Heritability of tea drinking and its relationship with cigarette smoking in the Chinese male adult twins.

The aims of this study are to estimate the contributions of genetic factors to the variation of tea drinking and cigarette smoking, to examine the roles of genetic factors in their correlation and further to investigate underlying causation between them. We included 11 625 male twin pairs from the Chinese National Twin Registry (CNTR). Bivariate genetic modelling was fitted to explore the genetic influences on tea drinking, cigarette smoking and their correlation. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was further used to explore the causal relationship between them. We found that genetic factors explained 17% and 23% of the variation in tea drinking and cigarette smoking, respectively. A low phenotypic association between them was reported (rph = 0.21, 95% confidence interval [CI]: [0.19, 0.24]), which was partly attributed to common genetic factors (rA = 0.45, 95% CI [0.19, 1.00]). In the ICE FALCON analysis with current smoking as the exposure, tea drinking was associated with his own (ßself = 0.39, 95% CI [0.23, 0.55]) and his co-twin's smoking status (ßco-twin = 0.25, 95% CI [0.10, 0.41]). Their association attenuated with borderline significance conditioning on his own smoking status (p = 0.045), indicating a suggestive causal effect of smoking status on tea drinking. On the contrary, when we used tea drinking as the predictor, we found familial confounding between them only. In conclusion, both tea drinking and cigarette smoking were influenced by genetic factors, and their correlation was partly explained by common genetic factors. In addition, our finding suggests that familial confounders account for the relationship between tea drinking and cigarette smoking. And current smoking might have a causal effect on weekly tea drinking, but not vice versa.

A score model based on pancreatic steatosis and fibrosis and pancreatic duct diameter to predict postoperative pancreatic fistula after Pancreatoduodenectomy.

PURPOSES: To establish a scoring model for the risk of postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD). METHODS: PD Patients from 7 institutions in 2 independent sets: developmental (n = 457) and validation cohort (n = 152) were retrospectively enrolled and analyzed. Pancreatic Fibrosis (PF) and Pancreatic Steatosis (PS) were assessed by pathological examination of the pancreatic stump. RESULTS: Stepwise univariate and multivariate analysis indicated that pancreatic duct diameter ≤ 3 mm, increased PS and decreased PF were independent risk factors for POPF and Clinically Relevant Postoperative Pancreatic Fistula (CR-POPF). Based on the relative weight and odds ratio of each factor in the POPF, a simplified scoring model was developed. And patients were stratified into high-risk group (22~28 points), medium-risk group (15~21 points) and low-risk group (8~14 points). The receiver operating characteristic curve demonstrated that the Area under the curve for the predictive model was 0.868 and 0.887 in the model design group and the external validation group. CONCLUSIONS: This study establishes a simplified scoring model based on accurately and quantitatively measuring the PS, PF and pancreatic duct diameter. The scoring model accurately predicted the risk of POPF.

Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity.

Aurora-A (Aur-A), a member of the serine/threonine Aurora kinase family, plays an important role in ensuring genetic stability during cell division. Previous studies indicated that Aur-A possesses oncogenic activity and may be a valuable therapeutic target in cancer therapy. However, the role of Aur-A in the most common thyroid cancer, papillary thyroid cancer (PTC), remains largely unknown. In patients with PTC, cancer cell migration and invasion account for most of the metastasis, recurrence, and cancer-related deaths. Cofilin-1 (CFL-1) is the most important effector of actin polymerization and depolymerization, determining the direction of cell migration. Here, we assessed the correlation between Aur-A and CFL-1 in PTC with lymph node metastasis. Tissue microarray data showed that simultaneous overexpression of Aur-A and CFL-1 correlated with lymph node metastasis in thyroid cancer tissue. Inhibition of Aur-A suppressed thyroid cancer cell migration in vitro and decreased lymph node metastasis in nude mice. Importantly, Aur-A increased the non-phosphorylated, active form of CFL-1 in TPC-1 cells, thus promoting cancer cell migration and thyroid cancer lymph node metastasis. Our findings indicate that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer.

Analysis of risk factors leading to postoperative urethral stricture and bladder neck contracture following transurethral resection of prostate.

PURPOSE: To determine risk factors of postoperative urethral stricture (US) and vesical neck contracture (BNC) after transurethral resection of prostate (TURP) from perioperative parameters. MATERIALS AND METHODS: 373 patients underwent TURP in a Chinese center for lower urinary tract symptoms suggestive of benign prostatic obstruction (LUTS/BPO), with their perioperative and follow-up clinical data being collected. Univariate analyses were used to determine variables which had correlation with the incidence of US and BNC before logistic regression being applied to find out independent risk factors. RESULTS: The median follow-up was 29.3 months with the incidence of US and BNC being 7.8% and 5.4% respectively. Resection speed, reduction in hemoglobin (ΔHb) and hematocrit (ΔHCT) levels, incidence of urethral mucosa rupture, re-catheterization and continuous infection had significant correlation with US, while PSA level, storage score, total prostate volume (TPV), transitional zone volume (TZV), transitional zone index (TZI), resection time and resected gland weight had significant correlation with BNC. Lower resection speed (OR=0.48), urethral mucosa rupture (OR=2.44) and continuous infection (OR=1.49) as well as higher storage score (OR=2.51) and lower TPV (OR=0.15) were found to be the independent risk factors of US and BNC respectively. CONCLUSIONS: Lower resection speed, intraoperative urethral mucosa rupture and postoperative continuous infection were associated with a higher risk of US while severer storage phase symptom and smaller prostate size were associated with a higher risk of BNC after TURP.

ACE2 gene polymorphisms are associated with elevated pulmonary artery pressure in congenital heart diseases.

BACKGROUNDS: Angiotensin converting enzyme 2 (ACE2) polymorphisms are related to the occurrence and prognosis of cardiovascular disease. However, whether ACE2 polymorphisms also affect pulmonary circulation in congenital heart disease (CHD) remains unclear. Thus, we investigated the relationship between ACE2 single nucleotide polymorphism (SNPs) and pulmonary circulation in CHD patients of Chinese Han ethnicity. METHODS: Enrolled CHD patients (n = 367) underwent gene sequencing of ACE2 SNPs rs2074192, rs2285666, and rs2106809. Patients with pulmonary hypertension were further examined for detailed hemodynamics. RESULTS: Female heterozygous patients had worse pulmonary circulation hemodynamic parameters compared to those of homozygotes. Female CHD patients with the CCA (OR = 0.53, 95% CI: 0.32-0.88) or CCG (OR = 0.59, 95% CI: 0.35-0.99) haplotype had a lower risk of elevated pulmonary artery pressure. CONCLUSION: In female CHD patients, ACE2 SNPs are related to pulmonary circulation hemodynamics. Female CHD patients with the CCA and CCG haplotype had a lower risk of pulmonary hypertension.

Colorimetric multi-channel sensing of metal ions and advanced molecular information protection based on fish scale-derived carbon nanoparticles.

Some nanosystems based on carbon nanomaterials have been used for fluorescent chemical/biosensing, elementary information processing, and textual coding. However, little attention has been paid to utilizing biowaste-derived carbon nanomaterials for colorimetric multi-channel sensing and advanced molecular information protection (including text and pattern information). Herein, fish scale-derived carbon nanoparticles (FSCN) were prepared and used for colorimetric detection of metal ions, encoding, encrypting and hiding text- and pattern-based information. The morphology and composition of FSCN were analyzed by TEM, XRD, FTIR, and XPS, and it was found that the FSCN-based multi-channel colorimetric sensing system can detect Cr6+ (detection limit of 56.59 nM and 13.32 nM) and Fe3+ (detection limit of 81.55 nM) through the changes of absorption intensity at different wavelengths (272, 370, and 310 nm). Moreover, the selective responses of FSCN to 20 kinds of metal ions can be abstracted into a series of binary strings, which can encode, hide, and encrypt traditional text-based and even two-dimensional pattern-based information. The preparation of carbon nanomaterials derived from waste fish scales can stimulate other researcheres' enthusiasm for the development and utilization of wastes and promoting resource recycling. Inspired by this work, more researches will continue to explore the world of molecular information technology.

Orthogonal test design for the optimization of superparamagnetic chitosan plasmid gelatin microspheres that promote vascularization of artificial bone.

The optimal conditions for the preparation of superparamagnetic chitosan plasmid (pReceiver-M29-VEGF165/DH5a) gelatin microspheres (SPCPGMs) were determined. Then, the performance of the SPCPGMs during neovascularization was evaluated in vivo. The SPCPGMs were prepared through a cross-linking curing method and then filled into the hollow scaffold of an artificial bone. Neovascularization at the bone defect position was histologically examined in samples collected 2, 4, 6, and 8 weeks after the operation. The cellular magnetofection rate of superparamagnetic chitosan nanoparticles/plasmid (pReceiver-M29-VEGF165/DH5a) complexes reached 1-3% under static magnetic field (SMF). Meanwhile, the optimal conditions for SPCPGM fabrication were 20% Fe3 O4 (w/v), 4 mg of plasmid, 5.3 mg of glutaraldehyde, and 500 rpm of emulsification rotate speed. Under oscillating magnetic fields (OMFs), 4-6 µg of plasmids was released daily for 21 days. Under the combined application of SMF and OMF, evident neovascularization occurred at the bone defect position 6 weeks after the operation. This result is expected to provide a new type of angiogenesis strategy for the research of bone tissue engineering.

[Quantitative determination of biogenic amine from Biomphalaria glabrata nervous system by UPLC MS/MS].

OBJECTIVE: To establish a method for the quantitative determination of serotonin and dopamine in the nervous system of Biomphalaria glabrata by using ultra high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC MS/MS) . METHODS: The B. glabrata nervous system was broken in the pure methanol solution after obtaining it by dissecting with microscope. Then, the supernatant containing the target substance after twice high speed centrifugation was got. The extraction was separated on an ACQUITY UPLC BEH Amide column with Waters TQ-XS series mass spectrometry detector, with ESI source and positive electrospray ionization mode when the machine testing. RESULTS: The detection limit of serotonin was 0.03 ng/ml and the limit of quantification was 0.1 ng/ml. The detection limit of dopamine was 0.05 ng/ml and the limit of quantification was 0.15 ng/ml. The recoveries of serotonin ranged from 90.68% to 94.72% over the range of 1 to 40 ng/ml. The recoveries of dopamine ranged from 91.68% to 96.12% over the range of 1.0 ng/ml to 40 ng/ml. CONCLUSIONS: The established UPLC MS/MS method is simple, stable and reproducible. It can be used for the quantitative analysis of serotonin and dopamine in the nervous system of B. glabrata snails.

Slingshot-1L, a cofilin phosphatase, induces primary breast cancer metastasis.

Slingshot (SSH) is a member of the conserved family of cofilin phosphatases that plays a critical role in cell membrane protrusion and migration by transforming inactive phosphorylated cofilin to an active form. SSH-like protein 1 (SSH-1L) expression is detected in various types of tumors; insulin induces the phosphatases activity of SSH-1L in a phosphoinositide 3-kinase-dependent manner. However, little is known about the expression and role of SSH-1L in breast cancer. Here, we analyzed 295 human breast cancer tissue specimens for SSH-1L expression by immunohistochemistry. The correlation between SSH-1L level and patients' clinical characteristics was analyzed with Pearson's χ2 test. The function of SSH-1L was evaluated by gene knockdown and quantitative real-time polymerase chain reaction detection of cofilin expression in MDA-MB-231, MCF-7, and SK-BR-3 human breast cancer cell lines. SSH-1L expression was detected in 88.1% of tissue specimens by immunohistochemistry and was strongly associated with increased metastasis and mortality. Loss of SSH-1L expression decreased the nonphosphorylated, active form of cofilin in SK-BR-3 and MDA-MB-231 cell lines, which was associated with reduced cell motility. Accordingly, SSH-1L/cofilin signaling played a critical role in primary breast cancer metastasis and was a potential therapeutic target for breast cancer treatment.

Presentation on mechanisms and applications of chalcopyrite and pyrite bioleaching in biohydrometallurgy - a presentation.

This review outlines classic and current research, scientific documents and research achievements in bioleaching, particularly in respect of the bioleaching of chalcopyrite and pyrite. The diversity and commonality of the microbial leaching process can be easily studied through comparing the bioleaching mechanism and the application of these two metal sulfides. The crystal, electronic and surface structures of chalcopyrite and pyrite are summarized in detail in this paper. It determines the specific and complicated interaction pathways, kinetics of the atmospheric/aqueous oxidation, and the control process of bioleaching of the minerals as the precondition. Bioleaching of metal sulfides is performed by a diverse group of microorganisms and microbial communities. The species of the bacteria which have a significant effect on leaching ores are miraculously diverse. The newly identified acidophilic microorganisms with unique characteristics for efficient bioleaching of sulfidic minerals are increasing sharply. The cell-to-cell communication mechanisms, which are still implicit, elusive and intangible at present day, have gradually become a research hotspot. The different mineralogy characteristics and the acid solubility of the metal sulfides (e.g., chalcopyrite and pyrite) cause two different dissolution pathways, the thiosulfate and the polysulfide pathways. The bioleaching mechanisms are categorized by contact (an electrostatic attachment) and noncontact (planktonic) process, with emphasis on the produce of extracellular polymeric substances and formation of biofilm on the surface of the metal sulfides in this paper. The division of the direct and indirect effect are not adopted due to the redox chain, the reduction of the ferric iron and oxidation of the ferrous iron. The molecular oxygen is reduced by the electrons extracted from the specific metal sulfide, via a redox chain forming a supercomplex spanning the periplasmic space and connecting both outer and inner membrane. The passivation of the mineral surface can obviously hinder the dissolution of metal sulfides during the bioleaching process, which is significantly affected by the kinetic model, microenvironment on the surface of ore and the leach conditions, such as temperature, pH and Eh. The new development of mechanism research, enhanced and intensified technologies on the bioleaching of chalcopyrite and pyrite, are conducted and summarized from the different branches of natural science. Some are depicted and explained based on molecular level in this paper. Catalyst and catalytic mechanisms in bioleaching and biooxidation for this two sulfide minerals have been concluded and applied for several decades, the continuous emergence of the new material and technology are also gradually applied into the biohydrometallurgy. The industrial applications of the bioleaching on chalcopyrite and pyrite are totally based on the understanding of the interaction mechanism between microbes and minerals, the optimization of ore leaching conditions and the development of new material and the leaching equipment. It is not incredible and unimaginable to take a different bioleaching process and diagram to deal with the two sulfuric metals, which is vital to succeed in elevating the leaching rate of copper.

MRI and ultrasonography detection of cervical lymph node metastases in differentiated thyroid carcinoma before reoperation.

OBJECTIVE: The purpose of this study was to compare the diagnostic capabilities of magnetic resonance imaging (MRI) and ultrasonography (US) for cervical lymph nodal metastases in differentiated thyroid carcinoma (DTC) before reoperation. MATERIAL AND METHOD: From June 2011 to May 2013, preoperative MRI and ultrasound data were collected from differentiated thyroid cancer patients who underwent a reoperation. The following characteristics were assessed: the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MRI and US. The MRI and ultrasound findings were correlated with the histological diagnosis after reoperation. RESULTS: One hundred and thirty-eight cases were included in the analysis. 88.4% (122/138) of which had evidence of residual thyroid cancer tissue or metastatic nodal involvement at final histology. Lymph nodal metastases were confirmed in the central compartment in 76.42% (81/106) of patients and in lateral compartment in 73.28% (85/116) of patients. The sensitivity, specificity and accuracy of MRI VS US for detecting central compartment metastases was 75% VS 41.67% (P=0.04), 90.91% VS 100% (P=1) and 80% VS 60% (P=0.618), respectively; For detecting lateral compartment metastases was 83.33% VS 77.78% (P=1), 25% VS 50% (P=0.606) and 65.38% VS 69.23% (P=1), respectively. There was statistically significant difference between the sensitivity of MRI and ultrasound for diagnose of central compartment metastases. The MRI features with the greatest correlation with positive lymph nodal metastases were fusion and enhancing lesions. The ultrasound features with the greatest correlation with positive lymph nodal metastases were hypoechoic and microcalcifications. CONCLUSION: MRI is more sensitive than ultrasonography in detecting central compartment metastases in papillary thyroid carcinoma. There is no significant difference in diagnosis of lateral neck node metastases between MRI and US.

Diabetes mellitus and risk of brain tumors: A meta-analysis.

Accumulating evidence suggests that a history of diabetes may be involved in the occurrence of various types of cancer. However, the association of diabetes with the risk of brain tumors remains unclear. We identified relevant studies by performing a literature search of PubMed and EMBASE (through to 24 May 2012) and by searching the reference lists of pertinent articles. All data were extracted independently by two investigators using a standardized data abstraction tool. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Inter-study heterogeneity was assessed using the Cochran's Q and I(2) statistical tests. A total of 13 studies were included in this meta-analysis, including the entire Danish population, 5,107,506 other participants and more than 2,206 cases of brain tumors. In the analysis of these 13 studies, we observed that diabetic individuals had a similar risk of brain tumors as non-diabetic individuals (SRR, 1.12; 95% CI, 0.89-1.42). There was significant evidence of heterogeneity among these studies (P<0.001; I(2), 93.5%). Sub-group analysis revealed that diabetic females had a 24.2% increased risk of brain tumors (SRR, 1.242; 95% CI, 1.026-1.502), which was not observed in diabetic males. No significant publication bias was found in this study. The findings of this meta-analysis indicate that diabetic individuals have a similar risk of brain tumors as non-diabetic individuals. However, a significant positive correlation between the risk of brain tumors and diabetes mellitus was revealed in females, but not in males.

Change of blood perfusion in Hegu acupoint after contralateral Hegu acupoint was stimulated.

OBJECTIVES: The objective of this study was to investigate the change of mean blood flux in Hegu acupoint after contralateral Hegu acupoint was stimulated. METHODS: Healthy volunteers (N=140) were placed in a temperature-controlled room as a resting state for 60 minutes. Then the measurements of skin blood flow were carried out in pre- and postacupuncture stimulation every 30 minutes over a total of 180 minutes using a Moor full-field laser perfusion imager. The change ratio of mean blood flux in Hegu acupoint was used to evaluate the contralateral stimulation effect in different groups. RESULTS: After acupuncture of the right Hegu acupoint (AR), the change ratio of mean blood flux in the left Hegu acupoint was increased significantly compared with the control group 60 minutes after acupuncture stimulation (p<0.01). Then the blood flow in the AR group was sustained at a higher level compared with that of the control group (p<0.05). However, the change ratio of mean blood flux in the right Hegu acupoint increased significantly in the 30 minutes after contralateral acupuncture stimulation (p<0.01). From that point on, the change ratio was sustained at a higher level in the AR group than in the control group until 150 minutes after stimulation (p<0.05). CONCLUSIONS: On stimulation of either the left or right side of Hegu acupoint, the change ratio of mean blood flux was increased in the contralateral Hegu acupoint in a period from 30, 60, to 150 minutes after stimulation, respectively.

RhoA regulates invasion of glioma cells via the c-Jun NH2-terminal kinase pathway under hypoxia.

The purpose of this study was to investigate the mechanism of glioma cell invasion in hypoxic conditions. We demonstrated that hypoxia increased cell invasion, matrix metalloproteinase-2 (MMP2) activity and time-dependent expression of hypoxia inducible factor-1α (HIF-1α) in human glioma cells. These data suggest that MMP2 may play a significant role in tumor invasion in hypoxic conditions. We investigated the mechanisms involved in the increased MMP2 activity and cell invasion in hypoxic conditions. Increased expression of phospho-Jun NH2-terminal kinase (p-JNK) and phospho-c-Jun (p-c-Jun) in glioma cells induced by hypoxia was detected. Furthermore, this effect may be reduced by inhibiting the JNK signaling pathway. We found that inhibition of RhoA geranylgeranylation by geranylgeranyltransferase inhibitor-2147 (GGTI-2147) or knockdown of RhoA by siRNA against RhoA reduced the expression of p-JNK and p-c-Jun, and decreased MMP2 activity and glioma cell invasion in hypoxic conditions. These data suggest a link among RhoA, JNK, c-Jun and MMP2 activity that is functionally involved in the increased glioma cell invasion induced by hypoxia.

Comparison of acute hemodynamic effects of aerosolized iloprost and inhaled nitric oxide in adult congenital heart disease with severe pulmonary arterial hypertension.

OBJECTIVE: To compare the acute hemodynamic effects of aerosolized iloprost and inhaled nitric oxide (NO) in adult congenital heart disease (CHD) patients with severe pulmonary arterial hypertension (PAH). METHODS: One hundred and eighty five adult CHDs with severe PAH were nonrandomized into two groups (iloprost, n=127; NO, n=58). Various hemodynamic parameters were measured before and after iloprost or NO inhalation. RESULTS: Iloprost and NO inhalation resulted in significant reductions in pulmonary arterial pressure (from 110.6±21.8 mmHg to 105.5±22.3 mmHg, p<0.05; from 113.1±18.7 mmHg to 107.2±19.9 mmHg, p<0.05, respectively) and pulmonary vascular resistance (PVR) (from 13.4±8.3 Wood units to 9.6±6.4 Wood units, p<0.01; from 13.7±7.1 Wood units to 9.3±4.9 Wood units, p<0.01, respectively) and increases in pulmonary blood flow (from 6.7±3.3 L/min to 9.4±5.8 L/min, p<0.05; from 6.6±3.1 L/min to 9.6±5.9 L/min, p<0.01, respectively) and the Qp/Qs ratio (from 1.5±0.8 to 2.1±1.4, p<0.01; from 1.5±0.8 to 2.0±1.3, p<0.01, respectively). When the effects of inhaled iloprost and NO were compared, similar reductions in pulmonary arterial pressure and pulmonary vascular resistance were observed. Aerosolized iloprost and inhaled nitric oxide (iNO) were generally well tolerated and no patient experienced any side effects during inhalation. CONCLUSION: Aerosolized iloprost can be effectively and safely used and might be an alternative to NO for testing pulmonary vascular reactivity and treating severe PAH in adult CHD patients.

Analysis of risk factors leading to postoperative urethral stricture and bladder neck contracture following transurethral resection of prostate

ABSTRACT Purpose: To determine risk factors of postoperative urethral stricture (US) and vesical neck contracture (BNC) after transurethral resection of prostate (TURP) from perioperative parameters. Materials and Methods: 373 patients underwent TURP in a Chinese center for lower urinary tract symptoms suggestive of benign prostatic obstruction (LUTS/BPO), with their perioperative and follow-up clinical data being collected. Univariate analyses were used to determine variables which had correlation with the incidence of US and BNC before logistic regression being applied to find out independent risk factors. Results: The median follow-up was 29.3 months with the incidence of US and BNC being 7.8% and 5.4% respectively. Resection speed, reduction in hemoglobin (ΔHb) and hematocrit (ΔHCT) levels, incidence of urethral mucosa rupture, re-catheterization and continuous infection had significant correlation with US, while PSA level, storage score, total prostate volume (TPV), transitional zone volume (TZV), transitional zone index (TZI), resection time and resected gland weight had significant correlation with BNC. Lower resection speed (OR=0.48), urethral mucosa rupture (OR=2.44) and continuous infection (OR=1.49) as well as higher storage score (OR=2.51) and lower TPV (OR=0.15) were found to be the independent risk factors of US and BNC respectively. Conclusions: Lower resection speed, intraoperative urethral mucosa rupture and postoperative continuous infection were associated with a higher risk of US while severer storage phase symptom and smaller prostate size were associated with a higher risk of BNC after TURP.