[A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in adult patients with hematological disease during the period 2014-2018].

Objective: To investigate the distribution of pathogens and the antibiotic resistance profile of bloodstream infections in adult patients with hematological diseases in the period 2014-2018 to provide evidence for the rational use of antibiotics. Methods: We retrospectively analyzed the bloodstream infections in patients with hematological diseases from January 2014 to December 2018 at the institute of Hematology & Blood Diseases Hospital; this included an assessment of the clinical characteristics, distribution of pathogens, and antibiotic resistance data. Results: There were 1935 episodes of BSIs in the 1478 patients who were studied; among these, 1700 episodes occurred in the neutropenic phase. The 7-day and 30-day all-cause mortality rates were 5.5% and 8.2%, respectively. Bloodstream infection was usually accompanied by respiratory tract, perianal zone mucositis, and digestive tract symptoms; the respective proportions were 12.4%, 12.3%, and 9.1%, respectively. Total 2025 strains were isolated; 1551 (76.6%) of the pathogens were gram-negative bacteria, mainly Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa; 423 (20.9%) were gram-positive bacteria, mainly Staphylococcus spp. and Streptococcus spp. Viridans; 51 (2.5%) were fungi, mainly Candida tropicalis. The resistance rates of Enterobateriaceae to piperacillin/tazobactam, carbapenems, amikacin were <10%. The resistance rates of K. pneumoniae to cefepime, piperacillin/tazobactam and meropenem increased annually. The resistance rates of Pseudomonas aeruginosa to piperacillin/tazobactam, quinolones, Aminoglycosides were <5% even when compared to carbapenems. Eleven stains of methicillin-resistant S. aureus and 1 stain of vancomycin-resistant Enterococcus faecium were detected. Conclusion: The pathogens of bloodstream infection in adult patients with hematological diseases are widely distributed. The resistance rates of different strains vary; the rates in some species had a tendency to increase. Antibiotics should be selected rationally as per the distribution of pathogens and resistance to antibiotics in different patient groups.

[Analysis of pathogens and clinical characteristics of bloodstream infection in neutropenic children with hematological malignancies from 2014 to 2018].

Objective: To investigate the microbiologic and clinical characteristics of bloodstream infection in neutropenic pediatric patients with hematological malignancies and provide data support for the rational use of antimicrobial agents in these patients. Methods: A retrospective analysis was performed on the clinical data, pathogen species distribution, and drug sensitivity data of bloodstream infection in neutropenic pediatric patients with hematological malignancies from the Institute of Hematology & Blood Diseases Hospital from January 2014 to December 2018. Results: Total 537 episodes of bloodstream infections occurred in 427 neutropenic children with hematological malignancies; the 30-day all-cause mortality rate was 3.7%. The clinical feature of 44.7% patients with bloodstream infection was only fever, and the pathogenic bacteria were mainly enterobacteriaceae bacteria. Bloodstream infection was usually accompanied by oral mucosa (20.7%) , respiratory tract (20.5%) , and digestive tract (14.3%) symptoms. The distribution of pathogens in patients with different symptoms of bloodstream infection varied (χ(2)=40.561, P=0.001) . Total 550 strains of pathogens were isolated, and the top 5 bacteria were Streptococcus aureus (109 strains, 19.8%) , Escherichia coli (99 strains, 18.0%) , Staphylococcus epidermidis (75 strains, 13.6%) , Klebsiella pneumoniae (67 strains, 12.2%) , and Staphylococcus aureus (32 strains, 5.8%) . The resistance rates of Enterobacteriaceae and Pseudomonas aeruginosa to piperacillin/tazobactam and carbapenems were <5%. The proportion of methicillin-resistant Staphylococcus aureus (MRSA) in Staphylococcus aureus was 9.7%. Conclusion: The proportion of pathogenic bacteria gram-positive cocci and gram-negative bacilli in the bloodstream infection of neutropenic children with hematological malignancies was approximately the same, suggesting that the use of antimicrobial agents should be broad-spectrum. Carbapenems, glycopeptides, and enzyme inhibitor complexes still have good effects.

[A preliminary study on molecular target identification of drugs in individualized treatment of malignant solid tumors in children].

Objective: To explore the role of drug-related molecular target identification in the individualized treatment of malignant solid tumors in children. Methods: The clinical data of 40 patients diagnosed with malignant solid tumors from Beijing Tongren Hospital, Capital Medical University, between June 2017 and March 2019 were retrospectively analyzed. Immunohistochemistry, polymerase chain reaction and sequencing methods were used to determine the expression levels and mutations of tumor drug molecular targets, and to compare the efficiency as well as the incidence of toxic side effects of chemotherapy using anti-tumor drugs with various molecular targets. Results: A total of 4 tumor drug-related targets were identified in 40 tumor tissue samples, namely DNA topoisomerase-ⅡA (TOPOⅡA), ß(3)-tubulin (Tubulinß(3)), DNA topoisomerase-Ⅰ(TOPOⅠ) and dihydrofolate reductase gene polymorphisms [DHFR (C829T)]. The effective rates of platinum-based agents, methotrexate, irinotecan, vinblastine and anthracycline for malignant solid tumors in children were 90.0% (36/40), 85.0% (34/40), 70.0% (28/40), 67.5% (27/40), 62.5% (25/40), respectively. The effective rates of chemotherapy with irinotecan, methotrexate, and vinblastine in mesenchymal tumors were 68.9% (20/29), 62.1% (18/29), 68.9% (20/29), respectively, which were considerably higher than 18.2% (2/11), 36.4% (4/11) and 36.4% (4/11) in non-mesenchymal tumors, with significant differences (χ(2)=5.487, 15.345, 17.278, all P<0.05). The effective rate of chemotherapy of platinum-based drugs for non-mesenchymal tumors was 72.3% (8/11), which was significantly higher than 58.6% (17/29) in mesenchymal tumors, and the difference was statistically significant (χ(2)=11.231, P<0.05). The intensity of toxic side effects in order from high to low was anthracycline > platinum > methotrexate > vinblastine > irinotecan. Conclusion: Tumor drug-related molecular targets and the sensitivity of tumors of different origins to the same anti-tumor drug as well as side effects are predicted, which provides a theoretical and clinical basis for individualized treatment of malignant tumors in children.

[Combination of CT mulitplane 3D reconstruction, radial endobronchial ultrasound and rapid on-site evaluation for diagnosing peripheral solitary pulmonary nodules].

Objective: To evaluate the diagnostic efficiency of combination of CT multiplane 3D reconstruction (CT-3DR), radial endobronchial ultrasound (R-EBUS), and rapid on-site evaluation (ROSE) for peripheral solitary pulmonary nodules (SPN). Methods: A total of 176 patients with peripheral solitary pulmonary nodule were included from the Nanjing Chest Hospital from March 2016 to March 2017. According to different methods, all the patients were divided into four groups: EG (i.e. R-EBUS+Guiding sheath (GS))group, CTE (i.e. CT-3DR+R-EBUS) group, RE (i.e. ROSE+R-EBUS) group, and triad (i.e. CT-3DR+ROSE+R-EBUS) group. Sampling was performed by transbronchial lung biopsy. The diagnostic yield and complications, procedure time and influencing factors in these four groups were retrospectively analyzed. The value of ROSE and combination of CT-3DR+ROSE+R-EBUS in diagnosis for SPN also was evaluated. Results: The diagnostic yield for total SPNs among four groups were 70.5% in EG group, 70.0% in CTE group, 69.0% in RE group and 74.0% in triad group, respectively. There was no significant difference among four groups (all P>0.05). The procedure time of EG group, CTE group, RE group and triad group were (34.0±6.3), (26.6±6.8), (27.2±7.8) and (19.4±5.4) min, respectively. The procedure time was the shortest in triad group compared with the other three groups (all P<0.001) and the time of CTE and RE groups were significantly shorter than the EG group (both P<0.001). The coincidence rates of CT-3DR navigation position with target bronchus were 87.5% in CTE group and 90.0% in triad group with no significant difference between these two groups (P>0.05). The diagnostic yield was higher for SPNs with their major diameter ≥2 cm than those with their major diameter<2 cm in all four groups (all P<0.05). The positive diagnostic yield was higher with ultrasonic probe located within SPN lesion than the probe adjacent to or deviated the lesion in all four groups (all P<0.05). In EG and RE groups, for those SPNs with the distance between the lesion and pleura≥2 cm, the diagnostic yield were higher than those withe the distance<2 cm (P<0.05) but no similar phenomenon was observed in CTE and triad groups. No significant correlation was detected between the diagnostic yield and the density of SPN lesions among four groups (all P>0.05). ROSE was used in RE and triad groups. The coincidence rate of ROSE with histopathology was 82.6% and the value of Kappa was 0.608. The diagnostic sensitivity, specificity, positive predictive value and negative predictive value of ROSE were 0.818, 0.846, 0.931 and 0.647, respectively. Conclusions: CT-3DR navigation and ROSE help to improve the diagnostic efficiency of R-EBUS for SPN. Combination of CT-3DR, R-EBUS and ROSE is of diagnostic value for peripheral SPN and with significant shortening of procedure time.

The lncRNA HOXA11-AS promotes glioma cell growth and metastasis by targeting miR-130a-5p/HMGB2.

OBJECTIVE: Long noncoding RNAs (lncRNAs) serve as important regulators of diverse types of cancer, including glioma. Nevertheless, their precise roles in cancers remain sufficiently unexplored. PATIENTS AND METHODS: Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was used to determine the levels of HOMEOBOX A11 antisense RNA (HOXA11-AS) and miR-130a-5p in glioma tissues and cell lines. Short hairpin RNAs (shRNAs) targeting HOXA11-AS or pcDNA3.1 were transfected into cells via a vector encoding HOXA11-AS to decrease or increase the level of HOXA11-AS. Cell Counting Kit-8 (CCK-8), colony formation, wound healing, flow cytometry and transwell assays were applied to assess the role of HOXA11-AS in glioblastoma cell growth, apoptosis and aggressiveness. The expression of N-cadherin and E-cadherin was determined using immunofluorescence staining. The expression of high-mobility group protein B2 (HMGB2) was determined using Western blot analysis in vitro and immunohistochemistry (IHC) staining in vivo. The direct target of HOXA11-AS and miR-130a-5p was confirmed using the Luciferase reporter assay. Glioblastoma cells were subcutaneously implanted into nude mice to determine the role of HOXA11-AS in tumor growth in vivo. RESULTS: In the current study, we demonstrated that the lncRNA HOXA11-AS was overexpressed in glioma. The overexpression of HOXA11-AS was correlated with advanced stages of glioma and poor prognosis. Downregulating HOXA11-AS expression significantly suppressed the proliferation, migration and invasion of glioma cells and increased their apoptosis. The growth of glioma cells in vitro was also suppressed by the downregulation of HOXA11-AS. Finally, we revealed that HOXA11-AS exerted its oncogenic effects by binding to miR-130a-5p, thereby neutralizing the suppressive effect of miR-130a-5p on HMGB2. CONCLUSIONS: Our results demonstrate that HOXA11-AS regulates the growth and metastasis of glioma by targeting the miR-130a-5p-HMGB2 signaling axis.

[Perianal swabs surveillance cultures of Carbapenem-resistant Enterobacteriaceae(CRE) can be hints for CRE bloodstream infection in patients with hematological diseases].

Objective: To analyze the hints role of surveillance cultures of Carbapenem-resistant Enterobacteriaceae (CRE) by perianal swabs in patients with hematological diseases, and seek risk factors of CRE bloodstream infection. Methods: The resistance of CRE from 2 914 patients with hematological diseases who cultured perianal swabs, CRE bloodstream infection and risk factors were analyzed during January 2016 to December 2017. Results: In this study, perianal swabs from 2 914 patients with hematological diseases were cultured, 74 patients were CRE positive, and bloodstream infection with CRE was found in 13 of these patients. A total of 87 CRE strains were isolated (The same patient only keep the first one for the same location), including 31 Klebsiella pheuminiae, 43 Escherichia coli, 8 Enterobacter cloacae and 6 other Enterobacteriaceae. The resistance rates to piperacillin / tazobactam, imipenem, meropenam, amikacin, levofloxacin, tigecycline were 91.9%, 74.4%, 98.8%, 17.6%, 74.4% and 8.0%, respectively. Resistance to carbapenem, aminoglycoside, quinolones and tegacycline were highly consistent between two sites from 13 patients, whose both perianal swabs and blood were positive in CRE cultures. Febrile neutropenic time, digestive tract symptoms and perianal infection were independent risk factors for bloodstream infection in patients with perianal swabs positive results, the odds ratios (OR) were 1.10 (P=0.029), 1.13 (P=0.005) and 1.23 (P=0.016), respectively. Conclusion: Perianal swabs surveillance cultures of CRE can be hints for CRE bloodstream infection in patients with hematological diseases, and also can provide suggestions for antibiotics. Long time of febrile neutropenic, digestive tract symptoms and perianal infection can be the early warning for CRE bloodstream infections.

The affordability for patients of a new universal MDR-TB coverage model in China.

BACKGROUND: China has piloted a new model of universal coverage for multidrug-resistant tuberculosis (MDR-TB), designed to rationalize hospital use of drugs and tests and move away from fee-for-service payment towards a standard package with financial protection against catastrophic health costs. OBJECTIVE: To evaluate the affordability to patients of this new model. DESIGN: This was an observational study of 243 MDR-TB cases eligible for enrolment on treatment under the project. We assessed the affordability of the project from the perspective of households, with a focus on catastrophic costs. RESULTS: Of the 243 eligible cases, 172 (71%) were enrolled on treatment; of the 71 cases not enrolled, 26 (37%) cited economic reasons. The 73 surveyed cases paid an average of RMB 5977 (US$920) out-of-pocket in search costs incurred outside the pilot model. Within the pilot, they paid another RMB 2094 (US$322) in medical fees and RMB 5230 (US$805) in direct non-medical costs. Despite 90% reimbursement of medical fees, 78% of households experienced catastrophic costs, including indirect costs. CONCLUSION: The objectives of the pilot model are aligned with health reform in China and universal health coverage globally. Enrollment would almost certainly be higher with 100% reimbursement of medical fees, but patient enablers will be required to truly eliminate catastrophic costs.

Ab initio molecular dynamics simulation of the effects of stacking faults on the radiation response of 3C-SiC.

In this study, an ab initio molecular dynamics method is employed to investigate how the existence of stacking faults (SFs) influences the response of SiC to low energy irradiation. It reveals that the C and Si atoms around the SFs are generally more difficult to be displaced than those in unfaulted SiC, and the corresponding threshold displacement energies for them are generally larger, indicative of enhanced radiation tolerance caused by the introduction of SFs, which agrees well with the recent experiment. As compared with the unfaulted state, more localized point defects are generated in faulted SiC. Also, the efficiency of damage production for Si recoils is generally higher than that of C recoils. The calculated potential energy increases for defect generation in SiC with intrinsic and extrinsic SFs are found to be higher than those in unfaulted SiC, due to the stronger screen-Coulomb interaction between the PKA and its neighbors. The presented results provide a fundamental insight into the underlying mechanism of displacement events in faulted SiC and will help to advance the understanding of the radiation response of SiC with and without SFs.

Prognostic value of the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification in stage IB lung adenocarcinoma.

BACKGROUND: Patients with pathological stage IB lung adenocarcinoma have a variable prognosis, even if received the same treatment. This study investigated the prognostic value of the new International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification in resected stage IB lung adenocarcinoma. METHODS: We identified 276 patients with pathological stage IB adenocarcinoma who had undergone surgical resection at the Nanjing Chest Hospital between 2005 and 2010. The histological subtypes of all patients were classified according to the 2011 IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification. Kaplan-Meier and Cox regression analyses were used to analyze the correlation between the IASLC/ATS/ERS classification and patients' prognosis. RESULTS: Two hundred and seventy-six patients with pathological stage IB adenocarcinoma had an 86.2% 5-year overall survival (OS) and 80.4% 5-year disease-free survival (DFS). Patients with micropapillary and solid predominant tumors had a significantly worse OS and DFS as compared to those with other subtypes predominant tumors (p = 0.003 and 0.001). Multivariate analysis revealed that the new classification was an independent prognostic factor for both OS and DFS of pathological stage IB adenocarcinoma (p = 0.009 and 0.003). CONCLUSION: Our study revealed that the new IASLC/ATS/ERS classification was an independent prognostic factor of pathological stage IB adenocarcinoma. This new classification is valuable of screening out high risk patients to receive postoperative adjuvant therapy.

Genomic changes at the early stage of somatic hybridization.

A broad spectrum of genetic and epigenetic changes is induced by wide hybridization and subsequent polyploidization, but the timing of these events remains obscure because early hybrid cells are very difficult to harvest and analyze. Here, we used both cytological and genetic marker approaches to analyze the constitution of very young somatic hybrid cells between japonica rice (Oryza sativa L. subsp japonica) and indica rice (Oryza sativa L. subsp indica) and between japonica rice and bread wheat (Triticum aestivum L.). Chromatin elimination, simple sequence repeats, and retrotransposon profile deletions were already apparent within six days of the fusion event. The evidence we have presented suggests that genomic changes induced by genomic shock occur soon after the formation of hybrid cells.

Choline and betaine intakes are associated with reduced risk of nasopharyngeal carcinoma in adults: a case-control study.

BACKGROUND: Intakes of choline and betaine have been inversely related to the risk of various neoplasms, but scant data exist on nasopharyngeal carcinoma (NPC). We examined the association between consumption of choline and betaine and risk of NPC. METHODS: We conducted a case-control study with 600 incident NPC patients and 600 controls 1 : 1 matched by age, sex and household type in Guangdong, China. Dietary intake was assessed by a food frequency questionnaire through face-to-face interview. RESULTS: Intakes of total choline, betaine and choline+betaine were inversely related to NPC after adjustment for various lifestyle and dietary factors (all P-trend <0.001). Adjusted odds ratios (95% CI) for quartile 4 (vs quartile 1) were 0.42 (0.29, 0.61) for total choline, 0.50 (0.35, 0.72) for betaine and 0.44 (0.30, 0.64) for betaine+total choline. Regarding various sources of choline, lower NPC risk was associated with greater intakes of choline from phosphatidylcholine, free choline, glycerophosphocholine and phosphocholine, but not sphingomyelin. CONCLUSION: These findings are consistent with a beneficial effect of choline and betaine intakes on carcinogenesis.

Polymorphisms of the ATP1A1 gene associated with mastitis in dairy cattle.

Mastitis affects the concentrations of potassium and sodium in milk. Since sodium-potassium adenosine triphosphatase (Na(+), K(+)-ATPase) is critical for maintaining the homeostasis of these two ions, and is involved in cell apoptosis and pathogenesis, we presumed that polymorphism of the ATP1A1 gene, which encodes the bovine Na(+), K(+)-ATPase α1 subunit could be associated with mastitis. The ATP1A1 gene was analyzed in 320 Holstein cows using PCR low ionic strength single-strand conformation polymorphism (PCR-LIS-SSCP) and DNA sequencing methods. A C/A SNP was identified at nucleotide position -15,739 in exon 17 of the ATP1A1 gene, but it did not induce any change in amino acids. We examined a possible association of polymorphism of the ATP1A1 gene with somatic cell score and 305-day milk yields. Individuals with genotype CC in ATP1A1 had significantly lower somatic cell scores and 305-day milk yields than those with genotype CA. We also examined changes in Na(+), K(+)-ATPase activity of red cell membranes. The Na(+), K(+)-ATPase activity was significantly higher in dairy cows with genotype CC compared to the other two genotypes, and the Na(+), K(+)-ATPase activity of the resistant group was significantly higher than that of the susceptible group in dairy cows. We conclude that this polymorphism has potential as a marker for mastitis resistance in dairy cattle.

Gamma delta tocotrienols reduce hepatic triglyceride synthesis and VLDL secretion.

AIM: Present study aimed to elucidate the suppression of serum lipids by gamma- and delta-tocotrienol (γδT3). METHODS: The lipid-lowering effects of γδT3 were investigated using HepG2 liver cell line, hypercholesterolemic mice and borderline-high cholesterol patients. RESULTS: In-vitro results demonstrated two modes of action. First, γδT3 suppressed the upstream regulators of lipid homeostasis genes (DGAT2, APOB100, SREBP1/2 and HMGCR) leading to the suppression of triglycerides, cholesterol and VLDL biosyntheses. Second, γδT3 enhanced LDL efflux through induction of LDL receptor (LDLr) expression. Treatment of LDLr-deficient mice with 1 mg/day (50 mg/kg/day) γδT3 for one-month showed 28%, 19% reduction in cholesterol and triglyceride levels respectively, whereas HDL level was unaltered. The lipid-lowering effects were not affected by alpha-tocopherol (αTP). In a placebo-controlled human trial using 120 mg/day γδT3, only serum triglycerides were lowered by 28% followed by concomitant reduction in the triglyceride-rich VLDL and chylomicrons. In contrast, total cholesterol, LDL and HDL remained unchanged in treated and placebo groups. The discrepancies between in-vitro, in-vivo and human studies may be attributed to the differential rates of post-absorptive γδT3 degradation and LDL metabolism. CONCLUSION: Reduction in triglycerides synthesis and transport may be the primary benefit caused by ingesting γδT3 in human.

Real-time imaging and detection of intracranial haemorrhage by electrical impedance tomography in a piglet model.

The aim of this study was to use electrical impedance tomography (EIT) to detect and image acute intracranial haemorrhage (ICH) in an animal model. Blood was infused into the frontal lobe of the brains of anaesthetized piglets and impedance was measured using 16 electrodes placed in a circle on the scalp. The EIT images were constructed using a filtered back-projection algorithm. The mean of all the pixel intensities within a region of interest--the mean resistivity value (MRV)--was used to evaluate the relative impedance changes in the target region. A symmetrical index (SI), reflecting the relative impedance on both sides of the brain, was also calculated. Changes in MRV and SI were associated with the injection of blood, demonstrating that EIT can successfully detect ICH in this animal model. The unique features of EIT may be beneficial for diagnosing ICH early in patients after cranial surgery, thereby reducing the risk of complications and mortality.

[Derivatives of arteannuin B with antileukemia activity].

Arteannuin B (I) was converted to hydroxy lactones (VII, VIII) by a mixture of formic acid and sulfuric acid. Compound VI and Compound VII both showed activity against leukemia P 388 cell in vitro. The rate of growth inhibition were 97.5% and 11.8% for (VI) and 80% and 52.6% for (VII) at the concentration of 10 and 1 micrograms/ml respectively. It seems that the antileukemia activity of 6-membered lactone is higher than that of 5-membered and the methylene group is necessary for the antileukemia activity.