Self-Assembled Microfiber-Like Biohydrogel for Ultrasensitive Whole-Cell Electrochemical Biosensing in Microdroplets.

A novel microfiber-like biohydrogel was fabricated by a facile approach relying on electroactive bacteria-induced graphene oxide reduction and confined self-assembly in a capillary tube. The microfiber-like biohydrogel (d = ∼1 mm) embedded high-density living cells and activated efficient electron exchange between cells and the conductive graphene network. Further, a miniature whole-cell electrochemical biosensing system was developed and applied for fumarate detection under -0.6 V (vs Ag/AgCl) applied potential. Taking advantage of its small size, high local cell density, and excellent electron exchange, this microfiber-like biohydrogel-based sensing system reached a linear calibration curve (R2 = 0.999) ranging from 1 nM to 10 mM. The limit of detection obtained was 0.60 nM, which was over 1300 times lower than a traditional biosensor for fumarate detection in 0.2 µL microdroplets. This work opened a new dimension for miniature whole-cell electrochemical sensing system design, which provided the possibility for bioelectrochemical detection in small volumes or three-dimensional local detection at high spatial resolutions.

Development of Beet necrotic yellow vein virus-based vectors for multiple-gene expression and guide RNA delivery in plant genome editing.

Many plant viruses with monopartite or bipartite genomes have been developed as efficient expression vectors of foreign recombinant proteins. Nonetheless, due to lack of multiple insertion sites in these plant viruses, it is still a big challenge to simultaneously express multiple foreign proteins in single cells. The genome of Beet necrotic yellow vein virus (BNYVV) offers an attractive system for expression of multiple foreign proteins owning to a multipartite genome composed of five positive-stranded RNAs. Here, we have established a BNYVV full-length infectious cDNA clone under the control of the Cauliflower mosaic virus 35S promoter. We further developed a set of BNYVV-based vectors that permit efficient expression of four recombinant proteins, including some large proteins with lengths up to 880 amino acids in the model plant Nicotiana benthamiana and native host sugar beet plants. These vectors can be used to investigate the subcellular co-localization of multiple proteins in leaf, root and stem tissues of systemically infected plants. Moreover, the BNYVV-based vectors were used to deliver NbPDS guide RNAs for genome editing in transgenic plants expressing Cas9, which induced a photobleached phenotype in systemically infected leaves. Collectively, the BNYVV-based vectors will facilitate genomic research and expression of multiple proteins, in sugar beet and related crop plants.

miR-24 suppression of POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) protects endothelial cell from diabetic damage.

The regulatory transcriptional factor PATZ1 is abnormally up-regulated in diabetic endothelial cells (ECs) where it acts as an anti-angiogenic factor via modulation of fatty acid-binding protein 4 (FABP4) signaling. The aim of the present work was to elucidate the upstream molecular events regulating PATZ1 expression in diabetic angiogenesis. The bioinformatics search for microRNAs (miRNAs) able to potentially target PATZ1 led to the identification of several miRNAs. Among them we focused on the miR-24 since the multiple targets of miR-24, which have so far been identified in beta cells, cardiomyocytes and macrophages, are all involved in diabetic complications. miR-24 expression was significantly impaired in the ECs isolated from diabetic hearts. Functionally, endothelial migration was profoundly inhibited by miR-24 suppression in Ctrl ECs, whereas miR-24 overexpression by mimics treatment effectively restored the migration rate in diabetic ECs. Mechanistically, miR-24 directly targeted the 3'untranslated region (3'UTR) of PATZ1, and miR-24 accumulation potentiated endothelial migration by reducing the mRNA stability of PATZ1. Together, these results suggest a novel mechanism regulating endothelial PATZ1 expression based on the down-regulation of miR-24 expression caused by hyperglycemia. Interfering with PATZ1 expression via miRNAs or miRNA mimics could potentially represent a new way to target endothelial PATZ1-dependent signaling of vascular dysfunction in diabetes.

The efficacy of lamivudine prophylaxis against hepatitis B reactivation in breast cancer patients undergoing chemotherapy: a meta-analysis.

BACKGROUND/PURPOSE: Lamivudine has been recommended as prophylaxis for the reactivation of hepatitis B virus (HBV) infection in patients undergoing chemotherapy. However, information on breast cancer patients in particular has been lacking. The purpose of this meta-analysis was to assess the overall efficacy of lamivudine prophylaxis compared to untreated patients with hepatitis B S-antigen (HBsAg) seropositive breast cancer who had undergone chemotherapy. METHODS: Studies that compared the efficacy of treatment with lamivudine prophylaxis versus no prophylaxis in HBsAg seropositive breast cancer patients were identified through Medline, Cochrane, and Embase databases. RESULTS: Six studies involving 499 patients were analyzed. The rates of HBV reactivation in patients with lamivudine prophylaxis were significantly lower than those with no prophylaxis (risk ratio [RR] = 0.23, 95% confidence interval [CI]: 0.13-0.39, p < 0.00001). Patients given lamivudine prophylaxis had significant reductions in the rates of hepatitis attributable to HBV compared with those not given treatment (RR = 0.20, 95% CI: 0.08-0.47, p = 0.002). The rates of moderate and severe hepatitis in patients with lamivudine prophylaxis were significantly lower compared with those patients who had not received prophylaxis (RR = 0.25, 95% CI: 0.10-0.62, p < 0.003; RR = 0.25, 95% CI: 0.10-0.59, p = 0.002). Patients given lamivudine prophylaxis had significantly fewer disruptions of chemotherapy (RR = 0.36, 95% CI: 0.21-0.64, p = 0.0004). There was no significant heterogeneity in the comparisons. CONCLUSION: Lamivudine prophylaxis in HBsAg seropositive breast cancer patients undergoing chemotherapy is effective in reducing HBV reactivation and HBV-associated morbidity and mortality.

Evidence in duck for supporting alteration of incubation temperature may have influence on methylation of genomic DNA.

Incubation temperature has an immediate and long-term influence on the embryonic development in birds. DNA methylation as an important environment-induced mechanism could serve as a potential link between embryos' phenotypic variability and temperature variation, which reprogrammed by DNA (cytosine-5)-methyltransferases (DNMTS) and Methyl-CpG binding domain proteins (MBPS) 3&5 (MBD3&5). Five genes in DNMTS and MBPS gene families were selected as target genes, given their important role in epigenetic modification. In this study, we aimed to test whether raising incubation temperature from 37.8°C to 38.8°C between embryonic days (ED) 1-10, ED10-20 and ED20-27 have effect on DNA methylation and whether DNMTS, MBPS play roles in thermal epigenetic regulation of early development in duck. Real-time quantitative PCR analysis showed that increased incubation temperature by 1°C has remarkably dynamic effect on gene expression levels of DNMTS and MBPS. Slight changes in incubation temperature significantly increased mRNA levels of target genes in breast muscle tissue during ED1-10, especially for DNMT1, DNMT3A and MBD5. In addition, higher temperature significantly increased enzyme activities of DNMT1 in leg muscle during ED10-20, liver tissue during ED1-10, ED20-27 and DNMT3A in leg muscle and breast muscle tissue during ED10-20. These results suggest that incubation temperature has an extended effect on gene expression levels and enzyme activities of DNMTS and MBPS, which provides evidence that incubation temperature may influence DNA methylation in duck during early developmental stages. Our data indicated that DNMTS and MBPS may involved in thermal epigenetice regulation of embryos during the early development in duck. The potential links between embryonic temperature and epigenetic modification need further investigation.

Measures to reduce mother-to-child transmission of Hepatitis B virus in China: a meta-analysis.

BACKGROUND: Mother-to-child transmission (MTCT) is the main mode of spread of hepatitis B virus (HBV) in China. We performed a meta-analysis to compare the effects of three measures for prevention of MTCT. METHODS: A meta-analysis was performed on randomized controlled trials and non-randomized studies comparing the index of MTCT among five groups of pregnant women: hepatitis B immunoglobulin (HBIG) administration, antiviral treatment, placebo, elective caesarean section, and vaginal delivery. RESULTS: Compared with the control group, the incidence of HBV intrauterine infection (RR = 0.42, 95 % CI 0.27-0.64, P < 0.0001) and the number of chronic hepatitis B (CHB) infants (RR = 0.44, 95 % CI 0.32-0.61, P < 0.00001) were lower in the HBIG administration group. In the antiviral treatment group, serum HBV DNA levels were lower (MD = -4.01, 95 % CI -5.07 to -2.94, P < 0.00001) at the time of delivery, and normalization of ALT levels was better (RR = 1.11, 95 % CI 1.06-1.17, P < 0.0001). Infant serum HBsAg positivity (RR = 0.45, 95 % CI 0.22-0.91, P = 0.03) and incidence of infant HBV transmission RR = 0.06, 95 % CI 0.01-0.24, P < 0.0001) were reduced in antiviral the treatment group. Infant serum anti-HBs positivity at birth (RR = 1.24, 95 % CI 0.89-1.74, P = 0.2) or at 6-7 months (RR = 0.98, 95 % CI 0.86-1.11, P = 0.73) was not significantly different between the caesarean section and vaginal delivery groups. The incidence of infant CHB infection may have been higher in the vaginal delivery group (RR = 2.20, 95 % CI 1.02-4.74, P = 0.04). CONCLUSIONS: Administration of HBIG or antiviral therapy to HBV carrier mothers during pregnancy is effective in reducing MTCT.

Gene expression patterns, and protein metabolic and histological analyses for muscle development in Peking duck.

In this study, we aimed to use duck breast muscle and leg muscle, the 2 main productive muscle organs, as a model to elucidate the molecular mechanism controlling how the 2 muscles have different deposition capabilities, and to analyze the mechanisms facilitating duck muscle development posthatching. Peking duck breast muscle and leg muscle were collected 3, 7, and 16 wk posthatching. The morphology of the myofibers was observed by paraffin sectioning the muscles. The expression of genes involved in protein metabolism [mammalian target of rapamycin (mTOR), RPS6-p70-protein kinase (S6K), forkhead box O1 (FoxO1), muscle RING finger 1 (MuRF1), and atrogin-1 (MAFbx)] was detected using real-time quantitative PCR and Western blot assays, and the results indicated that breast muscle had a stronger capacity for both protein synthesis and protein degradation compared with leg muscle. Satellite cell frequency declined during muscle development in both tissues, and the expression of Pax3/7, satellite cell marker genes, was not significantly different between breast muscle and leg muscle. No notable apoptosis was observed in either tissue. The results of this study suggest that protein metabolism signaling is the main reason promoting duck skeletal muscle mass gain.

[Gene expression changes of regucalcin and prohibitin in cirrhotic rat liver and the related effects of compound glutathione inosine injection intervention].

OBJECTIVE: To study expression of regucalcin (RGN) and prohibitin (PHB) genes in cirrhotic rat liver and to investigate the related effects of compound glutathione inosine injection (CGII) intervention. METHODS: Forty male Wistar rats were randomly divided into a control group (n=12) and a model group (n=28).The model was established by injecting sterile porcine serum (0.5 mL) into the rat abdominal cavity, twice weekly for 8 consecutive weeks; the control group rats were treated with physiological saline injection (0.5 mL) into the abdominal cavity with the same frequency and time span. During the modeling period, four rats from the model group were randomly selected at different time points to examine changes in liver pathology. Upon pathology confirmation of liver cirrhosis, the porcine serum injection was terminated. The remaining 24 rats in the model group were randomly divided into a fibrosis group and a CGII treatment group.The CGII group received CGII (intramuscular injection of 0.018 mL 100g-1 body weight) once a day for 6 continuous weeks; the fibrosis rats were treated with the same dosage of physiological saline with the same frequency and time span.Liver tissue morphology was examined by both hematoxylin-eosin and Masson's staining. RGN and PHB expression at the mRNA and protein levels in liver tissues were detected by real time RT-PCR and immunohistochemical staining, respectively. RESULTS: Both the mRNA and protein expression levels of RGN and PHB were significantly lower in the liver tissues of the fibrosis group than in the control group.CGII intervention led to significant alleviation of the liver fibrosis severity; moreover, the mRNA and protein expression levels of RGN and PHB were significantly higher than those in the fibrosis group. CONCLUSION: Down-regulation of regucalcin and prohibitin gene expression might contribute to the pathogenesis of liver cirrhosis.

Circulating copeptin level and the clinical prognosis of patients with chronic liver disease.

BACKGROUND: The relationship between copeptin and the severity of circulatory dysfunction and systemic stress response in patients with chronic liver disease (CLD) has been established. Nevertheless, the potential of serum copeptin levels to predict the prognosis of CLD patients remains unclear. AIM: To conduct a systematic review and meta-analysis to investigate the correlation between serum copeptin and transplant-free survival (TFS) in this population. METHODS: To achieve the objective of the meta-analysis, PubMed, Embase, the Cochrane Library, and the Web of Science were searched to identify observational studies with longitudinal follow-up. The Cochrane Q test was utilized to assess between-study heterogeneity, and the I2 statistic was estimated. Random-effects models were employed to combine the outcomes, taking into account the potential influence of heterogeneity. RESULTS: Ten datasets including 3133 patients were involved. The follow-up durations were 1 to 48 mo (mean: 12.5 mo). Overall, it was shown that a high level of serum copeptin was associated with a poor TFS [risk ratio (RR): 1.82, 95% confidence interval: 1.52-2.19, P < 0.001; I2 = 0%]. In addition, sensitivity analysis by omitting one dataset at a time showed consistent results (RR: 1.73-2.00, P < 0.05). Finally, subgroup analyses according to study country, study design, patient diagnosis, cutoff of copeptin, follow-up duration, and study quality score also showed similar results (P for subgroup difference all > 0.05). CONCLUSION: Patients with CLD who have high serum copeptin concentrations may be associated with a poor clinical prognosis.

Proposal to classify Ralstonia solanacearum phylotype I strains as Ralstonia nicotianae sp. nov., and a genomic comparison between members of the genus Ralstonia.

A Gram-negative, aerobic, rod-shaped, motile bacterium with multi-flagella, strain RST, was isolated from bacterial wilt of tobacco in Yuxi city of Yunnan province, China. The strain contains the major fatty acids of C16:0, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). The polar lipid profile of strain RST consists of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and unidentified aminophospholipid. Strain RST contains ubiquinones Q-7 and Q-8. 16S rRNA gene sequence (1,407 bp) analysis showed that strain RST is closely related to members of the genus Ralstonia and shares the highest sequence identities with R. pseudosolanacearum LMG 9673T (99.50%), R. syzygii subsp. indonesiensis LMG 27703T (99.50%), R. solanacearum LMG 2299T (99.28%), and R. syzygii subsp. celebesensis LMG 27706T (99.21%). The 16S rRNA gene sequence identities between strain RST and other members of the genus Ralstonia were below 98.00%. Genome sequencing yielded a genome size of 5.61 Mbp and a G + C content of 67.1 mol%. The genomic comparison showed average nucleotide identity (ANIb) values between strain RST and R. pseudosolanacearum LMG 9673T, R. solanacearum LMG 2299T, and R. syzygii subsp. indonesiensis UQRS 627T of 95.23, 89.43, and 91.41%, respectively, and the corresponding digital DNA-DNA hybridization (dDDH) values (yielded by formula 2) were 66.20, 44.80, and 47.50%, respectively. In addition, strains belonging to R. solanacearum phylotype I shared both ANIb and dDDH with strain RST above the species cut-off values of 96 and 70%, respectively. The ANIb and dDDH values between the genome sequences from 12 strains of R. solanacearum phylotype III (Current R. pseudosolanacearum) and those of strain RST were below the species cut-off values. Based on these data, we concluded that strains of phylotype I, including RST, represent a novel species of the genus Ralstonia, for which the name Ralstonia nicotianae sp. nov. is proposed. The type strain of Ralstonia nicotianae sp. nov. is RST (=GDMCC 1.3533T = JCM 35814T).

The influence of hepatitis B virus on antiviral treatment with interferon and ribavirin in Asian patients with hepatitis C virus/hepatitis B virus coinfection: a meta-analysis.

BACKGROUND: Clinical and laboratory studies have indicated that coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) can suppress one another, eliciting a dominant disease phenotype. To assess whether HBV can influence the antiviral effect of treatment on HCV, we performed a meta-analysis to comparatively analyze the response to interferon plus ribavirin treatment in patients with HBV/HCV coinfection and HCV mono-infection. METHODS: Published studies in the English-language medical literature that involved cohorts of HBV/HCV coinfection and HCV mono-infection were obtained by searching Medline, Cochrane and Embase databases. Studies that compared the efficacy of treatment with interferon plus ribavirin in HBV/HCV coinfection and HCV mono-infection were assessed. End-of-treatment virological response (ETVR), sustained virological response (SVR), HCV relapse rate, and alanine aminotransferase (ALT) normalization rate were compared between HBV/HCV coinfection and HCV mono-infection patients. RESULTS: Five trials involving 705 patients were analyzed. At the end of follow-up serum ALT normalization rates in patients with HCV mono-infection were significantly higher than in patients with HBV/HCV coinfection (odds ratio (OR) = 0.56, 95% confidence interval (CI): 0.40-0.80, P = 0.001). The ETVR and SVR achieved in HBV/HCV coinfection patients were comparable to those in HCV mono-infection patients (OR = 1.03, 95% CI: 0.37-2.82, P = 0.96 and OR = 0.87, 95% CI: 0.62-1.21, P = 0.38, respectively). The rate of relapse for HCV or HCV genotype 1 was not significantly different between HBV/HCV coinfection patients and HCV mono-infection patients (OR = 1.55, 95% CI: 0.98-2.47, P = 0.06; HCV genotype 1: OR = 2.4, 95% CI: 1.17-4.91, P = 0.19). CONCLUSIONS: Treatment with interferon and ribavirin achieves similar ETVR and SVR in HBV/HCV coinfection and HCV mono-infection. HBV/HCV coinfection patients had distinctively lower end of follow-up serum ALT normalization.

Association between serum platelet-derived growth factor BB and degree of liver damage, fibrosis and hepatitis B e antigen (HBeAg) status in CHB patients.

BACKGROUND/AIMS: The objective of this study was to determine the association of PDGF-BB with degree of liver damage, fibrosis and HBeAg status in CHB patients. METHODOLOGY: A total of 740 patients with previously untreated chronic hepatitis B were included in the study. We conducted the correlations analysis of se-rum PDGF-BB with the age, gender, medical history, se-rum HBV-DNA, liver function parameters and serum fibrosis markers (HA, PCIII, CIV, LN), analyzed the cor-relations of degree of liver damage with liver fibrosis markers and the serum levels of PDGF-BB and compared serum liver fibrosis markers and levels of PDGF- BB between HbeAg-negative and HbeAg-positive CHB patients. RESULTS: Liver function parameters and se-rum liver fibrosis markers were significantly correlated with serum PDGF-BB (p<0.01). Liver fibrosis markers and serum levels of PDGF-BB in CHB were positive correlated with degree of liver damage. Serum levels of PDGF-BB in HBeAg-negative CHB was significantly higher than that in the HBeAg-positive CHB (p<0.05). CONCLUSIONS: Serum levels of PDGF-BB can reflect degree of liver damage and degree of liver fibrosis in CHB.Serum levels of PDGF-BB in HBeAg-negative CHB were higher than the HBeAg-positive CHB.

Lamivudine plus adefovir combination therapy versus entecavir monotherapy for lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis.

BACKGROUND: Chronic hepatitis B virus (HBV) infection represents a serious global health problem and resistance to lamivudine (LAM) has become a serious clinical challenge. Previous rescue therapy for the treatment of chronic LAM-resistant hepatitis B infected patients included switching to entecavir (ETV) and adding adefovir (ADV) or tenofovir (TFV). At present, switching to ETV is not recommended for rescue therapy for LAM-resistant chronic hepatitis B (CHB). The aim of this report was to determine whether add-on ADV was a superior rescue strategy in the treatment of CHB patients with LAM resistance. METHODS: We searched Medline/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library. Relative risks (RRs) of virologic response, virologic breakthrough, normalization of serum alanine aminotransferase (ALT) levels and HBeAg seroconversion rates were studied. Factors predicting virologic response, standardized mean differences (SMD) in HBV DNA levels and safety were reviewed. RESULTS: Six eligible trials (451 patients in total) were included in the analysis. The rate of virologic breakthrough in the ETV group was higher than that in the LAM plus ADV group. There were no statistical differences in virologic response, ALT normalization and HBeAg seroconversion in either group 48 weeks post treatment. LAM plus ADV combination therapy produced faster and greater HBV DNA reduction rates 24 weeks post therapy compared to ETV monotherapy. HBV DNA baseline levels and the initial virologic response (IVR) were predictive of the virologic response. Additionally, combination therapy or monotherapy were both well tolerated. CONCLUSIONS: LAM plus ADV combination therapy was more effective and produced longer-lasting effects than switching to ETV monotherapy in treating CHB patients with LAM resistance. However, considering the practical benefits and limitations of ADV, individualized therapy will be needed in patients with prior history of LAM resistant infections.

Unusual immunohistochemical "null" pattern of four mismatch repair proteins in gastric cancer: A case report.

BACKGROUND: Immunohistochemical (IHC) staining for mismatch repair (MMR) proteins is useful for gastric cancer treatment and prognosis. Different IHC staining patterns reflect the complex biological phenomena underlying MMR deficiency. We herein report a rare IHC staining pattern of four MMR-related proteins in gastric cancer. CASE SUMMARY: A "null" IHC staining pattern of four MMR-related proteins, including MLH1, PMS2, MSH2, and MSH6, in a 67-year-old male patient with gastric cancer pT3N3aM0 revealed promoter hypermethylation of MLH1. Next-generation sequencing showed that these four genes exhibited changes. One of these was the somatic mutation of the missing copy number in exon 14 of MSH2. Mutation analysis using peripheral blood showed no germline mutations in these four genes. The patient had no history of personal or family tumor history. We classified this case as sporadic. The patient returned to normal after operation, and there were no signs of tumor metastasis and recurrence. After six cycles of adjuvant chemotherapy, the patient was discharged in a stable condition. The patient had a mild reaction to chemotherapy and a good prognosis. At present, 16 mo after the operation, the patient's condition is stable. CONCLUSION: Abnormal MMR protein expression, helpful for individualized follow-up care, helped identify a sporadic case lacking familial clinical management implications.

[Study on somato-type distribution and its correlations with body mass index, blood lipids and hepato-enzymes in 1 163 patients with non-alcoholic fatty liver disease].

OBJECTIVE: To investigate the distribution of somato-types in Chinese medicine and its correlations with body mass index (BMI), blood lipids and hepato-enzymes in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: From January 2008 to December 2008, the somato-types of 1 163 NAFLD patients were categorized, and its correlations with BMI, blood lipids and hepato-enzymes were analyzed. RESULTS: Among the 1 163 patients, 401 were categorized as qi-deficiency type and 371 as phlegm-dampness type, accounting for 66.38%. Levels of BMI, blood lipids (TC, TG, LDL) and hepato-enzymes (ALT, AST, GGT) in patients of phlegm-dampness type were higher than those in patients of other types, the differences were statistically significant (P<0.05). CONCLUSIONS: Qi-deficiency type and phlegm-dampness type are the dominant pathogenetic somsto-types in patients with NAFLD; abnormal BMI, blood lipids and hepato-enzymes may present in those of phlegm-dampness type more frequently.

Efficacy and safety of nebivolol in hypertensive patients: a meta-analysis of randomized controlled trials.

PURPOSE: Our meta-analysis was undertaken to evaluate the efficacy and safety of nebivolol compared with other second-generation ß blockers for hypertensive patients. METHODS: We searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov databases for randomized controlled trials (RCTs). The efficacy endpoints included systolic blood pressure (SBP), diastolic blood pressure (DBP), reduction of SBP and DBP, heart rate (HR), and adverse events (AEs). FINDINGS: Eight RCTs with 1514 patients met the inclusion criteria. HR was significantly lower in patients receiving other second-generation ß blockers compared with patients receiving nebivolol. There was no difference the reduction of blood pressure (SBP and DBP) or the reduction of SBP or DBP between the groups. The incidence of AEs was lower in patients taking nebivolol compared with patients taking other second-generation ß blockers. CONCLUSIONS: No significant difference was demonstrated between nebivolol and other second-generation ß blockers in the reduction of blood pressure, SBP, and DBP. The tolerability of nebivolol was significantly better compared with other second-generation ß blockers, and nebivolol was also associated with a stable HR and a lower risk of AEs compared with other second-generation ß blockers.

Author Correction: Triple-negative invasive breast carcinoma: the association between the sonographic appearances with clinicopathological feature.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Atypical juvenile hereditary hemochromatosis onset with positive pancreatic islet autoantibodies diabetes caused by novel mutations in HAMP and overall clinical management.

BACKGROUND: Atypical clinical symptoms of juvenile hereditary hemochromatosis (JHH) often leads to misdiagnosis and underdiagnosis bringing ominous outcomes, even death. METHODS: The whole exome was sequenced and interpreted. A literature review assisted to analyze and verify the phenotype-genotype relationships. We revealed the entire process of diagnosis, treatments, and outcome of two diabetic onset of JHH families to provide new insights for genotype-phenotype relation with novel compound heterozygous mutations in the hepcidin antimicrobial peptide (HAMP, OMIM: 606464). RESULTS: Two probands were diagnosed and treated as type 1 diabetes initially because of specific symptoms and positive islet autoantibodies. Poor control of hyperglycemia and progressive symptoms occurred. Sequencing informed that the compound heterozygous and homozygous mutations c.166C>G and c.223C>T in HAMP caused type 1 diabetic-onset JHH. The two patients accessed irregular phlebotomy treatments, and then, experienced poor prognosis. We summarized the process of overall clinical management of reported 26 cases comparing to our novel atypical diabetic onsets Juvenile Hereditary Hemochromatosis cases. CONCLUSION: It was first reported that positive pancreatic islet autoantibodies diabetes onset of JHH resulted from loss-of-function mutations of HAMP, of which the atypical JHH should be differentially diagnosed with type 1 diabetes at the onset. Early administration of phlebotomy and vital organs protection and surveillance might be important for the treatment of atypical JHH.

[The protective effect of recombinant rat ghrelin on gastric mucosa in rats with hemorrhagic shock].

OBJECTIVE: To investigate the effect of recombinant rat ghrelin on gastric mucosa in rats with hemorrhagic shock. METHODS: Eighteen healthy male Sprague-Dawley (SD) rats were randomly assigned into three groups: control group, hemorrhagic shock group, and ghrelin treatment group, with 6 rats for each group. The hemorrhagic shock model was reproduced in hemorrhagic shock group and ghrelin treatment group, and recombinant rat ghrelin (20 microg/kg) was intravenously administered to rats in ghrelin treatment group when resuscitation begun. Two hours after resuscitation, the gastric mucosal blood flow (GMBF) was determined with laser Doppler flowmetry (LDF). The light microscope and transmission electron microscope (TEM) were used to assess gastric mucosal injury. RESULTS: The GMBF of the rats in hemorrhagic shock group was significantly lower than that in control group [(260.4+/-49.6) bpu vs. (418.6+/-57.3) bpu, P<0.01], and the gastric mucosa was injured, presenting cell necrosis, cytolysis and focal ulceration. The GMBF of the rats in ghrelin treatment group was remarkably richer than that in hemorrhagic shock group [(352.9+/-72.9) bpu vs. (260.4+/-49.6) bpu, P<0.05], but had no significant difference compared with that in control group (P>0.05), and the gastric mucosa injuries were greatly improved in the rats of ghrelin treatment group. CONCLUSION: Recombinant rat ghrelin, through enhancing the GMBF, can ameliorate the gastric mucosal ischemic/reperfusion injury in rats with hemorrhagic shock.

[Comparisons of volatile components in different parts of three species of Rhizoma Curcumae].

OBJECTIVE: To provide the scientific basis for the reasonable development and use of the leaves of Rhizoma Curcumae. METHODS: To extract the volatile oil from roots and leaves of three species Rhizoma Curcumae by steam distillation and isolate these products with the method of gas chromatography-mass spectrum. Taking Nist98 standard mass spectrometer database and contrast as control, the structure of the mass spectrogram was identified, and the relative contents of the components were determined with area normalization method. RESULTS: The anti-tumor active constituents such as curdione and germacrone in the leaves had the greater content than in its rhizome. CONCLUSION: The varieties of volatile components in different parts of three species of Rhizoma Curcumae are similar, but their contents are obviously various. We can make the leaves of Rhizoma Curcumae for recycling use.