Adult ; Benzene ; Biomarkers, Tumor ; blood ; Female ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Serum ; chemistry

ObjectiveTo investigate the extracorporeal clearance rate of imipenem in severe infection patients in the mode of continuous vena-venous hemofiltration (CVVH) during continuous renal replacement therapy (CRRT), in order to approach if the concentration of imipenem in plasma could achieve effective levels of anti-infection, and to explore the effect of time and anticoagulation measure on imipenem clearance during CRRT treatment.Methods A prospective observational study was conducted. All adult severe infection patients complicating acute kidney injury (AKI) in the Department of Critical Care Medicine of the Fourth Hospital of Hebei Medical University from March 2013 to September 2014, who were prescribed imipenem as part of their required medical care, and CRRT for treatment of AKI were enrolled. 0.5 g doses of imipenem was administered intravenously every 6 hours or 8 hours according to random number table, and infused over 0.5 hour. The unfractionated heparin was used for anticoagulation in the patients without contraindications, and no anticoagulation strategy was used in the patients with high risk of bleeding. At 24 hours after first time of administration, postfilter venous blood and ultrafiltrate samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 5, 6, and 8 hours after imipenem administration. The concentration of imipenem in above samples was determined with liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS).Results A total of 25 patients were enrolled. Thirteen patients received imipenem intravenously every 6 hours, and 12 patients, every 8 hours. The anticoagulation was conducted with heparin in 13 cases, and 12 cases without anticoagulation. The intra-day precision, inter-day precision, matrix effect, and recovery rate in low, medium, and high concentration of plasma and ultrafiltrate, and the stability of samples under different conditions showed a good result, the error of accuracy was controlled in the range of±15%. With the application of Prismaflex blood filtration system and AN69-M100 filter, under the mode with CVVH, the total clearance rate of imipenem was (8.874±2.828) L/h when the actual dose of replacement fluid was (31.63±1.48) mL·kg-1·h-1, the total CRRT clearance rate of imipenem in vitro was (2.211±0.539) L/h, which accounting for (30.1±15.7)% of the total drug clearance. In 6 hours interval dosage regimen, the percentages of the time> 4×minimum inhibitory concentration (MIC) at specific 4×MIC of 2, 4, 6, and 8μg/mL of imipenem were more than 40% of the dosing interval. But in the 8 hours interval dosage regimen, when the level was above the 4×MIC of 4μg/mL, maintaining time would drop below 40% of the dosing interval, with significant differences compared with that in 6 hours interval dosage regimen [4×MIC = 2μg/mL: (60.84±20.25)%vs. (94.01±12.46)%,t = 4.977,P = 0.001; 4×MIC = 4μg/mL: (39.85±15.88)% vs. (68.74±9.57)%,t = 5.562, P = 0.000; 4×MIC = 6μg/mL: (27.58±13.70)% vs. (53.97±8.36)%,t = 5.867,P = 0.000; 4×MIC = 8μg/mL:(18.87±12.43)% vs. (43.48±7.83)%,t = 5.976,P = 0.000]. No significant change in sieving coefficient of imipenem was found within a short time (6 hours), which indicated that there was no effect of anticoagulation on clearance of imipenem by AN69-M100 filter, and no statistical significance was found with repeated measure analysis (F = 0.186, P> 0.05).ConclusionsThe clearance rate of imipenem is increased significantly in vitro under the mode of CVVH with the actual dose of replacement fluid was (31.63±1.48) mL·kg-1·h-1 in severe infective patients with severe sepsis complicating AKI, affecting the level of plasma drug concentration, need to adjust the dosage regimen. When the time of the dosing interval was shortened, the concentration of imipenem in patients' plasma could be increased significantly. In a short period of time, the sieving coefficient of imipenem through AN69 filter is not affected by anticoagulation measures and time cleaning efficiency will not decline.

Objective To investigate the influence of Zhuanggu granule on the concentration of IL-1β and TN-F-α in knee cavity of patients with knee degenerated osteoarthritis. Methods A total of eighty patients with knee degenerated osteoarthritis were recruited into a Zhuanggu granule group (30 cases), a Sulphuric acid Glucosamine group (15 cases) and a Sodium Hyaluronate group (15 cases) according to Doll grouping method. After all groups were treated for 4 weeks, the changes of concentration of IL-1β and TNF-α was detected before and after the therapy Results After the treatment, the concentration of IL-1β and TNF-α in Zhuangu granule group was significantly lower than the other two groups (Sodium Hyaluronate and sulphuric Glucosamine group). Conclusion Zhuangu Granule could influence the concentration of IL-1β and TNF-α in patients of knee degenerated osteoarthritis.

Objective: To observe the effect of Juglone on invasion and metastasis of Hela cells and explore the possible mechanism. Methods: HeLa cells were cultured and treated with 10,20,50,100μmol/L Juglone for 24 hours. The morphology changes of HeLa cells were observed with an inverted microscope. The viability of HeLa cells was detected by MTT assay. The cell scratch test was used to detect cell migration ability after treatment of Juglone. The ability of cell invasion was measured by Transwell chamber. The expression of matrix metalloprateinases (MMP)-2 and MMP-9 were detected by Western blotting. Results: Compared with control group, the viability of HeLa cells decreased after treatment with different concentrations of Juglone for 24 hours, and the cell morphology was changed in a dose-dependent manner. Scratch test results showed that the level of cell movement ability decreased significantly with the increase of the concentration of Juglone. Transwell invasion assay showed that Juglone had a strong inhibitory effect on the invasiveness of HeLa cells in vitro. Western blotting results showed that Juglone inhibited the expression of MMP-2 and MMP-9 protein in HeLa cells. Conclusion: Juglone can inhibit the invasion and metastasis in HeLa cells, and its possible mechanism may be related to down regulating the expression of MMP-2 and MMP-9.

Background The alteration of dominance eye is associated with visual quality in patients with age-related cataract or after cataract-surgery.However,the study on the relationship of dominance eye shift with vision following cataract-surgery is lack.Objective This study was to observe the influence of age-related cataract and cataract surgery on ocular dominance in the elderly.Methods A serial cases-observational study was designed.Eighty-seven patients with age-related cataract were collected from December 2011 to April 2012 in Affiliated Eye Hospital of Wenzhou Medical University,and phacoemulsification combined with intraocular lens (IOL) implantation was performed in all the patients.The patients were grouped into binocular vision difference (best corrected distance vision) ≥2 lines group (42 patients) and ≤ 1 line group (45 patients) on the standard logarithmic visual acuity chart.The frequency and shift of dominant eye were determined by card-hole method or thumb method before operation and 1 day,1 week,1 month and 3 months after operation.The difference in the frequencies of dominant eye between before and after operation was analyzed with MecNmar test.Results The median of best corrected distance vision (LogMAR) was 0.40 (0.00-1.40) in preoperation and 0.00 (-0.08-0.30) in postoperation,with significant difference between them (Z=-9.481,P =0.000).In the binocular vision difference ≥ 2 lines group,the dominant eyes were 24 in the right eyes and 18 in the left eyes.The milder cataractous eyes were identified as dominant eyes in 33 (78.57％) patients and heavier cataractous eyes were determined as dominant eyes in 9 (21.43％) patients before operation.However,the right eye was evidenced as dominant eye in 31 patients and the left eye was in 11 patients after operation.In the 42 patients,dominant eye shifted from the left eyes to the right eyes in 10 patients and from the right eyes to the left eyes in 3 patients,and 4 patients presented an unstable change binocularly.In 45 patients of the binocular vision difference ≤ 1 line group,the dominant eyes were the right eyes in 27 patients and the left eyes in 18 eyes in preoperation ; while after operation,dominant eye altered form the left eyes to the right eyes in 3 patients and form the right eyes to the left eyes in 1 patient,and unstable change occurred in 5 patients.There were no significant differences in the frequency of dominant eyes between before and after operation both the two groups (group A:P =0.092 ; group B:P =0.727).Conclusions Age-related cataract impact on eye dominance.Dominance eye may occur alteration binocularly following cataract surgery,which is one of causes of visual discomfort.

Objective To observe the inhibitory effect of 6-gingerol on the invasion and migration of human papilloma virus (HPV)-positive and HPV-negative cervical cancer cells, and explore the possible mechanism. Methods Human HPV-positive cervical cancer cells (HeLa) and HPV-negative cells (C33A) were cultured, and added with 6-gingerol at different concentration of 0, 5, 10, 20, 50 μmol/L, the untreated cells play as control, then cultured for 24 h. 10 μmol/L 6-gingerol was determined as the best concentration, then all the cells were treated with 10 μmol/L 6-gingerol for 24 h, 48 h and 72 h respectively. The cell proliferation was detected by MTS method, and cell scratch test was performed to detect the effect of 6-gingerol on cell migration ability. The effect of 6-gingerol on cellular invasion was detected by Transwell chamber. Western blotting was used to detect the expression of matrix metalloproteinase MMP-2, MMP-9, E-cadherin and N-cadherin. Results MTS assay showed that the activity of HeLa and C33A cells decreased with the increase of 6-gingerol concentration and action time, while the activity of HeLa cells decreased more significantly than that of C33A cells at different concentrations or time points. Transwell invasion chamber test showed that the HeLa cells treated with 6-gingerol for 24 h and 48 h, and C33A cells treated with 6-gingerol for 48 h, the cellular invasion ability decreased significantly. The scratch test revealed that the wound healing rate decreased significantly of HeLa cells 24 h and 48 h after 6-carbenol action and of C33A cells 48 h after 6-carbenol action. Western blotting results showed that, treating with 10 μmol/L of 6-gingerol for 24 h, the expressions of E-cadherin increased and of N-cadherin, MM P-2 and MMP-9 declined in HeLa cells with statistical differences (P<0.05); while in C33A cells, the expressions of E-cadherin increased markedly, and of N-cadherin, MM P-2 and MMP-9 showed no significant differences (P>0.05) compared to that of unprocessed group. Conclusions 6-gingerol can inhibit the proliferation of HPV-positive cervical cancer cells and cell invasion. The mechanism may be associated with the effect of 6-gingerol on influencing the expression of epithelial-mesenchymal transition-related proteins.

MicroRNAs(miRNAs)are a class of small RNA molecules which play a pivotal role in the regulation of genes involved in diverse processes.Recently,many viral-encoded miRNAs have been discovered,which suggests that viruses also use this fundamental mode of gene regulation.Although the functions of most viral- encoded miRNAs are unknown,some of them are involved in evading CTL,mediating latent infection,apoptosis suppression,etc.Uncovering the role of viral miRNAs in the pathopoiesis offers an immense opportunity not only to develope effective antiviral therapies,but also to identifying novel molecular targets for developing antiviral reagents.Therefore,recent progress on vmiRNAs was reviewed.

MicroRNAs (miRNAs) are a newly identified class of non-protein-coding small RNAs that play important roles in multiple biological processes. Recent evidence indicates that the expression of many miRNAs is both temporally and spatially regulated by RNA editing, differential processing and tissue-specific enhancers, and the potential for ultimately designing molecular medicines based on the modulation of miRNAs seems good. A better understanding of the mechanism which regulates miRNAs is very helpful to reveal the pathogenesis of some diseases, discover novel molecular targets for treatment by interference, and develop an effective gene therapy. Therefore, the latest progress in the mechanism regulating miRNAs is summarized.

Objective To explore the effect of lysophosphatidic acid(LPA)on blood-brain barrier(BBB) permeability and its possible mechanism.Methods LPA or LPA+suramin(L+S)were stereotaxically injected into the right eaudate nucleus in SD rats in vivo.Evans blue(EB)was used to quantitatively measure the permeability of BBB at different time points.The expression of matrix metalloproteinase-9 was detected by immunohistochemistry technique.The pathological ultrastruetural changes of BBB were assessed by transmission electron microscopy.Results The BBB permeability began to increase after LPA administered into ipsilateral eaudate nucleus,and reached the peak at 24h.Then the permeability of BBB gradually lowered after 48h.In comparison with the same time points of control group,there were quite significant differences(P＜0.01).After L+S was injected,the change of BBB permeability had differences in comparison with those of LPA group in the same time points,(P＜0.05).MMP-9 positive cells were mainly vascular endothelial cells.The numbers of MMP-9 positive blood vessels grew at 6h in LPA group,and the expression of it reached maximum at 24h,then the number of it decreased at 48h,showing significant statistical differences in comparison with the L+S group(P＜0.01),It was observed microscopically that ultrastrueture of BBB of the LPA group was changed sharply,such as basement membrane roughed and fragmented,astroeyte end-feet swolled markedly and perivaseular space enlarged obviously.But there were no remarkable changes in BBB in L+S group.Conclusion LPA can induce increase of BBB permeability and its possible mechanism is the strong expression of MMP-9 protein produeted by endothelial cells through the mediation of LPA receptor,leading to degradation of basement membrane.

OBJECTIVE:To investigate the effect of clinical pharmacist intervention on prophylactic application of antibiotics in cardiothoracic surgery. METHODS:Medical records of patients underwent cardiothoracic surgery were collected from our hospi-tal during Mar. to Apr. in 2014 (before intervention) and during Jun. to Jul. in 2014 (after intervention). Those were divided into pre-intervention group(n=115)and post-intervention group(n=119). The prophylactic application effect of antibiotics was com-pared before and after intervention. RESULTS:After intervention,the rates of prophylactic application were decreased significantly from 96.5% to 72.3%;the rationality rate of antibiotics selection was improved significantly from 27.9% to 94.2%;The course of prophylactic medication decreased significantly from(5.4±2.8)days to(2.3±1.8)days;the difference had statistical significance before and after intervention(P<0.01). The postoperative infection rate was decreased from 13.0% to 5.9%,the difference had no statistical significance(P=0.074). The average hospitalization time,average drug costs,and average hospitalization expenses were decreased significantly,the difference had statistical significance(P<0.05 or P<0.01). CONCLUSIONS:Clinical pharmacist inter-vention to prophylactic application of antibiotics in cardiothoracic surgery can control the infection effective and guarantee reason-able and safe use of drugs during perioperative period.