Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Objective:To explore the microbiological and disease distribution characteristics of multidrug-resistant bacteria in patients hospitalized in a critical care rehabilitation ward, and to analyze the risk factors leading to multidrug-resistant bacterial infections.Methods:Microbiology screening data describing 679 patients admitted to a critical care rehabilitation ward were retrospectively analyzed to divide the subjects into a multidrug-resistant group (positive for multidrug-resistant bacterial infections, n=166) and a non-multidrug-resistant group (negative for multidrug-resistant bacterial infections, n=513). The risk factors were then analyzed using logistic regression. Results:Among 369 strains of multidrug-resistant bacteria observed, 329 were gram-negative bacteria (89.2%), mainly Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. They were distributed in sputum (56.9%) and mid-epidemic urine (28.2%) specimens. Patients whose primary disease was hemorrhagic or ischemic cerebrovascular disease accounted for 40.96% and 23.49% of the multidrug-resistant bacterial infections, respectively. Logistic regression analysis showed that albumin level, dependence on mechanical ventilation, central venous cannulation, or an indwelling urinary catheter or cystostomy tube were significant independent predictors of such infections.Conclusion:The multidrug-resistant bacterial infections of patients admitted to the critically ill rehabilitation unit are mainly caused by gram-negative bacteria. Their occurrence is closely related to low albumin levels and mechanical ventilation, as well as to bearing an indwelling central venous catheter, a urinary catheter or a cystostomy catheter.

Objective To evaluate the effect of microRNA-182-5p (miR-182-5p) on proliferation and apoptosis of non-small cell lung cancer (NSCLC) A549 cells by targeting forkhead box O3a (FOXO3a).Methods The difference of miR-182-Sp expression between human normal lung epithelial cells BEAS-2B and NSCLC cells A549 was compared.The A549 cells were chosen,and miR-182-Sp mimic (miR-182-Sp mimic group),miR-182-Sp inhibitor (miR-182-5p inhibitor group),negative control mimic (NC mimic group) and negative control inhibitor (NC inhibitor group) were transfected respectively.The expression of miR-182-Sp was detected by reverse transcription-polymerase chain reaction (RT-PCR).The protein expression of FOXO3a was detected by Western blotting.The cell proliferation activity was detected by methyl thiazolyl tetrazolium (MTT) method.The cell apoptosis was detected by flow cytometry.The targeted relationship between miR-182-5p and FOXO3a was detected by dual-luciferase experiment.Results The miR-182-5p expression of A549 cells and BEASo2B cells respectively was 3.21 ±0.24 and 1.01 ±0.11,and the difference was statistically significant (t =14.209,P＜0.001).The miR-182-5p expression of NC mimic group,miR-182-5p mimic group,NC inhibitor group and miR-182-5p inhibitor group respectively was 1.09 ± 0.20,12.80 ± 1.10,1.03 ± 0.11and 0.47 ± 0.08,and the difference was statistically significant (F =87.872,P ＜ 0.001).The FOXO3a expression of the above four groups respectively was 118.34 ± 16.71,50.89 ± 11.58,125.33 ± 20.87 and 289.26 ± 34.51,and the difference was statistically significant (F =62.125,P ＜ 0.001).The 72 h proliferation activity of the four groups respectively was 1.12 ± 0.13,1.70 ± 0.14,1.07 ± 0.13 and 0.71 ± 0.11,and the difference was statistically significant (F =31.336,P ＜ 0.001).The proliferation activity of miR-182-5p mimic group was significantly higher than that of NC mimic group (P ＜ 0.05),and the proliferation activity of miR-182-5p inhibitor group was significantly lower than that of NC inhibitor group (P ＜0.05).The apoptosis rate of the four groups respectively was (5.51 t±1.80)％,(1.41 ±0.50)％,(6.24 ± 1.71)％ and (47.93 ± 5.12) ％,and the difference was statistically significant (F =211.081,P ＜ 0.001).The apoptosis rate of miR-182-5p mimic group was significantly lower than that of NC mimic group (P ＜ 0.05),and the apoptosis rate of miR-182-5p inhibitor group was significantly higher than that of NC inhibitor group (P ＜0.001).The miRNA target genes prediction software test results showed that miR-182-5p could act on FOXO3a 3' untranslated region (UTR).Compared with transfection NC mimic,co-transfection miR-182-5p mimic and FOXO3a-Wt could make luciferase activity of A549 significantly decreased (1.20 ±0.14 vs.0.62 ±0.10;t =5.839,P =0.004).Conclusion miR-182-5p can enhance proliferation and inhibit apoptosis of A549 cell by targeting FOXO3a.

OBJECTIVE:To provide reference for rational use of antibiotics to treat Pseudomonas aeruginosa (PA) infection in the clinic. METHODS:Resistant rate of PA in our hospital during 2011-2015 were analyzed retrospectively. Antibiotics use densi-ty(AUD)of 10 commonly used antibiotics were analyzed statistically,and the correlation of resistant rate with AUD was investi-gated by Spearman correlation analysis. RESULTS:One thousaud and eleven strains of PA were isolated in our hospital during 2011-2014,detection rate of PA always occupied the top 5 place. Top 3 antibiotics in the list of AUD were levofloxacin,ceftazi-dime,cefoperazone sodium and tazobactam sodium. AUD of piperacillin sodium and tazobactam sodium,levofloxacin,ciprofloxa-cin and meropenem were positively correlated with resistant rate of PA(r were 1.000,0.900,1.000,1.000,P<0.05). AUD of ce-foperazone sodium and tazobactam sodium were negatively correlated with resistant rate of PA(r=-0.900,P<0.05). AUD of imi-penem and cilastatin sodium,ceftazidime,gentamicin,aztreonam and amikacin had no correlation with resistant rate of PA(P>0.05). CONCLUSIONS:There is correlation between AUD of antibiotics and resistant rate of PA. It is of important significance to detect resistant rate of PA and the use of antibiotics regularly. Antibiotics should be selected cautiously in accordance with bacterial monitoring data,results of drug sensitivity tests,the amount and resistant rate of antibiotics,etc,in order to reduce resistant PA.

Objective To investigate the correlation between the characteristics of the computed tomography (CT) perfusion parameters and the expression of D2-40 with lymphatic vessel density (LVD) in cervical carcinomas.Methods A total of 42 patients with cervical carcinoma was divided into two groups with and without lymph node metastasis.Patients were evaluated with CT perfusion scan before operation.Monoclonal antibody D2-40 was used for immunohistochemistry to detect the LVD in the carcinoma tissue specimen.CT perfusion parameters and LVD of two groups were compared,and their relationship was analyzed.Results CT perfusion parameters including blood flow (BF),peak enhancement image (PEI),and blood volume (BV) in the lymph node metastasis group were significantly higher than those in the no lymph node metastasis group (t =-2.206,-2.29,-2.336,P ＜ 0.05).The time to peak (TTP) was significantly lower in the lymph node metastasis group than the no node metastasis group (t =6.908,P ＜ 0.01).The LVD in the lymph node metastasis group was significantly higher than the no lymph node metastasis group (t =-5.092,P ＜ 0.01).The CT perfusion parameters (BF,PEI,BV) and LVD of cervical carcinomas had a significantly positive correlation (r =0.65,0.56,0.61,P ＜ 0.01).The TTP and LVD had a significantly negative correlation(r =-0.55,P ＜ 0.01).Conclusions CT perfusion imaging and higher LVD help to diagnose the lymph node metastasis of a cervical carcinoma,and have important guidance role in the surgical options for cervical cancers.

Objective To study the diagnostic value of CT combined CA125 and HE4 in differentiating the ovarian cancer from the benign.Methods A case-control study included 52 ovarian cancer patients,47 patients with benign ovarian tumors,and 40 healthy control subjects.Preoperative serum levels of HE4 and CA125 were measured and CT was performed.Results The serum levels of CA125 and HE4 in the ovarian cancer groups [(264.37 ± 138.46) KU/L,(280.38 ± 135.14)pmol/L] were significantly high-er than that in the benign ovarian neoplasm group [(52.51 ±5.29) KU/L,(40.52 ± 10.34) pmol/L] and healthy control group [(10.69 ±6.15)KU/L,(37.24 ±9.84) pmol/L] (P ＜0.01).The serum levels of CA125 showed statistically significant difference between the benign ovarian neoplasm groups and healthy control groups (P ＜ 0.05).The serum levels of HE4 did not show statistically significant difference between the benign ovarian neoplasm groups and healthy control groups (P ＞ 0.05).The diagnostic sensitivity (65.4％,80.8％,75.0％),specificity (74.5％,85.1％,76.6％),and accuracy (69.7％,82.8％,75.8％) of each CA125,HE4,CT method for ovarian cancer did not show statistically significant difference (P ＞0.05).The diagnostic sensitivity (92.3％),specificity (93.6％) and accuracy (94.8％) of combination of CA125 and HE4 and CT were significantly higher and showed statistically significant difference compared with one method (x2 =7.461 18.711,P ＜ 0.01),but no significant difference compared with any two methods (P ＞ 0.05).Conclusions The serum levels of HE4 and CA125 in the ovarian cancer group were significantly higher,and CT in combination with those two serum indices improved the diagnostic sensitivity,specificity,and accuracy of ovarian cancer.

Objective To investigate effect of Dahuang Fuzi decoction on alveolaur epithelial barrier in rats with lung injury with severe acute pancreatitis. Method Ninty-six health SD rats were randomly divided into three groups: sham operation group, SAP-ALI group, Dahuang Fuzi decoction group, and then according to the time point of sacrifice after operation, each group was subdivided into 3,6,12,24 hour subsets ( each, n = 8). After the belly of a rat in the sham operation group was cut open, the pancreas was flipped several times,and then a stoma was made in the jejunum to form its fistula. In the SAP-ALl group,1 mL/kg sodium taurocholate was reversely injected into the pancreatobile duct to establish the model of SAP, and then the jejimum fistula was performed. The SAP-ALI model in Dahuang Fuzi decoction group was treated by injection of 10ml of Dahuang Fuzi decoctionon into the fistula respectively. Blood was collected from heart to detect serum amvlase and endotoxin (ET) levels before the rat being executed. The lung histopathologic changes, pulmonary injury scores and wet/dry weight(W/D) ratios were observed after the rats were executed. The alveolar liquid clearance rate(ALCR), total lung water content (TLW), extravascular lung water content(EVLW) and alveolar epithelial permeability (AEP) were examined in 3,6, 12,24 h after injury.Results There was continuous increase of AEP,TLW and EVLW,as well as progressive reduction of ALCR compared with sham operation group at 3,6,12,24 h after operation. Compared with SAP-ALI group, there was continuous decrease of AEP,TLW and EVLW, and elevated of ALCR at 3,6,12,24 h after operation.Conclusions Dahuang Fuzi decoction can significantly reduce alveolaur epithelial barrier and degree of lung tissue of SAP-ALI rats by inhibiting the elevation of LPS and inflammation reaction.