[Sacubitril/valsartan attenuates left ventricular remodeling and improve cardiac function by upregulating apelin/APJ pathway in rats with heart failure].

Objective: To investigate the effect and mechanism of sacubitril/valsartan on left ventricular remodeling and cardiac function in rats with heart failure. Methods: A total of 46 SPF-grade male Wistar rats weighed 300-350 g were acclimatized to the laboratory for 7 days. Rats were then divided into 4 groups: the heart failure group (n=12, intraperitoneal injection of adriamycin hydrochloride 2.5 mg/kg once a week for 6 consecutive weeks, establishing a model of heart failure); heart failure+sacubitril/valsartan group (treatment group, n=12, intragastric administration with sacubitril/valsartan 1 week before the first injection of adriamycin, at a dose of 60 mg·kg-1·d-1 for 7 weeks); heart failure+sacubitril/valsartan+APJ antagonist F13A group (F13A group, n=12, adriamycin and sacubitril/valsartan, intraperitoneal injection of 100 µg·kg-1·d-1 APJ antagonist F13A for 7 weeks) and control group (n=10, intraperitoneal injection of equal volume of normal saline). One week after the last injection of adriamycin or saline, transthoracic echocardiography was performed to detect the cardiac structure and function, and then the rats were executed, blood and left ventricular specimens were obtained for further analysis. Hematoxylin-eosin staining and Masson trichrome staining were performed to analyze the left ventricular pathological change and myocardial fibrosis. TUNEL staining was performed to detect cardiomyocyte apoptosis. mRNA expression of left ventricular myocardial apelin and APJ was detected by RT-qRCR. ELISA was performed to detect plasma apelin-12 concentration. The protein expression of left ventricular myocardial apelin and APJ was detected by Western blot. Results: Seven rats survived in the heart failure group, 10 in the treatment group, and 8 in the F13A group. Echocardiography showed that the left ventricular end-diastolic diameter (LVEDD) and the left ventricular end-systolic diameter (LVESD) were higher (both P<0.05), while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the heart failure group than in the control group (both P<0.05). Compared with the heart failure group, rats in the treatment group were featured with lower LVEDD and LVESD (both P<0.05), higher LVEF and LVFS (both P<0.05), these beneficial effects were reversed in rats assigned to F13A group (all P<0.05 vs. treatment group). The results of HE staining showed that the cardiomyocytes of rats in the control group were arranged neatly and densely structured, the cardiomyocytes in the heart failure group were arranged in disorder, distorted and the gap between cells was increased, the cardiomyocytes in the treatment group were slightly neat and dense, and cardiomyocytes in the F13A group were featured similarly as the heart failure group. Masson staining showed that there were small amount of collagen fibers in the left ventricular myocardial interstitium of the control group, while left ventricular myocardial fibrosis was significantly increased, and collagen volume fraction (CVF) was significantly higher in the heart failure group than that of the control group (P<0.05). Compared with the heart failure group, the left ventricular myocardial fibrosis and the CVF were reduced in the treatment group (both P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). TUNEL staining showed that the apoptosis index (AI) of cardiomyocytes in rats was higher in the heart failure group compared with the control group (P<0.05), which was reduced in the treatment group (P<0.05 vs. heart failure group), this effect again was reversed in the F13A group (P<0.05 vs. treatment group). The results of RT-qPCR and Western blot showed that the mRNA and protein levels of apelin and APJ in left ventricular myocardial tissue of rats were downregulated in heart failure group (all P<0.05) compared with the control group. Compared with the heart failure group, the mRNA and protein levels of apelin and APJ were upregulated in the treatment group (all P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). ELISA test showed that the plasma apelin concentration of rats was lower in the heart failure group compared with the control group (P<0.05); compared with the heart failure group, the plasma apelin concentration of rats was higher in the treatment group (P<0.05), this effect was reversed in the F13A group (P<0.05 vs. treatment group). Conclusion: Sacubitril/valsartan can partially reverse left ventricular remodeling and improve cardiac function in rats with heart failure through modulating Apelin/APJ pathways.

[Correlation among serum levels of Irisin, insulin resistance and abdominal obesityin patients with first-episode schizophrenia].

Objective: To explore the possible role of Irisin in antipsychotic drug-induced insulin resistance and abdominal obesity in patients with schizophrenia and to provide a theoretical basis for the prevention of antipsychotic drug-induced obesity. Methods: Fifty-five patients with first-episode schizophrenia, from the First Affiliated Hospital of Zhengzhou University, between January 2016 and December 2017, were admitted as well as fifty healthy controls during the same period. Serum Irisin levels were measured by enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose (FBG), fasting insulin (INS), homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride (TG), total cholesterol (TCHO), highdensity lipoprotein (HDL), low density lipoprotein (LDL) were detected. Results: The average Irisin level ((233±228) mmol/L) was higher than that in the normal control group ((124±89) mmol/L) (P<0.05).Repeated measurement analysis of variance showed that the average levels of the height, waist, FBG, INS, TCHO, TG, HDL, LDL, BMI, HOMA-IR and Irisin at the end of the 12(th) and 24(th) week's treatment were higher than baseline (P<0.05). After correlation analysis, the level of Irisinat baseline was positively correlated with HOMA-IR (r=0.383, P<0.05). At the 12(th) week, the level of Irisin was positively correlated with waist circumference, and HOMA-IR (r=0.360, r=0.475, all P<0.05). Multiple linear regression analysis showed that at the 12(th) week's treatment, compared with the baseline period, changes of Irisin was positively correlated with waist circumference and HOMA-IR, respectively (ß=0.453, ß=0.420, both P<0.05). Conclusion: Irisin may be involved in the process of metabolic regulation and bean early predictor of antipsychotic drug-induced insulin resistance and abdominal obesity.

[Effects of oxidative stress on cognitive impairment in first episode schizophrenia].

Objective: To observe the relationship between serum oxidative stress as well as brain-derived neurotrophic factor (BDNF) and cognitive function in first-episode drug-free schizophrenics, and to explore the possible effect of oxidative stress in cognitive impairment of first-episode schizophrenia. Methods: A total of 125 first-episode drug-free schizophrenics (schizophrenia group) from the First Affiliated Hospital of Zhengzhou University and 80 healthy individuals (control group) were enrolled. The serum concentration of oxidized glutathione (GSSG) was measured by the Microenzyme method the serum concentration of nitric oxide (NO) was measured by one-step method, the BDNF level was measured by enzyme linked immunosorbent assay and Matrics Consensus Cognitive Battery(MCCB) was used to evaluate the cognitive function. Results: (1)The serum level of BDNF in schizophrenia group (2 763±1 728 pg/ml) was significantly lower than that in control group (4 165±1 299 pg/ml)(P<0.001). And the serum levels of GSSG and NO in schizophrenia group ((36±9), (81±65) µmol/L) were significantly higher than that in control group ((27±11), (24±16) µmol/L) (P<0.001). In comparison with the control group scores were significantly lower in the seven domains of cognitive function in the schizophrenia group (all P<0.001). (2)After controlling the confounding factors like age, gender, cultural differences and course of disease by partial correlation analysis, the correlation analysis showed that: serum level of BDNF in schizophrenia group had positive correlation with Information processing rate T points, attentional facilitating T points, working memory T points and Reasoning and problem solving T points (r=0.417, 0.206, 0.247, 0.318, all P<0.05). In schizophrenia group the serum level of GSSG had a negative correlation with information processing rate T points and reasoning and problem solving T points (r=-0.321, -0.231, all P<0.05). The serum level of NO was negatively related to Information processing rate T points working memory T points Verbal learning T points(r=-0.201, -0.193, -0.237, all P<0.05). Conclusions: Oxidative stress may be involved in the cognitive impairment of schizophrenia Oxidation products are risk factors for cognitive impairment of schizophrenia and BDNF is a protective factor of cognitive function.

Colletotrichum species associated with anthracnose of Pyrus spp. in China.

Colletotrichum species are plant pathogens, saprobes, and endophytes on a range of economically important hosts. However, the species occurring on pear remain largely unresolved. To determine the morphology, phylogeny and biology of Colletotrichum species associated with Pyrus plants, a total of 295 samples were collected from cultivated pear species (including P. pyrifolia, P. bretschneideri, and P. communis) from seven major pear-cultivation provinces in China. The pear leaves and fruits affected by anthracnose were sampled and subjected to fungus isolation, resulting in a total of 488 Colletotrichum isolates. Phylogenetic analyses based on six loci (ACT, TUB2, CAL, CHS-1, GAPDH, and ITS) coupled with morphology of 90 representative isolates revealed that they belong to 10 known Colletotrichum species, including C. aenigma, C. citricola, C. conoides, C. fioriniae, C. fructicola, C. gloeosporioides, C. karstii, C. plurivorum, C. siamense, C. wuxiense, and two novel species, described here as C. jinshuiense and C. pyrifoliae. Of these, C. fructicola was the most dominant, occurring on P. pyrifolia and P. bretschneideri in all surveyed provinces except in Shandong, where C. siamense was dominant. In contrast, only C. siamense and C. fioriniae were isolated from P. communis, with the former being dominant. In order to prove Koch's postulates, pathogenicity tests on pear leaves and fruits revealed a broad diversity in pathogenicity and aggressiveness among the species and isolates, of which C. citricola, C. jinshuiense, C. pyrifoliae, and C. conoides appeared to be organ-specific on either leaves or fruits. This study also represents the first reports of C. citricola, C. conoides, C. karstii, C. plurivorum, C. siamense, and C. wuxiense causing anthracnose on pear.

[Correlation of serum level of homocysteine and insulin resistance with cognitive dysfunction in first-episode schizophrenics].

Objective: To explore the relationship of serum level of homocysteine (Hcy) and insulin resistance with cognitive function in first-episode drug-free schizophrenics. Methods: A total of 80 first-episode drug-free schizophrenics (schizophrenia group) from the First Affiliated Hospital of Zhengzhou University and 70 healthy individuals (control group) were enrolled.The serum concentration of Hcy was measured by the enzymatic cycling assay, the concentration of serum fast blood-glucose(FPG) by glucose oxidase method and fast insulin (FINS) by electrical chemiluminescence immunoassay.Then insulin resistance index was calculated in the form of HOMA-IR.Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate the cognitive function. Results: (1) The serum level of Hcy in schizophrenia group [(24±6) µmoL/L]was significantly higher than that in control group[(16±4) µmoL/L] (P<0.001). And the serum level of FINS in schizophrenia group [(8.0±2.1) mU/L] was significantly higher than that in control group[(6.0±1.3) mU/L] (P<0.001). The HOMA-IR of schizophrenia group (1.6±0.5) was higher than that of control group (1.3±0.4) (P<0.001). The serum level of Hcy in schizophrenia group had positive correlations with serum FINS level, HOMA-IR and negative symptoms (r=0.365, 0.354 and 0.233, all P<0.05). In comparison with the control group , scores were significantly lower in the seven domains of cognitive function in the schizophrenia group (all P<0.05). (2) In schizophrenia group, the serum level of Hcy had a negative correlation with Information processing rate P points, Attentional facilitating P points , and Verbal learning P points (r=-0.231, -0.339, -0.255, all P<0.05); the serum level of FINS was negatively related to Attentional facilitating P points, Working memory P pointsand Visual memory P points (r=-0.317, -0.309, -0.318, all P<0.05); HOMA-IR had a negative correlation with Attentional facilitating P points, Working memory P points, and Visual memory P points (r=-0.286, -0.224, -0.266, all P<0.05). After the influencing factors were adjusted by multiple regression, the associations of serum Hcy level with Information processing rate P points, Attentional facilitating P points and Verbal learning P points were still evident, and HOMA-IR was still related with Attentional facilitating P points and Visual memory P points (all P<0.05). Conclusion: The increase of serum Hcy and insulin resistance in first-episode schizophrenics, both have some relevance with cognitive dysfunction.

[Survey of the depressive disorders prevalence and related risk factors among male new drug users in certain drug rehabilitation center of Changsha city].

Objective: To understand the depressive disorders prevalence and related risk factors among new drug users in a male drug rehabilitation center. Methods: The cross-sectional study was used. A total of 250 new drug users from a male drug rehabilitation center were recruited during March, 2017. The drug users who only use new type of drugs single or use traditional drugs at the same time were collected as the new drug users. Their general information and drug-related information were collected by self-made questionnaire, and depressive disorders and sleep quality information were collected by the self-reported Patient Health Questionnaire-9 (PHQ-9) and the self-reported Pittsburgh Sleep Quality Index Questionnaire respectively. Logistic regression test was used to establish associations between variables. Results: Of all 250 drug users, the mean age (P(25), P(75)) was 30 (26, 35) years old, and 32.8% (82) had the depressive disorders. The individuals taking drug dose over 0.4 g daily before entering drug rehabilitation center had significantly more risk of the depressive disorders for 3.18 (1.71-5.90) than those not over 0.4 g daily.The individuals who bad sleep quality had significantly more risk of the depressive disorders for 6.07 (95%CI:3.31-11.12) than those had good sleep quality.The individuals who were depressive patients before the first drug use for 2.39 (95%CI: 1.12-5.10) than those were not depressive patients before the first drug use. Conclusion: There were a high rate of the depressive disorders among new drug users in the rehabilitation center; In addition, several risk factors including the individuals taking drug dose over 0.4 g daily and bad sleep quality, history of the depressive disorders were negatively associated with depressive disorders.

Comparative proteomic analysis of different developmental stages of swamp buffalo testicular seminiferous tubules.

With ageing, many protein components change markedly during mammalian spermatogenesis. Most of these proteins have yet to be characterized and verified. Here, we have employed two-dimensional electrophoresis coupled to tandem mass spectrometry to explore the different proteins from pre-pubertal, pubertal and post-pubertal swamp buffalo testicular seminiferous tubules. The results showed that 25 protein spots were differentially expressed among developmental stages, and 13 of them were successfully identified by mass spectrometry. Of which four proteins were up-regulated and three proteins were down-regulated with age, and the remaining six proteins were fluctuated among developmental stages. Bioinformatics analysis indicates that these proteins were probably related to cellular developmental process (53.8%), cell differentiation (53.8%), spermatogenesis (15.4%), apoptotic process and cell death (30.8%). Expression profiles of calumenin (CALU) and galectin-1 (LGALS1) were further verified via Western blotting. In summary, the results help to develop an understanding of molecular mechanisms associated with buffalo spermatogenesis.

Relieving effect of Artemisia argyi aqueous extract on immune stress in broilers.

This experiment aimed to investigate the relieving action of Artemisia argyi aqueous extract (AAE) on immune stress in broiler chickens. A 2 × 2 factorial design was used to test the effect of 2 dietary treatments (adding 0 or 1000 mg/kg AAE) and 2 immune stress treatments (injecting saline or lipopolysaccharide (LPS)). A total of 96 one-day-old Arbor Acres (AA) broilers were randomly divided into four treatment groups with six replicates, four birds in each replicate. Broilers in Treatment groups 1 and 2 were fed with the basal diet, and those in Treatment groups 3 and 4 were fed with the experimental diet supplemented with 1000 mg/kg AAE. On days 14, 16, 18 and 20, broilers in both Treatments 1 and 3 were injected intra-abdominally with LPS solution at the dose of 500 µg LPS per kg BW with the LPS dissolved in sterile saline at a concentration of 100 µg/ml, and those in Treatments 2 and 4 were injected intra-abdominally with equal amount of sterile 0.9% saline. Blood samples were collected on days 21 and 28. The results showed that dietary supplementation of AAE prevented reductions in average daily gain (ADG) and average daily feed intake (ADFI) of broilers caused by LPS on d 15-21. On day 21, the injection of LPS increased serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT); meanwhile, feeding AAE reduced the rise of CORT caused by LPS. Immune parameters such as interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), immunoglobulin G (IgG) and immunoglobulin A (IgA) were also improved by LPS, but the content of IL-2 and IgG in broilers fed with AAE diet was significantly lower than that of broilers fed with control diet. All the data suggested that diets supplemented with AAE could relieve the immune stress response of broilers.

MYBA2 gene involved in anthocyanin and flavonol biosynthesis pathways in grapevine.

MYBA2 transcription factor (Myb-related gene) affects the coloring in grapevine berry and plays an important role in the biosynthesis of anthocyanin. The MYBA2 gene was cloned from Vitis vinifera L. cv. Cabernet Sauvignon and polyclonal antibodies for VvmybA2 were prepared. The VvmybA2 gene expression patterns were observed in seven tissues (the leaf, stem, flower, bud, root, berry, and tendril) and during the berry development stage at transcriptional and translational levels, respectively. The results indicated that the expression of VvmybA2 was approximately 11-fold higher in the berry than that in the other six tissues, and increased rapidly from 60 days after full bloom reaching a maximum on day 80. Furthermore, both the anthocyanin content and UDP-glucose:flavonoid-3-O-glucosyltransferase (UFGT) gene expression levels increased rapidly 60 days after full bloom. Moreover, correlation analysis indicated that the transcriptional and translational expression levels of the VvmybA2 gene were significantly positively correlated with not only UFGT and DFR genes but also with the anthocyanin content during berry development. These results suggested that VvmybA2 could not only regulate the transcription of both UFGT and DFR but also is involved in the expression of the UFGT gene associated with color determination in grape berries.

[Apoptosis and expression of Caspase 3 and Caspase 4 in neurocytes of refractory human temporal lobe epilepsy].

OBJECTIVE: To study apoptosis and expression of Caspase 3 and Caspase 4 in temporal lobe neurocytes of refractory human temporal lobe epilepsy (TLE). METHODS: The temporal tissue samples were obtained from 30 cases of refractory TLE (TLE group) and 10 cases of brain trauma (contrast group) between January 1993 and May 2008. The surgical specimens were paraffin-embedded samples from Department of Pathology of Fujian Medical University and Department of Neurosurgery, the First Affiliated Hospital of Fujian Medical University. S-P staining of immunohistochemistry was used to detect the expression of Caspase 3 and Caspase 4 in temporal lobe neurocytes of TLE group and contrast group. Their expression was then analyzed. The terminal deoxynucleoitidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to visualize and analyze the neurocytes' apoptosis of two groups. RESULTS: The expression of Caspase 3 and Caspase 4 in neurocytes of TLE group were both higher than that of contrast group (t=12.905, P<0.01; t=11.880, P<0.01). The apoptotic index (AI) of neurocytes in TLE group also increased than that of contrast group (t=9.664, P<0.01). CONCLUSION: Caspase 3 and Caspase 4 may mediate neurocytes apoptosis in temporal lobe tissue of refractory human TLE.

Ca/Mg infusions for the prevention of oxaliplatin-related neurotoxicity in patients with colorectal cancer: a meta-analysis.

BACKGROUND: Oxaliplatin-related neurotoxicity is the main limitation for its continuation in adjuvant and palliative chemotherapy for patients with colorectal cancer. The purpose of this meta-analysis was to determine the efficacy of calcium and magnesium (Ca/Mg) infusions in oxaliplatin-induced neurotoxicity. METHODS: Two independent authors conducted database searches of the literature to find clinical-controlled trials analyzing Ca/Mg infusions in oxaliplatin-induced neurotoxicity. The keywords used to search were oxaliplatin, neurotoxicity, calcium, magnesium, neuropathy, and peripheral. Clinical studies that included at least one primary or secondary event were eligible for the analysis, where primary events were incidences of acute and cumulative neurotoxicity, and secondary events were the total doses and cycles of oxaliplatin, response rate (RR), overall survival (OS), and progression-free survival (PFS). Odds ratios (ORs) and weighted mean differences (MD) were analyzed using models of fixed and random effects. RESULTS: This meta-analysis comprised four prospective randomized clinical trials and three retrospective clinical trials involving 1170 colorectal cancer patients, of which 802 received Ca/Mg infusions (Ca/Mg group) and 368 did not (control group). According to the National Cancer Institute-Common Terminology Criteria for Adverse Events, the incidence of grade 3 acute neurotoxicity in those who received Ca/Mg was significantly lower than that of the control group (OR=0.26; 95% confidence interval (CI), 0.11 to 0.62; P=0.0002). The total rate of cumulative neurotoxicity, and that of grade 3 in particular, was significantly lower in the Ca/Mg group than in the control group (OR=0.42; 95% CI 0.26-0.65; P=0.0001; OR=0.60; 95% CI 0.39-0.92; P=0.02, respectively). The differences in total doses and cycles of oxaliplatin were also significant between the Ca/Mg and control group (MD=246.73 mg/m2; 95% CI 3.01-490.45; P=0.05; MD=1.55; 95% CI 0.46-2.63; P=0.005, respectively). No significant differences were found in median PFS (MD=0.71 month; 95% CI -0.59-2.01; P=0.29), median OS (MD=0.10 month; 95% CI -0.41-0.61; P=0.70) or RRs (OR=0.82; 95% CI 0.61-1.10; P=0.18). CONCLUSION: Ca/Mg infusions tend to decrease the incidence of oxaliplatin-induced acute and cumulative neurotoxicity and thus enhance patients' tolerance to oxaliplatin, without significantly altering the efficacy of chemotherapy.

[Current status of influencing factors for postoperative anastomotic leakage in low rectal cancer].

The incidence of anastomotic leakage, a common and serious postoperative complication of low rectal cancer, remains high. Clarifying the risk factors for anastomotic leakage in patients with low rectal cancer after surgery can help guide clinical treatment and help patients improve their prognosis. The current literature suggests that the risk factors affecting the occurrence of anastomotic leakage after low rectal cancer include three aspects: (1) individual factors: male gender, high body mass index, malnutrition, smoking, alcoholism, and metabolic diseases; (2) tumor factors: the lower margin of tumor <5 cm from the anal verge, tumor diameter >2.5 cm, late tumor stage, high level of tumor markers and preoperative intestinal obstruction; (3) surgical factors: long operative time (>180 min), intraoperative bleeding (≥70 ml), more than 2 cartridges of stapling for anastomosis, contamination of the operative field, epidural analgesia and intraoperative hypothermia. Notably, the surgical approach (laparoscopic, open and hand-assisted laparoscopic surgery) was not a factor influencing the occurrence of postoperative anastomotic leakage in low rectal cancer. The findings on the effects of receiving neoadjuvant therapy, gut microbiota,intestinal bowel preparation, insufficient time for preoperative antibiotic prophylaxis, left colonic artery dissection, intraoperative blood transfusion, pelvic drainage, transanal drainage and combined organ resection, and postoperative diarrhea on postoperative anastomotic leakage in low rectal cancer are controversial. However, clinical workers can still take measures to reduce the risk of anastomotic leakage according to the above risk factors by making a good assessment before surgery, actively avoiding them during and after surgery, and taking measures for each step, so as to bring maximum benefits to patients.

A gamma ray spectrometer with Compton suppression on the HL-2A tokamak.

A new broad-energy, high-resolution gamma ray spectrometer (GRS) with Compton suppression function has been developed recently in the HL-2A tokamak to obtain the gamma ray information in the energy range of 0.1-10 MeV. This is the first time to develop an anti-Compton GRS for a magnetic confinement fusion device. The anticoincidence detector consists of a large-volume high purity germanium (HPGe) crystal (Φ63 × 63 mm2) as the primary detector and eight trapezoidal bismuth germinate (BGO) scintillators (trapezoid crystal with 30 mm thickness) as the secondary detector. The anti-coincidence data processing is implemented by a digital-based data acquisition system with fast digitization and software signal processing technology. Using radioisotope gamma ray sources and Monte Carlo N-Particle code, the energy and efficiency of the spectrometer have been calibrated and quantitatively tested. The Compton continuum suppression factor reaches 4.2, and the energy resolution (Full Width at Half Maximum) of the 1.332 MeV full energy peak for 60Co is 2.1 keV. Measurements of gamma ray spectra with Compton suppression using the spectrometer have been successfully performed during HL-2A discharges with different conditions. The performance of the spectrometer and the first experimental results are presented in this paper.

Quantitative proteome analysis reveals annexin A3 as a novel biomarker in lung adenocarcinoma.

Metastasis is a common phenomenon and the major lethal cause of lung adenocarcinoma (AdC). To discover novel potential biomarkers associated with lymph node metastasis and prognosis in lung AdC, we assessed differences in protein expression between primary lung AdC with (LNM AdC) and without lymph node metastasis (non-LNM AdC) using a quantitative proteomic approach. Laser capture microdissection was performed to purify the cancer cells from primary lung AdC tissues. The differential proteins between the pooled microdissected non-LNM AdC and LNM AdC tissues were identified by two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). In this study, twenty proteins were found to be differentially expressed in two types of lung AdC. ANXA3, significantly up-regulated in LNM AdC compared with non-LNM AdC, was validated by western blotting. Immunohistochemistry showed that ANXA3 over-expression was frequently observed in LNM AdCs and matched lymph node metastases compared with non-LNM AdCs. ANXA3 over-expression was significantly associated with advanced clinical stage (p < 0.001) and lymph node metastasis (p < 0.001) and increased relapse rate (p < 0.001) and decreased overall survival (p < 0.001) in lung AdCs. Cox regression analysis indicated ANXA3 over-expression was an independent prognostic factor. Our results indicate that ANXA3 might serve as a novel biomarker for lymph node metastasis and prognosis in lung AdC, and play an important role in lung AdC progression.

Comparative proteomic analysis of beta-catenin-mediated malignant progression of esophageal squamous cell carcinoma.

beta-catenin has emerged as a key regulator of Wnt signaling pathway, which plays an important role in the development and progression of various cancers. Its accumulation in nucleus of the esophagus squamous epithelium might be the crucial step for the carcinogenesis of esophageal squamous cell carcinoma (ESCC). To detect the proteins correlated with beta-catenin function, we used the established cell lines of pGen-3-con (Eca109 cells transfected by control vector) and pGen-3-CTNNB1 (Eca109 cells transfected by beta-catenin siRNA) as cell models for further analysis. Two-dimensional gel electrophoresis technology was performed to separate the proteins of pGen-3-con and pGen-3-CTNNB1 cell lines, respectively. The differential protein spots were analyzed by software analysis, subjected to in-gel digestion, and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Consequently, 13 differentially expressed proteins between the two cell lines were identified, of which 14-3-3sigma, prohibitin, and nm23-H1 were further verified by western blotting and quantitative real-time reverse transcriptase-polymerase chain reaction. Then, the tissue microarray and immunohistochemical analysis were employed to research their relationship in ESCC and their corresponding normal mucosa tissues. The upregulation of prohibitin or the downregulation of 14-3-3sigma and nm23-H1 proteins was significantly associated with the proliferation, invasion depth, and lymph node metastasis of ESCC. There were statistically significant correlations between the expression of beta-catenin and the three proteins. The results presented here might provide potential protein markers to elucidate the mechanism of beta-catenin-mediated biologic characteristics for ESCC.

Cost-effectiveness analysis of capecitabine plus bevacizumab versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer from Chinese societal perspective.

PURPOSE: The aim of the study was to evaluate the cost-effectiveness of capecitabine plus bevacizumab compared with capecitabine alone in elderly patients with metastatic colorectal cancer (CRC) from a Chinese societal perspective. METHODS: A decision-analytic Markov model was conducted to simulate the process of metastatic CRC. Three distinct health states: progression-free survival (PFS), progressive disease and death were included. Clinical data were derived from the AVEX trial. Health effectiveness was denoted in quality-adjusted life years (QALYs) and health utilities were derived from previously published studies. Incremental cost-effectiveness ratio (ICER) was regarded as the primary endpoint and willingness-to-pay (WTP) threshold was set at $26,753.37/QALY (3 × per capita GDP of China, 2017). One-way sensitivity analyses and probabilistic sensitivity analysis were also performed to explore the parameters uncertainty in the study. RESULTS: Over a 10-year life horizon, capecitabine plus bevacizumab gained 1.14 QALYs at an average cost of $21,609.48, while the effectiveness and cost of capecitabine group were 0.99 QALYs and $7274.83, respectively. The ICER between the two groups was $95,564.33/QALY. Parameters that mostly influenced the results of the model were utility of PFS state, duration of PFS state for capecitabine plus bevacizumab, total cost of PFS state for capecitabine plus bevacizumab and price of bevacizumab. The probabilities of capecitabine plus bevacizumab and capecitabine as the dominant option were 0% and 100% at the WTP threshold of $26,753.37/QALY. CONCLUSIONS: The results of the study showed that capecitabine plus bevacizumab is unlikely to be a cost-effective treatment option for elderly patients with metastatic CRC.

[Multicenter investigation of extracorporeal membrane oxygenation application in pediatric intensive care unit in China].

Objective: To survey the conduction and evaluate the effectiveness of extracorporeal membrane oxygenation (ECMO) therapy in pediatric intensive care unit (PICU) in China mainland. Methods: In a questionnaire-based survey, we retrospectively reviewed the application of ECMO in children's hospital and general hospital in China mainland to summarize and analyze the categories of diseases and prognosis of children treated with ECMO therapy. Results: By December 31, 2017, a total of 23 hospitals using ECMO, including 22 tertiary referral hospitals and 1 secondary hospital, among which 16 were children's hospitals and 7 were general hospitals. Thirty-seven ECMO equipment was available. A total of 518 patients treated with ECMO, within whom 323 (62.4%) successfully weaned from ECMO and 262 (50.6%) survived to discharge. Among 375 pediatric patients, 233 (62.1%) were successfully weaned from ECMO and 186 (49.6%) survived to discharge. Among 143 newborn patients, 90 (62.9%) successfully weaned from ECMO, 76 (53.1%) survived to discharge. ECMO was applied in veno-arterial (VA) mode to 501 (96.7%) patients, veno-venous (VV) mode to 14 (2.7%) patients, and VV-VA conversion mode to 3 (0.6%) patients. Sixty-nine patients required extracorporeal cardiopulmonary resuscitation (ECPR), including 20 newborn patients (29.0%) and 38 pediatric patients (71.0%), who were all with cardiovascular disease. Neonatal respiratory distress syndrome (26/61), persistent pulmonary hypertension of the newborn (PPHN) (12/61), and meconium aspiration syndrome (MAS) (11/61) are the most common pulmonary diseases in newborn patients; among whom, infants with PPHN had highest survival rate (10/12), followed by MAS (9/11). Among newborn patients with cardiovascular diseases, those who admitted were after surgery for congenital cardiac disease were the most common (54/82), while those with septic shock had the highest survival rate (2/3). In pediatric pulmonary diseases, acute respiratory distress syndrome was the most common (42/93), while plastic bronchitis was with the highest survival rate (4/4), followed by viral pneumonia (13/16). Among pediatric cardiovascular diseases, congenital cardiac defect was the most common (124/282), while fulminant myocarditis had the highest survival rate (54/77). Conclusion: The application of ECMO as a rescue therapy for children with severe cardiopulmonary failure has dramatically developed in China mainland.

[Shen cha zheng ji yan fang (Inspection of the Collection of TCM Proved Prescriptions) , the first official collection of proved prescriptions in Modern China].

Yan Xishan, the local ruler of Shanxi Province in modern period, claiming that the folk TCM prescriptions should be collected, inspected and maintained because of its definite effect. The government of Shanxi Province provided a lot of resources in collecting TCM proved prescriptions since 1929. The TCM Improving Society of Shanxi made more effort on the inspecting process, with a reasonable incentive system and standardized methods established. As a result, the Shen cha zheng ji yan fang (Inspection of the Collection of TCM Proved Prescriptions) was published, characterized by the principles of "cheap, convenient and effective" . It was the beginning of official collection and collation of TCM proved prescriptions in modern China.

Long non-coding RNA LINC00261 sensitizes human colon cancer cells to cisplatin therapy.

Colon cancer is one of the most common digestive tumors. The present study aimed to explore the functional role, as well as the underlying mechanism of long non-coding RNA LINC00261 in colon cancer. Expression of LINC00261 was analyzed in colon cancer cell lines and human normal cell lines. Acquired resistance cell lines were then built and the acquired resistance efficiency was detected by evaluating cell viability. Thereafter, the effects of LINC00261 overexpression on cisplatin-resistant colon cancer cells were measured, as well as cell apoptosis, viability, migration, and invasion. Subsequently, we investigated the interaction of LINC00261 and ß-catenin. The results showed that the LINC00261 gene was down-regulated in colon cancer cell lines and tissues, and in cisplatin-resistant cells. LINC00261 overexpression might relieve cisplatin resistance of colon cancer cells via promoting cell apoptosis, and inhibiting cell viability, migration, and invasion. Moreover, LINC00261 might down-regulate nuclear ß-catenin through restraining ß-catenin from cytoplasm into nuclei or it could also promote ß-catenin degradation and inhibit activation of Wnt pathway. Finally, LINC00261 reduced cisplatin resistance of colon cancer in vivo and enhanced the anti-colon cancer effect of cisplatin through reducing tumor volume and weight.

[The first official organization of traditional Chinese medicine in modern China-TCM Improvement Research Association].

In modern China, most of the mass organizations of traditional Chinese medicine (TCM) were civilian and established by the individuals with self support financially.The TCM Improvement Research Association of Shanxi Province was the first official TCM organization in modern China. For the purpose of ruling and recognition of TCM, Yan Xishan, the chief executive of Shanxi province, gave a full support to its creation, development, and operation of the Association with the military and political officials in the government served as part-time staff members of a few of important position in the Association. The Association was given funding and policy support by official ways. The local administrative departments cooperated with the Association affairs actively. Because of the stable organization and the abundant fund, the TCM Improvement Research Association developed quickly and steadily. As a result, the Association had been playing an important and increasing role in academic research, TCM education, medical and epidemic prevention and so on. It had become one of the great national TCM academic societies with prolonged existence. As an official Association, it was characterized with a dual property: a better foundation for development and little independency.