[Risk factors and resistance patterns of invasive Acinetobacter Baumannii infection in Children].

Objective: To understand the risk factors and antibiotics-resistant patterns of invasive Acinetobacter baumannii infection in Children. Methods: This retrospective study was conducted in 6 tertiary hospitals from January 2016 to December 2018. The basic information, clinical data and the results of antimicrobial susceptibility testing were collected from the 98 pediatric inpatients with Acinetobacter baumannii isolated from blood or cerebrospinal fluid and analyzed. According to the susceptibility of the infected strains to carbapenems, they were divided into carbapenem-sensitive Acinetobacter baumannii (CSAB) group and carbapenem-resistant Acinetobacter baumannii (CRAB) group. According to the possible sources of infection, they were divided into nosocomial infection group and community infection group. Chi-square test or Fisher exact test were used to analyze categorical variables and rank sum test were used to analyze continuous variables. The risk factors of invasive CRAB infection in children were analyzed by Logistic regression. Result: There were 56 males and 42 females in 98 cases. The onset age of patients was 8 (2, 24) months. There were 62 cases (63%) from rural area. A total of 87 cases (89%) were confirmed with bloodstream infection, and 12 cases (12%) confirmed with meningitis (1 case was accompanied with bloodstream infection). In these patients, 66 cases (67%) received invasive medical procedures or surgery, 54 cases (55%) received carbapenems-containing therapy. Twenty-four cases were infected with CRAB, and 74 cases with CSAB. The onset age of cases in CRAB group was lower than that in CSAB group (4 (1, 9) vs. 10 (4, 24) months, Z=-2.16, P=0.031). The proportions of hospitalization in intensive care unit, carbapenem antibiotics using, pneumonia and adverse prognosis in CRAB group were higher than those in CSAB group (6 cases (25%) vs. 4 cases (5%), 18 cases (75%) vs. 36 cases (49%), 17 cases (71%) vs. 17 cases (23%), 6 cases (25%) vs. 4 cases (5%), χ2=5.61, 5.09, 18.32, 5.61, all P<0.05). Seventy-seven cases were nosocomial infection and 21 cases were hospital-acquired infection. The proportion of children hospitalized in high-risk wards for nosocomial infections, length of hospitalization, number of antimicrobial therapy received and duration of antimicrobial therapy were higher in the hospital associated infection group than those in the community acquired infection group (all P<0.05). Logistic regression analysis showed that children from rural area (OR=8.42, 95%CI 1.45-48.88), prior mechanical ventilation (OR=12.62, 95%CI 1.31-121.76), and prior antibiotic therapy (OR=4.90, 95%CI 1.35-17.72) were independent risk factors for CRAB infection. The resistance percentage of CSAB isolates to many classes of antibiotics was <6% except to gentamicin, which was as high as 20% (13/65). All CRAB isolates of resistant to ampicillin-sulbactam (20/20), cefepime (23/23), piperacillin (17/17), meropenem (23/23) and imipenem (24/24) were 100%. The resistance percentage to other antibiotics were up to 42%-96%. Conclusions: Most of invasive Acinetobacter baumannii infection in children in China are hospital-acquired. The outcome of invasive CRAB infection was poorer than that of CSAB infection. The drug resistance rate of CRAB strains isolated is high. Living in rural area, prior invasive mechanical ventilation and prior antibiotic therapy were independent risk factors for invasive CRAB infection. The prevention and control of nosocomial infection and appropriate use of antibiotics to reduce Acinetobacter baumannii infection.

BMSCs attenuate hepatic fibrosis in autoimmune hepatitis through regulation of LMO7-AP1-TGFß signaling pathway.

OBJECTIVE: In a previous study, we reported that transplantation of bone mesenchymal stem cells (BMSCs) significantly attenuated liver damage in a mouse autoimmune hepatitis (AIH) model. Moreover, expression of the LIM domain protein, LMO7, correlated positively with the invasive capacity of hepatoma cells. However, whether LMO7 plays a role in inflammation and fibrosis of AIH remains unknown. This investigation aimed to explore the effect of BMSC transplantation on LMO7 and the role of LMO7 in hepatic fibrosis. MATERIALS AND METHODS: S100-induced murine AIH and LPS-induced hepatocyte injury models were successfully established. Three doses of BMSCs were injected into AIH mice via the tail vein. LPS-treated AML12 cells were co-cultured with BMSCs in vitro. Small interfering (si) LMO7 RNA and T5224 (a specific inhibitor of AP-1) were used to demonstrate the relationship between LMO7-AP1-transforming growth factor (TGF)-ß. RESULTS: Pathological examination and serum alanine and aspartate aminotransferase levels indicated that liver damage was notably ameliorated in the BMSC-treated mice. LMO7 level was upregulated, while AP-1 and TGF-ß levels were downregulated upon intervention with BMSCs. AP-1 expression was upregulated in the siLMO7 group, whereas TGF-ß level was downregulated in the T5224 group when compared to those in the control group. CONCLUSIONS: BMSC transplantation significantly limits liver fibrosis and upregulates the expression of LMO7. LMO7 inhibits the TGF-ß pathway by inhibiting AP-1. This implies that BMSCs are a potential means of treating liver fibrosis. This approach has important implications for the treatment of AIH and other fibrotic diseases.

Radio-sensitizing effects of microRNA-27a elevation in lung cancer cells by inhibiting ZEB1 expression and activating DNA damage repair pathway.

MicroRNAs (miRNAs or miRs) exert either as tumor-inhibiting or oncogenic roles in tumorigenesis of lung cancer. In the present study, we identified a novel microRNA (miR)-27a as being involved in the radiosensitivity of lung cancer cells. Therefore, we sought to characterize its potential underlying mechanism in lung cancer cell sensitivity to radiotherapy. To this end, A549 and H460 cells irradiated with 8 Gy irradiation (IR) were used as a cell model. RT-qPCR exhibited that the expression of miR-27a increased, whereas ZEB1 was poorly expressed in A549 and H460 cells exposed to IR. As reflected by dual-luciferase reporter gene assay, miR-27a could target and inversely modulate ZEB1 expression. Gain- and loss-of-function experiments exhibited that miR-27 inhibition promoted proliferation of IR-treated A549 and H460 cells and reduced the sensitivity of A549 and H460 cells to radiotherapy, which was rescued by silencing of ZEB1. Further, miR-27a inhibition disrupted the homologous recombination (HR)-mediated DNA repair, evidenced by reduced ATM, pCHK2 and Rad51 levels. Collectively, miR-27a activates HR-mediated DNA repair by inhibiting ZEB1 expression to enhance the radiosensitivity of lung cancer cells, highlighting a therapeutic target for lung cancer radiosensitivity.

[Molecular epidemiological characteristics of methicillin-resistant Staphylococcus aureus during 2017-2018 at a hospital in Shanghai].

Objective: To identify the epidemic clones of MRSA isolates at a hospital in shanghai. Methods: A total of 72 MRSA isolates have been isolated from a second grade hospital between 2017 and 2018, including 32 CA-MRSA isolates, 13 HA-MRSA isolates and 26 MRSA isolates from environment. In this study, MLST and PFGE typing methods were used to analyze the molecular epidemiology of the MRSA isolates. Results: A total of 72 MRSA isolates have been obtained including 46 isolates from clinical specimens, 26 isolates from environments. The 46 MRSA isolates from clinical specimens consisted of 33 CA-MRSA (community-acquired MRSA) and 13 HA-MRSA (hospital-acquired MRSA). Furthermore, these patients infected with MRSA isolates were mostly distributed in the department of geriatrics (34.8%, 16/46), internal medicine (26.1%, 12/46) and surgery (26.1%, 12/46). MLST typing results showed that ST764 was predominant in isolates from both clinical specimens and hospital environments. Furthermore, PFGE typing results showed that most ST764 MRSA had high homolog (>90%). Conclusion: ST764 MRSA isolates might spread in community, hospital and environments. Therefore, continuous monitoring of MRSA and its variation may be useful in understanding the involvement of epidemic clone, and in searching new strategies to control MRSA infection.

[Effects of butylphthalide on plasma nitric oxide and endothelin-1 in severe elderly OSAHS patients].

Objective:To investigate the effect of butylphthalide on plasma nitric oxide(NO) and endothelin-1(ET-1) in severe elderly OSAHS patients. Method:A total of 120 severe elderly OSAHS patients were chosen by PSG measurement. According to random number table method, OSAHS patients were randomly divided into non-invasive ventilation control group(n=40), butylphthalide treatment group(n=40) and butylphthalide combined with non-invasive ventilation group (n=40). Non-invasive ventilation control group was given double level airway positive pressure ventilation treatment for six months, butylphthalide treatment group accepted oral butylphthalide therapy for six months, butylphthalide combined with non-invasive ventilation group was given double level airway positive pressure ventilation treatment and accepted oral butylphthalide therapy for six months. The changes of plasma NO and ET-1 were detected by immunoenzyme adsorption before treatment and three and six months after treatment. Result:The difference of plasma NO and ET-1 before treatment in the three groups was not statistically significant (P>0.05). Compared with before treatment, the level of plasma NO decreased and the level of plasma ET-1 increased in the three groups after three and six months treatment (P<0.01). Compared with butylphthalide treatment group, the level of plasma NO increased and the level of plasma ET-1 decreased after 3 and 6 months of treatment in both non-invasive ventilation control group and butylphthalide combined with non-invasive ventilation group (P<0.05). Compared with non-invasive ventilation control group, the level of plasma NO increased and the level of plasma ET-1 decreased after 3 and 6 months of treatment in butylphthalide combined with non-invasive ventilation group (P<0.05). Conclusion:Butylphthalide may improve the vascular endothelial function of severe elderly OSAHS patients by increasing the level of NO and decreasing the level of ET-1 in plasma.

[Progress in studies on obstructive sleep apnea and intestinal microecological balance].

SummaryObstructive sleep apnea （OSA） is closely related to the development of various diseases. Hypoxic perfusion caused by OSA can mediate the occurrence of inflammatory reactions or aggravate metabolic disorders to affect intestinal microecological balance. Intestinal bacteria can participate in the development of inflammatory reaction or metabolic disorder by itself or its components, and the oxidative stress reaction of the body develops in a vicious circle. The mechanism has not yet been fully elucidated, so we reviewed the research progress on OSA and intestinal microecological balance.

[Effect of butylphthalide on oxidative stress and cognitive function in old obstructive sleep apnea hypopnea syndrome patients].

Objective:To explore the effect of butylphthalide on oxidative stress and cognitive function in old obstructive sleep apnea hypopnea syndrome (OSAHS)patients.Method:A total of 90 old OSAHS patients with cognitive impairment were choosed with Polysomnography（PSG）. By random number table method OSAHS patients were randomly divided into non-invasive ventilator group (n=30), butylphthalide with non-invasive ventilator group(n=30) and treatment group of butylphthalide(n=30). Non-invasive ventilator group was given continuous positive airway pressure treatment for three months, butylphthalide with non-invasive ventilator group accepted oral butylphthalide therapy and continuous positive airway pressure treatment for three months, treatment group of butylphthalide only accepted oral butylphthalide therapy for three months. Cognitive function of three groups wered observed by the Montreal cognitive assessment scale (MoCA) before and after treatment, at the same time, the changes of serum superoxide dismutase(SOD) and malondialdehyde(MDA) were detected by immunoenzyme-linked adsorption.Result:The differences of serum SOD and MDA before treatment among the three groups were not statistically significant (P＞0.05). Compared with before treatment, the level of serum SOD increased and the level of MDA decreased in the three groups (P<0.05). Compared with non-invasive ventilator group after treatment，the level of SOD increased and the level of MDA decreased in butylphthalide with non-invasive ventilator group (P<0.05)， the level of SOD decreased and the level of MDA increased in treatment group of butylphthalide (P<0.05). Compared with treatment group of butylphthalide after treatment, the level of SOD increased and the level of MDA decreased in butylphthalide with non-invasive ventilator group (P<0.05); The scores of MoCA on cognitive function before treatment in the three groups was not statistically significant (P＞0.05). After treatment the scores of MoCA on cognitive function in the three groups were higher than those before treatment (P<0.05). Compared with non-invasive ventilator group after treatment， the scores of MoCA increased in butylphthalide with non-invasive ventilator group (P<0.05),the the scores of MoCA decreased in treatment group of butylphthalide (P<0.05). Compared with treatment group of butylphthalide after treatment, the scores of MoCA increased in butylphthalide with non-invasive ventilator group (P<0.05).Conclution: Butylphthalide can improve the activity of antioxidant enzymes in the serum of old patients with OSAHS, inhibit the oxygen free radical and lipid peroxidation and to a certain extent improve the cognitive function.

[Correlation study between the levels of serum MCP-1,SAA and cognitive function in patients with COPD-OSAHS].

Objective:To study the correlation among the serum monocyte chemoattractant protein-1 (MCP-1),serum amyloid A(SAA) and the level of cognitive function in patients with chronic obstructive pulmonary disease and obstructive sleep apnea hypopnea syndrome overlap syndrome(OS).Method:Sixty patients with OS were in the experimental group, and 33 patients with COPD were in control group. The serum levels of MCP-1 and SAA were measured, and the correlation among MCP-1, SAA and cognitive function was observed by the Montreal scale.Result:①The serum levels of MCP-1 and SAA in OS group were (159.85±21.38)ng/L and (122.64±42.49)ng/L respectively,which in control group were (135.02±15.31)ng/L and (71.37±10.16)ng/L respectively.There were the was statistically significant difference between the two groups(P<0.05). ②Montreal scale score and its sub items in OS group were lower than the control group.The difference was statistically significant (P<0.05).③There was significant negative correlation between Montreal scale and the serum levels of MCP-1(r=-0.654,P<0.05) and SAA (r=-0.617,P<0.05) in OS group.Conclusion:Patients in the OS group had obvious cognitive impairment compared with the ones in control group, which suggested that OSAHS might be an independent risk factor for cognitive impairment. The cognitive function of OS patients was negatively related to MCP-1 and SAA, which suggested that MCP-1 and SAA played a role in the occurrence of cognitive impairment in OS patients.

[Diagnostic efficiency of NO/ET-1 and HCY level in severe OSAHS patients with cognitive impairment].

Objective:To investigate the diagnostic efficiency of HCY and NO/ET-1 to cognitive dysfunction in patients with severe obstructive sleep apnea hypopnea syndrome, and to interfere with the cognitive function of severe OSAHS patients. Method: Eighty-six patients with OSAHS were divided into mild group (22 cases), moderate group (23 cases), severe group (41 cases) and healthy physical examination group (50 cases). The levels of serum HCY and NO/ET-1 were compared between the four groups. The Montreal cognitive assessment scale was used to evaluate the incidence of mild cognitive impairment in severe OSAHS group, and the correlation between the level of serum HCY, NO/ET-1 and cognitive function in severe OSAHS group was analyzed. Result:The level of serum HCY in patients with severe OSAHS with cognitive impairment was(32.28±3.92)µmol/L, higher than that of the cognitive moderate group(26.34±4.05)µmol/L, and mild group (18.62±3.29)µmol/L. The level of serum NO/ET-1 in patients with severe OSAHS with cognitive impairment was (0.69±0.19), higher than that of the cognitive moderate group(2.76±0.28), and mild group (3.98±0.37), the difference was statistically significant (P<0.05). In severe group, there was a negative correlation between the level of serum HCY and the score of MoCA and its subscores (P<0.05), and there was a positive correlation between the total scores of NO/ET-1 and MoCA and their subscores (P<0.05), and negative correlation between HCY and NO/ET-1 (P<0.05). The area under the ROC curve of predicting serum HCY and NO/ET-1 levels in severe OSAHS patients with cognitive impairment were 0.788(95%CI0.654-0.921) and 0.770 (95%CI0.642-0.899). Conclusion:Serum HCY and NO/ET-1 were the factors influencing the formation of cognitive impairment in severe OSAHS patients. The level of HCY was negatively correlated with the degree of cognitive impairment, and NO/ET-1 was positively correlated with the degree of cognitive impairment.

Pro-inflammatory cytokine-mediated ferroportin down-regulation contributes to the nigral iron accumulation in lipopolysaccharide-induced Parkinsonian models.

Pro-inflammatory cytokines induced by inflammation and iron accumulation in the substantia nigra (SN) have been implicated in the pathogenesis of Parkinson's disease (PD). In the present study, we aimed to investigate the relationship between inflammation and iron accumulation in a lipopolysaccharide (LPS)-induced Parkinsonian rat model. The activation of glial cells and elevated levels of pro-inflammatory cytokines were observed in the SN of LPS models, accompanied by iron deposits in the same region. Moreover, ferroportin (Fpn), the only channel for iron export, was down-regulated. SH-SY5Y dopaminergic cells were pre-incubated with conditioned media enriched in pro-inflammatory cytokines, and abnormal iron deposits and a drop of Fpn were observed. The expression of heme oxygenase-1 (HO-1) was also upregulated in vivo and in vitro. These results suggested that pro-inflammatory cytokines might induce Fpn downregulation, which leads to iron accumulation and dopaminergic neurons' degeneration in PD. HO-1 may also contribute to the iron accumulation in neurons, but its mechanism needs to be further investigated.

Dynamic contrast-enhanced MRI of benign prostatic hyperplasia and prostatic carcinoma: correlation with angiogenesis.

AIM: To investigate the diagnostic and differential diagnostic values of dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) in prostatic diseases, and to investigate the correlation between the parameters of SI-T curves and angiogenesis. MATERIALS AND METHODS: Twenty-one patients with proven prostatic carcinoma (Pca) and 29 patients with proven benign prostatic hyperplasia (BPH) were examined using DCE MRI. Diagnostic characteristics for differentiation were examined using threshold values for maximum peak time, enhancement degree, and enhancement rate. Then, the signal intensity-time curves (SI-T curves) were analysed, and the correlations between the parameters of SI-T curves and the expression levels of vascular endothelial growth factor (VEGF) and microvascular density (MVD) were investigated. All patents underwent prostatectomy. DCE MRI and histological findings were correlated. RESULTS: Pca showed stronger enhancement with an earlier peak time, higher enhancement, and enhancement rate (p<0.05). Regarding the type of SI-T curves, in the BPH group six were type A, 10 were type B, and 13 were type C, whereas in the Pca group, 14 were type A, six were type B, and only one was type C (Chi-square test, chi2=13.57, P<0.005). The VEGF and MVD expression levels of Pca were higher than those of BPH. Peak time was negatively correlated with the expression levels of VEGF and MVD, whereas the enhancement degree and enhancement rate showed positive correlations (Pearson correlation, p<0.05). CONCLUSION: Based on T2-weighted imaging, DCE MRI curves can help to differentiate benign from malignant prostate tissue. In the present study the type C curve was rarely seen with malignant disease, but these results need confirmation.