[Research progress on urogenital function preservation in extralevator abdominoperineal resection].

Extralevator abdominoperineal excision (ELAPE) has been suggested to potentially improve oncological outcomes in advanced low rectal cancer patients. However, the urogenital function impairment as one of the main complications deteriorates the quality of life in these patients. The key point to prevent urogenital function impairment is to avoid autonomic nerve injury, including the superior and inferior hypogastric nerve plexus and neurovascular bundle. Three areas should be especially focused during surgery, including the posterolateral aspect of the prostate during the separation of the rectum from prostate, the lateral wall of ischioanal fossa and the area in front of anal canal. Previous presumption supposed that extended resection, though promoting oncologic outcomes, might lead to enlarged injury to surrounding vessels and nerves that deteriorated patients' urogenital function. But recent studies show that postoperative urogenital function outcomes of rectal cancer patients who underwent ELAPE are not inferior to conventional APE after the induction of minimal invasive approaches including laparoscopic and robotic surgery. Their quality of life can be comparable with patients who underwent conventional APE, and are even better in some particular area. Moreover, as further improvement of ELAPE procedure has been made, the concept of individualized ELAPE addressed the importance of personalized surgical procedure based on tumor stage and location, dedicating to avoid injury to vessels and nerves through preserving more surrounding tissues. Urogenital function outcomes, as part of postoperative outcomes, get more and more attention in recent years. We review current studies on urogenital function after ELAPE from anatomy to clinical research, in order to raise surgeons' attention of nerve preservation technique and to improve their understanding of ELAPE procedure.

[Validation and optimization of the indicator system of risk assessment for mechanical cuts].

Objective: To validation and optimization the indicator system of risk assessment for mechanical cuts. Methods: The risk assessment index system of mechanical cutting injury established earlier was used to assess the risk of mechanical cutting injury in 40 cases of mechanical cutting injury registered from January 2015 to December 2017 and 40 similar positions without accidents in the same period. The multiple stepwise regression analysis was used to screen the indicator system, and to adjust the weight coefficient of each index. The total coincidence rate and Kappa value were compared between before and after optimization respectively. Results: The new index system has 3 first-class indicators, 10 second-class indicators and 14 three-class indicators, fewer than the old index system which has 3 first-class indicators, 10 second-class indicators, 34 three-class indicators. There three indicators have revamped in the first-class. The total of coincidence rates of the new and old indicator systems were 67.50% and 90.00%, the difference was statistically significant (P<0.01). The Kappa value were 0.35 and 0.80, respectively. Conclusion: The evaluation results with new indicator systems is more consistent with the actual hazard detection the the old indicator systems, and scientific, reasonable and practical, and the indicator system of risk assessment for mechanical cuts can be used for the risk assessment of mechanical cutting injuries.

[Role of NLRP3 inflammasome in the pathogenesis of alcoholic liver disease].

Chronic excess alcohol intake triggers the formation of enterogenic endotoxemia. TLR4 ligand localization activates nuclear transcription factor NF-κB by inducing the up-regulation of NLRP3 inflammasome and the biologically inactive IL-1ß and IL-18 precursors to form initiation of pro-inflammatory signals. Under the influence of ethanol, the damaged hepatocyte release uric acid, and adenosine triphosphate and induces NLRP3 inflammasome assembly and functional activation in Kupffer cells to promote the release of inflammatory mediators, such as interleukin-1ß and interleukin-18, that cascade mediates inflammation and drive alcoholic liver disease from steatosis to inflammation and fibrosis. The NLRP3 inflammasome acts as a ligand-sensing element and plays an important role in mediating the immune and inflammatory response in the course of alcoholic liver disease. Thus, exploring the activation mechanism of NLRP3 inflammasome and its pathogenic role may provide a new idea in the clinical treatment of alcoholic liver disease.

[Experimental study of silybin-phospholipid complex intervention on amiodarone-induced fatty liver in mice].

Objective: To probe into the mechanism and interventional effects of silybin-phospholipid complex on amiodarone-induced steatosis in mice. Methods: Eight-week-old male C57BL/6 mice were divided into three groups (5 mice in each group): a control group (WT) with normal diet, a model group with amiodarone 150mg/kg/d by oral gavage (AM), and an intervention group on amiodarone 150mg/kg/d combined with silybin-phospholipid complex(AM+SILIPHOS. All mice were fed their assigned diet for one week. Then, one week later, serum alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol and high-density lipoprotein were detected of each group. A liver pathological change was observed by oil red O and H&E staining. Ultrastructural pathological changes of hepatocytes were observed to evaluate the intervention effect by transmission electron microscopy. RT-q PCR was used to detect the expression of peroxisome proliferator-activated receptor alpha and its regulated lipid metabolism genes CPTI, CPTII, Acot1, Acot2, ACOX, Cyp4a10 and Cyp4a14 in liver tissues. Intra-group comparison was done by paired t-test. One-way ANOVA was used for comparison between groups and semi-quantitative data were tested using Mann-Whitney U test. Results: Oil Red O and H&E staining results of liver tissue in the intervention group showed that intrahepatic steatosis was significantly reduced when compared to model group. Transmission electron microscopy showed that the model group had pyknotic nuclei, mitochondrial swelling, structural damage, and lysosomal degradation whereas the intervention group had hepatic nucleus without pyknosis, reduced mitochondrial swelling and slight structural damage than that of model group. RT-q PCR results showed that the expression of peroxisome proliferator-activated receptor alpha, CPTI, CPTII, Acot1, Acot2, ACOX, Cyp4a10 and Cyp4a14 were increased in the model group but the expression of CPTI, Cyp4a14, Acot1 and peroxisome proliferator-activated receptor alpha were decreased in the intervention group (P < 0.05). Conclusion: Silybin-phospholipid complex can alleviate amiodarone-induced steatosis, and its mechanism may play a role in protecting mitochondrial function and regulating fatty acid metabolism. Thus, silybin-phospholipid complex has potential intervention effect on amiodarone-induced fatty liver.

Metabolism studies of paeoniflorin in rat liver microsomes by ultra-performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS).

To explore metabolism mechanism of paeoniflorin in the liver and further understand intact metabolism process of paeoniflorin, a rapid, convenient and effective assay is described using ultra-performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS). The strategy was confirmed in the following primary processes: firstly, different concentration of paeoniflorin, rat liver microsomes, coenzymes and different incubated conditions were optimized to build a biotransformation model of rat liver microsomes in vitro by high performance liquid chromatography with diode array detection (HPLC-DAD); secondly, the metabolites of paeoniflorin in rat liver microsomes were detected and screened using UPLC-Q-TOF-MS/MS by comparing the total ion chromatogram (TIC) of the experimental group with those of control groups; finally, the molecular formulae and corresponding chemical structures of paeoniflorin metabolites were identified by comparing the MS and MS/MS spectra with the self-constructed database and simulation software. Based on this analytical strategy, 20 metabolites of paeoniflorin were found and 6 metabolites (including four new compounds) were tentatively identified. It was shown that hydrolysis and oxidation were the major metabolic pathways of paeoniflorin in rat liver microsomes, and the main metabolic sites were the structures of pinane and the ester bond. These findings were significant for a better understanding of the metabolism of paeoniflorin in rat liver microsomes and the proposed metabolic pathways of paeoniflorin might provide fundamental support for the further research in the pharmacological mechanism of Paeoniae Radix Rubra (PRR).

[The combination of percutaneous iohexol-ethanol injection with radiofrequency ablation for the treatment of primary liver cancer in high-risk locations].

Objective: To investigate the safety and efficacy of radiofrequency ablation (RFA) with percutaneous iohexol-ethanol injection (PIEI), compared with RFA plus transcatheter arterial chemoembolization (TACE) for patients with primary liver cancer(PLC)in high-risk locations. Methods: From January 2012 to December 2014, 54 patients with PLC in high-risk locations were enrolled. They were divided into Group A (RFA combined with PIEI) and Group B (RFA plus TACE). The efficacy and adverse events were assessed. Results: 54 patients had 74 lesions in high-risk locations. There were 26 cases with 40 lesions in Group A, and 28 cases with 34 lesions in Group B. The complete ablation rate of Group A was significantly higher than that of Group B (92.5% vs 70.6%, P=0.014). The two-year local tumor progressionrateand two-year overall survival rate were similar between these two groups (Group A 20.0% vs Group B 38.2%, P=0.083; 90.3% vs 84.3%, P=0.523). Furthermore, the surgery-related severe adverse events of Group A (7.1%, one case of liver abscess and one case ofhematobilia) were more common than that of Group B (0%, P=0.491). No significant differences were found in common adverse events including fever, pain, elevation of aminotransferase and bilirubin. Conclusions: Compared with RFA plus TACE, RFA plus PIEI resulted inbetter complete ablation rate in patients with primary liver cancer in high risk locations. Prospective, randomized, controlled trials are warranted for further evaluation.

Relationships between childhood growth parameters and adult blood pressure: the Fels Longitudinal Study.

Previous research has shown that childhood body size is associated with blood pressure in adulthood, and that early and rapid growth rates are correlated with adverse cardiovascular outcomes. Our objectives are to estimate associations between childhood body size growth parameters and adult blood pressure, and to examine the effect of early attainment of critical growth milestones on adult blood pressure, relative to normal or late attainment. Lifetime height and body mass index (BMI) measurements in childhood, and systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements in adulthood are taken from participants in the Fels Longitudinal Study. Childhood growth curves are estimated separately for stature and BMI using the Preece-Baines and third-degree polynomial models, respectively. Associations between the resulting parameter estimates and adult blood pressure are then examined using linear mixed models. Our findings show that the ages of achievement of the stature-based growth onset and peak velocity, as well as the age of achievement of the BMI-based adiposity rebound, are negatively associated with adult blood pressure, implying that early height or BMI growth can lead to increased blood pressure in adulthood. There were subtle differences in these relationships based on age and gender, and also between SBP and DBP. These results expand on the existing literature, showing that not only childhood body size, but also the timing of childhood growth can have a deleterious effect on adult cardiovascular health.

Pressure Induced Stripe-Order Antiferromagnetism and First-Order Phase Transition in FeSe.

To elucidate the magnetic structure and the origin of the nematicity in FeSe, we perform a high-pressure ^{77}Se NMR study on FeSe single crystals. We find a suppression of the structural transition temperature with pressure up to about 2 GPa from the anisotropy of the Knight shift. Above 2 GPa, a stripe-order antiferromagnetism that breaks the spatial fourfold rotational symmetry is determined by the NMR spectra under different field orientations and with temperatures down to 50 mK. The magnetic phase transition is revealed to be first-order type, implying the existence of a concomitant structural transition via a spin-lattice coupling. Stripe-type spin fluctuations are observed at high temperatures, and remain strong with pressure. These results provide clear evidence for strong coupling between nematicity and magnetism in FeSe, and therefore support a universal scenario of magnetic driven nematicity in iron-based superconductors.

Compensated Semimetal LaSb with Unsaturated Magnetoresistance.

By combining angle-resolved photoemission spectroscopy and quantum oscillation measurements, we performed a comprehensive investigation on the electronic structure of LaSb, which exhibits near-quadratic extremely large magnetoresistance (XMR) without any sign of saturation at magnetic fields as high as 40 T. We clearly resolve one spherical and one intersecting-ellipsoidal hole Fermi surfaces (FSs) at the Brillouin zone (BZ) center Γ and one ellipsoidal electron FS at the BZ boundary X. The hole and electron carriers calculated from the enclosed FS volumes are perfectly compensated, and the carrier compensation is unaffected by temperature. We further reveal that LaSb is topologically trivial but shares many similarities with the Weyl semimetal TaAs family in the bulk electronic structure. Based on these results, we have examined the mechanisms that have been proposed so far to explain the near-quadratic XMR in semimetals.

Biofortification of rice with lysine using endogenous histones.

Rice is the most consumed cereal grain in the world, but deficient in the essential amino acid lysine. Therefore, people in developing countries with limited food diversity who rely on rice as their major food source may suffer from malnutrition. Biofortification of stable crops by genetic engineering provides a fast and sustainable method to solve this problem. In this study, two endogenous rice lysine-rich histone proteins, RLRH1 and RLRH2, were over-expressed in rice seeds to achieve lysine biofortification. Their protein sequences passed an allergic sequence-based homology test. Their accumulations in rice seeds were raised to a moderate level by the use of a modified rice glutelin 1 promoter with lowered expression strength to avoid the occurrence of physiological abnormalities like unfolded protein response. The expressed proteins were further targeted to protein storage vacuoles for stable storage using a glutelin 1 signal peptide. The lysine content in the transgenic rice seeds was enhanced by up to 35 %, while other essential amino acids remained balanced, meeting the nutritional standards of the World Health Organization. No obvious unfolded protein response was detected. Different degrees of chalkiness, however, were detected in the transgenic seeds, and were positively correlated with both the levels of accumulated protein and lysine enhancement. This study offered a solution to the lysine deficiency in rice, while at the same time addressing concerns about food safety and physiological abnormalities in biofortified crops.

Rumex acetosa L. induces vasorelaxation in rat aorta via activation of PI3-kinase/Akt- AND Ca(2+)-eNOS-NO signaling in endothelial cells.

Rumex acetosa L. (RA) (Polygonaceae) is an important traditional Chinese medicine (TCM) commonly used in clinic for a long history in China and the aerial parts of RA has a wide variety of pharmacological actions such as diuretic, anti-hypertensive, anti-oxidative, and anti-cancer effects. However, the mechanisms involved are to be defined. The purpose of the present study was to evaluate the vasorelaxant effect and define the mechanism of action of the ethanol extract of Rumex acetosa L. (ERA) in rat aorta. ERA was examined for its vascular relaxant effect in isolated phenylephrine-precontracted rat thoracic aorta and its acute effects on arterial blood pressure. In addition, the roles of the nitric oxide synthase (NOS)-nitric oxide (NO) signaling in the ERA-induced effects were tested in human umbilical vein endothelial cells (HUVECs). The phosphorylation levels of Akt and eNOS were assessed by Western blot analysis in the cultured HUVECs. ERA induced endothelium-dependent vasorelaxation. The ERA-induced vasorelaxation was abolished by L-NAME (an NOS inhibitor) or ODQ (a sGC inhibitor), but not by indomethacin. Inhibition of PI3-kinase/Akt signaling pathway markedly reduced the ERA-induced vasorelaxation. In HUVECs, ERA increased NO formation in a dose-dependent manner, which was inhibited by L-NAME and by removing extracellular Ca(2+). In addition, ERA promoted phosphorylation of Akt and eNOS, which was prevented by wortmannin and LY294002, indicating that ERA induces eNOS phosphorylation through the PI3-kinase/Akt pathway. Further, in anesthetized rats, intravenously administered ERA decreased arterial blood pressure in a dose-dependent manner through an activation of the NOS-NO system. In summary, the ERA- induced vasorelaxation was dependent on endothelial integrity and NO production, and was mediated by activation of both the endothelial PI3-kinase/Akt- and Ca(2+)-eNOS-NO signaling and muscular NO-sGC-cGMP signaling.

Note: A novel normalization scheme for laser-based plasma x-ray sources.

A kHz repetition rate laser pump-X-ray probe system for ultrafast X-ray diffraction is set up based on a laser-driven plasma X-ray source. A simple and reliable normalization approach has been developed to minimize the impact of large X-ray pulse intensity fluctuation on data quality. It utilizes one single X-ray area detector to record both sample and reference signals simultaneously. Performance of this novel normalization method is demonstrated in reflectivity oscillation measurement of a superlattice sample at sub-ps resolution.

Changes in the activity and the expression of detoxification enzymes in silkworms (Bombyx mori) after phoxim feeding.

Silkworm (Bombyx mori) is an economically important insect. However, non-cocoon caused by chemical insecticide poisoning has largely hindered the development of sericulture. To explore the roles of detoxification enzymes in B. mori after insecticide poisoning, we monitored the activity changes of cytochrome P450 monooxygenase, glutathione-S-transferase, and carboxylesterase in B. mori midgut and fatbody after phoxim feeding. At the same time, the expression levels of detoxification enzyme-related genes were also determined by real-time quantitative PCR. Compare to the control levels, the activity of P450 in the midgut and fatbody was increased to 1.72 and 6.72 folds; the activity of GST was no change in midgut, and in fatbody increased to 1.11 folds; the activity of carboxylesterase in the midgut was decreased to 0.69 folds, and in fatbody increased to 1.13 folds. Correspondingly, the expression levels of detoxifying enzyme genes CYP6ae22, CYP9a21, GSTo1 and Bmcce were increased to 15.99, 3.32, 1.86 and 2.30 folds in the midgut and to 3.58, 1.84, 2.14 and 4.21 folds in the fatbody after phoxim treatment. These results demonstrated the important roles of detoxification enzymes in phoxim metabolism. In addition, the detected activities of such enzymes were generally lower than those in cotton bollworms (Helicoverpa armigera), which may contribute to the high susceptibility of B. mori to insecticides. Our findings laid the foundation for further investigations of the molecular mechanisms of organophosphorus pesticide metabolism in B. mori.

Transcriptional characteristics of gene expression in the midgut of domestic silkworms (Bombyx mori) exposed to phoxim.

Silkworm (Bombyx mori) is not only an economically important insect but also a model system for lepidoptera. As a vital organ of digestion and nutrient absorption, the midgut of insects also serves as the first physiological barrier to chemical pesticides. In this study, microarray was performed to profile the gene expression changes in the midgut of silkworms exposed to phoxim. After 24h of phoxim exposure (4.0µg/mL), 266 genes displayed at least 2.0-fold changes in expression levels. Among them, 192 genes were up-regulated, and 74 genes were down-regulated. The most significant changes were 14.88-fold up-regulation and 23.36-fold down-regulation. According to gene ontology annotation and pathway analysis, differentially expressed genes were mainly classified into different groups based on their potential involvements in detoxification, immunne response, stress response, energy metabolism and transport. Particularly, the transcription levels of detoxification-related genes were up-regulated, such as cytochrome P450s, esterases and glutathione-S-transferase (GST), indicating increased detoxification activity in the midgut. Our study provides new insights into the molecular mechanism of pesticide metabolism in the midgut of insects, which may promote the development of highly efficient insecticides.

Age variation and sexual dimorphism in the sixteen diagnostic clusters of risk factors for the metabolic syndrome.

OBJECTIVE: To document age- and sex-related differences in the 16 phenotypes of risk factors for the metabolic syndrome (MS) among adults in the Fels Longitudinal Study (FLS). METHODS: Data on risk factors for the MS were analyzed in 471 white men and 503 white women in the FLS. We used the Cochran-Armitage test to compare age- and sex-related differences in the prevalence of the 16 diagnostic clusters of positive risk factors. RESULTS: Of the 974 subjects, 238 were found to meet diagnostic criteria for 15 of a possible 16 phenotypes of the MS. The prevalence of the MS was four times greater in subjects older than 40 years than in subjects 20-40 years old. Older subjects had more risk factors exceeding criterion values than younger subjects. Among those who met three-to-five criteria for the MS, younger subjects were more likely to have dyslipidemia, less likely to have high blood pressure (HBP), and two times less likely to have impaired fasting plasma glucose (IFG) than subjects 40+ years old. Older men were more likely than older women to have HBP and IFG. . We found that if one of the five risk factors reaches a criterion value, the values for the other four risk factors move closer to their own diagnostic criterion values in apparent synchrony. CONCLUSIONS: Subjects 40+ years old are four times likelier to have the MS than younger subjects, and older men are at higher risk than older women. The mean values for each of the five risk factors get progressively worse as the number of risk factors meeting diagnostic criteria increases. Therefore, when one factor is found to meet its diagnostic criterion, levels of the other four risk factors should be measured. The different phenotypic patterns that comprise the MS should prompt clinicians to target specific risk factors for prevention or treatment. Certain phenotypes were found more commonly in women and certain others more commonly in men. Similarly, certain phenotypes were found more commonly in older than in younger age groups. These age- and sex-specific phenotypes should help clinicians to identify subjects at highest risk for certain risk factors and to initiate specifically tailored preventive and therapeutic interventions. Our observations should also stimulate clinical investigators and epidemiologists to ascertain what factors determine the sex and age specificity of certain phenotypes of the MS.

Transformation of LRP gene into Brassica napus mediated by Agrobacterium tumefaciens to enhance lysine content in seeds.

Lysine rich protein (LRP) gene derived from the seed of Psophocarpus tetragonolobus was transformed into Brassica napus, employing cotyledon petiole as explants and by using the Agrobacterium tumefaciens strain LBA4404. Transformation efficiency was found to be closely related with phytohormone concentration, infection incubation, and co-cultured time. A medium containing 4 mg/l 6-benzyladenine (6-BA) and 0.3 mg/l naphthalene acetic acid (NAA) was used for plant regeneration. With infection incubation of A. tumefaciens (OD600 = 0.4) for 20 min and co-culture of infected cotyledon petiole for 3 days, the highest transformation efficiency of 8.5% was obtained. To confirm LRP gene expression, PCR and Southern blot analysis were performed on leaf-isolated DNA from regenerated plants resistant to kanamycin. All transgenic plants of the generation T0 formed fertile seeds, which were sowed for the inheritance study of generational T1 and amino acid analysis. It was found that the lysine content of seeds from T1 generation increased by 16.7% compared with non-transgenic lines.