Metagenomic next-generation sequencing for the diagnosis of fever of unknown origin in pediatric patients with hematological malignancy.

BACKGROUND AND AIMS: The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in identifying microbiological etiologies in pediatric patients with hematological malignancies undergoing fever of unknown origin (FUO). METHODS: A total of 147 children with hematological malignancy suffering febrile diseases without definite microbiological etiologies under conventional tests were enrolled. The clinical record, serum inflammatory biomarkers and mNGS results were analyzed. RESULTS: At least one microorganism was identified by mNGS in 112 of 147 patients (76.2 %). Two or more types of organisms were detected simultaneously in 35.7 % (40/112) of samples. Of the 112 cases with positive mNGS results, the reported microorganisms were considered as etiologies of fever in 50 (44.6 %) cases. The initial antimicrobial regimens were adjusted according to the mNGS results in 48 cases, with 41 patients' febrile diseases resolved. Totally, 27.9 % (41/147) of patients benefit from mNGS. High IL-6 (>390 pg/mL) level was associated with bacterial infection and could help to interpret the results of mNGS. CONCLUSION: mNGS is a novel approach to determine the microbiological etiology of FUO in hematological malignancy patients, which benefits about a quarter of all patients tested. Integration of IL-6 can improve the diagnostic precision of bacterial infection.

The Two-Component System RstA/RstB Regulates Expression of Multiple Efflux Pumps and Influences Anaerobic Nitrate Respiration in Pseudomonas fluorescens.

Multidrug resistance (MDR) efflux pumps are involved in bacterial intrinsic resistance to multiple antimicrobials. Expression of MDR efflux pumps can be either constitutive or transiently induced by various environmental signals, which are typically perceived by bacterial two-component systems (TCSs) and relayed to the bacterial nucleoid, where gene expression is modulated for niche adaptation. Here, we demonstrate that RstA/RstB, a TCS previously shown to control acid-induced and biofilm-related genes in Escherichia coli, confers resistance to multiple antibiotics in Pseudomonas fluorescens by directly regulating the MDR efflux pumps EmhABC and MexCD-OprJ. Moreover, we show that phosphorylation of the conserved Asp52 residue in RstA greatly enhances RstA-DNA interaction, and regulation of the multidrug resistance by RstA/RstB is dependent on the phosphorylation of the RstA Asp52 residue by RstB. Proteome analysis reveals RstA/RstB also positively regulates the efflux pump MexEF-OprN and enzymes involved in anaerobic nitrate respiration and pyoverdine biosynthesis. Our results suggest that, by coupling the expression of multiple efflux pumps and anaerobic nitrate respiration, RstA/RstB could play a role in defense against nitrosative stress caused by anaerobic nitrate respiration. IMPORTANCE Microenvironmental hypoxia typically increases bacterial multidrug resistance by elevating expression of multidrug efflux pumps, but the precise mechanism is currently not well understood. Here, we showed that the two-component system RstA/RstB not only positively regulated expression of several efflux pumps involved in multidrug resistance, but also promoted expression of enzymes involved in anaerobic nitrate respiration and pyoverdine biosynthesis. These results suggested that, by upregulating expression of efflux pumps and pyoverdine biosynthesis-related enzymes, RstA/RstB could play a role in promoting bacterial tolerance to hypoxia by providing protection against nitrosative stress.

EmhR is an indole-sensing transcriptional regulator responsible for the indole-induced antibiotic tolerance in Pseudomonas fluorescens.

Indole is well known as an interspecies signalling molecule to modulate bacterial physiology; however, it is not clear how the indole signal is perceived and responded to by plant growth promoting rhizobacteria (PGPR) in the rhizosphere. Here, we demonstrated that indole enhanced the antibiotic tolerance of Pseudomonas fluorescens 2P24, a PGPR well known for its biocontrol capacity. Proteomic analysis revealed that indole influenced the expression of multiple genes including the emhABC operon encoding a major multidrug efflux pump. The expression of emhABC was regulated by a TetR-family transcription factor EmhR, which was demonstrated to be an indole-responsive regulator. Molecular dynamics simulation showed that indole allosterically affected the distance between the two DNA-recognizing helices within the EmhR dimer, leading to diminished EmhR-DNA interaction. It was further revealed the EmhR ortholog in Pseudomonas syringae was also responsible for indole-induced antibiotic tolerance, suggesting this EmhR-dependent, indole-induced antibiotic tolerance is likely to be conserved among Pseudomonas species. Taken together, our results elucidated the molecular mechanism of indole-induced antibiotic tolerance in Pseudomonas species and had important implications on how rhizobacteria sense and respond to indole in the rhizosphere.

Effect of SMOF lipid on parenteral nutrition-associated cholestasis and other complications in premature infants / 中国小儿急救医学

Objective:To compare the effect of SMOF lipids composed of soybean oil, medium chain triglycerides, olive oil, and fish oil with medium-long chain mixed fat emulsions(Lipofundin) on parenteral nutrition-associated cholestasis(PNAC) in premature infants.Methods:Clinical data were collected from premature infants hospitalized in the neonatal intensive care unit of Shanghai Children′s Hospital from January 2018 to December 2019 with gestational age ≤34 weeks, birth weight ≤2 000 g, and duration of parenteral nutrition ≥14 days.They were devided into SMOF lipid group and Lipofundin group, and the incidence of PNAC, neonatal necrotizing enterocolitis(NEC), bronchopulmonary dysplasia(BPD), retinopathy of prematurity(ROP), periventricular-intraventricular hemorrhage(PVH-IVH), late-onset sepsis and liver function were compared between two groups.Results:The incidence of PNAC in the SMOF lipid group was significantly lower than that in Lipofundin group( P=0.042). The average level of ALT and AST in SMOF lipid group were markedly lower than those in Lipofundin group( P<0.05). The time to reach full enteral feeding of SMOF lipid group was shorter than that of Lipofundin group( P=0.005). There was no significant difference in the incidence of NEC, BPD, ROP, PVH-IVH, and late-onset sepsis between two groups( P>0.05). Conclusion:Compared with lipofundin, SMOF lipid can reduce the incidence of PNAC in premature infants, and has no significant effect on the incidence of NEC, BPD, ROP, PVH-IVH and late-onset sepsis.

A single dose SARS-CoV-2 simulating particle vaccine induces potent neutralizing activities

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for which a vaccine is urgently needed to control its spreading. To facilitate the representation of a native-like immunogen without being infectious, here, we reported a SARS-CoV-2 vaccine candidate (designated ShaCoVacc) by incorporating spike-encoding mRNA inside and decorating spike protein on the surface of the virus simulating particles (VSPs) derived from lentiviral particles. We characterized the mRNA copy number, glycosylation status, transduction efficiency, and innate immune property of the new vaccine platform. Importantly, we showed the ShaCoVacc induced strong spike-specific humoral immune responses and potent neutralizing activities by a single injection. Additionally, we disclosed the epitopes of spike-specific antibodies using peptide microarray and revealed epitopes susceptible to specific neutralizing antibodies. These results support further development of ShaCoVacc as a candidate vaccine for COVID-19 and VSP may serve as a new vaccine platform for emerging infectious diseases.

Research on the effect and mechanism of hepatoma cells HepG2 exosome on its own methylation / 医学研究生学报

ObjectiveThe prognosis of patients with advanced liver cancer is poor and there is no effective treatment so far. This paper observed the effect of hepatoma cells HepG2 exosomes on its own methylation and attempted to explore its mechanism.MethodsThere was experimental group and control group in the research. The medium has been changed when the cells grow to 60% in a DMEM culture dish with 10% serum. Cells in the control group were cultured in serum-free DMEM medium while the experimental group were cultured in serum-free DMEM medium added 100 L (0.5mg/mL) exosomes, and the supernatant was retained after incubation for 48h. HepG2 cells were cultured and exosomes were extracted by overspeed differential centrifugation, and identified by particle size analysis, transmission electron microscopy, Western blot and other methods. The effect of exosomes of hepatocellular carcinoma cells HepG2 on cell proliferation was analyzed by scratch test. Fluorescence antibody staining was used to observe the change of automethylation level. Fluorescence quantitative PCR was used to detect mRNA expression levels of methyltransferase-related genes DNMT3A, DNMT3B, DNMT1, and apoptosis-related genes Bax and BcI2.ResultsUnder inverted fluorescence microscope, red fluorescent exosomes could be seen entering the cell, surrounding the blue fluorescent nucleus or on the nucleus, indicating that DiI entered the cell membrane or cytoplasm. The area ratio of 6 and 12 h in the experimental group [(57.25±2.06, 83.92±3.17) %] was significantly higher than that in the control group [(28.32±1.22, 40.03±1.74) %] (P<0.05). The genes expressions of Bax, DNMT3A and DNMT3B in the experimental group were higher than those in the control group (P<0.05). The expression of BcI2 was lower than that of the control group (P<0.05).ConclusionThe exosomes of hepatoma cell HepG2 can enhance DNA methylation level by changing the transcriptional expression of DNMT3A, DNMT3B and other genes to affect the expression of apoptose-related genes Bax and BcI2, and to promote the proliferation and growth capacity of hepatoma cell HepG2.

Relationship between short chain fatty acids in faeces and digestive diseases in neonates / 国际儿科学杂志

With the deepening of study of neonatal intestinal flora metabolomics, the relationship between short-chain fatty acids(SCFA)and neonatal digestive diseases has become the focus of domestic and foreign scholars.Short-chain fatty acids have an important impact on the occurrence and development of digestive diseases such as neonatal necrotizing enterocolitis by inhibiting the immune response, suppressing allergic and inflammatory reactions and affecting intestinal mucosal innate immune function and mucosal development, which providing research ideas for the diagnosis and treatment of such diseases.

Inhibitory effect of resveratrol on MNNG-induced endometrial carcinogenesis based on estrogen metabolism regulation / 中国药理学通报

Aim To observe the changes of estrogens and their metabolites in endometrial cancer mice, and preliminarily explore its potential mechanism of action from the perspective of estrogen homeostasis regulation. Methods EC mouse model was induced by MNNGT. The mice were randomly divided into control group, Res group, MNNG group and MNNG + Res group. HE staining was used to determine tumorigene-sis. qPCR was used to detect the mRNA expression levels of Ccndl, CK-19 , Erbb2. E1, E2, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 16α-OHE2 2-OHE!, 4-OHEj, 2-OHE1 and 4-OHE1 in serum and litems of mice were detected by LC-MS/MS. Results The number of endometrial glands in MNNG group sig-nificantly increased, while the sulcus could be observed in the foci. MNNG + Res group had mild edema of the myometrium, and the endometrium tended to assume its normal state. The mRNA expressions of Cc-ndl and Erbb2 of MNNG group were significantly high-er than those in control group, significantly decreased after combined administration of Res. In MNNG group, the levels of 2-MeOE2, 2-MeOE, and 4-MeOE, in serum and uterine tissue samples significantly decreased, while the content of 4-OHE2 significantly increased . While after treatment with Res, the content of 2-MeOE2 and 2-MeOE1 in uterine tissue significantly increased, 4-MeOE, in serum tissue also increased significantly, while 4-0HE2 content markedly decreased in serum and uterine tissues. Conclusions For the imbalance of estrogen homeostasis in EC mice, res-veratrol can up-regulate the content of estrogen metabolite 2-MeOE2 , reduce the content of 4-OHE2, and in-hibit the development of EC.

Transcriptional Regulator PhlH Modulates 2,4-Diacetylphloroglucinol Biosynthesis in Response to the Biosynthetic Intermediate and End Product.

Certain strains of biocontrol bacterium Pseudomonas fluorescens produce the secondary metabolite 2,4-diacetylphloroglucinol (2,4-DAPG) to antagonize soilborne phytopathogens in the rhizosphere. The gene cluster responsible for the biosynthesis of 2,4-DAPG is named phlACBDEFGH and it is still unclear how the pathway-specific regulator phlH within this gene cluster regulates the metabolism of 2,4-DAPG. Here, we found that PhlH in Pseudomonas fluorescens strain 2P24 represses the expression of the phlG gene encoding the 2,4-DAPG hydrolase by binding to a sequence motif overlapping with the -35 site recognized by σ70 factors. Through biochemical screening of PhlH ligands we identified the end product 2,4-DAPG and its biosynthetic intermediate monoacetylphloroglucinol (MAPG), which can act as signaling molecules to modulate the binding of PhlH to the target sequence and activate the expression of phlG Comparison of 2,4-DAPG production between the ΔphlH, ΔphlG, and ΔphlHG mutants confirmed that phlH and phlG impose negative feedback regulation over 2,4-DAPG biosynthesis. It was further demonstrated that the 2,4-DAPG degradation catalyzed by PhlG plays an insignificant role in 2,4-DAPG tolerance but contributes to bacterial growth advantages under carbon/nitrogen starvation conditions. Taken together, our data suggest that by monitoring and down-tuning in situ levels of 2,4-DAPG, the phlHG genes could dynamically modulate the metabolic loads attributed to 2,4-DAPG production and potentially contribute to rhizosphere adaptation.IMPORTANCE 2,4-DAPG, which is synthesized by biocontrol pseudomonad bacteria, is a broad-spectrum antibiotic against bacteria, fungi, oomycetes, and nematodes and plays an important role in suppressing soilborne plant pathogens. Although most of the genes in the 2,4-DAPG biosynthetic gene cluster (phl) have been characterized, it is still not clear how the pathway-specific regulator phlH is involved in 2,4-DAPG metabolism. This work revealed the role of PhlH in modulating 2,4-DAPG levels by controlling the expression of 2,4-DAPG hydrolase PhlG in response to 2,4-DAPG and MAPG. Since 2,4-DAPG biosynthesis imposes a metabolic burden on biocontrol pseudomonads, it is expected that the fine regulation of phlG by PhlH offers a way to dynamically modulate the metabolic loads attributed to 2,4-DAPG production.

Study on correlation between serum Klotho protein level with vascular calcification in patients with chronic kidney disease / 重庆医学

Objective To investigate the correlation between serum Klotho protein level with vascular calcification in the pa-tients with chronic kidney disease (CKD) .Methods One hundred and seven inpatients with CKD in the nephrology department of the hospital from January 2014 to December 2014 were selected and 20 age-and sex-matched persons undergoing healthy physical examination served as the control group .Serum Klotho ptotein level was measured by ELISA .Abdominal aortic calcification(AAC) was assessed by abdominal lateral X-rays .Meanwhile the brachial arterial flow-mediated dilatation (FMD) and carotid intima-media thickness (cIMT) were determined by the color Doppler ultrasound .The difference of serum Klotho protein levels were compared between the CKD patients and healthy people .The relationship between the serum Klotho protein level with CKD-mineral and bone disorder (CKD-MBD) and vascular dysfunction such as vascular calcification ,.endothelial dysfunction and cIMT was investigated and its clinical significance was analyzed .Results Serum Klotho protein level and FMD in the CKD group were significantly lower than those in the control group ,while the cIMT and AAC scores were significantly higher than those in the control group .Serum Klotho level was significantly decreased along with the progression of CKD .Serum Klotho protein level were negatively correlated with the age(r= -0 .348 ,P< 0 .01) ,log iPTH (r= -0 .366 ,P< 0 .01) ,cIMT (r= -0 .192 ,P< 0 .05) and AAC score (r= -0 .251 ,P<0 .01) ,and positively correlated with eGFR (r=0 .387 ,P<0 .01) ,1 ,25-dihydroxyvitamin D3 level (r=0 .311 ,P<0 .01) and FMD (r=0 .190 ,P<0 .05) in the CKD patients .The Klotho protein level in the patients with FMD ≥6 .0 ,cIMT<1 .0 mm and AAC score=0 were significantly higher than those in the patients with FMD <6 .0 ,cIM T≥1 .0 mm and AAC score >0 . The multivariate Logistic regression analysis showed that age (OR=3 .63 ,95% CI:1 .75 -8 .89 ,P=0 .002) ,MBP (OR=2 .98 , 95% CI:1 .45-7 .69 ,P=0 .009) ,albuminuria (OR= 1 .97 ,95% CI:1 .16 -3 .73 ,P= 0 .022) ,serum Klotho protein level (OR=0 .60 ,95% CI:0 .39-0 .98 ,P=0 .007) were the independent predictive factors of vascular calcification .Conclusion Serum Klotho protein level in the CKD patients is significantly decreased along with CKD progression ;serum Klotho protein level decrease is an independent predictive factor of vascular calcification .

The inflammatory state and protein-energy wasting in the maintenance peritoneal dialysis population / 重庆医学

Objective To investigate micro-inflammatory state and protein-energy wasting (PEW) states in maintenance peritoneal dialysis(MPD) patients,then analysis of the correlation between them.Methods Ninty-six cases of MPD patients in this Hospital were selected from March 2012 to September 2015.The status of nutrition were assessed by Quantitative Subjective and global Assessment(SGA),malnutrition-inflammation score(MIS) and albumin(Alb),micro-inflammatory state was assessed by enzyme-linked immunoassay(ELISA) method serum hypersensitive c-reactive protein (hs-CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6).At the same time,various serological markers like serum Alb,serum total protein(TP),serum prealbumin(PA),hemoglobin(Hb),transferrin(TF),serum creatinine(Scr),urea nitrogen(BUN),cholesterol(Teh) were measured.Results The incidence of PEW in MPD patients was 36.50％,among which 62.86 ％ of them were over 65 years old,57.10％ were over 2 years of dialysis time and 40.00％ with diabetic nephropathy.MPD patients with hs-CRP＞5 mg/L accounted for 58.33％,of which over 65 year old accounted for 42.86％,MPD age longer than 2 years accounted for 60.71％,32.14％ of them with diabetic nephropathy.The proportion of diabetic nephropathy,average age,dialysis duration time,hs-CRP,TNF-α and IL-6 in PEW group were higher than non-PEW group(P＜0.05);BM,TP,Alb,PA,Hb,TCh,MAC and MAMC were lower ban non-PEW group(P＜0.05).Compared with the hs-CRP≤5 mg/L group,average age,the time of dialysis duration,TNF-α,IL-6 were higher and TP,Alb,PA,TF,Hb,the proportion of Kt/V≥1.72 were lower in the hs-CRP＞5 mg/L group.After the correction of age,sex,dialysis ages,it was found that the level of hs-CRP in MPD patients was negatively correlated with the level of Alb,PA,TF,Tch,Scr,TG;The level of IL-6 was negatively correlated with the levels of Alb,PA,TF,Tch,TG.The level of TNF-α in MPD patients showed different degrees of negative correlation with the leves of Alb,PA,TF,TG,Tch(all P＜0.05).Multivariate analysis showed that elderly,the time of dialysis duration,the microinflammatory state,and hypoalbuminemia were the independent risk factors of PEW.Conclusion PEW and micro-inflammatory state are very common in PHD patients.Patients with longer duration of dialysis,elderly or associated with diabetic nephropathy are more likely to suffer PEW and micro-inflammatory.Elderly,the time of dialysis duration,microinflammatory state,hypoalbuminemia are the independent risk factors of PEW.

Analysis and Treatment of Paclitaxel-induced Muscle Soreness / 中国药房

OBJECTIVE:To observe the occurrence of paclitaxel(PTX)-induced muscle soreness and therapeutic efficacy and safety of diclofenac sodium. METHODS:Among 84 patients with malignant tumor receiving PTX chemotherapy,56 patients suf-fered from PTX-induced muscle soreness,among which 22 female patients suffered from medium and severe muscle soreness and then were randomly divided into group A and B,with 11 cases in each group. Group A was given Diclofenac sodium sustained-re-lease tablet 75 mg orally,once a day;group B was given Paracetamol and tramadol hydrochloride tablets one tablet orally,once a day,and then given Promethazine hydrochloride injection 100 mg subcutaneously,2-3 times a day when muscle soreness could not be born. Treatment course of both groups lasted for 5 d. The distribution of muscle soreness were observed. The onset time and dura-tion of muscle soreness were also observed as well as pain relief and the occurrence of ADR in group A and B. RESULTS:Among 84 cases,the incidence of muscle soreness was 66.67%,among which mild pain accounted for 23.81%,moderate pain accounted for 13.10%,and severe pain accounted for 29.76%. Among 56 patients with muscle soreness,earliest muscle soreness occurred on the day of medication,and most of muscle soreness occurred on 1-3 days after medication,mainly manifesting as sore,activity limitation when severe,associated with fatigue. The pain relief rate of group A and B were 100%,but the incidence of adverse re-actions in group A was significantly lower than group B,with statistical significances(P<0.05).CONCLUSIONS:Diclofenac sodi-um is similar to paracetamol and tramadol hydrochloride in the treatment of PTX-induced muscle soreness,but it is better than paracetamol and tramadol hydrochloride in safety.

Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-κB signaling in macrophages and protecting endothelial cells.

Gouty arthritis is a rheumatic disease that is characterized by the deposition of monosodium urate (MSU) in synovial joints cause by the increased serum hyperuricemia. This study used a three-dimensional (3D) flowing microfluidic chip to screen the effective candidate against MSU-stimulated human umbilical vein endothelial cell (HUVEC) damage, and found kinsenoside (Kin) to be the leading active component of Anoectochilus roxburghi, one of the Chinese medicinal plant widely used in the treatment of gouty arthritis clinically. Cell viability and apoptosis of HUVECs were evaluated, indicating that direct Kin stimulation and conditioned medium (CM) from Kin-treated macrophages both negatively modulated with MSU crystals. Additionally, Kin was capable of attenuating MSU-induced activation of nuclear factor-κB/mitogen-activated protein kinase (NF-κB/MAPK) signaling, targeting IκB kinase-α (IKKα) and IKKß kinases of macrophages and influencing the expressions of NF-κB downstream cytokines and subsequent HUVEC bioactivity. Inflammasome NLR pyrin domain-containing 3 (NALP3) and toll-like receptor 2 (TLR2) were also inhibited after Kin treatment. Also, Kin downregulated CD14-mediated MSU crystals uptake in macrophages. In vivo study with MSU-injected ankle joints further revealed the significant suppression of inflammatory infiltration and endothelia impairment coupled with alleviation of ankle swelling and nociceptive response via Kin treatments. Taken together, these data implicated that Kin was the most effective candidate from Anoectochilus roxburghi to treat gouty arthritis clinically.

Effects of FAR on myocardial fibrosis of diabetic rats / 中国药理学通报

Aim To study the effects of Free Anthra-quinone from Rhubarb (FAR)on myocardial CTGF and collagen expression and interstitial fibrosis in dia-betic rats.Methods The male SD rats were randomly divided into normal group (CON),diabetic cardiomy-opathy group (DCM) and FAR treatment group (FAR).Streptozocin was intraperitoneally injected in-to the animals in the latter 2 groups to induce diabetic rat model.The model was expected to be stable for 2 weeks before the treatment.At the end of the 8th week in treatment,fasting plasma glucose and heart mass in-dex were measured.Masson staining was used to ob-serve the myocardial fibrosis.RT-PCR was used to de-tect the mRNA levels of CTGF,procollagen type Ⅰand collagen type Ⅲ.Immunohistochemical method was used to detect the content of CTGF.ELISA was used to detect the depositions of collagen type I and collagen type Ⅲ. Results Compared with CON group,fasting plasma glucose,heart mass index,the degree of myocardial fibrosis,and the expressions of CTGF,collagen type I and collagen type Ⅲ in left ven-tricular myocardial tissue of DCM group were signifi-cantly increased. However, compared with DCM group,fasting plasma glucose,heart mass index,the degree of myocardial fibrosis,and the expressions of CTGF,collagen type I and collagen type Ⅲ in left ven-tricular myocardial tissue of FAR-treated rats were sig-nificantly decreased.Conclusion FAR retards the process of myocardial fibrosis in diabetic rats by down-regulating the expression of CTGF,reducing the syn-thesis and depositions of collagen type I and collagen type Ⅲ.

Effect of sitagliptin on the expression of NO/iNOS in type 2 diabetic nephropathy / 中国生化药物杂志

Objective To investigate effect of sitagliptin ( SIT) on the expression of inducible nitric oxide synthase ( iNOS) and nitric oxide ( NO) in type 2 diabetic nephropathy.Methods 30 rats were randomly divided into normal group (NC group), diabetic nephropathy group (DN group) and sitagliptin treatment group (SIT group).The type 2 diabetes mellitus (T2DM) rats were induced by a high fat diet (HFD) plus repeated low dose streptozocin (STZ) injections.At the end of the 12th week in treatment,there were 6 rats in each group, the NO level was determined by Griess method.mRNA levels of iNOS RT-PCR was detect ed by.The expression of iNOS protein was detected by western blot and immunohistochemical method. ResuIts Compared with the NC group, the expression of iNOS and NO of DN group increased significantly.However, compared with DN group, the expression of iNOS and NO of SIT group decreased significantly.ConcIusion SIT can decrease the expression of iNOS and NO, which implies SIT may protect the type 2 diabetic kidney.

The role of acute hyperinsulinemia in the development of cardiac arrhythmias.

Patients with perturbed metabolic control are more prone to develop cardiac rhythm disturbances. The main purpose of the present preclinical study was to investigate the possible role of euglycemic hyperinsulinemia in development of cardiac arrhythmias. Euglycemic hyperinsulinemia was induced in conscious rabbits equipped with a right ventricular pacemaker electrode catheter by hyperinsulinemic euglycemic glucose clamp (HEGC) applying two different rates of insulin infusion (5 and 10 mIU/kg/min) and variable rate of glucose infusion to maintain euglycemia (5.5 ± 0.5 mmol/l). The effect of hyperinsulinemia on cardiac electrophysiological parameters was continuously monitored by means of 12-lead surface ECG recording. Arrhythmia incidence was determined by means of programmed electrical stimulation (PES). The possible role of adrenergic activation was investigated by determination of plasma catecholamine levels and intravenous administration of a beta adrenergic blocking agent, metoprolol. All of the measurements were performed during the steady-state period of HEGC and subsequent to metoprolol administration. Both 5 and 10 mIU/kg/min insulin infusion prolonged significantly QTend, QTc, and Tpeak-Tend intervals. The incidence of ventricular arrhythmias generated by PES was increased significantly by euglycemic hyperinsulinemia and exhibited linear relationship to plasma levels of insulin. No alteration on plasma catecholamine levels could be observed; however, metoprolol treatment restored the prolonged QTend, QTc, and Tpeak-Tend intervals and significantly reduced the hyperinsulinemia-induced increase of arrhythmia incidence. Euglycemic hyperinsulinemia can exert proarrhythmic effect presumably due to the enhancement of transmural dispersion of repolarization. Metoprolol treatment may be of benefit in hyperinsulinemia associated with increased incidence of cardiac arrhythmias.

Evaluation of postsurgical adhesion prevention using different formulated sodium hyaluronate membranes / 生物医学工程学杂志

The rat abdominal wall defect and cecal abrasion model was adopted in this study to investigate the anti-adhesion effect of different formulated sodium hyaluronate membranes. Both injured surfaces of abdominal wall and cecum in experiment groups A, B, and C were covered using the corresponding formulated membrane A (composed of sodium hyaluronate and chitosan), membrane B (sodium hyaluronate), and membrane C (composed of sodium hyaluronate and carboxymethyl chitosan), respectively. And no material was used in the surgical as control group. Seven days after the surgery, the grade and score of abdominal adhesion of rats were evaluated according to Phillips' and Nair's classification methods respectively. Then tissue samples were collected and prepared for histological examination. The rank sum tests of scores of adhesion between groups were carried out. It showed that there was no significant difference of adhesion scores among experimental group A and control group (P > 0.05). But the differences were statistically significant (P < 0.01) among group B or C and control group, which indicated the anti-adhesive effect of B formulation and C formulation sodium hyaluronate membranes. The histological examination showed in group A that there was heavy inflammatory cell invasion and necrosis in the newly formed adhesive fibrous tissue, especially in the zone of remaining membrane A. Normal injury healing process was observed in rat abdominal wall and cecal surface covered using membrane B or C. The A formulation sodium hyaluronate membrane had poor biocompatibility which resulted in no anti-adhesion effect. The prevention of adhesion formation by B formulation and C formulation sodium hyaluronate membranes were confirmed in this experiment and would be worthy of further exploitation.

Endovascular repair of a tuberculous aneurysm of descending thoracic aorta / 中华医学杂志(英文版)

Tuberculous aortic aneurysm (TBAA) is an extremely rare clinical event with life-threatening implication. Management for this condition is challenging and its therapeutic option has not been yet established. A few recent reports described endovascular repair rather than open surgery as the method for treatment. Although this remains controversial, endovascular exclusion has been gaining acceptance for some surgeons. We present a case of TBAA who was treated by endovascular stent grafting for a descending thoracic aortic aneurysm with simultaneous anti-tuberculous medication. The outcome was favorable.

Damage of nasal mucociliary movement after intensity-modulated radiation therapy of nasopharyngeal carcinoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Radiation usually results in paranasal sinusitis in patients with nasopharyngeal carcinoma (NPC), which influences patients' quality of life. This study aimed to determine the relationships between dose distribution in the nasal cavity and nasal mucous injury in patients with NPC treated by intensity-modulated radiation therapy (IMRT), and to find the tolerable radiation dose for the nasal mucous.</p><p><b>METHODS</b>Sixty-six patients with NPC treated by IMRT between October 2006 and November 2008 were enrolled. The irradiation dose in the nasal cavity was determined by the computer with the IMRT work platform. Mucociliary transport rate (MTR) was detected by modified saccharine test before IMRT, at the end of IMRT, and at 3, 6, and 12 months after IMRT.</p><p><b>RESULTS</b>The data were available for 129 nasal cavities. The cavities receiving a mean dose below or equal to 37 Gy showed substantial preservation of nasal mucous after IMRT. The MRT decreased to (62.82 ± 38.59)%, (56.78 ± 37.79)%, (64.05 ± 39.37)%, and (71.13 ± 39.55)% of pre-IMRT value at 4 time points after IMRT, with significant differences among the data (P < 0.05). In contrast, when the cavities received a mean dose higher than 37 Gy, no significant differences in MTR among the time points were observed. At 3 months after IMRT, the MTR was the lowest (38.27% of pre-RT value).</p><p><b>CONCLUSIONS</b>A mean radiation dose of ≤ 37 Gy for the nasal cavity is an optimal dose to protect the nasal cavity function.</p>

Inflammatory abdominal aortic aneurysm: clinical features and long term outcome in comparison with atherosclerotic abdominal aortic aneurysm / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Inflammatory abdominal aortic aneurysms (IAAAs) are rare but distinct clinical entities of atherosclerotic abdominal aortic aneurysms (aAAAs). In this study we report a 20-year single institution experience for IAAA and analyze their clinical features and long term outcome in comparison with aAAA.</p><p><b>METHODS</b>Between 1988 and 2008, 412 cases of abdominal aortic aneurysms (AAAs) underwent elective surgical operations, 11 (2.7%) of whom were diagnosed as IAAAs and 389 (94.4%) were diagnosed as aAAAs. The former group was matched in a case control fashion to a group of 33 patients with aAAAs having similar characteristics of age, gender, and preoperative risk factors. All available clinical, pathologic, and postoperative variables were retrospectively reviewed, and the two groups were compared.</p><p><b>RESULTS</b>The two groups did not differ significantly in clinical characteristics and preoperative risk factors, although patients with IAAAs were significantly more symptomatic (100% vs. 42.4%, P = 0.001) and had larger aneurysms on admission ((7.4 +/- 0.7) cm vs. (6.3 +/- 0.9) cm, P = 0.006). In IAAAs, the preoperative erythrocyte sedimentation rate was found to be significantly elevated compared to aAAA group ((44.5 +/- 9.1) mm/h vs. (11.4 +/- 5.4) mm/h, P < 0.05). Surgical morbidity and mortality rates did not differ between the two groups. The operation time for patients with IAAAs was significantly longer than that for patients with aAAAs ((308 +/- 36) minutes vs. (224 +/- 46) minutes, P < 0.05), but the cross-clamp time was similar in both groups ((41.5 +/- 6.2) minutes vs. (41.8 +/- 6.2) minutes, P = 0.92). A five-year survival rate analysis showed no significant difference between the two groups (P = 0.711).</p><p><b>CONCLUSIONS</b>Despite having more symptoms, larger size and longer operation time, patients with IAAA can now be treated with approaches that cause low morbidity and mortality, similar to patients with aAAA. Long term outcome of IAAA patients is of no difference from aAAA patients.</p>