Objective To evaluate the reliability of using imipenem,meropenem,cefoperazonesulbactam,piperacillin-tazobactam in the treatment of hospital-acquired Gram-negative bacterial infections with Monte Carlo simulation(MCS).Methods The MIC of the four agents collected from hospital-acquired infections were detected in accordance with broth dilution method of Clinical and Laboratory Standard Institute (CLSI).MCS were conducted with MICs and the pharmacokinetics parameters of the four agents based on conventional dose regimens.The cumulative fraction of response (CFR) of time over MIC target attainment in different dosing regimen were generated.Results A total of 2 541 strains,including 2 093 strains of Enterobacteriaceae and 448 strains of glucose non-fermentative bacilli were collected.The MIC90 of imipenem and meropenem against Enterobacteriaceae were less than 1 mg/L in general,whereas MICg0 of two agents with β-1actamase inhibitors was around 64 mg/L.As to glucose non-fermenting bacteria,MICs of all the four agents were very high,especially to Acinetobacter baumannii,which indicated MIC50 more than 32 mg/L.MCS revealed that carbapenems had significantly higher CFR than those with β-1actamase inhibitors.Imipenem and meropenem (1 g,q8 h) obtained CFRs of 74.69％ and 81.42％,respectively.The CFR of cefoperazone-sulbactam (2 g,q8 h) and piperacillin-tazobactam (4 g,q6 h) (both excluding β-1actamase inhibitors) were just 49.59％ and 27.66％ respectively,which increased after excluding A.baumannii in piperacillin-tazobactam.Conclusions The conventional dose regimens of imipenem and meropenem are reliable for the empiric therapy of Gram-negative hospital-acquired bacterial infections.Piperacillin-tazobactam is suggested to use with higher doses or prolonged infusion time to satisfy the time of drug concentration exceeded the MIC (T ＞ MIC) requirement.More clinical studies of cefoperazone-sulbactam should be conducted to optimize its regimen and guarantee its efficacy.

BACKGROUND: With wide application of biotechnological substitute materials, pelvic repair and reconstruction develop to a certain degree. Biomaterial patch is a major substitute for repairing injured pelvic fascia tissue, so it is widely used for pelvic reconstruction.OBJECTIVE: To investigate the feasibility, efficacy, and clinical value of biomaterial patch to pelvic reconstruction in the females.METHODS: Articles related to pelvic functional disorder, pelvic reconstruction, and application of patch implant were retrieved from PubMed (http://www.ncbi.nlm.nih.gov/PubMed) and (http://www.wanfangdata.com.cn) with the key words of "reconstruction of whole pelvic floor, mesh, synthetic mesh implants" in both Chinese and English between 1990 and 2008. Duplication studies were excluded. A total of 54 articles were initially retrieved, and 17 ones were included in the final analysis.RESULTS AND CONCLUSION:Pelvic organ prohpse, which was a major symptom of pelvic disorder in the females, caused by defect of pelvic supporting structure, injury, and functional disorder. Traditional operation could not solve fundamental question.At present, substitute materials for pelvic repair and reconstruction mainly include biomaterial patch (self-substitute materials, homogeneity substitute materials, and heterogeneity substitute materials) and artificial patch. All of them could substitute the injured pelvic fascia tissue; therefore, they were major substitute materials of pelvic tissue and widely used for pelvic reconstruction. Patch which was used for pelvic reconstruction realized the recovery of anatomic structure and caused functional recovery, with simple and easy processing. Additionally, patch application did not prolong operative time and cause complication, but induced well tolerance, security and reliability, and remarkable short-term effect on patients. However, the long-term efficacy should be further studied. The modified pelvic reconstruction is clinically valuable for patients with varying prolapsed sites.

Objective To study the molecular mechanism of IL-17A induced the secretion of CXCL 12 in non-small cell lung cancer cell line A549.Methods Cultured non-small cell lung cancer cell line A549 in vitro with recombination cytokine IL-17A or STAT3 signal path-way inhibitor pre-incubated for 1 hour, and then the level of CXCL12 were detected by enzyme-linked immunosorbent assay .And chemotaxis assay was used to analyze the chemotactic movement of neutrophil .Results After IL-17A stimulation,the secretion of CXCL12 by non-small cell lung cancer cell line A549 was significantly increased(P<0.01),which is in a dose and time dependent manner .However,IL-17A in-duced the secretion of CXCL12 by A549 was significantly decreased after pre-incubated by the STAT3 inhibitor(P<0.01).In addition,neu-trophil could have chemotaxis by cell suspension obtained from IL-17A stimulated A549 cell line,but such chemotaxis would be declined while CXCL12 was neutralized.Conclusion IL-17A could induce the secretion of CXCL12 in non-small cell lung cancer cell line A549 through STAT3 signal pathway , so as to promote the chemotaxis of neutrophil .

Objective: To explore the mechanism of Fujian Tablet in promoting neural regeneration by observing the effect of Fujian Tablet on the expression of slit in MCAO rats at different stages. Methods: 240 SD rats were randomly divided into normal control, sham operation, model and medicine groups, which were randomly divided into five subsets with 12 rats according to the day 3 and week 1, 2, 4, 6 stages. The rat models with middle cerebral artery occlusion were successfully established by the improved Longa EZ. The medicine group was gived with Fujian Tablet, other groups were given with commensurability distilled water. The expession of slit in the region around the infarction was observed by immunohistochemical method. Results: In the medicine group, slit -positive cells were obviously different with normal control group (P

In order to explore the effects of testicular infection of murine cytomegalovirus (MCMV) on mature sperm viability at different periods following MCMV inoculation in mice, 91 BALB/c mice without MCMV infection were randomly divided into two groups: an experimental group (n = 56) and a control group (n = 35). The mice in the experimental group were treated by inoculating MCMV intratesticularly, while those in the controlled group were directly inoculated with DMEM without MCMV. The mice in both groups were sacrificed separately on the day 1, 1. 5, 2, 4, 6, 9 and 14 post-inoculation (D1) 1. 5, 2, 4, 6, 9 and 14 PI). The MCMV M83 mRNA gene was detected in the testis by in situ hybridization (ISH) with MCMV late-mRNA probe labeled with digoxin. Sperm viability of mature sperm in the epididymis cauda was measured. The results demonstrated the positive signal of ISH of MCMV was found mainly in the cytoplasm of the testicular interstitial cells and spermatogenic cells in the experimental group. Compared with that in the controlled group, the sperm viability in the experimental group was decreased significantly on D1 PI and D1.5 PI (P < 0.05). No statistically significant difference in the sperm viability was found after D2 PI between two groups (P > 0.05). This suggested that sperm viability in mice might be descended significantly shortly after MCMV infection and might return to normal with time, indicating that MCMV acute infection might temporarily degrade sperm quality and influence procreation transiently.
Cytomegalovirus Infections/*physiopathology ; Mice, Inbred BALB C ; Orchitis/*virology ; Random Allocation ; Sperm Motility/*physiology ; Spermatozoa/cytology ; Spermatozoa/*physiology

The effect of triptolide (TP) on the expression of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) was explored in rat adjuvant induced arthritis (AA). AA was induced in Wistar rats. Arthritis rats were treated with TP and methotrexate (MTX) at the onset (day 9) of arthritis. On the peak of arthritis (day 24), the expression of RANKL and OPG protein in the joints and RANKL mRNA in peripheral blood mononuclear cells (PBMC) was detected. TNF-alpha and IL-1beta levels in peripheral blood were determined. Bone erosion scores were also evaluated. The results showed that bone erosion scores in TP and MTX groups were lower than in AA group (P < 0.01); The expression levels of RANKL in the synovium (P < 0.01) and bone (P < 0.05), and OPG level in synovium (P < 0.05) were lower in TP group than in AA group (P < 0.05). In TP group, the expression levels of RANKL mRNA and TNF-alpha, IL-1beta in PBMC were lower than in AA group (all P < 0.01). It was concluded that TP could inhibit rat adjuvant arthritis bone erosion by suppressing the expression of RANKL.

The relationship between tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and inhibitory effects of triptolide on TNF-alpha production from peripheral blood mononuclear cells (PBMC) of healthy humans was investigated. Genomic DNA from 41 healthy people was typed for TNF-alpha--308 polymorphism by allele-specific polymorphism chain reaction (AS-PCR). The TNF-alpha concentration in the supernatant was measured by ELISA. The results showed that the production of TNF-alpha from TNF-alpha--308 non-G/G genotype PBMC was higher than that from TNF-alpha--308 G/G genotype PBMC after stimulated by LPS. Triptolide could lower the production of TNF-alpha from G/ G genotype PBMC, but had no effect on the level of TNF-alpha from non-G/G genotype PBMC. It was concluded that TNF-alpha gene polymorphism was related to the TNF-alpha production from triptolide-inhibited PBMC culture in healthy humans.

Little is reported about the role of PTEN gene in the progression and prognosis of GISTs. This study examined the clinical implications of the tumor suppressor gene PTEN as a prognostic factor in the GISTs. Immunohistological staining and immunoblotting were employed to examine the PTEN protein expression, and its association with clinical measures. Clinicopathological features were reviewed by a retrospective examination of medical records. Reduced PTEN expression was significantly associated with tumor diameter, mitotic figure count, metastasis and pathological stage of tumor (P<0.05), and was not correlated with age, gender and tumor location (P>0.05). The 3-year survival rate of the patients with reduced PTEN expression was significantly lower than those with high PTEN expression (P<0.01). These results suggest that the expression of PTEN gene was significantly linked with the progression and metastasis of GISTs and it is an independent prognostic factor.

AIM: To explore whether the inhibitory effect of triptolide on IL - 1β production by PBMC is asso ciated with IL - 1β gene polymorphisms. METHODS: IL - 1β gene polymorphism was analyzed in 31 healthy volunteers. From genomic DNA, the C - T polymorphism at IL - 1 β - 511 was typed by PCR - RFLP. Meanwhile the IL - 1 β was also measured in the supernatants of the cultured and stimulated peripheral blood mononuclear cells (PBMC) by ELISA. RE SULTS: After LPS stimulation in PBMC cultures of healthy subjects, the secretion levels of IL - 1 β in 9 volunteers who carried IL - 1β -511 T/T genotype were higher than in volunteers who are not T/T genotype (P ＜0.05). Triptolide sup pressed the production of IL - 1β significantly in LPS - treated human PBMC carried C/C and C/T genotype ( P ＜ 0.05 ), but this significant inhibitory effect of triptolide was not seen in T/T genotype ( P ＞ 0.05 ). CONCLUSION: The gene polymorphism at IL - 1β - 511 was related to the production of IL - 1β, and the inhibitory effect of triptolide on the produc tion of IL - 1β was different in C/C, C/T, T/T genotype of IL - 1β -511, which may be one of the reasons for the phe nomenon that people respond differently to triptolide.

BACKGROUND: Common threewingnut root has the functions of anti-inflammation and immune inhibition, etc., and it has been used at present to treat various autoimmune diseases including rheumatoid arthritis.. Common threewingnut root has complex components, and triptolide is acknowledged as one of the important effective components of common threewingnut root.OBJECTIVE: To establish rat models of type Ⅱ collagen induced arthritis, and observe the effects of triptolide on the contents of interleukin-6,interleukin-10 and tumor necrosis factor alpha (TNF-α) in peripheral serum and synovial fluid.DESIGN: A randomized control animal experiment.SETTING: Department of Integrated Traditional and Western Medicine,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: The experiments were carried out in the Tongji Hospital from November 2004 to July 2005. Fifty healthy male Wistar rats of clean degree were purchased from the experimental animal center of Tongji Medical College, Huazhong University of Science and Technology [qualification number of animal [scxk(E)2004-2007]. Triptolide (nobatch number because of temporary production) was bought from Fujian Institute of Medical Sciences, and the purity was above 98.5%.METHODS: ① Ten of the 50 rats were randomly selected as the normal controls, and the others were made into models. Type Ⅱ collagen emulsion was injected intradermally at five points along the back and tail of the rats,0.05 mL for each point, and injected intradermally at two points after 15 days. The rats in the normal control group were treated with saline in the same way. The effects of the model establishment were evaluated according to the scoring standards of arthritis index at 30 days after the first immunity, and the rats scored 6 points or above were taken as successful models and enrolled in the experiments. Twenty successful rat models were randomly divided into arthritis model group (n=10) and triptolide treated group (n=10). ② Triptolide (100 mg/L)was dispensed into parenteral solution with propylene glycol (0.05 in volume fraction), and then intramuscularly injected into hindlimb of rats in the triptolide treated group (0.04 mL/100 g), once every three days for 30 days. The rats in the normal control group were given isovolume saline, and those in the arthritis model group were treated with isovolume propylene glycol (0.05 in volume fraction). ③ The materials were removed at 30 days after administration. The contents of interleukin-6, interleukin-10 and TNF-α in peripheral serum and synovial fluid were detected with enzyme-linked immunosorbant assay(ELISA).MAIN OUTCOME MEASURES: The effects of triptolide on contents of TNF-α, interleukin-6 and interleukin-10 in peripheral serum and synovial fluid were observed.RESULTS: Fifty male Wistar rats of clean degree were selected, 10 were used as normal controls, and 20 of the other 40 rats were successfully made isto models and enrolled in the analysis of results. ① The TNF-α contents in peripheral serum and synovial fluid were the highest in the arthritis model group, and obviously decreased after treatment of triptolide [(35.09±8.82), (15.35±3.56) ng/L; (44.17±8.94), (22.54±4.76) ng/L; P＜ 0.01], which were similar to those in the normal control group (P ＞ 0.05).② The contents of interleukin-6 in peripheral serum and synovial fluid were the highest in the arthritis model group, and were obviously decreased after treatment of triptolide [(76.58 ±6.81), (42.45 ±5.72) rig/L;(88.69±10.56), (48.67±5.97) ng/L; P ＜ 0.01], but did not recover to the levels in the normal control group (P ＜ 0.05). ③ The contents of interleukin-10 in peripheral serum and synovial fluid were the lowest in the arthritis model group, and obviously increased after treatment of triptolide[(17.53±2.07), (21.23±2.91) ng/L; (10.59±2.96), (14.74±1.85) ng/L; P＜ 0.01], which were similar to those in the normal control group (P ＞ 0.05).CONCLUSION: Triptolide can treat arthritis by modulating the contents of cytokines.