Development and internal validation of a clinical prediction model for osteopenia in Chinese middle-aged and elderly men: a prospective cohort study.

BACKGROUND: Early identification of patients at risk of osteopenia is an essential step in reducing the population at risk for fractures. We aimed to develop and validate a prediction model for osteopenia in Chinese middle-aged and elderly men that provides individualized risk estimates. METHODS: In this prospective cohort study, 1109 patients who attend regular physical examinations in the Second Medical Centre of Chinese PLA General Hospital were enrolled from 2015.03 to 2015.09. The baseline risk factors included dietary habits, exercise habits, medical histories and medication records. Osteopenia during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Internal validation was conducted using bootstrapping to correct the optimism. The independent sample T-test analysis, Mann_Whitney U test, Chi-Square Test and multivariable Cox regression analysis were utilized to identify predictive factors for osteopenia in Chinese middle-aged and elderly men. A nomogram based on the seven variables was built for clinical use. Concordance index (C-index), receiver operating characteristic curve (ROC), decision curve analysis (DCA) and calibration curve were used to evaluate the efficiency of the nomogram. RESULTS: The risk factors included in the prediction model were bone mineral density at left femoral neck (LNBMD), hemoglobin (Hb), serum albumin (ALB), postprandial blood glucose (PBG), fatty liver disease (FLD), smoking and tea consumption. The C-index for the risk nomogram was 0.773 in the prediction model, which presented good refinement. The AUC of the risk nomogram at different time points ranged from 0.785 to 0.817, exhibiting good predictive ability and performance. In addition, the DCA showed that the nomogram had a good clinical application value. The nomogram calibration curve indicated that the prediction model was consistent. CONCLUSIONS: Our study provides a novel nomogram and a web calculator that can effectively predict the 7-year incidence risk of osteopenia in Chinese middle-aged and elderly men. It is convenient for clinicians to prevent fragility fractures in the male population.

Heparin-binding hemagglutinin of Mycobacterium tuberculosis inhibits autophagy via TLR4 and drives M2 polarization in macrophages.

BACKGROUND: Tuberculosis (TB), predominantly caused by Mycobacterium tuberculosis (MTB) infection, remains a prominent global health challenge. Macrophages are the frontline defense against MTB, relying on autophagy for intracellular bacterial clearance. However, MTB can combat and evade autophagy, and it influences macrophage polarization, facilitating immune evasion and promoting infection. We previously found that heparin-binding hemagglutinin (HBHA) inhibits autophagy in A549 cells; however, its role in macrophage autophagy and polarization remains unclear. METHODS: Bacterial cultures, cell cultures, western blotting, immunofluorescence, macrophage infection assays, siRNA knockdown, and ELISA were used to investigate HBHA's impact on macrophages and its relevance in Mycobacterium infection. RESULTS: HBHA inhibited macrophage autophagy. Expression of recombinant HBHA in Mycobacterium smegmatis (rMS-HBHA) inhibited autophagy, promoting bacterial survival within macrophages. Conversely, HBHA knockout in the Mycobacterium bovis Bacillus Calmette-Guérin (BCG) mutant (BCG-ΔHBHA) activated autophagy and reduced bacterial survival. Mechanistic investigations revealed that HBHA may inhibit macrophage autophagy through the TLR4-dependent PI3K-AKT-mTOR signaling pathway. Furthermore, HBHA induced macrophage M2 polarization. CONCLUSIONS: Mycobacterium may exploit HBHA to suppress the antimicrobial immune response in macrophages, facilitating intracellular survival, and immune evasion through autophagy inhibition and M2 polarization induction. Our findings may help identify novel therapeutic targets and develop more effective treatments against MTB infection.

Predicting ventilator-associated pneumonia in elderly patients requiring mechanical ventilation through the detection in tracheal aspirates.

OBJECTIVE: In this study, we evaluated the clinical utility of tracheal aspirates α-amylase (AM), pepsin, and lipid-laden macrophage index (LLMI) in the early diagnosis of ventilator-associated pneumonia (VAP) in elderly patients on mechanical ventilation. METHODS: Within 96 hours of tracheal intubation, tracheal aspirate specimens were collected from elderly patients on mechanical ventilation; AM, pepsin, and LLMI were detected, and we analyzed the potential of each index individually and in combination in diagnosing VAP. RESULTS: Patients with VAP had significantly higher levels of AM, pepsin, and LLMI compared to those without VAP (P < 0.001), and there was a positive correlation between the number of pre-intubation risk factors of aspiration and the detection value of each index in patients with VAP (P < 0.001). The area under a receiver operating characteristic (ROC) curve (AUC) of AM, pepsin, and LLMI in diagnosis of VAP were 0.821 (95% CI:0.713-0.904), 0.802 (95% CI:0.693-0.892), and 0.621 (95% CI:0.583-0.824), the sensitivities were 0.8815, 0.7632, and 0.6973, the specificities were 0.8495, 0.8602, and 0.6291, and the cutoff values were 4,321.5 U/L, 126.61 ng/ml, and 173.5, respectively. The AUC for the combination of indexes in diagnosing VAP was 0.905 (95% CI:0.812-0.934), and the sensitivity and specificity were 0.9211 and 0.9332, respectively. In the tracheal aspirate specimens, the detection rate of AM ≥ cutoff was the highest, while it was the lowest for LLMI (P < 0.001). The detection rates of AM ≥ cutoff and pepsin ≥ cutoff were higher within 48 hours after intubation than within 48-96 hours after intubation (P < 0.001). In contrast, the detection rate of LLMI ≥ cutoff was higher within 48-96 hours after intubation than within 48 hours after intubation (P < 0.001). The risk factors for VAP identified using logistic multivariate analysis included pre-intubation aspiration risk factors (≥3), MDR bacteria growth in tracheal aspirates, and tracheal aspirate AM ≥ 4,321.5 U/L, pepsin ≥ 126.61 ng/ml, and LLMI ≥ 173.5. CONCLUSION: The detection of AM, pepsin, and LLMI in tracheal aspirates has promising clinical utility as an early warning biomarker of VAP in elderly patients undergoing mechanical ventilation.

Heat shock protein 70 is involved in polaprezinc driven cell protection against Helicobacter pylori-induced injury.

Polaprezinc (PZ) plays a role in the protection of gastric mucosa and inhibiting Helicobacter pylori (H. pylori) growth in vitro. The objective of this study was to determine the protective effects of PZ on human gastric epithelial cells (GES-1) against H. pylori-induced damage, while also examining heat shock protein 70 (HSP70) as a potential underlying factor in this protection. Our findings revealed that PZ exerted bactericidal effects against H. pylori strains. We also observed that PZ mitigated the H. pylori-induced damage to GES-1 cells by increasing cell viability, reducing LDH release, and decreasing the secretion of pro-inflammatory factors such as MCP-1 and IL-6. Co-culturing PZ with GES-1 cells significantly up-regulated the GES-1 HSP70 expression in both a time and dose-dependent manner. Pre-incubating (for 12 h) or co-culturing (for 24 h) GES-1 cells with PZ reversed the down-regulation of HSP70 in GES-1 cells caused by H. pylori infection. However, when quercetin was used to inhibit the up-regulation of HSP70 in GES-1 cells, the protective effect of PZ on GES-1 cells was significantly reduced. Based on the results of this study, PZ exhibits a protective role on GES-1 cells against H. pylori injury, as well as a direct bactericidal effect on H. pylori. HSP70 is involved in the PZ-driven host cell protection against H. pylori injury. These findings provide insight into alternative strategies for H. pylori treatment.

A novel lncRNA DFRV plays a dual function in influenza A virus infection.

Long noncoding RNAs (lncRNAs) have been associated with a variety of biological activities, including immune responses. However, the function of lncRNAs in antiviral innate immune responses are not fully understood. Here, we identified a novel lncRNA, termed dual function regulating influenza virus (DFRV), elevating in a dose- and time-dependent manner during influenza A virus (IAV) infection, which was dependent on the NFκB signaling pathway. Meanwhile, DFRV was spliced into two transcripts post IAV infection, in which DFRV long suppress the viral replication while DFRV short plays the opposite role. Moreover, DFRV regulates IL-1ß and TNF-α via activating several pro-inflammatory signaling cascades, including NFκB, STAT3, PI3K, AKT, ERK1/2 and p38. Besides, DFRV short can inhibit DFRV long expression in a dose-dependent manner. Collectively, our studies reveal that DFRV may act as a potential dual-regulator to preserve innate immune homeostasis in IAV infection.

Dual targeting of MEK and PI3K effectively controls the proliferation of human EGFR-TKI resistant non-small cell lung carcinoma cell lines with different genetic backgrounds.

BACKGROUND: Molecular targeted therapy for non-small cell lung carcinoma (NSCLC) is restricted due to resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This study evaluated the effects of dual targeting of MEK and PI3K in human EGFR-TKI resistant NSCLC cell lines. METHODS: EGFR-TKI resistant NSCLC cell lines H1975, H460, and A549, with different mutation and amplification status in EGFR, K-RAS, PIK3CA, and MET genes, were treated with a MEK162 (MEK inhibitor) and BKM120 (PI3K inhibitor) combination or a BIBW2992 (EGFR inhibitor) and ARQ197 (MET inhibitor) combination and assayed for cell proliferation, apoptosis, and cell cycle distribution. RESULTS: Dual targeting of MEK and PI3K efficiently inhibited the cell proliferation, induced apoptosis and the G0/G1 cell cycle, and decreased the phosphorylation of ERK1/2, AKT, S6, and 4E-BP1. H460 cells with K-RAS and PIK3CA mutation were most sensitive to MEK162 and BKM120 combinations. H1975 cells with EGFR and PIK3CA mutation and MET amplification were sensitive to BIBW2992 and ARQ197 combinations. CONCLUSION: Dual targeting regulated the proliferation of EGFR-TKI-resistant NSCLC cells, especially mutants in K-RAS and PIK3CA that are promising for EGFR-TKI-resistant NSCLC therapeutics.

Effect of Temperature on Metronidazole Resistance in Helicobacter pylori.

Efficacy of Helicobacter pylori (H. pylori) eradication therapy has declined due to rapid rises in antibiotic resistance. We investigated how increased temperature affected H. pylori (NCTC 11637) growth and its sensitivity to metronidazole in vitro. We performed transcriptomic profiling using RNA-sequencing to identify differentially expressed genes (DEGs) associated with increased temperature. Transcriptional pathways involved in temperature-driven metronidazole resistance changes were analyzed through bioinformatic and literature curation approaches. We showed that H. pylori growth was inhibited at 41°C and inhibition was more apparent with prolonged incubation. Resistance to metronidazole was also reduced-minimum inhibitory concentration for metronidazole decreased from > 256 µg/ml at 37°C to 8 µg/ml at 41°C after culturing for 3 days. RNA-sequencing results, which were highly concordant within treatment conditions, revealed more than one third of genes (583/1,552) to be differentially expressed at increased temperatures with similar proportions up and down-regulated. Quantitative real-time PCR validation for 8 out of 10 DEGs tested gave consistent direction in gene expression changes. We found enrichment for redox and oxygen radical pathways, highlighting a mechanistic pathway driving temperature-related metronidazole resistance. Independent literature review of published genes associated with metronidazole resistance revealed 46 gene candidates, 21 of which showed differential expression and 7 out of 9 DEGs associated with "redox" resistance pathways. Sanger sequencing did not detect any changes in genetic sequences for known resistance genes rdxA, frxA nor fdxB. Our findings suggest that temperature increase can inhibit the growth and reduce H. pylori resistance to metronidazole. Redox pathways are possible potential drivers in metronidazole resistance change induced by temperature. Our study provides insight into potential novel approaches in treating antibiotic resistant H. pylori.

Association of active Helicobacter pylori infection and anemia in elderly males.

BACKGROUND: The prevalence of Helicobacter pylori (H. pylori) infection increases with age. However, the relationship between H. pylori infection and anemia in the elderly population remains to be identified. The aim of this study is to explore whether H. pylori infection is associated with anemia in a male elderly cohort. METHODS: A cross-sectional study was designed using data collected from asymptomatic male senior citizens (≥ 65 years old) who received an assessment of their health status at the General Hospital of Chinese PLA from January 2015 to December 2015. H. pylori infection was confirmed by the 13C-urea breath test. Blood samples from the participants were taken to assay for hemoglobin and other erythroid-related indices - serum iron, ferritin, and C-reactive protein (CRP). Anemia was defined as hemoglobin values lower than 120.0 g/L. Charlson Comorbidity Index (CCI) was applied to establish baseline comorbidities. RESULTS: Data from 646 subjects were analyzed. The mean age of the study cohort was 79.4 ± 8.9 years. The overall prevalence of H. pylori infection was 35.3%. The prevalence of anemia in the H. pylori positive group was higher than that in the negative group (5.3% vs. 2.2%, P = .033). Among the patients who had higher CCI scores (> 2), the prevalence of anemia in the H. pylori positive and negative groups were 10.3 and 1.4%, respectively (P = .009). Compared to the H. pylori negative group, the odds ratio for anemia of the H. pylori positive group was 2.53 (P = .033). No correlation between H. pylori infection and serum iron and ferritin levels was found. The mean corpuscular volume of the H. pylori positive and negative group was 91.17 ± 3.94 fl and 91.17 ± 4.09 fl (mean ± SD), respectively (P = .986). The CRP level in the H. pylori positive group was higher than that in the H. pylori negative group (Median: 0.17 mg/dL vs. 0.10 mg/dL, P < .001). CONCLUSION: H. pylori infection seems to be associated with normocytic and normochromic anemia in elderly males, especially in those with more comorbidities. Further clinical studies are needed to verify the association.

Prospective investigation of carbapenem-resistant Klebsiella pneumonia transmission among the staff, environment and patients in five major intensive care units, Beijing.

BACKGROUND: Following the alarming outbreak of carbapenem-resistant Klebsiella pneumonia (CRKP) in five intensive care units (ICUs) of a tertiary care hospital in China, a prospective investigation of CRKP colonized/infected patients was conducted. AIM: To describe the diffusion and transmission of CRKP among epidemiologically linked ICU patients, staff and environment. METHODS: Enhanced CRKP infected/colonized case monitoring was performed by the real-time nosocomial infection surveillance system (RT-NISS). The immediate surroundings of each CRKP patient bed unit and the staff hands/gloves/gowns were sampled and then evaluated for the presence of CRKP. Antimicrobial susceptibility tests, pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) were used to identify and to characterize these isolates. FINDINGS: Among 2750 patients monitored, 67 CRKP patients were newly labeled and 11 patients' CRKP isolates were available. A total of 31.34% (21/67) bed units were positive at one or more surrounding surfaces, 7.99% (49/613) environmental samples and 3.57% (4/112) ICU staff samples were CRKP positive. The selected CRKP isolates (N = 64) exhibited intermediate to high resistance levels to the antibiotics tested apart from colistin and tigecycline. RT-NISS data combined with MLST and PFGE revealed nine likely transmission clusters. WGS analysis of these CRKP isolates revealed extensive sharing of multiple antimicrobial resistance genes and plasmid replicons among these isolates. Two carbapenemase genes blaKPC-2 (62/64) and blaOXA-48 (2/64) were identified. These CRKP isolates carried one or more plasmid replicons. CONCLUSIONS: The contamination of ICU environment and staff's hands, gloves or gowns is frequent with CRKP patients. Our study also supports the hypothesis that an association between environmental contamination and transmission of CRKP bacteria in ICUs.

A multiplex loop-mediated isothermal amplification assay for rapid screening of Acinetobacter baumannii and D carbapenemase OXA-23 gene.

Background: Acinetobacter baumannii is a health burden responsible for various nosocomial infections, and bacteremia in particular. The resistance of A. baumannii to most antibiotics including carbapenem has increased. OXA-23-producing A. baumannii is the chief source of nosocomial outbreaks with carbapenem-resistant A. baumannii Successful antibiotic treatment relies on the accurate and rapid identification of infectious agents and drug resistance. Here, we describe a multiplex loop-mediated isothermal amplification (LAMP) assay for simultaneous and homogeneous identification for A. baumannii infection screening and drug-resistance gene detection. Methods: Four primer pairs were designed to amplify fragments of the recA gene of A. baumannii and the oxa-23 gene. The reaction with a 25 µl of final volume was performed at 63°C for 60 min. For comparative purposes, we used a traditional method of bacterial identification to evaluate assay efficacy. Results: The multiplex LAMP assay enables simultaneous and homogeneous detection of the recA gene of A. baumannii and the oxa-23 gene and requires less than 21 min with no pre-requisite for DNA purification prior to the amplification reaction. The detection is specific to A. baumannii, and the coincidence rate of the multiplex LAMP and the traditional method was 100%. Conclusions: Our data indicate that the multiplex LAMP assay is a rapid, sensitive, simultaneous and homogeneous method for screening of A. baumannii and its drug-resistance gene.

Predictive value of α-amylase in tracheal aspirates for ventilator-associated pneumonia in elderly patients.

OBJECTIVE: This study aims to investigate the correlation between α-amylase in tracheal aspirates and risk factors of aspiration, as well as ventilator-associated pneumonia (VAP), in elderly patients undergoing mechanical ventilation and explore the clinical value of α-amylase for predicting VAP. METHODS: Tracheal aspirates were collected from elderly patients within 2 weeks after tracheal intubation in mechanical ventilation, and α-amylase was detected. Patients were grouped according to the presence of VAP. The correlation between α-amylase and risk factors of aspiration before intubation, as well as VAP, were analyzed. RESULTS: The sample of this study comprised 147 patients. The average age of these patients was 86.9 years. The incidence of VAP was 21% during the study period. Tracheal aspirate α-amylase level increased with the increase in the number of risk factors for aspiration before intubation, α-amylase level was significantly higher in the VAP group than in the non-VAP group, the area under the receiver operating characteristic curve (ROC) of the diagnostic value of α-amylase for VAP was 0.813 (95% CI: 0.721-0.896), threshold value was 4,681.5 U/L, sensitivity was 0.801 and specificity was 0.793. Logistic multivariate analysis revealed the following risk factors for VAP: a number of risk factors before intubation of ≥3, a Glasgow score of <8 points, the absence of continuous aspiration of subglottic secretion and a tracheal aspirate α-amylase level of >4681.5 U/L. CONCLUSION: Tracheal aspirate α-amylase can serve as a biomarker for predicting VAP in elderly patients undergoing mechanical ventilation.

[Protective effects of Genistein on human renal tubular epithelial cells damage of microwave radiation].

OBJECTIVE: To observe the effects of microwave irradiation on human proximal renal tubular epithelial cells (HKC) and protec-tive effects of genistein. METHODS: HKC cells were divided into control group, microwave irradiation group and genistein group(n=6) re-spectively. The genistein group cells were pre-incubated with 30µmol/L genistein in DMEM for 2 hours. After irradiation for 24 hours, the concentrations of lactate dehydrogenase(LDH) and ß-N-acetyl glucosaminidase(NAG) in culture solution were measured to evaluate cell injury. Cells were curetted to measure the levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Cell apoptosis and necrosis were de-tected with Hoechst 33258 stain. RESULTS: Compared with the control group, the NAG activity of the microwave irradiation group was signifi-cantly increased(P < 0.01), and NAG activity of genistein pre-incubated group was significantly decreased(P < 0.01). The levels of LDH in microwave irradiation group were also increased significantly (P < 0.01 vs control group). LDH levels could be decreased obviously (P < 0.01 vs microwave irradiation group) after genistein pre-incubate. Hoechst 33258 fluorescent staining revealed that the nucleus crimpled, cres-cent liked and chromatin condensed, even nucleus disintegrated. Our research showed that microwave irradiation could lead to large amount of cell apoptosis and necrosis, and genistein pre-treatment could reduce the ratio of apoptosis and necrosis than that in microwave irradiation group (P < 0.01). The concentration of MDA in microwave irradiation group was higher than that in control group (P < 0.01). At the same time, the activity of SOD was significantly reduced (P < 0.01). Pre-incubated with genistein could not decrease the MDA levels, but could increase the activities of SOD (P < 0.01 vs microwave irradiation group). CONCLUSIONS: microwave irradiation can induce human proximal renal tubular epithelial cells injury. The protective effects of genistein may partly correlated with decreasing oxidative stress damage and cell apoptosis in HKC cells.

Biological features of biofilm-forming ability of Acinetobacter baumannii strains derived from 121 elderly patients with hospital-acquired pneumonia.

This study is to investigate a biological activity of Acinetobacter baumannii isolates from sputum specimens of 121 elderly patients with hospital-acquired pneumonia. The ability of the isolates to form biofilms was quantitatively assessed by crystal violet staining, and adhesive property was examined using Giemsa staining. Biofilm-forming ability by the isolates was employed to test antimicrobial resistance and examine sources and clinical manifestations. The isolates grew as biofilm on abiotic surface at the indicated temperatures after a 48 h of incubation. 27.3 % of the isolates were strongly biofilm-positive in the samples, and 84.8 % displayed high adhesion ability (P < 0.05). All of the isolates showed antibiotic resistance at different levels, and the isolates produced strong biofilm exhibited low-level resistance to gentamicin, minocycline and ceftazidime (P < 0.05). The patients' experience in ICU, use of antibiotics and estimation of APACHE II (<17) were related to incidence of strong biofilm formation with no clinical manifestations found in the study. All clinical isolates are able to form biofilms which refer to adhesive efficiency and antibiotic resistance. Patient experiences in ICU surveillance, use of antibiotics and APACHE II scores are involved in biofilm-forming ability by the nosocomial pathogen derived from the hospitalized patients.

Protective effect of heme oxygenase-1 on Wistar rats with heart failure through the inhibition of inflammation and amelioration of intestinal microcirculation.

BACKGROUND: Myocardial infarction (MI) has likely contributed to the increased prevalence of heart failure (HF). As a result of reduced cardiac function, splanchnic blood flow decreases, causing ischemia in villi and damage to the intestinal barrier. The induction of heme oxygenase-1 (HO-1) could prevent, or lessen the effects of stress and inflammation. Thus, the effect and mechanism thereof of HO-1 on the intestines of rats with HF was investigated. METHODS: Male Wistar rats with heart failure through ligation of the left coronary artery were identified with an left ventricular ejection fraction of < 45% through echocardiography and then divided into various experimental groups based on the type of peritoneal injection they received [MI: saline; MI + Cobalt protoporphyrin (CoPP): CoPP solution; and MI + Tin mesoporphyrin IX dichloride (SnMP): SnMP solution]. The control group was comprised of rats without coronary ligation. Echocardiography was performed before ligation for a baseline and eight weeks after ligation in order to evaluate the cardiac function of the rats. The bacterial translocation (BT) incidence, mesenteric microcirculation, amount of endotoxins in the vein serum, ileum levels of HO-1, carbon oxide (CO), nitric oxide (NO), interleukin (IL)-10, tumour necrosis factor-α (TNF-α), and the ileum morphology were determined eight weeks after the operation. RESULTS: The rats receiving MI + CoPP injections exhibited a recovery in cardiac function, an amelioration of mesenteric microcirculation and change in morphology, a lower BT incidence, a reduction in serum and ileac NO and TNF-α levels, and an elevation in ileac HO-1, CO, and interleukin-10 (IL-10) levels compared to the MI group (P < 0.05). The rats that received the MI + SnMP injections exhibited results inverse to the MI (P < 0.05) group. CONCLUSIONS: HO-1 exerted a protective effect on the intestines of rats with HF by inhibiting the inflammation and amelioration of microcirculation through the CO pathway. This protective effect could be independent from the recovery of cardiac function.

A noncytolytic antibody-like extendin-4-IgG4 fusion protein as a long-acting potential anti-diabetic agent.

BACKGROUND: GLP-1 and its analogs have a variety of anti-diabetic effects. However, short half-life and rapid degraded by DPP-IV limits the therapeutic potential of the native GLP-1. So, many DPP-IV-resistant and long-acting GLP-1 analogs were developed. In this study, an antibody-like extendin-4-IgG4 fusion protein was developed. METHODS: The γ4 constant region contains two amino acid substitutions relative to native γ4 (S228P and L235E) lead to affinity for FcγRI to be low and stability of the IgG4 molecular. The fusion protein was expressed in CHO cells and assembled into an immunoglobulin-like structure with molecular weight of approximately 130 kDa. RESULTS: The Exendin-4-IgG4 fusion protein was found to affinity bind GLP-1R in vitro. In vivo when compared the potency and duration of glucose-lowering effects in diabetic (db/db) mice at the same dose, exendin-4 resulted in a glucose-lowering effect that persisted only for 6 hours, but the extendin-4-IgG4 fusion protein for more than 168 hours. Injecting subcutaneously with a high dose of the fusion protein led normal BALB/c mice to the lower blood glucose level but did not cause serious hypoglycemia. Especially, the half-life time of the fusion protein in cynomolgus monkeys was about 180 hours, almost the longest half-life time among the developed GPL-1 analogues, which suggested a longer half-life time in human. CONCLUSIONS: The intact antibody-like fusion protein has more advantages than the Fc fusion protein including the intent of prolonging the half-life. These results also suggested the fusion protein was a safe and long-acting potential anti-diabetic agent.

Association between thrombelastography system and vascular obstructions and hemorrhage: a two-year follow-up study of elderly Chinese patients.

OBJECTIVES: This study was designed to test the hypothesis that prior thrombelastography (TEG) indices are associated with subsequent vascular obstructions and hemorrhage events in aged populations, as well as to obtain knowledge about the distribution of TEG indices in elderly Chinese patients. METHODS: We conducted a two-year follow-up study. The study population consisted of patients older than 65 years who had TEG in the Chinese PLA General Hospital between January 2007 and December 2010. Four hundred and three patients were enrolled in our study. They received TEG measurements upon being enrolled in this study. We collected information on demographics, clinical examinations, and outcomes during the observational period. Structural equation modeling (SEM) was used to analyze the relationship between "synthesized" TEG parameter indices and the outcome via an indicator pathway. RESULTS: We found that in the "model of hemorrhage" (adjusted by confounding of anticoagulants), the model fit indices with chi-square/df = 9.555/7, CFI of 0.997, TLI of 0.994, and standardized root mean square residual (SRMR) of 0.034; while in the "model of vascular obstruction events" (adjusted by confounding of Anticoagulants), the model fit indices with chi-square/df = 6.070/7, CFI of 1.000, TLI of 1.002, and standardized root mean square residual (SRMR) of 0.000. The "model of vascular obstruction events" showed that the "synthesized" TEG parameter was significantly associated with vascular obstruction events, while this significance was not found in the "model of hemorrhage". CONCLUSIONS: Previous TEG indices are significantly associated with the subsequent vascular obstruction events in the elderly population. Future study can test this association and provide more information for clinical use.

A retrospective analysis of carbapenem-resistant Acinetobacter baumannii-mediated nosocomial pneumonia and the in vitro therapeutic benefit of cefoperazone/sulbactam.

BACKGROUND: Acinetobacter baumannii has been reported increasingly as a significant causative organism of various nosocomial infections, including hospital-acquired pneumonia (HAP). The aim of this study was to investigate the clinical characteristics of HAP induced by carbapenem-resistant A. baumannii (CRAB) in elderly patients and the in vitro antimicrobial effects of cefoperazone/sulbactam combination therapy. METHODS: Seventy-one elderly patients in the geriatric ward of the General Hospital of the People's Liberation Army (PLAGH) with CRAB-induced HAP were analyzed retrospectively. The checkerboard method was used to determine the in vitro drug sensitivity of 60 CRAB strains to antimicrobial combinations (cefoperazone/sulbactam with meropenem, minocycline, or levofloxacin). The occurrence of carbapenemase genes was detected by PCR. RESULTS: CRAB-induced HAP occurred mostly in patients with underlying diseases. Prior to onset, most patients had received antimicrobial therapies including broad-spectrum ß-lactams, invasive mechanical ventilation, and catheterization. The 30-day survival rate was 95.1% in patients using cefoperazone/sulbactam, with or without combination with antimicrobial drugs, and 73.3% in patients not using cefoperazone/sulbactam (p<0.05). When cefoperazone/sulbactam was used in combination with minocycline, levofloxacin, and meropenem, minimum inhibitory concentrations MIC50 and MIC90 were reduced for each drug. The genes OXA-23 and OXA-51 were amplified in 96.7% of the strains, but the genes OXA-24, OXA-58, SIM, VIM, and IMP were not amplified. CONCLUSIONS: CRAB-induced HAP occurred mostly in patients with anemia or decreased levels of serum albumin, but with elevated levels of C-reactive protein and creatinine. Cefoperazone/sulbactam in combination with minocycline, meropenem, and levofloxacin had a synergistic and additive in vitro bacteriostatic action on CRAB.

[Effects of tank operation on renal function of crews].

OBJECTIVE: To explore the effects of harmful factors in tank cabins on renal function of tank crews. METHODS: One hundred and fifty two tank crews as the observation group and 37 soldiers without tank environment exposure as control group were selected in the study. α1-microglobulin(α1-MG), ß2-microglobulin(ß2-MG), IgG, N-acetyl-ß-glucosidase (NAG) and urinary albumin excretion rate (UAER) in morning and 24 h urine were measured. RESULTS: Compared to the control group, the levels of α1-MG, ß2-MG, NAG, UAER in observation group were increased significantly (P < 0.05). ß2-MG, NAG, UAER of Soldiers with more than 50 motorized hours in observation group were significantly higher than those of control group (P < 0.05). ß2-MG, NAG and UAER of soldiers divorced from tank occupation more than 3 years decreased to the normal levels. ß2-MG of soldiers divorced from tank occupation more than 10 years was significantly higher than that of 6-10 years group. CONCLUSION: Tank occupational exposure influences the renal function of tank crews but not to a degree of clinical kidney disease. The renal function of crews divorced from tank occupation may recover but dysfunction of renal tubular reabsorption still exists.

Predicting hemorrhage and obstruction in the elderly population using thromboelastographic indices.

OBJECTIVE: To estimate the value of the different thromboelastogram indices for predicting hemorrhage and vascular obstruction in an elderly population. METHODS: This was a prospective cohort study of patients 65 years and older without hemato-logic disorders who received thromboelastography (TEG) examination at the Chinese People's Liberation Army General Hospital from January 2007 to December 2010. Detailed information was collected at recruitment including their TEG test results. Subjects were then followed during outpatient visits and hospitalization. The primary outcome measures were hemorrhage and vascular obstruction. Receiver-operating characteristics (ROC) curves were used to compare the predictive value of the four TEG indices, reaction time (R), clot formation time (K), maximal amplitude (MA), alpha angle (ANGLE) and their combination for predicting hemorrhage and vascular obstruction. The maximal Youden's index was used to estimate optimal cut-off values for the indices. Areas under the ROC curves were used to estimate overall predictive accuracies. RESULTS: A total of 403 elderly patients met inclusion criteria and were included: 373 male and 30 females with mean age 83.0 ± 7.3 years and range of 65-103 years. Hemorrhage occurred in 25 (6.2%) patients and vascular obstruction in 78 (19.4%) patients during the 2-year follow up. The currently recommended TEG cut-off values were poorly predictive of vascular obstruction and modestly predictive of hemorrhage. Based on maximal Youden's, the optimal cutoffs of the TEG indices for predicting vascular obstruction were: R = 7, K = 1.5, MA = 63.5, and ANGLE = 67.1. A combination of all four showed the best predictive value (area under the ROC curve of 0.60, sensitivity 85.9%, and specificity 34.7%). The optimal cut-off values for predicting hemorrhage were: R = 7.8, K = 2.3, MA = 50.5, ANGLE = 53.7. A combination of R and MA was also most predictive of hemorrhage (area under ROC curve 0.66, sensitivity 60%, and specificity 71.7%). CONCLUSION: The currently adopted cut-off values for TEG indices are poorly and modestly predictive of hemorrhage and obstruction, respectively, in the elderly population. Optimal cutoff values determined by ROC curve analysis improved the prediction of vascular obstruction and hemorrhage.

Association between thrombelastography system and thromboembolic and bleeding events in Chinese aged people.

OBJECTIVES: This study was designed to obtain the knowledge about TEG indexes distribution in Chinese aged people, as well as to test the hypothesis that previous TEG indexes are associated with the subsequent thromboembolic and bleeding events in the aged population. METHODS: We conducted a two-year follow-up study in Chinese PLA General Hospital, Beijing, China. 403 aged people were enrolled in our study. They received TEG measurements at least once when they entered this study. We collected their demographical characteristics, clinical examination information and their outcome during their observational period. Structural equation modeling (SEM) was used to analyze the relationship between the four indexes from TEG and the outcome via a pathway of indicator. RESULTS: We found that in the "model of bleeding" (adjusted by confounding of Anticoagulants), the model fit indices with chi-square/df = 9.555/7, CFI was 0.997, TLI was 0.994 and standardized root mean square residual (SRMR) was 0.034; while in the "model of thromboembolic events" (adjusted by confounding of Anticoagulants), the model fit indices with chi-square/df = 6.070/7, CFI was1.000, TLI was 1.002 and standardized root mean square residual (SRMR) was 0.000. The "model of thromboembolic events" showed that the four indexes (R, K, MA and ANGLE) were all significantly associated with thromboembolic events, while this significance was not found in the "model of bleeding". CONCLUSIONS: Previous TEG indexes are significantly associated with the subsequent thromboembolic events in the aged population. Future study can test this association and provide more information for the clinical use.