[Effects of ppk1 deletion on the drug susceptibility of uropathogenic Escherichia coli producing ESBLs].

To investigate the effect and the mechanism of ppk1 gene deletion on the drug susceptibility of uropathogenic Escherichia coli producing extended-spectrum beta-lactamases (ESBLs-UPEC). The study was an experimental study. From March to April 2021, a strain of ESBLs-UPEC (genotype was TEM combined with CTX-M-14) named as UE210113, was isolated from urine sample of the patient with urinary tract infection in the Laboratory Department of Guangzhou Eighth People's Hospital, meanwhile its ppk1 gene knock-out strain Δpk1 and complemented strain Δpk1-C were constructed by suicide plasmid homologous recombination technique, which was used to study the effect of ppk1 gene on ESBLs-UPEC drug sensitivity and its mechanism. The drug susceptibility of UE210113, Δpk1, and Δpk1-C were measured by Vitek2 Compact System and broth microdilution method. The quantitative expression of ESBLs, outer membrane protein and multidrug efflux systems encoding genes of UE210113, Δpk1 and Δpk1-C were performed by using qRT-PCR analysis. By using two independent sample Mann-Whitney U test, the drug susceptibility results showed that, compared with UE210113 strain, the sensitivities of Δpk1 to ceftazidime, cefepime, tobramycin, minocycline and cotrimoxazole were enhanced (Z=-2.121,P<0.05;Z=-2.236,P<0.05;Z=-2.236,P<0.05;Z=-2.121,P<0.05), and the drug susceptibility of Δpk1-C restored to the same as which of UE210113 (Z=0,P>0.05). The expression levels of ESBLs-enconding genes blaTEM and blaCTX-M-14 in Δpk1 were significantly down-regulated compared with UE210113, but the expression was not restored in Δpk1-C. The expression of outer membrane protein gene omp F in Δpk1 was significantly up-regulated, while the expression of omp A and omp C were down-regulated. The results showed that the expression of multidrug efflux systems encoding genes tol C, mdt A and mdtG were down-regulated in Δpk1 compared with UE210113. The expression of all of the outer membrane protein genes and the multidrug efflux systems genes were restored in Δpk1-C. In conclusion,the lost of ppk1 gene can affect the expression of the outer membrane protein and multidrug efflux systems encoding genes of ESBLs-UPEC, which increase the sensitivity of ESBLs-UPEC to various drugs.

Effects of treatment processes on AOC removal and changes of bacterial diversity in a water treatment plant.

The effectiveness of different treatment processes on assimilable organic carbon (AOC) removal and bacterial diversity variations was evaluated in a water treatment plant. The van der Kooij technique was applied for AOC analysis and responses of bacterial communities were characterized by the metagenomics assay. Results show that the AOC concentrations were about 93, 148, 43, 51, 37, and 38 µg acetate-C/L in effluents of raw water basin, preozonation, rapid sand filtration (RSF), ozonation, biofiltration [biological activated carbon (BAC) filtration], and chlorination (clear water), respectively. Increased AOC concentrations were observed after preozonation, ozonation, and chlorination units due to the production of biodegradable organic matters after the oxidation processes. Results indicate that the oxidation processes were the main causes of AOC formation, which resulted in significant increases in AOC concentrations (18-59% increment). The AOC removal efficiencies were 47, 28, and 60% in the RSF, biofiltration, and the whole system, respectively. RSF and biofiltration were responsible for the AOC treatment and both processes played key roles in AOC removal. Thus, both RSF and biofiltration processes would contribute to AOC treatment after oxidation. Sediments from the raw water basin and filter samples from RSF and BAC units were collected and analyzed for bacterial communities. Results from scanning electron microscope analysis indicate that bacterial colonization was observed in filter materials. This indicates that the surfaces of the filter materials were beneficial to bacterial growth and AOC removal via the adsorption and biodegradation mechanisms. Next generation sequencing analyses demonstrate that water treatment processes resulted in the changes of bacterial diversity and community profiles in filters of RSF and BAC. According to the findings of bacterial composition and interactions, the dominant bacterial phyla were Proteobacteria (41% in RSF and 56% in BAC) followed by Planctomycetes and Acidobacteria in RSF and BAC systems, which might affect the AOC biodegradation efficiency. Results would be useful in developing AOC treatment and management processes in water treatment plants.

lncRNA CASC2 suppresses the growth of hemangioma cells by regulating miR-18a-5p/FBXL3 axis.

Dysregulation of lncRNA cancer susceptibility candidate 2 (CASC2) is involved in the pathogenesis of multiple malignancies. However, the underlying mechanisms by which lncRNA CASC2 regulates the proliferation of hemangiomas (HAs) remain undocumented. Herein, the expression levels of lncRNA CASC2 and VEGF in proliferating or involuting phase HAs were assessed by qRT-PCR analysis, and the effects of lncRNA CASC2 on HAs cell growth were evaluated by MTT, colony formation assays and Western blot analysis. lncRNA CASC2 specific binding with miR-18a-5p was confirmed by luciferase report assay. Consequently, we found that the expression of lncRNA CASC2 was reduced in proliferating phase HAs as compared with the involuting phase HAs or normal tissues, and possessed a negative correlation with VEGF expression in proliferating phase HAs. Restored expression of lncRNA CASC2 repressed cell viability and colony formation and downregulated VEGF expression, while silencing lncRNA CASC2 showed the opposite effects. Moreover, lncRNA CASC2 was confirmed to bind with miR-18a-5p, which could reverse lncRNA CASC2-induced anti-proliferative effects by targeting FBXL3 in HAs cells. Altogether, our findings demonstrated that lncRNA CASC2 suppressed the growth of HAs cells by regulating miR-18a-5p/FBXL3 axis.

The global transcriptomic signature in sinonasal tissues reveals roles for tissue type and chronic rhinosinusitis disease phenotype.

BACKGROUND: RNA sequencing (RNA-Seq) allows the characterization of a global transcriptomic signature in a least-biased fashion, but few studies have applied this method to investigate the pathophysiology of CRS. METHODS: We collected mucosal tissue samples from 6 CRS without nasal polyps (CRSsNP), 6 CRS with nasal polyps (CRSwNP), and 6 control patients. Additional matched polyp samples were collected from the 6 CRSwNP patients. RNA was extracted and sequenced on the Illumina HiSeq-2500. Differential gene expression and pathway analyses were performed. RESULTS: CRSsNP showed evidence of upregulated interferon-mediated immunity, MHC-class-I mediated antigen presentation, CXCR3 binding, neutrophil chemotaxis and degranulation, and potential downregulation of genes related to cilia movement and production. CRSwNP polyp tissue showed upregulation of B-cell mediated immune responses, but reduced expression of genes related to epithelial morphogenesis and haemostasis. Polyps also showed a generalized reduction of positive gene regulation. The sinonasal transcriptomic signature was largely determined by tissue type (polyp versus mucosa) and disease phenotype, with minimal signal originating from the individual patient. CONCLUSION: RNA-Seq is a useful tool to explore the complex pathophysiology of CRS. Our findings stress the importance of tissue selection in molecular research utilizing sinonasal tissue, and demonstrate the limitation of the sNP/wNP paradigm (and the importance of endotyping). On the other hand, classical CRSsNP/wNP disease phenotypes played some role in determining the global transcriptomic signature, and should not be hastily discarded. The value of RNA-Seq-described transcriptomic signatures in exploring endotypes is yet to be explored in future studies.

[Application value of urinary IGFBP7 and TIMP-2 in acute kidney injury with decompensated hepatitis B virus-related liver cirrhosis].

Objective: To investigate the application value of new urinary biomarkers insulin-like growth factor binding protein 7 (IGFBP7) and tissue matrix metalloproteinase inhibitor-2 (TIMP-2) in acute kidney injury with decompensated hepatitis B virus-related liver cirrhosis. Methods: 45 newly hospitalized cases with decompensated hepatitis B virus-related liver cirrhosis were selected. Among them, 19 cases were combined with AKI on admission (cirrhosis-AKI group), 26 cases without AKI (cirrhosis-non-AKI group), and 12 healthy cases (normal control group). First-morning urine samples were collected and IGFBP7 and TIMP-2 were detected by enzyme-linked immunosorbent assay (ELISA). Urinary IGFBP7 and serum creatinine (SCr) were dynamically monitored after hospitalization in cirrhosis-non-AKI group. Normally distributed measurement data were compared by t-test, and non-normally distributed measurement data were compared by rank sum test. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic accuracy of the indicators. Results: Urinary IGFBP7, IGFBP7 with TIMP-2 (IGFBP7×TIMP-2) in cirrhosis-AKI group (n = 19) were equally higher than that of the cirrhosis-non-AKI group (P < 0.05). Urinary IGFBP7, TIMP-2 and IGFBP7×TIMP-2 in cirrhosis-AKI group or cirrhosis-non-AKI group were significantly higher than those of the normal control group (P < 0.01). The AUC of urinary IGFBP7 and urinary IGFBP7×TIMP-2 for diagnosis of AKI were 0.703 (95% CI 0.547-0.860) and 0.700 (95% CI 0.541-0.859), respectively. In the liver cirrhosis-non-AKI group (n = 26), 5 cases of AKI were newly diagnosed according to the changes in SCr during hospitalization (progressive group). Urinary IGFBP7 was significantly increased 2 days before the diagnosis of AKI. The concentration of urinary IGFBP7 at admission in the progressive group (n = 5) was higher than that of the non-progressive group (n = 21) (P < 0.05). Conclusion: Urinary IGFBP7 and TIMP-2 concentrations were significantly increased in patients with decompensated hepatitis B virus-related liver cirrhosis. When AKI occurred, urinary IGFBP7 and IGFBP7×TIMP-2 was further increased. Urinary IGFBP7 is valuable for early AKI diagnosis, and may play a role in predicting AKI occurrence.

Predicting gastro-oesophageal variceal bleeding in hepatitis B-related cirrhosis by CT radiomics signature.

AIM: To develop liver a computed tomography (CT) radiomics model to predict gastro-oesophageal variceal bleeding (GVB) secondary to hepatitis B-related cirrhosis. MATERIALS AND METHODS: Electronic medical records and image data of liver triple-phase contrast-enhanced CT examinations of 295 patients with hepatitis B-related cirrhosis were collected retrospectively from two hospitals. Two hundred and thirty-six and 59 patients were enrolled randomly into the training and validation cohorts, respectively; and 75 in the training cohort and 16 in the validation cohort endured GVB while the others did not during follow-up period. Radiomics features of the liver were extracted from the portal venous phase images, and clinical features came from medical records. The tree-based method and univariate feature selection were used to select useful features. The radiomics model, clinical model, and integration of radiomics and clinical models were built using the useful image features and/or clinical features. Predicting performance of three models was evaluated with the area under receiver-operating characteristic curve (AUC), accuracy, and F-1 score. RESULTS: Twenty-one useful radiomics features and/or three clinical features were selected to build prediction models that correlated with GVB. AUC of integration of radiomics and clinical models was larger than of clinical or radiomics models for the training cohort (0.83±0.09 versus 0.64±0.08 or 0.82±0.10) and the validation cohort (0.64 versus 0.61 or 0.61). Integration of radiomics and clinical models obtained good performance in predicting GVB for both the training and validation cohorts (accuracy: 0.76±0.07 and 0.73, and F-1 score: 0.77±0.09 and 0.72, respectively). CONCLUSION: Integration of the radiomics and clinical models may be a non-invasive method to predict GVB.

Biosorption of lead(II) from aqueous solution by lactic acid bacteria.

The biosorption of Pb(II) from aqueous solutions by lactic acid bacterium, Lactobacillus brevis, was studied. The effects of initial pH, contact time, initial Pb(II) concentration, bacterial concentration, rotation speed and temperature of biosorption of Pb(II) from aqueous solutions were investigated. The optimal condition for Pb2+ ions adsorption was observed at pH 6, with the rotational speed of 120 rpm.min-1, bacterial concentration of 3 g.L-1, temperature of 40 °C and contact time of 12 h. The correlation regression coefficients showed that the biosorption process can be well fitted with the Redlich-Peterson, Langmuir, Freundlich and Temkin isotherm models. The equilibrium adsorption capacity reached 53.632 mg.g-1. Binding energy value was 0.264 kJ/mol, which indicated that the adsorption process seemed to involve chemisorption and physisorption. Kinetics of adsorption was found to fit well with the pseudo-second-order and Elovich kinetic equations. Thermodynamic parameters revealed the feasibility, spontaneity and endothermic nature of adsorption.

Influence of Hydrostatic Pressure on the Corrosion Behavior of Superhydrophobic Surfaces on Bare and Oxidized Aluminum Substrates.

It is generally recognized that superhydrophobic surfaces in water may be used for corrosion resistance due to the entrapped air in the solid/liquid interface and could find potential applications in the protection of ship hull. For a superhydrophobic surface, as its immersion depth into water increases, the resultant hydrostatic pressure is also increased, and the entrapped air can be squeezed out much more easily. It is therefore predicted that high hydrostatic pressure would cause an unexpected decrease in corrosion resistance for the vessels in deep water (e.g., submarines) because of the unstable entrapped air. In this work, in order to clarify the role of hydrostatic pressure in the corrosion behavior of superhydrophobic surfaces, two typical superhydrophobic surfaces (SHSs) were prepared on bare and oxidized aluminum substrates, respectively, and then were immersed into the NaCl aqueous solutions with different depths of ∼0 cm (hydrostatic pressure ∼0 kPa), 10 cm (1 kPa), and 150 cm (15 kPa). It was found out for the SHSs on the oxidized Al, as the hydrostatic pressure increased, the corrosion behavior became severe. However, for the SHSs on the bare Al, their corrosion behavior was complex due to hydrostatic pressure. It was found that the corrosion resistance under 1 kPa was the highest. Further mechanism analysis revealed that this alleviated corrosion behavior under 1 kPa resulted from suppressing the oxygen diffusion through the liquid and reducing the subsequent corrosion rate as compared with 0 kPa, whereas the relatively low hydrostatic pressure (HP) could stabilize the entrapped air and hence enhance the corrosion resistance, compared with 15 kPa. The present study therefore provided a fundamental understanding for the applications of SHSs to prevent the corrosion, especially for various vessels in deep water.

[Clinical outcome of allogeneic hematopoietic stem cell transplantation with FLAG sequential busulfan/cyclophosphamide conditioning regimen for refractory/relapsed acute myeloid leukemia].

Objective: To investigate the therapeutic effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with FLAG sequential busulfan/cyclophosphamide(Bu/Cy) conditioning regimen for refractory/relapsed acute myeloid leukemia. Methods: From February 2012 to June 2017, 21 patients with refractory/relapsed acute myeloid leukemia underwent allo-HSCT with FLAG sequential Bu/Cy conditioning regimen. Transplantation-related complications and clinical outcome were retrospectively analyzed. Results: After conditioning, no hepatic veno-occlusive disease (VOD) and grade Ⅲ hemorrhagic cystitis occurred. 76.2% (16/21) patients had fever with 4 septicemia. One patient died of septic shock before engraftment. Twenty patients achieved neutrophil engraftment with a median time of 13 days (range, 10 to 21 days). Seventeen patients achieved platelet engraftment with a median time of 18 days (range, 9 to 25 days). The cumulative incidence of acute graft-versus-host disease (aGVHD) was 39.5%, and 3 patients developed grade Ⅲ-Ⅳ aGVHD. Of 19 patients who survived more than 100 days after transplantation, 4 had local chronic graft-versus-host disease (cGVHD). Of 21 patients, the median survival time was 15 months (range, 0.5 to 67 months) post-transplantation. Transplantation-related mortality rate was 28.7%. Leukemia relapse occurred in 4 patients with a median time of 4 months (range, 3 to 8 months) after transplantation. The cumulative relapse rate at 1 year was 21.4%. The 1-year and 3-year overall survival (OS) rates were 60.7% and 54.9% respectively. Log-rank analysis revealed that bone marrow blasts ≥ 20% or extramedullary leukemia before transplantation, poor platelet engraftment and grade Ⅲ-Ⅳ aGVHD were significantly related to shortened OS (P<0.05). Conclusions: Allo-HSCT with FLAG sequential Bu/Cy conditioning regimen in patients with refractory/relapsed myeloid leukemia has acceptable transplantation-related risk and relapse rate. The 1-year and 3-year OS rates are comparable with those in remission patients.

[Role of BoBs technology in early missed abortion chorionic villi].

Objective: To investigate the value of bacterial artificial chromosome-on-beads (BoBs) technology in the genetic analysis of early missed abortion chorionic villi. Methods: Early missed abortion chorionic villi were detected with both conventional karyotyping method and BoBs technology in Peking Union Medical Hospital from July 2014 to March 2015. Compared the results of BoBs with conventional karyotyping analysis to evaluate the sensitivity, specificity and accuracy of this new method. Results: (1) A total of 161 samples were tested successfully in the technology of BoBs, 131 samples were tested successfully in the method of conventional karyotyping. (2) All of the cases obtained from BoBs results in (2.7±0.6) days and obtained from conventional karyotyping results in (22.5±1.9) days. There was significant statistical difference between the two groups (t=123.315, P<0.01) . (3) Out of 161 cases tested in BoBs, 85 (52.8%, 85/161) cases had the abnormal chromosomes, including 79 cases chromosome number abnormality, 4 cases were chromosome segment deletion, 2 cases mosaic. Out of 131 cases tested successfully in conventional karyotyping, 79 (60.3%, 79/131) cases had the abnormal chromosomes including 62 cases chromosome number abnormality, 17 cases other chromosome number abnormality, and the rate of chromosome abnormality between two methods was no significant differences (P=0.198) . (4) Conventional karyotyping results were served as the gold standard, the accuracy of BoBs for abnormal chromosomes was 82.4% (108/131) , analysed the normal chromosomes (52 cases) and chromosome number abnormality (62 cases) tested in conventional karyotyping, the accuracy of BoBs for chromosome number abnormality was 94.7% (108/114) . Conclusion: BoBs is a rapid reliable and easily operated method to test early missed abortion chorionic villi chromosomal abnormalities.

Suppression of Host Innate Immune Response by Hepatitis C Virus via Induction of Autophagic Degradation of TRAF6.

Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an important adaptor molecule that mediates the TNFR family and interleukin-1 (IL-1)/Toll-like receptor (TLR) signaling cascades. These pathways are important for the host to control viral infections. In this report, we demonstrated that hepatitis C virus (HCV) depleted TRAF6 from its host cells through a posttranslational mechanism. This depletion was independent of proteasomes, as it was not affected by the proteasome inhibitor MG132, but it was suppressed by bafilomycin A1, which led to the association of TRAF6 with autophagosomes. As bafilomycin A1 is a vacuolar ATPase inhibitor that inhibits autophagic protein degradation, these results suggested that HCV depleted TRAF6 via autophagy. The degradation of TRAF6 was apparently mediated by the p62 sequestosome protein, which is a factor important for selective autophagy, as it could bind to TRAF6 and its silencing stabilized TRAF6. The depletion of TRAF6 suppressed activation of NF-κB and induction of proinflammatory cytokines and enhanced HCV replication. In contrast, the overexpression of TRAF6 suppressed HCV replication. These results revealed a novel mechanism that was used by HCV to disrupt the host innate immune responses for viral replication and persistence. IMPORTANCE: HCV can cause severe liver diseases and is one of the most important human pathogens. It establishes chronic infections in the great majority of patients that it infects, indicating that it has evolved sophisticated mechanisms to evade host immunity. TRAF6 is an important signaling molecule that mediates activation of NF-κB and expression of proinflammatory cytokines and interferons. In this study, we found that HCV infection suppressed the host innate immune response through the induction of autophagic degradation of TRAF6. This finding provided important information for further understanding how HCV evades host immunity to establish persistence.

Metformin treatment of antipsychotic-induced dyslipidemia: an analysis of two randomized, placebo-controlled trials.

Dyslipidemia is one of the most common adverse effects in schizophrenia patients treated with antipsychotics. However, there are no established effective treatments. In this study, data were pooled from two randomized, placebo-controlled trials, which were originally designed to examine the efficacy of metformin in treating antipsychotic-induced weight gain and other metabolic abnormalities. In total, 201 schizophrenia patients with dyslipidemia after being treated with an antipsychotic were assigned to take 1000 mg day-1 metformin (n=103) or placebo (n=98) for 24 weeks, with evaluation at baseline, week 12 and week 24. The primary outcome was the low-density lipoprotein cholesterol (LDL-C) levels. After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l-1 at baseline to -0.86 mmol l-1 at the end of week 24, decreased by 1.02 mmol l-1 (P<0.0001); and 25.3% of patients in the metformin group had LDL-C ≥3.37 mmol l-1, which is significantly <64.8% in the placebo group (P<0.001) at week 24. Compared with the placebo, metformin treatment also have a significant effect on reducing weight, body mass index, insulin, insulin resistance index, total cholesterol and triglyceride, and increasing high-density lipoprotein cholesterol. The treatment effects on weight and insulin resistance appeared at week 12 and further improved at week 24, but the effects on improving dyslipidemia only significantly occurred at the end of week 24. We found that metformin treatment was effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effects improving antipsychotic-induced insulin resistance appeared earlier than the reducing dyslipidemia.

Haemodynamic Variations of Flow to Renal Arteries in Custom-Made and Pivot Branch Fenestrated Endografting.

OBJECTIVE: This study aimed to investigate variation of blood flow to renal arteries in custom-made and pivot branch (p-branch) fenestrated endografting, using a computational fluid dynamics (CFD) technique. METHODS: Idealised models of custom-made and p-branch fenestrated grafting were constructed on a basis of a 26 mm stent graft. The custom-made fenestration was designed with a 6 mm diameter, while the 5 mm depth renal p-branch was created with a 6 mm inner and 15 mm outer fenestration. Two configurations (option A and option B) were constructed with different locations of p-branches. Option A had both renal p-branches at the same level, whereas option B contained two staggered p-branches at lower positions. The longitudinal stent orientation in both custom-made and p-branch models was represented by a takeoff angle (ToA) between the renal stent and distal stent graft centreline, varying from 55° to 125°. Computational simulations were performed with realistic boundary conditions governing the blood flow. RESULTS: In both custom-made and p-branch fenestrated models, the flow rate and wall shear stress (WSS) were generally higher and recirculation zones were smaller when the renal stent faced caudally. In custom-made models, the highest flow rate (0.390 L/min) was detected at 70° ToA and maximum WSS on vessel segment (16.8 Pa) was attained at 55° ToA. In p-branch models, option A and option B displayed no haemodynamic differences when having the same ToA. The highest flow rate (0.378 L/min) and maximum WSS on vessel segment (16.7 Pa) were both calculated at 55° ToA. The largest and smallest recirculation zones occurred at 90° and 55° ToA respectively in both custom-made and p-branch models. Custom-made fenestrated models exhibited consistently higher flow rate and shear stress and smaller recirculation zones in renal arteries than p-branch models at the same ToA. CONCLUSIONS: Navigating the renal stents towards caudal orientation can achieve better haemodynamic outcomes in both fenestrated devices. Custom-made fenestrated stent grafts are the preferred choice for elective patients. Further clinical evidence is required to validate the computational simulations.

Double-balloon catheter versus prostaglandin E2 for cervical ripening and labour induction: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour has become an increasingly common procedure. Ripening methods, including mechanical devices and pharmacological agents, improve the success rate of labour induction. OBJECTIVE: To compare the efficacy and safety of the double-balloon catheter with prostaglandin E2 agents used for labour induction. SEARCH STRATEGY: We searched electronic sources from MEDLINE, Embase and Web of Science, the Cochrane Library Database of Systematic Reviews, and ClinicalTrials.gov website. SELECTION CRITERIA: Only randomised controlled trials comparing the PGE2 agents with the double-balloon catheter for cervical ripening and labour induction in women with unfavourable cervices were included in the analysis. DATA COLLECTION AND ANALYSIS: The main outcomes included the vaginal delivery rate within 24 hours and risk of caesarean section. We calculated relative risks and mean differences using fixed- and random-effects models. MAIN RESULTS: Nine studies (1866 patients) were included in this systematic review. Both the double-balloon catheter and PGE2 agents were comparable with regard to rate of caesarean section (RR 0.92; 95% CI 0.79, 1.07), vaginal delivery within 24 hours (RR 0.95; 95% CI 0.78, 1.16) and maternal adverse events, but the risk of excessive uterine activity (RR 10.02; 95% CI 3.99, 25.17) and need for neonatal intensive care unit admissions (RR 1.31; 95% CI 1.01, 1.69) were significantly increased in women who received PGE2 agents. CONCLUSIONS: The double-balloon catheter demonstrated greater safety and cost-effectiveness than PGE2 agents for cervical ripening and labour induction. The efficacy profiles of both methods were similar. TWEETABLE ABSTRACT: Double-balloon catheter versus prostaglandin E2 for cervical ripening and labour induction.

Knockdown of HMGB1 inhibits cell proliferation and induces apoptosis in hemangioma via downregulation of AKT pathway.

The high mobility group box 1 (HMGB1) as a conserved non-histone nuclear protein has been involved in a variety of biological processes of cancer, such as cell proliferation, apoptosis, angiogenesis and metastasis. Despite the increased expression of HMGB1 in many malignant tumors, the functions and molecular mechanisms by which HMGB1 contributes to the formation of hemangioma (HA) remain unclear. In the present study, immunohistochemistry was used to detect the expression levels of HMGB1 in different phases of human HAs. Cell function experiments, including MTT, cell colony formation and flow cytometry analysis were performed to evaluate the effects of HMGB1 knockdown on cell proliferation and apoptosis in HA CRL-2586 EOMA cells. As a consequence, we found that HMGB1 expression was significantly increased in proliferating phase HAs compared with the involuting phase HAs and normal skin tissues (P less than 0.01). Moreover, knockdown of HMGB1 gene in vitro suppressed EOMA cell proliferation and colony formation and induced cell apoptosis and cycle arrest at G0/G1 phase by downregulation of PCNA, CyclinD1, p-AKT and upregulation of p53 and cleaved PARP. Taken together, our findings demonstrate that HMGB1 may be implicated in the formation of HA through upregulation of AKT pathway, and represent a potential therapeutic target for treating HA.

The persistence of intracellular Staphylococcus aureus in the sinuses: a longitudinal study.

BACKGROUND: Staphylococcus aureus (S. aureus) can reside within the sinonasal mucosa in chronic rhinosinusitis patients and causes recurrent infections. Within the host cell, S. aureus can evade host immune detection enabling its own survival. We hypothesise that S. aureus can persist within the sinonasal epithelium for a prolonged period without immune activation. METHODOLOGY: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) undergoing two sinus surgeries were included. Immunohistochemistry and Haematoxylin and Eosin stains were used to determine intracellular S. aureus (ICSA) status and inflammatory cell count, respectively. One-way ANOVA and paired t-tests were performed for comparison between ICSA subgroups and within each subgroup, respectively. RESULTS: Histopathological specimens from 34 patients (68 procedures) were included. ICSA positivity (ICSA+) was seen in 43 specimens (63.2%) from 26 (76%) patients. 18 (52.9%) of those were ICSA+ in both operations while 8 (23.5%) patients were ICSA+ in only one of the operations. 8 (23.5%) patients were ICSA negative in both operations. There was no difference in the number of eosinophils, lymphocyte and neutrophils between ICSA subgroups. CONCLUSIONS: This study demonstrated that S. aureus is found intracellularly within CRSwNP tissue at multiple time points without an increase in the number of eosinophils, lymphocytes and neutrophils. This finding supports our hypothesis that ICSA is able to escape from host detection and resides within the sinonasal mucosa despite intense treatment.

Lack of autophagy induces steroid-resistant airway inflammation.

BACKGROUND: Neutrophilic corticosteroid-resistant asthma accounts for a significant proportion of asthma; however, little is known about the mechanisms that underlie the pathogenesis of the disease. OBJECTIVE: We sought to address the role of autophagy in lung inflammation and the pathogenesis of corticosteroid-resistant neutrophilic asthma. METHODS: We developed CD11c-specific autophagy-related gene 5 (Atg5)(-/-) mice and used several murine models to investigate the role of autophagy in asthmatic patients. RESULTS: For the first time, we found that deletion of the Atg5 gene specifically in CD11c(+) cells, which leads to impairment of the autophagy pathway, causes unprovoked spontaneous airway hyperreactivity and severe neutrophilic lung inflammation in mice. We found that severe lung inflammation impairs the autophagy pathway, particularly in pulmonary CD11c(+) cells in wild-type mice. We further found that adoptive transfer of Atg5(-/-), but not wild-type, bone marrow-derived dendritic cells augments lung inflammation with increased IL-17A levels in the lungs. Our data indicate that neutrophilic asthma in Atg5(-/-) mice is glucocorticoid resistant and IL-17A dependent. CONCLUSION: Our results suggest that lack of autophagy in pulmonary CD11c(+) cells induces neutrophilic airway inflammation and hyperreactivity.

Technical standards for hepatitis B virus X protein (HBx) research.

Chronic infection with hepatitis B virus (HBV) is a risk factor for developing hepatocellular carcinoma (HCC). The life cycle of HBV is complex and has been difficult to study because HBV does not infect cultured cells. The HBV regulatory X protein (HBx) controls the level of HBV replication and possesses an HCC cofactor role. Attempts to understand the mechanism(s) that underlie HBx effects on HBV replication and HBV-associated carcinogenesis have led to many reported HBx activities that are likely influenced by the assays used. This review summarizes experimental systems commonly used to study HBx functions, describes limitations of these experimental systems that should be considered, and suggests approaches for ensuring the biological relevance of HBx studies.

[Effect of the Chinese Herbal Medicinal Ingredients in Huoxiang Zhengqi Liquid on Alcohol Metabolism in Rats].

OBJECTIVES: To study the changes of alcohol content and pharmacokinetic parameter in rats after taking Huoxiang Zhengqi liquid. METHODS: The rats were randomly divided into three groups and given with white alcohol at the dose of 3.0 mL/kg, low-dose and high-dose Chinese medicine liquor, respectively. The blood was collected before administration and 5 min, 10 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h and 8 h after administration by cutting rats' tails. The concentrations of alcohol in blood were detected by headspace-gas chromatography method. The main pharmacokinetic parameters were calculated by DAS 2.0, and then analyzed by SPSS 17.0. RESULTS: The difference of maximum blood concentrations between high-dose Chinese medicine alcohol group and white alcohol group was statistically significant （P<0.05）. There was no significant difference in other pharmacokinetic parameters among three groups （P>0.05）. CONCLUSIONS: The Chinese herbal medicinal ingredients in the Huoxiang Zhengqi liquid has no effect on the metabolism and elimination of ethanol in rats. The research provides useful reference for the qualitative assessment and processing of traffic accident cases involved in Huoxiang Zhengqi liquid and the studies related to drug-interaction.