Enriched environment improves sevoflurane-induced cognitive impairment during late-pregnancy via hippocampal histone acetylation

Fetal exposure to sevoflurane induces long-term cognitive impairment. Histone acetylation regulates the transcription of genes involved in memory formation. We investigated whether sevoflurane exposure during late-pregnancy induces neurocognitive impairment in offspring, and if this is related to histone acetylation dysfunction. We determined whether the effects could be reversed by an enriched environment (EE). Pregnant rats were exposed to 2.5% sevoflurane or control for 1, 3, or 6 h on gestational day 18 (G18). Sevoflurane reduced brain-derived neurotrophic factor (BDNF), acetyl histone H3 (Ac-H3), and Ac-H4 levels and increased histone deacetylases-2 (HDAC2) and HDAC3 levels in the hippocampus of the offspring on postnatal day 1 (P1) and P35. Long-term potentiation was inhibited, and spatial learning and memory were impaired in the 6-h sevoflurane group at P35. EE alleviated sevoflurane-induced cognitive dysfunction and increased hippocampal BDNF, Ac-H3, and Ac-H4. Exposure to 2.5% sevoflurane for 3 h during late-pregnancy decreased hippocampal BDNF, Ac-H3, and Ac-H4 in the offspring but had no effect on cognitive function. However, when the exposure time was 6 h, impaired spatial learning and memory were linked to reduced BDNF, Ac-H3, and Ac-H4, which could be reversed by EE.

Clinicopathologic features and prognostic analyses of locally recurrent renal cell carcinoma patients after initial surgery / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the clinicopathologic features and potential prognostic predictors of locally recurrent renal cell carcinoma patients after initial surgery.@*METHODS@#Authors retrospectively analyzed data extracted from 81 patients who were treated for postoperative locally recurrence of renal cell carcinoma from January 2006 to June 2016 in the Department of Urology, Peking University First Hospital. Postoperative locally recurrence of renal cell carcinoma was defined as disease recurring in the remnant kidney, renal fossa, adjacent abdomen, ipsilateral adrenal and retroperitoneal lymph nodes.@*RESULTS@#In the study, 81 patients were finally included, of whom 43 were initially treated in our hospital and 38 were initially treat in other centers. Partial nephrectomy (PN) was performed for 38 cases (26 in our hospital and 12 in other hospitals) as initial treatment and radical nephrectomy (RN) was conducted for the remnant 43 cases (17 in our hospital and 26 in other hospitals). Overall median recurrence time was 26 months (range: 3-164 months), in which 26 months (range: 3-55 months) for PN cases and 30 months (range: 4-164 months) for RN cases (P=0.009). Sixty-nine patients had single site recurrence, including remnant kidney (n=29), renal fossa (n=20), abdomen (n=4), ipsilateral lymph nodes (n=5), ipsilateral adrenal (n=11), while 12 patients had multiple sites recurrence. Seventy-eight patients were managed by complete surgical resection, while three patients were managed by radiofrequency ablation. Postoperative pathological diagnoses included clear cell carcinoma (n=72), papillary renal cell carcinoma (n=8, 7 cases with type 1, 1 case with type 2) and Xp11 translocation/TFE3 gene fusion renal cell carcinoma (n=1). Complete pathologic information of the initial surgery could be extracted from 43 patients who were initially treated in our hospital. Seventeen patients with initial radical nephrectomy were staged as T1a (n=4), T1b (n=2), T2a (n=1), T3a (n=8), and T3b (n=2). Twenty-six patients with initial partial nephrectomy were staged as T1a (n=18), T1b (n=7), and T3a (n=1). For PN cohort, the patients with T1a stage disease had longer median recurrence time than those with beyond T1a stage disease, and the difference was significant (29 months vs. 18 months, P=0.041). At the end of the follow-up, 58 patients were alive, 4 died and 19 lost the follow-up. Overall, 3-year and 5-year disease free survival rates were 81.9%, and 53.6%, respectively.@*CONCLUSION@#The present research reported a large-scale single central experience of locally recurrent renal cell carcinoma. The recurrence time of the PN group is shorter than that of the RN group. For patients after PN surgery, median recurrence time is longer for patients with T1a stage tumor when compared with those with stage beyond T1a. Patients can obtain relative long-term survival after complete secondary surgery resection.

Partial nephrectomy for T3aN0M0 renal cell carcinoma: shall we step forward?

ABSTRACT Objectives: To evaluate the prognosis of non-metastatic T3a renal cell carcinoma (RCC) with partial nephrectomy (PN). Patients and Methods: We retrospectively evaluated 125 patients with non-metastatic T3a RCC. Patients undergoing PN and radical nephrectomy (RN) were strictly matched by clinic-pathologic characteristics. Log-rank test and Cox regression model were used for univariate and multivariate analysis. Results: 18 pair patients were matched and the median follow-up was 35.5 (10-86) months. PN patients had a higher postoperative eGFR than RN patients (P=0.034). Cancer-specific survival (CSS) and recurrence-free survival (RFS) did not differ between two groups (P=0.305 and P=0.524). On multivariate analysis, CSS decreased with positive surgical margin and anemia (both P <0.01) and RFS decreased with Furhman grade, positive surgical margin, and anemia (all P<0.01). Conclusions: For patients with non-metastatic pT3a RCC, PN may be a possible option for similar oncology outcomes and better renal function.

Resistance profile ofSalmonella isolates in hospital across China：results from CHINET Antimicrobial Resistance Surveillance Program, 2005-2014 / 中国感染与化疗杂志

Objective To investigate the distribution and changing resistance proifle ofSalmonella isolates in hospitals across China during the period from January 2005 to December 2014.Methods Seventeen general hospitals and two children’s hospitals were involved in this program. Antimicrobial susceptibility testing was carried out by means of a unified protocol using Kirby-Bauer method or MIC determination. The results were analyzed according to CLSI 2014 breakpoints.Results The proportion ofSalmonella isolates increased with time from 0.2% in 2005 to 0.7% in 2014. A total of 3 478Salmonella strains were collected from 19 hospitals. The proportion ofSalmonella typhimurium andSalmonella enteritidis was 27.4% and 24.4%, respectively. During the 10-year period, theSalmonella strains showed highest resistance rate to ampicillin (33.3%-64.8%), but low resistance to cefoperazone-sulbactam (0-5.3%) and ciprofloxacin (2.4%-14.3%).S. typhimurium showed higher resistance rate thanS. typhi,S. paratyphi andS. enteritidis. About 76.8% and 50.5% ofS. typhimurium were resistant to ampicillin and trimethoprim-sulfamethoxazole. The average prevalence of multi-drug resistantSalmonellawas 3.9% in the ten-year period, the highest (7.5%) was in 2005, the lowest (1.5%) in 2013.Conclusions During the period from 2004 to 2015, majority of theSalmonella isolates in hospitals across China wasS. typhimurium andS. enteritidis. Ampicillin and trimethoprim-sulfamethoxazole are no longer appropriate for empirical treatment ofS. typhimurium infection due to high resistance rate.Salmonella isolates are relatively more susceptible to third-generation cephalosporins and quinolones. Ongoing monitoring is necessary to identify multi-drug resistant strains ofSalmonella.

Distribution and Drug Resistance of Pathogenic Bacteria in Lower Respiratory Tract Infection / 医药导报

Objective To investigate distribution and drug resistance of pathogenic bacteria in lower respitatory tract infection. Methods Distribution and drug resistance of pathogenic bacteria in lower respitatory tract infection of patients in ICU and non-ICU of our hospital during 2013 were retrospectivly analyzed. The pathogens were identified by manual methods routinely and those difficult to be identified were analyzed by using the VITEK-2-COMPACT instrument. Antimicrobial susceptibility of these isolates were tested by Kirby-Bauey methods routinely. Results In total, 956 strains were isolated from lower respitatory tract infection of patients in ICU, including 231 strains of gram-positive cocci (24. 2%), 680 strains of gram-negative bacteria (71. 1%), 45 strains of fungi (4. 7%). In patients of non-ICU, 4 464 strains were isolated, including 1 090 strains of gram-positive cocci (24. 4%), 3 226 strains of gram-negative bacteria (72. 3%), and 148 strains of fungi (3. 3%). Staphylococcus aureus, acinetobacter baumannii and pseudomonas aeruginosa were the most frequent isolates in patients of ICU and non-ICU. The overall prevalence of methicillin resistant staphylococcus aureus (MRSA) in staphylococcus aureus was 87. 0%in ICU and 74. 0% in non-ICU. MSSA was sensitive to the most antibiotics ( more than 80. 0% of the strains were sensitive to common antibiotics) except penicillin, erythromycin and clindamycin. MRSA was sensitive to trimethoprim-sulfamethoxazole and fosfomycin (more than 75. 0% of the strains were sensitive to the antibiotics) except for vancomycin, teicoplanin and linezolid. Acinetobacter baumannii was more resistant to the antibiotics (less than 40. 0% of the strains were susceptible to the antibiotics). Pseudomonas aeruginosa from ICU was more resistant to the antibiotics ( less than 50. 0% of the strains were sensitive to the antibiotics) than that from non-ICU. Stenotrophomonas maltophilia was sensitive to trimethoprim-sulfamethoxazole, levofloxacin and minocycline (more than 80. 0% of the strains were sensitive to the antibiotics). Escherichia coli and Klebsiella pneumoniae were sensitive to Piperacillin-tazobactam and Amikacin except for meropenem and imipenem ( more than 80. 0% of the strains were sensitive to the antibiotics) . Conclusion Gram-negative bacteria was the most frequent isolate in lower respitatory tract infection of our hospital during 2013. Staphylococcus aureus, acinetobacter baumannii and pseudomonas aeruginosa were the most frequent isolates in ICU and non-ICU. Resistance to the antibiotics was more common in ICU than in non-ICU. Antibiotics should be prescribed according to bacterial resistance results reasonably in order to prevent the spread of drug-resistant strains.

PI3K/Akt/mTOR pathway participates in neuroprotection by dexmedetomidine inhibits neuronic autophagy following traumatic brain injury in rats.

Dexmedetomidine (Dex) has been demonstrated to provide neuroprotective effect against brain injury in the central nervous system. However, the underlying mechanism of this neuroprotection remains unclear. In this study, we explored whether Dex has the protective potential in rat models of traumatic brain injury(TBI). More importantly, our study further investigated the role of neuronic autophagy induced by PI3K/Akt/mTOR pathway in this neuroprotective action. Adult male Sprague-Dawley rats were subjected to a diffuse cortical impact injury caused by a modified weight-drop device and Dex (15ug/kg, i.v.) was administered immediately after TBI. Wet-dry weight method was used to evaluate brain edema. Motor function outcome was assessed by Neurologic Severity Score and the spatial learning ability was evaluated in a Morris water maze. The co-localization of microtubule-associated protein 1 light chain 3(LC3) and neuronal nuclei (NeuN), or LC3 and mammalian target of rapamycin (mTOR) were analyzed by immunofluorescence respectively. The expression of LC3, Phosphorylated protein kinase B (p-Akt) and p-mTOR were quantified using Western blot analysis. Our results showed treatment of rats exposed to TBI with Dex caused not only marked reduction in cerebral edema, motor and cognitive functions deficits, but also a decrease in LC3 levels and a increase in p-Akt and p-mTOR levels. Taken together, these findings indicated that treatment with Dex after TBI could inhibited neuronic autophagy in the hippocampus mediated by the activation of the PI3K/Akt/mTOR pathway, finally promoting neurological recovery.

CHINET 2012 surveillance of antibiotic resistance in Acinetobacter baumannii isolates in China / 中国感染与化疗杂志

Objective To investigate the antimicrobial resistance in the A cinetobacter baumannii strains in different parts of China during 2012 .Methods A total of 8 739 clinical isolates of Acinetobacter were collected from 13 general hospitals and two children’s hospitals ,of which most were A . baumannii (89 .6% , 7 827/8 739 ) . Antimicrobial susceptibility testing was carried out by means of Kirby-Bauer method according to the unified protocol . The susceptibility testing data were analyzed by WHONET 5 .6 software according to CLSI 2013 breakpoints .Results Majority (85 .4% ) of the Acinetobacter strains were isolated from inpatients .The remaining 14 .6% were from outpatients and emergency room patients .Of the 7 827 strains of A .baumannii , 10 .9% ,35 .2% ,35 .7% and 43 .4% were resistant to tigecycline ,minocycline ,cefoperazone-sulbactam and amikacin , respectively .The percentage of A .baumannii resistant to imipenem and meropenem was 63 .5% and 68 .2% ,respectively . The antimicrobial resistant pattern varied in different hospitals . The resistance of A . baumannii varied between different clinical departments .A number of pandrug resistant (PDR) (20 .0% ,1 567/7 827) and multidrug-resistant (MDR) (45 .0% , 3 521/7 827 ) A . baumannii were identified . Conclusions A . baumannii is the most popular pathogenic bacteria among Acinetobacter .The antibiotic resistance of A .baumannii is still increasing .Cefoperazone-sulbactam and minocycline has good in vitro antibacterial activity against A .baumannii .The antibiotic resistance of A .baumannii varies greatly with hospital and department .

Surveillance of antimicrobial resistance in clinical isolates from Tongji Hospital in 2012 / 中国感染与化疗杂志

Objective To investigate the antimicrobial resistance in the clinical strains isolated from Tongji Hospital to the antimicrobial agents commonly used in 2012.Methods Antimicrobial susceptibility was tested by Kirby-Bauer method.The minimum inhibitory concentration (MIC) of penicillin and ceftriaxone for Streptococcus pneumoniae and vancomycin for Staphylococcus spp.were determined by E-test.All data were analyzed by WHONET 5.6 software.Results A total of 8 191 strains were isolated in 2012,including gram-positive bacteria (2 815,34.4%)and gram-negative bacteria (5 376,65.6%). The top five pathogenic bacteria isolated from outpatients were Escheria coli,Pseudomonas aeruginosa,coagulase-negative Staphylococcus (CNS),Klebsiella spp.and Staphylococcus aureus.For the isolates from non-ICU inpatients,the top five were E.coli,S.aureus,Acinetobacter spp.,Klebsiella spp.and P.aeruginosa.For those isolated from ICU patients,the top five were Acinetobacter spp.,S.aureus,P.aeruginosa,Enterococcus spp.and E.coli.The prevalence of MRSA and MRCNS was 58.1% and 64.3%,respectively.Seventeen strains of vancomycin resistant Enterococcus were identified, including 13 strains of E.faecium with VanA and 4 strains of E.gallinarum with VanA and VanC.The percentage of antimicrobial resistance in E.faecium was significantly higher than that in E.faecalis (P<0.05).A total of 94 strains of carbapenem-resistant Enterobacteriaceae were detected.The prevalence of penicillin-non-susceptible S.pneumoniae in children was much higher than that in adults. The prevalence of carbapenem-resistant P.aerugonosa and Acinetobacter spp. was 28.1% and 56.2% respectively.Beta-lactamase was produced in 41.8% of the H.influenzae and 98.6% of the M. catarrhalis isolates. Conclusions The prevalence of multidrug resistant strains has been increasing, especially vancomycin-resistant Enterococcus and carbapenem-resistant Enterobacteriaceae.

Correlation bewteen associated genes and biofilm phenotype in Staphylococcus epidermidis / 国际检验医学杂志

Objective To investigate the relationship of icaA,aap ,atlE,sarA gene with biofilm phenotype in Staphyloccus epi-dermidis .Methods Tissue culture plates assays were used to assess biofilm-forming ability of 78 Staphyloccus epidermidis strains.The presence of icaA,atlE,aap ,sarA gene was amplified with PCR method,the relationship between these genes and bio-film phenotype was evaluated by χ2 test and the difference of the biofilm OD′s value in TSB and TSB+3% NaCl by icaA + strains and icaA - strains was evaluated by Wilcoxon sign test,respectively.Results The positive rates of icaA,atlE,aap ,sarA gene were 24.4%(19/78),79.5%(62/78),73.8%(57/78),82.1%(64/78),respectively.40 biofilm-positive strains were detected(51.3%), among which 16 strains carried icaA gene,24 strains showed weak biofilm-forming ability.Those genes above with biofilm forma-tion were statistically correlated.Moreover,there was a relation between the icaA gene and the high biofilm-producing phenotype. There was a significant difference between the biofilm OD values in TSB and TSB+3% NaCl by icaA + strains and icaA - strains, respectively.Conclusion Multiple genes are involved in Staphylococcus epidermidis biofilm-positive phenotype,but the icaA gene contributes to the high biofilm-forming phenotype.Biofilm phenotype is also influenced by environmental factors.

Evaluation of efficacy and safety of sunitinib regimen in 22 patients with metastatic renal cell carcinoma: at least 12-month follow-up / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sunitinib has been proved an effective new option for treatment of metastatic renal cell carcinoma (mRCC). Analysis of clinical data of 22 patients, who were exposed to sunitinib for at least 1 year, was conducted to evaluate the long-term efficacy and safety of sunitinib for the treatment of mRCC.</p><p><b>METHODS</b>A total of 54 patients with mRCC were treated with sunitinib malate, 50 mg/d orally, on a 4-weeks-on and 2-weeks-off dosing schedule in Peking University First Hospital. Treatment continued until disease progression, unacceptable adverse events (AEs), or death. Among them, 22 patients continued treatment for at least 1 year. The clinical data of these 22 patients were prospectively collected for analysis. AEs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0. Tumor response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors.</p><p><b>RESULTS</b>Median progression-free survival was 19.5 months until last follow-up. The best efficacy results achieved were complete response, partial response, and stable disease for 2, 9, and 11 patients, respectively. Objective response rate was 50%. The most common AEs were hand-foot syndrome (95%) and hypertension (91%). Other common AEs were thyroid-stimulating hormone elevation (82%), platelet decrease (77%), and loss of appetite (77%). Only one patient withdrew from treatment for cardiac infarction. Another nine patients experienced dose modifications or short-term suspensions.</p><p><b>CONCLUSION</b>Long-term exposure to sunitinib malate showed encouraging efficacy in the treatment of mRCC. At the same time, the tolerability was good.</p>

Distribution and antibiotic resistance of pathogenic bacteria isolated from blood samples of pediatric patients in Hubei area / 中国感染与化疗杂志

Objective To investigate the distribution and antibiotic resistance of bacterial isolates from blood samples in pediatric patients in tertiary hospitals in Hubei area from 2006 to 2007.Methods Pathogenic bacteria isolated from blood samples of pediatric patients were collected from 17 tertiary hospitals in Hubei area from 2006 to 2007. All strains were isolated and identified by routine Methods . Antimicrobial susceptibility testing was conducted on all isolates using Kirby-Bauer Methods . Results A total of 941 strains were collected from January to December of 2006. The most common microorganism was coagulase-negative Staphylococcus (573, 60.9%), followed by Staphylococcus aureus (127, 13.5%), Enterococcus faecalis (33, 3.5%), Escherichia coli (16, 1.7%). A total of 969 strains were collected from January to December of 2007. The most common species was coagulase negative Staphylococcus (583, 60.2%), followed by S. aureus (162, 16.7%), E. faecalis (28, 2.9%), E. coli (21, 2.2%), E. faecium (11, 1.1%), Salmonella choleraesuis (11, 1.1%). Of the isolates collected during 2006, the prevalence of methicillin-resistant S. aureus (MRSA) was 71.7%. The prevalence of ESBLs was 56.2% in E. coli. Of the isolates collected during 2007, the prevalence of MRSA was 79.6%. The prevalence of ESBLs was 47.6% in E. coli. MRSA strains were more resistant to antibiotics than methicillin-susceptible S. aureus (MSSA). No glycopeptide-resistant strain was identified in Staphylococcus. Conclusions Staphylococcus is the most frequently isolated pathogen from blood samples of pediatric patients in tertiary hospitals in Hubei area.

Alteration of microbial population distribution and drug resistance of clinical bacterial isolates in patients with severe multiple trauma / 中华创伤杂志

Objective To study the alteration of microbial population distribution and resistance of clinical bacterial isolates in patients with severity muhiple injuries. Methods The distributed Features of 432 strains of infection germs detected among the patients with severe muhiple iniuries admitted into hospital from January 2004 to December 2006 were statistically analyzed during. Results In the total 432 strains,the G accounted for 62.9%(272/432),dominated mainly by pathogens including Pseudomonas aeruginosa,Acinetobacter baumanni I and Escherichia Coli.The G+accounted for 37%(160/432),mainly including Staphylococcus anreus,enterococci and coagulase negative staphylococcus (CNS).Mixed infection rate was 41.1%.The isolating rate of enterococci.CNS and Sten Matophilia was obviously upgraded. Conclusions The source of infection in patients with severity multiple injuries is Gram-negative bacterium,suggesting that surveillance of bacterial resistance and rational use of antimicrobial agents should be emphasized during clinical therapy.