited the downstream production of inflammatory mediators. Moreover, the inflammatory cytokines IL-6 and IL-1ß were regulated by IRAK4, whereas TNF-α and NO were more dependent on TLR4 activation. Thus, miR-27a might regulate the LPS-induced production of inflammatory cytokines in microglia independently of TLR4 and IRAK4. Taken together, our results suggest that miR-27a is associated with microglial activation and the inflammatory response.

Enhanced autophagy reveals vulnerability of P-gp mediated epirubicin resistance in triple negative breast cancer cells.

Epirubicin (EPI) is widely used for triple negative breast cancer (TNBC), but a substantial number of patients develop EPI resistance that is associated with poor outcome. The underlying mechanism for EPI resistance remains poorly understood. We have developed and characterized an EPI-resistant (EPI-R) cell line from parental MDA-MB-231 cells. These EPI-R cells reached stable growth in the medium containing 8 µg/ml of EPI. They overexpressed P-glycoprotein (P-gp) and contained numerous autophagic vacuoles. The suppression of P-gp overexpression and/or autophagy restored the sensitivity of these EPI-R cells to EPI. We further show that autophagy conferred resistance to EPI on MDA cells by blocking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated pro-apoptotic signals. Together, these results reveal a synergistic role of P-gp, autophagy, and NF-κB pathways in the development of EPI resistance in TNBC cells. They also suggest that blocking the P-gp overexpression and autophagy may be an effective means of reducing EPI resistance.

Cost-effective framework for basic surgical skills training.

BACKGROUND: The importance of basic surgical skills is entirely agreed among surgical educators. However, restricted by ethical issues, finance etc, the basic surgical skills training is increasingly challenged. Increasing cost gives an impetus to the development of cost-effective training models to meet the trainees' acquisition of basic surgical skills. In this situation, a cost-effective training framework was formed in our department and introduced here. METHODS: Each five students were assigned to a 'training unit'. The training was implemented weekly for 18 weeks. The framework consisted of an early, a transitional, an integrative stage and a surgical skills competition. Corresponding training modules were selected and assembled scientifically at each stage. The modules comprised campus intranet databases, sponge benchtop, nonliving animal tissue, local dissection specimens and simulating reality operations. The training outcomes used direct observation of procedural skills as an assessment tool. The training data of 50 trainees who were randomly selected in each year from 2006 to 2011 year, were retrospectively analysed. RESULTS: An excellent and good rate of the surgical skills is from 82 to 88%, but there is no significant difference among 6 years (P > 0.05). The skills scores of the contestants are markedly higher than those of non-contestants (P < 0.05). The average training cost per trainee is about $21.85-34.08. CONCLUSION: The present training framework is reliable, feasible, repeatable and cost-effective. The skills competition can promote to improve the surgical skills level of trainees.

Bayesian variable selection for disease classification using gene expression data.

MOTIVATION: An important application of gene expression microarray data is the classification of samples into categories. Accurate classification depends upon the method used to identify the most relevant genes. Owing to the large number of genes and relatively small sample size, the selection process can be unstable. Modification of existing methods for achieving better analysis of microarray data is needed. RESULTS: We propose a Bayesian stochastic variable selection approach for gene selection based on a probit regression model with a generalized singular g-prior distribution for regression coefficients. Using simulation-based Markov chain Monte Carlo methods for simulating parameters from the posterior distribution, an efficient and dependable algorithm is implemented. It is also shown that this algorithm is robust to the choices of initial values, and produces posterior probabilities of related genes for biological interpretation. The performance of the proposed approach is compared with other popular methods in gene selection and classification via the well-known colon cancer and leukemia datasets in microarray literature. AVAILABILITY: A free Matlab code to perform gene selection is available at http://www.sta.cuhk.edu.hk/xysong/geneselection/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[Multicentral randomized controlled studies on acupuncture at Shaoze (SI 1) for treatment of postpartum hypolactation].

OBJECTIVE: To explore effect of acupuncture at Shaoze (SI 1) for treatment of postpartum hypolactation. METHODS: Multicentral randomized controlled and single blind clinical trial was adopted, and 276 cases were divided into a treatment group and a control group, 138 cases in each group. The treatment group were treated with electroacupuncture (EA) at Shaoze (SI 1) and the control group with EA at Shangyang (LI 1). After treatment of 2 courses, the therapeutic effects and changes of cumulative score of TCM symptoms, mammary filling degree, lactation amount, prolactin level were evaluated and investigated. RESULTS: The cured and markedly effective rate was 97.8% in the treatment group and 24.3% in the control group with a significant difference between the two groups (P < 0.05). The treatment group in improvement of the cumulative score of TCM symptoms and the mammary filling degree, and increasing the lactation amount and the prolactin level were better than the control group (P < 0.01). CONCLUSION: Acupuncture at Shaoze (SI 1) has obvious therapeutic effect on hypolactation.

[Three-dimensional cell culture and histology of vasculogenic mimicry in hepatocellular carcinoma].

BACKGROUND & OBJECTIVE: Vasculogenic mimicry (VM) is a blood supply pattern in malignant tumors. Mimic vessel walls are formed by tumor cells, not by endothelial cells. Previous studies of VM are limited on malignant tumors with high aggression and bi-directional differentiation potentials, but seldom on epithelium-originated tumors. This study was to observe VM in hepatocellular carcinoma (HCC) by 3-dimensional culture of HCC cell line HepG2 and immunohistochemistry. METHODS: Three-dimensional culture system of HepG2 cells was constructed to observe VM. The presence of VM in 15 specimens of HCC was observed by immunohistochemical and histological double staining of CD31 and PAS, or Ferritin and PAS. RESULTS: During 3-dimensional culture, HepG2 cells stretched out thin and long apophyses at the second day, and linked each other to form wreath and net-work structure at the seventh day. All of the 15 HCC simples showed CD31-positive for endothelial cells, and Ferritin-positive for tumor cells. The immunohistochemical and histological double staining also proved that VM, formed by CD31-negative and Ferritin-positive tumor cells, existed in 7 of the 15 simples of HCC. Tumor cells were separated from the tubes by PAS-positive matter like basement membrane. Red blood cells could be seen in the tubes. The number of VM was less in well differentiated simples than in poorly differentiated samples; CD31-positive tumor cells were observed in poorly differentiated samples. CONCLUSIONS: HepG2 cells have the capacity of self-metamorphosing and vasculorizing. Tumor cells can obtain oxygen and nutrition through VM.

[Effects on development of the testicle in diet-induced obesity rats].

OBJECTIVE: We established diet-induced obesity animal model and observed the influence of obesity on testicle of the male rats. METHODS: Rats in model group were fed with fat-enriched diet for 6 weeks. We measured the body weight and the testis weight and observed the development of testicle by microscope, and compared with those of control group. Meanwhile, we measured the serum levels of testosterone (T) and estradiol (E2). RESULTS: The average body weight in model group rats was higher 29% than that in control group at 6 weeks old, 30% at 9 weeks old. We observed under microscope that most of the convoluted seminiferous tubule developed no good in model group, the 4 layer cells was sparse and the arrangement of them was not in order. The testosterone to estradiol ratios(T/E2) in model group was significant lower then that of control group (P < 0.05). CONCLUSION: The fat-enriched fat diet can induce obesity. It influenced the development of the testicle. This probably related to decrease of the testosterone to estradiol ratios.