[Efficacy of high-dose dual therapy for Helicobacter pylori infection eradication in servicemen: a randomized controlled trial].

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ2=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ2<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ2<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ2=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ2=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.

Proximate Mechanisms of Host Plant Location by a Specialist Phytophagous Insect, the Grape Berry Moth, Paralobesia Viteana.

There are contrasting hypotheses regarding the role of plant volatiles in host plant location. We used the grape berry moth (GBM; Paralobesia viteana)-grape plant (Vitis spp.) complex as a model for studying the proximate mechanisms of long distance olfactory-mediated, host-plant location and selection by a specialist phytophagous insect. We used flight tunnel assays to observe GBM female in-flight responses to host (V. riparia) and non-host (apple, Malus domestica; and gray dogwood, Cornus racimosa,) odor sources in the form of plant shoots, extracts of shoots, and synthetic blends. Gas chromatography-electroantennographic detection and gas chromatography/mass spectrometry analyses were used to identify antennal-active volatile compounds. All antennal-active compounds found in grape shoots were also present in dogwood and apple shoots. Female GBM flew upwind to host and non-host extracts and synthetic blends at similar levels, suggesting discrimination is not occurring at long distance from the plant. Further, females did not land on sources releasing plant extracts and synthetic blends, suggesting not all landing cues were present. Additionally, mated and unmated moths displayed similar levels of upwind flight responses to all odor sources, supporting the idea that plant volatiles are not functioning solely as ovipositional cues. The results of this study support a hypothesis that GBM females are using volatile blends to locate a favorable habitat rather than a specific host plant, and that discrimination is occurring within the habitat, or even post-landing.

Favorable outcomes of culture-based Helicobacter pylori eradication therapy in a region with high antimicrobial resistance.

BACKGROUND: The eradication rate of Helicobacter pylori has declined, mainly due to antimicrobial resistance. To overcome resistance-associated treatment failure, the efficacy of culture-based, susceptibility-guided therapy was demonstrated as the first-line eradication therapy for H pylori infection. AIMS: To evaluate the efficacy of culture-based therapy as the first-line eradication therapy in regions with high levels of antimicrobial resistance. METHODS: Helicobacter pylori-positive patients without previous eradication treatment history were recommended to undergo culture to determine the minimal inhibitory concentration (MIC). If they consented, 7-day clarithromycin-containing PPI triple; 7-day esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; or 7- or 14-day esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy were administered based on the agar dilution-determined MIC. Eradication, treatment compliance, and adverse events were examined. RESULTS: In total, 74 patients were enrolled, and 69 patients completed the protocols. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 6.7%, 31.0%, 41.8%, and 39.2%, respectively. The patients were allocated to the PPI triple (n = 50), MEA (n = 8) or quadruple (n = 16) therapy. The eradication rate in the intention-to-treat analysis was 93.1% (69 of 74 patients). The eradication rates in the per-protocol analysis were 100.0% (69 of 69 patients). Epigastric pain, nausea, and vomiting were less common than those of other empirical therapies. CONCLUSIONS: Culture-based, susceptibility-guided therapy is effective first-line eradication therapy, especially in regions with high levels of antimicrobial resistance.

Kidney Transplantation in HIV-Positive Patients: A Single-Center, 16-Year Experience.

Hahnemann University Hospital has performed 120 kidney transplantations in human immunodeficiency virus (HIV)-positive individuals during the last 16 years. Our patient population represents ∼10% of the entire US population of HIV-positive kidney recipients. In our earlier years of HIV transplantation, we noted increased rejection rates, often leading to graft failure. We have established a multidisciplinary team and over the years have made substantial protocol modifications based on lessons learned. These modifications affected our approach to candidate evaluation, donor selection, perioperative immunosuppression, and posttransplantation monitoring and resulted in excellent posttransplantation outcomes, including 100% patient and graft survival at 1 year and patient and graft survival at 3 years of 100% and 96%, respectively. We present key clinical data, including a granular patient-level analysis of the associations of antiretroviral therapy regimens with long-term survival, cellular and antibody-mediated rejection rates, and the causes of allograft failures. In summary, we provide details on the evolution of our approach to HIV transplantation during the last 16 years, including strategies that may improve outcomes among HIV-positive kidney transplantation candidates throughout the United States.

Effect of CuSO4 and nano copper on serum antioxidant capacity in Weaned piglets.

Copper is the most essential trace element in the animal body. Nano-sized copper particles have been widely used in a number of different animal species in modern medicinal practice. The present study was designed to examine the effect of dietary copper sulfate/(CuSO4) and nano copper supplementation on serum antioxidant capacity of weaning piglets. A total of 28 Duroc piglets (21 days, and weighing ~7 kg) were randomly divided into three equal groups. The control group (n=4) was administered with a normal standard diet; however the CuSO4 (n=12) and nano copper (n=12) groups were treated with 50, 100 and 200 mg/kg/day body weight, respectively. After 28 days, blood serum copper-zinc superoxide dismutase (CuZn-SOD), ceruloplasmin (CP), malondialdehyde (MDA), myeloperoxidase (MPO), total antioxidant capacity (T-AOC), peroxidase (POD), nitric oxide (NO), nitric oxide synthase (NOS), hydrogen peroxide (H2O2) and inhibition of hydroxyl radical (CIHR) were analyzed from all groups. The results indicated that nano copper supplementation has significant (P less than 0.05) effect on the serum antioxidant capability as compared to dietary CuSO4 group in weaned piglets. Nano-size copper 100 mg/kg/day supplementation was confirmed to improve the immunity level by strengthening the antioxidant capacity of weaning piglets. Dietary supplementation with 100 mg/kg body weight nano copper could be a potential substitute for weaned piglets.

A prospective association between dietary folate intake and type 2 diabetes risk among Korean adults aged 40 years or older: the Korean Multi-Rural Communities Cohort (MRCohort) Study.

It has not been well established whether dietary folate intake reduces the risk of diabetes development. We aimed to clarify the prospective association between dietary folate intake and type 2 diabetes (T2D) risk among 7333 Korean adults aged 40 years or older who were included in the Multi-Rural Communities Cohort. Dietary folate intake was estimated from all 106 food items listed on a FFQ, not including folate intake from supplements. Two different measurements of dietary folate intake were used: the baseline consumption and the average consumption from baseline until just before the end of follow-up. The association between folate intake and T2D risk was determined through a modified Poisson regression model with a robust error estimator controlling for potential confounders. For 29 745 person years, 319 cases of diabetes were ascertained. In multivariable analyses, dietary folate intake was inversely associated with risk of T2D for women, not for men. For women, the incidence rate ratio of diabetes in the third tertile compared with the first tertile was 0·57 (95 % CI 0·38-0·87, P for trend=0·0085) in the baseline consumption model and 0·64 (95 % CI 0·43-0·95, P for trend=0·0244) in the average consumption model. These inverse associations was found in both normal fasting blood glucose group and impaired fasting glucose group among women. Among non-users of multinutrients and vitamin supplements, the significant inverse association remained. Thus, higher dietary intake of folate is prospectively associated with lower risk of diabetes for women.

[Correlation between serum 25-hydroxyvitamin D level and core symptoms of autism spectrum disorder in children].

Objective: To explore the relationship between serum 25-hydroxyvitamin D levels and core symptoms of autism spectrum disorder (ASD) in children. Method: In this cross-sectional study, ASD children 4 to 6 years of age who were diagnosed in Department of Developmental and Behavioral Pediatrics, First Hospital of Jilin university from January to May 2017 were assigned to ASD group, and children for routine growth and development assessment in Jilin province were assigned to control group. The two groups were well matched for age and sex, and none of them had received vitamin D supplementation. Serum 25-hydroxyvitamin D levels were measured by HPLC-MS/MS method. The patients of the ASD group were assessed with autism behavior checklist (ABC), childhood autism rating scale (CARS), social response scale (SRS), and autism treatment evaluation checklist (ATEC). The levels of vitamin D were divided into normal(>0.03 ng/L), insufficient (0.01-0.03 ng/L) and deficient (<0.01 ng/L). Levels of serum vitamin D between the two groups were compared by two independent sample t-test, and the difference in the percentages of normal, insufficient and deficient levels of vitamin D was tested by chi-square test, and correlations between vitamin D levels and the total scores or subscales of ABC, CARS, SRS and ATEC were analyzed by Pearson correlation analysis. Result: The 87 subjects in the ASD group included 75 males and 12 females, with a mean (±SD) age of (4.7±0.7) years. The 301 subjects in the control group included 249 males and 52 females, with a mean (±SD) age of (4.8±0.8) years. Serum vitamin D level in ASD children was significantly lower than that of the control group ( (0.021±0.008) vs. (0.036±0.016) ng/L, t=-8.17, P<0.01), and the between-group percentage difference of normal, insufficient and deficient levels of vitamin D was statistically significant (12 (14%) vs. 186 (62%) , 67 (77%) vs. 113 (37%) , 8 (9%) vs. 2 (1%) , χ(2)=72.1, P<0.01). There were negative correlations between serum vitamin D level in ASD children and total ABC score or ABC subscale scores (body behavior, self-care, language and social interaction)(r=-0.531,-0.397,-0.283,-0.248,-0.262, P=0.000, 0.000, 0.007, 0.020, 0.014). There were negative correlations between serum vitamin D level in ASD children and total CARS score and CARS subscale scores (imitation, nonverbal communication and general impression) (r=-0.352, -0.216, -0.248, -0.216, P=0.001, 0.046, 0.021, 0.046). There were negative correlations between serum vitamin D level in ASD children and SRS behavior subscale or ATEC social interaction subscale (r=-0.536, P=0.005, r=-0.400, P=0.014). Conclusion: Serum 25-hydroxyvitamin D level in children with ASD is obviously lower than that in the healthy control group, and there are negative correlations between vitamin D levels and core symptoms of ASD. Trial registration Chinese Clinical Trial Registry, ChiCTR-CCC-13004498.

An efflux pump (MexAB-OprM) of Pseudomonas aeruginosa is associated with antibacterial activity of Epigallocatechin-3-gallate (EGCG).

BACKGROUND: Pseudomonas aeruginosa is a notorious multidrug resistant nosocomial pathogen. An efflux pump (MexAB-OprM) is the main contributor to the multidrug resistance in clinical isolates of P. aeruginosa. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound extracted from green tea, exhibits antibacterial activity. It is unclear that molecular details of the antibacterial activity of EGCG, EGCG-effect on antibiotic susceptibility, and clinical relevance of EGCG in bacteria. PURPOSE: This study aimed to determine the roles of the efflux pump and an efflux pump inhibitor (phenylalanine-arginine ß-naphthylamide; PAßN) in the antibacterial activity of EGCG and the EGCG-effect on antibiotic susceptibility. METHODS: Twenty-two multidrug resistant clinical isolates of P. aeruginosa and a wild type P. aeruginosa PAO1 were used to determine antibacterial activity of EGCG and EGCG-effect on antibiotic susceptibility. An efflux pump (MexAB-OPrM) mutant strain, its complemented strain carrying an intact mexAB-oprM, and their parental strain were used to determine roles of MexAB-OprM in the antibacterial activity of EGCG and EGCG-mediated antibiotic susceptibility. PAßN was also used to evaluate EGCG as a possible efflux pump inhibitor. RESULTS: EGCG inhibited cellular growth and killed 100% of cells at 64-512 µg/ml and at 256-1024 µg/ml, respectively, in all tested 22 clinical isolates including the wild type strain. A subinhibitory concentration of EGCG significantly enhanced susceptibility to antibiotics, unexceptionally to chloramphenicol and tetracyclines (≥4-fold) of the clinical isolates. Both the antibacterial activity of EGCG and the EGCG-mediated antibiotic susceptibility were enhanced more in the efflux pump mutant strain (mexB::Gm) than the parental strain, suggesting additionally accumulated-EGCG produced the more antibacterial activity in the mutant strain. EGCG was synergistically interacted with PAßN with enhancing susceptibility to all tested antibiotics (up to >500-fold) at higher levels than either EGCG alone or PAßN alone, suggesting EGCG may also inhibit the efflux pump with additional accumulation of the antibiotics. CONCLUSION: The results demonstrate that EGCG exhibits antibacterial activity and enhances antibiotic effects against clinical isolates of P. aeruginosa. EGCG may inhibit the efflux pump (MexAB-OprM) through which are associated with the antibacterial activity of EGCG and the EGCG-mediated antibiotic susceptibility in P. aeruginosa.

HEMATOLOGIC AND PLASMA BIOCHEMICAL VALUES OF CINEREOUS VULTURE (AEGYPIUS MONACHUS).

The aim of this study was to establish hematologic and plasma biochemical reference intervals for clinically healthy cinereous vultures ( Aegypius monachus ) in a rehabilitation setting before release. Animals used in this study were cinereous vultures hospitalized in a wildlife center located in the province of Gyeongsangnam-do, the Republic of Korea. Blood samples were collected from 31 cinereous vultures before their release between 2011 and 2014 at the Gyeongnam Wildlife Center. Complete blood count and plasma biochemical analyses were performed within 2 hr of the blood sampling. Reference intervals were calculated from the 10th to the 90th percentile, together with the mean, SD, and lowest and highest observed values. The results of this study may be useful in evaluating the physical condition and clinical monitoring of cinereous vultures in captivity before release and contribute to the determination of reference ranges for healthy cinereous vultures.

[Clinical diagnosis and treatment of three cases with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome].

Objective: To study the clinical characteristics, methods of diagnosis and treatment of hyperornithinemia-hyperammonemia- homocitrullinuria (HHH) syndrome. Method: From July 2011 to August 2016, 3 Chinese patients with HHH syndrome were enrolled in this study. The clinical course, biochemical features, brain MRI findings, and gene mutations were analyzed. Result: The three patients' age at onset of symptoms was 3 months to 7 years, and the age of diagonosis was 3 years and 10 months to 9 years and 10 months. All of them presented with intolerance to protein-rich foods from the infant period, development retardation and abnormal posture. Case 1 and 2 had moderate mental retardation. Serum ammonia 25-276 µmol/L (reference range<60 µmol/L), alanine aminotransferase (ALT) 20-139 IU/L (reference range 9-50 IU/L), ornithine 29.12-99.44 µmol/L(reference range 15-100 µmol/L), urinary orotic acid 1.49-29.75 mmol/mol Cr (reference range 0-7 mmol/mol Cr), uracil 6.09-103.97 mmol/mol Cr (reference range 0-1.5 mmol/mol Cr). The cranial MRI revealed lesions in the basal ganglia, abnormal white matter signal, progressive demyelination and cerebral atrophy. On their SLC25A15 gene, a novel homozygous missense mutation c. 416A>G (p.E139G) was identified in case 1, a known pathogenic homozygous nonsense mutation c. 535C>T was found in case 2 and 3. Liver transplantation had been performed when case 1 was 6 years old. Significant improvements were observed in dietary habit, mental and motor functions, and biochemical parameters. After the dietary intervention with the supplements of arginine, L-carnitine, case 2 was improved, spastic paraplegia of case 3 had no mitigation. Liver transplant was recommended. Conclusion: HHH syndrome has an aversion to protein-rich food, and the patients have recurrent vomiting and progressive neurological dysfunction. Clinical diagnosis of HHH syndrome is difficult and patients may present with incomplete biochemical phenotype. The genetic analysis is key for the diagnosis. Depending on their condition, individuals with HHH syndrome can be treated with a low-protein diet, drugs and liver transplantation.

The effect of engagement in an HIV/AIDS integrated health programme on plasma HIV-1 RNA suppression among HIV-positive people who use illicit drugs: a marginal structural modelling analysis.

OBJECTIVES: HIV treatment-as-prevention campaigns emphasize early diagnosis and immediate access to care and antiretroviral therapy for HIV-positive individuals in order to increase levels of plasma HIV RNA viral load (VL) suppression. However, the possible role of harm reduction-based programmes in this objective has not yet been well evaluated. The objective of the study was to examine the relationship between being a client of the Dr. Peter Centre (DPC; an HIV/AIDS-focused adult integrated health programme) and VL suppression among highly active antiretroviral therapy (HAART)-exposed HIV-positive people who use illicit drugs (PWUD) in Vancouver, Canada. METHODS: Data were derived from the AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS) study, a study of a community-recruited cohort of HIV-positive PWUD. A marginal structural model using inverse probability of treatment weights was used to estimate the longitudinal relationship between being a DPC client and exhibiting a VL < 50 HIV-1 RNA copies/mL plasma. RESULTS: Between 2005 and 2014, 746 HAART-exposed participants were included in the study, of whom 269 (36.1%) reported being a DPC client at some time during the study period. A marginal structural model estimated a 1.54 greater odds of achieving VL suppression (95% confidence interval 1.20-1.99) among DPC clients. CONCLUSIONS: Our findings demonstrate that participating in an innovative HIV/AIDS-focused adult integrated health programme that provides a broad range of clinical, harm reduction, and support services may contribute to optimizing the benefits of HAART in terms of morbidity, mortality and viral transmission among PWUD, and as a result help to fulfill the goals of the treatment-as-prevention strategy.

Antibacterial activity of epigallocatechin-3-gallate (EGCG) and its synergism with ß-lactam antibiotics sensitizing carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

BACKGROUND: Infections caused by Acinetobacter baumannii were responsive to conventional antibiotic therapy. However, recently, carbapenem-associated multidrug resistant isolates have been reported worldwide and present a major therapeutic challenge. Epigallocatechin-3-Gallate (EGCG) extracted from green tea exhibits antibacterial activity. PURPOSE: We evaluated the antibacterial activity of EGCG and possible synergism with antibiotics in carbapenem-associated multidrug resistant A. baumannii. A potential mechanism for synergism was also explored. MATERIALS AND METHODS: Seventy clinical isolates of A. baumannii collected from geographically different areas were analyzed by minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of EGCG. Checkerboard and time-killing assays were performed to exam the synergism between EGCG and antibiotics. The effects of EGCG on a multidrug efflux pump inhibitor (1-[1-naphthylmethyl] piperazine; NMP) and ß-lactamase production were also examined in A. baumannii. RESULTS: Sixty-three of 70 clinical isolates of A. baumannii carried carbapenemase-encoding genes with carbapenem-associated multidrug resistance. Levels of MIC and MBC of EGCG ranged from 64 to 512µg/ml and from 128 to ≥1024µg/ml, respectively among the clinical isolates. MIC90 and MBC86 levels were 256µg/ml and 512µg/ml of EGCG, respectively. Subinhibitory concentration of EGCG in combination with all antibiotics tested, including carbapenem, sensitized (MICs fall≤1.0µg/ml) all carbapenem-associated multidrug resistant isolates. Checkerboard and time-killing assays showed synergism between EGCG and meropenem (or carbenicillin) counted as fractional inhibitory concentration of < 0.5 and cell numbers' decrease per ml of >2log10 within 12h, respectively. EGCG significantly increased the effect of NMP but was unrelated to ß-lactamase production in A. baumannii, suggesting EGCG may be associated with inhibition of efflux pumps. CONCLUSION: Overall we suggest that EGCG-antibiotic combinations might provide an alternative approach to treat infections with A. baumannii regardless of antibiotic resistance.

Age-Related Response of Rumen Microbiota to Mineral Salt and Effects of Their Interactions on Enteric Methane Emissions in Cattle.

Mineral salt bricks are often used in cow raising as compensation for mineral losses to improve milk yield, growth, and metabolic activity. Generally, effects of minerals are partially thought to result from improvement of microbial metabolism, but their influence on the rumen microbiota has rarely been documented to date. In this study, we investigated the response of microbiota to mineral salt in heifer and adult cows and evaluated ruminal fermentation and enteric methane emissions of cows fed mineral salts. Twelve lactating Holstein cows and twelve heifers fed a total mixed ration (TMR) diet were randomly allocated into two groups, respectively: a treatment group comprising half of the adults and heifers that were fed mineral salt and a control group containing the other half fed a diet with no mineral salt supplement. Enteric methane emissions were reduced by 9.6% (P < 0.05) in adults ingesting a mineral salt diet, while concentrations of ruminal ammonia, butyrate, and propionate were increased to a significant extent (P < 0.05). Enteric methane emissions were also reduced in heifers ingesting a mineral salt diet, but not to a significant extent (P > 0.05). Moreover, the concentrations of ammonia and volatile fatty acids (VFAs) were not significantly altered in heifers (P > 0.05). Based on these results, we performed high-throughput sequencing to explore the bacterial and archaeal communities of the rumen samples. Succiniclasticum and Prevotella, two propionate-producing bacteria, were predominant in samples of both adults and heifers. At the phylotype level, mineral salt intake led to a significant shift from Succiniclasticum to Prevotella and Prevotellaceae populations in adults. In contrast, reduced abundance of Succiniclasticum and Prevotella phylotypes was observed, with no marked shift in propionate-producing bacteria in heifers. Methanogenic archaea were not significantly abundant between groups, either in adult cows or heifers. The shift of Succiniclasticum to Prevotella and Prevotellaceae in adults suggests a response of microbiota to mineral salt that contributes to higher propionate production, which competes for hydrogen utilized by methanogens. Our data collectively indicate that a mineral salt diet can alter interactions of bacterial taxa that result in enteric methane reduction, and this effect is also influenced in an age-dependent manner.

Evolutionarily conserved dual lysine motif determines the non-chaperone function of secreted Hsp90alpha in tumour progression.

Both intracellular and extracellular heat shock protein-90 (Hsp90) family proteins (α and ß) have been shown to support tumour progression. The tumour-supporting activity of the intracellular Hsp90 is attributed to their N-terminal ATPase-driven chaperone function. What molecular entity determines the extracellular function of secreted Hsp90 and the distinction between Hsp90α and Hsp90ß was unclear. Here we demonstrate that CRISPR/Case9 knocking out Hsp90α nullifies tumour cells' ability to migrate, invade and metastasize without affecting the cell survival and growth. Knocking out Hsp90ß leads to tumour cell death. Extracellular supplementation with recombinant Hsp90α, but not Hsp90ß, protein recovers tumourigenicity of the Hsp90α-knockout cells. Sequential mutagenesis identifies two evolutionarily conserved lysine residues, lys-270 and lys-277, in the Hsp90α subfamily that determine the extracellular Hsp90α function. Hsp90ß subfamily lacks the dual lysine motif and the extracellular function. Substitutions of gly-262 and thr-269 in Hsp90ß with lysines convert Hsp90ß to a Hsp90α-like protein. Newly constructed monoclonal antibody, 1G6-D7, against the dual lysine region of secreted Hsp90α inhibits both de novo tumour formation and expansion of already formed tumours in mice. This study suggests an alternative therapeutic approach to target Hsp90 in cancer, that is, the tumour-secreted Hsp90α, instead of the intracellular Hsp90α and Hsp90ß.

Molecular cloning and characterization of a C-type lectin in yellow catfish Tachysurus fulvidraco.

This study represents the first report of a C-type lectin (ctl) in yellow catfish Tachysurus fulvidraco. The complete sequence of ctl complementary (c)DNA consisted of 685 nucleotides. The open reading frame potentially encoded a protein of 177 amino acids with a calculated molecular mass of c.y 20.204 kDa. The deduced amino-acid sequence contained a signal peptide and a single carbohydrate recognition domain with four cysteine residues and GlnProAsp (QPD) and TrpAsnAsp (WND) motifs. Ctl showed the highest identity (56.0%) to the predicted lactose binding lectin from channel catfish Ictalurus punctatus. Quantitative real-time (qrt)-PCR analysis showed that ctl messenger (m)RNA was constitutively expressed in all examined tissues in normal fish, with high expression in trunk kidney and head kidney, which was increased following Aeromonas hydrophila challenge in a duration-dependent manner. Purified recombinant Ctl (rCtl) from Escherichia coli BL21 was able to bind and agglutinate Gram-positive and Gram-negative bacteria in a calcium-dependent manner. These results suggested that Ctl might be a C-type lectin of T. fulvidraco involved in innate immune responses as receptors (PRR).

[Effects of selenium supplement on atherogenesis of ApoE-knockout mice fed high fat diet].

OBJECTIVE: To investigate the effects of selenium supplement on atherogenesis and endothelial function in ApoE-knockout mice fed high fat diet. METHODS: ApoE-knockout mice fed with selenium-deficient and high fat diet were randomly allocated into 3 groups based on random number table including control group (not supplied with sodium selenite, n=10), low dosage selenium supplement group (supplied water with 0.1 mg/L sodium selenite, n=10) and high dosage selenium supplement group (supplied water with 0.2 mg/L sodium selenite, n=10). After 15 weeks, the following values were measured: the concentrations of selenium in heart and liver, the levels of serum lipid, the parameters of antioxidant function including activities of superoxide dismutase(SOD) and glutathion peroxidase (GSH-Px) and malondialdehyde (MDA) level in serum, the parameters of endothelial function including serum nitric oxide (NO), endothelin 1(ET-1), and vascular endothelial growth factor (VEGF) levels, and ET-1 and VEGF levels in aorta roots. The atherosclerotic lesions in aorta roots were analyzed with oil red O staining. RESULTS: (1) The selenium concentrations in heart and liver were significantly higher in high dosage and low dosage selenium supplement groups compared to control group (both P<0.05). (2) The levels of triglyceride, total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol and high-density lipoprotein cholesterol were similar among groups (all P>0.05). (3) The activity levels of serum SOD were significantly higher in low dosage ((113.8±12.5)U/ml) and high dosage selenium supplement group ((152.3±11.3)U/ml) compared to control group ((90.7±10.7)U/ml, all P<0.05). The activity levels of serum GSH-Px were significantly higher in low dosage ((53.9±7.2)U/ml) and high dosage ((69.6±8.7)U/ml) selenium supplement groups than that of control group ((36.4±5.6)U/ml, all P<0.05). The serum MDA levels in low dosage ((4.73±1.05)nmol/ml) and high dosage ((4.13±1.21)nmol/ml) selenium supplement groups were significantly lower than that of control group ((5.97±1.08)nmol/ml, all P<0.05). (4) The serum NO concentrations in low dosage ((61.5±12.8)µmol/L) and high dosage ((79.0±14.6)µmol/L)selenium supplement groups were significantly higher than that of control group((42.7±9.1)µmol/L, all P<0.05). The concentrations of serum ET-1 in low dosage ((52.8±6.3)ng/L)and high dosage ((46.3±4.7)ng/L)selenium supplement groups were significantly lower than that of control group((72.2±6.3)ng/L, P<0.05). The concentrations of serum VEGF in low dosage ((97.4±16.5)ng/L)and high dosage ((83.5±22.0)ng/L)selenium supplement groups were significantly lower than that of control group((125.8±18.6)ng/L, P<0.05). The expression levels of ET-1 and VEGF in aorta roots among low dosage and high dosage selenium supplement groups were significantly lower compared to control group (all P<0.05). (5) The plaque area of aorta roots in low dosage ((0.95±0.19)×10(5) µm(2))and high dosage selenium supplement ((0.75±0.15)×10(5) µm(2)) groups were significantly smaller than that of control group((1.13±0.23)×10(5) µm(2)), and the plaque area in high dosage selenium supplement group was significantly smaller than in low dosage selenium supplement group (P<0.05). CONCLUSION: Supplement of selenium can attenuate atherogenesis in ApoE-knockout mice fed high fat diet, which is possibly mediated via reducing lipid peroxidation and improving endothelial functions.

Perioperative acupuncture modulation: more than anaesthesia.

Accumulated evidences from clinical trials and updated reviews suggest that the role of acupuncture in perioperative medicine extends beyond the classical scope of anaesthesia and has been underestimated. Perioperative acupuncture reduces not only the consumption of anaesthetics and analgesics, but also anaesthesia-related complications, and protects organs in the perioperative period. These beneficial effects make acupuncture a promising approach in perioperative management, especially with respect to enhanced surgery recovery and specific surgical populations, such as elderly patients and 'triple-low' patients. Furthermore, efforts have been made to optimize the clinical application of perioperative acupuncture.

A survey of outcomes and management of patients post fragility fractures in China.

UNLABELLED: We found that the fragility hip and vertebral fractures caused excess mortality rates in this Chinese female population, which was unexpectedly lower than those in western countries and other Asian countries. This was the first nationwide survey relating to post-fracture outcomes conducted among Chinese population in Mainland China. INTRODUCTION: This study aimed to investigate the mortality, self-care ability, diagnosis, and medication treatment of osteoporosis following fragility hip and vertebral fractures through a nationwide survey among female patients aged over 50 in Mainland China. METHODS: This was a multicenter, retrospective cohort study based on medical chart review and patient questionnaire. Female patients aged 50 or older admitted for low-trauma hip or vertebral fractures and discharged from Jan 1, 2008 to Dec 31, 2012 were followed. RESULTS: Total of 1151 subjects of hip fracture and 842 subjects of vertebral fracture were included. The mean age was 73.4 ± 10.0, and the median of duration from index fracture to interview was 2.6 years. The overall 1-year, 2-year, 3-year, 4-year, and 5-year cumulative mortality rates were 3.5, 7.0, 11.2, 13.1, and 16.9 %, respectively. The first year mortality rates in hip (3.8 %, 95% CI 3.3-4.4 %) and vertebral fracture (3.1 %, 95% CI 2.5-3.7 %) were significantly higher than that in the general population (1.6 %). Impaired self-care ability was observed in 33.2, 40.6, and 23.8 % of overall, hip fracture, and vertebral fracture group, respectively. The overall diagnosis rate of osteoporosis was 56.8 %, and bone mineral density (BMD) measurement had never been conducted in 42.0 % among these women. After the index fracture, 69.6 % of them received supplements and/or anti-osteoporotic medications, among which 39.6 % only received calcium with/without vitamin D supplementation. CONCLUSIONS: The osteoporotic hip and vertebral fractures caused excess mortality rates in this population of Mainland China. The current diagnosis and medical treatment following the fragility fractures is still insufficient in Mainland China.

Transcutaneous electric acupoint stimulation reduces intra-operative remifentanil consumption and alleviates postoperative side-effects in patients undergoing sinusotomy: a prospective, randomized, placebo-controlled trial.

BACKGROUND: Although opioids are widely used as analgesics in general anaesthesia, they have unpleasant side-effects and can delay postoperative recovery. Acupuncture and related techniques are effective for acute and chronic pain, and reduces some side-effects. We assessed the effect of transcutaneous electric acupoint stimulation (TEAS) on intra-operative remifentanil consumption and the incidences of anaesthesia-related side-effects. METHODS: Sixty patients undergoing sinusotomy were randomly assigned to TEAS or control group. TEAS consisted of 30 min of stimulation (6-9 mA, 2/10 Hz) on the Hegu (LI4), Neiguan (PC6), and Zusanli (ST36) before anaesthesia. The patients in the control group had the electrodes applied, but received no stimulation. Bispectral index was used to monitor the depth of anaesthesia. Perioperative haemodynamics were recorded, and peripheral blood samples were collected to measure the levels of mediators of surgical stress. The primary end point was intraoperative remifentanil consumption and the secondary endpoints were recovery quality and anaesthesia-related side-effects. RESULTS: Patients in the TEAS group required 39% less remifentanil during surgery than controls [0.0907 (SD 0.026) µg kg(-1) min(-1) vs 0.051 (0.018) µg kg(-1) min(-1)]. There were no differences in intra-operative haemodynamics or surgical stress between groups. However, the time to extubation and recall in the control group was 16.8 (6.8) min and 23.0 (5.0) min, respectively, significantly longer than that in the TEAS group (P<0.01). TEAS also decreased the incidence of dizziness and pruritus within the first 24 h after surgery (P<0.01). CONCLUSION: The use of TEAS significantly reduced intra-operative remifentanil consumption and alleviated postoperative side-effects in patients undergoing sinusotomy. CLINICAL TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT01700855).

Molecular characterization and analysis of a novel calcium-dependent protein kinase from Eimeria tenella.

The calcium-dependent protein kinases (CDPKs) are unique enzymes found only in plants, green algae, ciliates and apicomplexan parasites. In this study, a novel CDPK gene of Eimeria tenella, designed EtCDPK3, was cloned using rapid amplification of cDNA ends (RACE) based on the expressed sequence tag (EST). The entire cDNA of EtCDPK3 contained 1637 nucleotides encoding 433 amino acids and the deduced EtCDPK3 protein had canonical characteristic domains identified in other CDPKs, including a well-conserved amino-terminal kinase domain and a carboxy-terminal calmodulin-like structure with 4 EF-hand motifs for calcium binding. The expression profiles of the EtCDPK3 gene in different development stages were investigated by real-time quantitative PCR. Messenger RNA levels from the EtCDPK3 gene were higher in sporozoites than in other stages (unsporulated oocysts, sporulated oocysts and merozoites). Western blot analysis showed that rabbit antiserum against recombinant EtCDPK3 could recognize a native 49 kDa protein band of parasite. Indirect immunofluorescent antibody labelling revealed dispersed localization of EtCDPK3 during the first schizogony and intense specific staining. EtCDPK3 was located at the apical end of the sporozoites after early infection of DF-1 cells and the protein was highly expressed. Inhibition of EtCDPK3 function using specific antibodies reduced the ability of E. tenella to invade host cells. These results suggested that EtCDPK3 may be involved in invasion and survival of the parasite intracellular stages of E. tenella. Because this kinase family is absent from hosts, it represents a valid target that could be exploited for chemotherapy against Eimeria spp.