ABSTRACT
Objective:To explore the etiological diagnostic value of metagenomic next-generation sequencing (mNGS) in peritoneal dialysis (PD)-related peritonitis.Methods:The study was a retrospective cohort study. The clinical data of patients with PD-related peritonitis who were treated and underwent microbial cultivation and mNGS test at the same time from June 2020 to July 2021 in the Affiliated Drum Tower Hospital, Medical School of Nanjing University were analyzed. The positive rate, detection time and consistency between mNGS test and traditional microbial culture were compared.Results:A total of 18 patients with age of (50.4±15.4) years old and median dialysis time of 34.0 (12.4, 62.0) months were enrolled in the study, including 11 males and 7 females. Pathogenic microorganisms were isolated in 17 patients by mNGS test, with a positive rate of 17/18, which was higher than 13/18 of microbial culture, but the difference was not statistically significant ( P=0.219). Both mNGS test and microbial culture isolated positive pathogenic bacteria in 12 patients, and mNGS test isolated the same types of pathogenic bacteria as microbial cultivation did in 11 patients. In five patients with negative microbial culture, mNGS test also isolated pathogenic microorganisms, including 3 cases of Staphylococcus epidermidis, 1 case of Mycobacterium tuberculosis and 1 case of Ureaplasma urealyticum. In 1 patient, microbial culture isolated pathogenic bacteria ( Escherichia coli) whereas mNGS test did not. The detection time of mNGS was 25.0 (24.0, 27.0) h, which was significantly shorter than 89.0 (72.8, 122.0) h of microbial culture ( Z=3.726, P<0.001). Conclusions:mNGS test can improve the detection rate of pathogenic microorganisms in PD-related peritonitis and greatly shorten the detection time, and has good consistency with microbial culture. mNGS may provide a new approach for pathogen identification of PD-related peritonitis, especially refractory peritonitis.
ABSTRACT
Objective:To study the differences of intestinal flora between neonatal rats with intrauterine hypoxia and healthy neonatal rats using high-throughput sequencing technology to determine the effects of intrauterine hypoxia on neonatal intestinal flora.Methods:Intrauterine hypoxia model were established in neonatal rats. On d1 and d7 after birth, intestinal samples were collected from intrauterine hypoxic group and normal control group and assigned into INH1 group (intrauterine hypoxia d1), INH7 group (intrauterine hypoxia d7), NOR1 group (normal control d1) and NOR7 group (normal control d7). 16S rRNA sequencing were conducted using these samples and the differences in the diversity, richness and composition of the flora among the groups were compared.Results:(1) The Alpha diversity of the intestinal flora in the INH1 group was higher than the NOR1 group. Specifically, both sobs and chao indices, representing the richness of the flora, in INH1 group were significantly higher than the NOR1 group (sobs index: 114.5±35.6 vs. 50.5±21.3, chao index: 135.6±38.5 vs. 73.9±28.8)( P<0.05). Compared with the NOR7 group, the mean values of sobs, ace, chao, simpson and shannon indices in the INH7 group showed no significant differences ( P>0.05). (2) At the phylum and genus level, the dominant bacterial groups in the intrauterine hypoxia group on d1 were firmicutes and streptococcus and proteus and escherichia for the normal control group. The difference of intestinal flora between intrauterine hypoxia group and the normal control group on d7 was smaller than the difference between the two groups on d1. Compared with INH1 group, the INH7 group had increased escherichia composition and decreased streptococcus composition. Conclusions:Intrauterine hypoxia changes the initial colonization and later affects the abundance and structural composition of the intestinal flora in newborn rats.
ABSTRACT
Myocardial dysfunction is an essential complication of sepsis and a significant cause of death in patients with sepsis.Sepsis has been shown to mediate myocardial dysfunction through multiple molecular pathways.With the application of technologies such as 16SrRNA and shotgun sequencing and the in-depth understanding of related pathophysiological mechanisms, it has been discovered that there is a complex interaction between gut microbiota and sepsis.Not only does sepsis change the gut microbiota, but the gut microbiota also widely affects the occurrence and development of sepsis.Some treatment methods based on gut microbiota are also considered to have good application prospects.In addition, intestinal microecology has been proved by a large number of studies to be related to various cardiovascular diseases.However, the current understanding of the mechanism by which the gut microbiota plays a role in sepsis-mediated myocardial dysfunction is still minimal.This article summarizes the pathophysiological mechanisms of sepsis, gut microbiota, and myocardial dysfunction that affect each other, which is helpful to deepen the understanding and thinking of researchers in the related fields.
ABSTRACT
Objective:To assess the prognostic value of modified Charlson comorbidity index (mCCI) combined with serum albumin for long-term prognosis in peritoneal dialysis (PD) patients.Methods:From January 1, 2007 to June 30, 2015, patients who started PD in Nanjing Drum Tower Hospital were enrolled in this retrospective cohort study. Clinical data including gender, age, underlying diseases, laboratory examination and prognosis were collected. The mCCI at the beginning of PD was calculated. Whether the duration of PD exceeded 5 years was used as an indicator to evaluate the prognosis. The patients were divided into≥5 years group and<5 years group according to the duration of PD, and the data were compared between the two groups. Cox regression model was constructed to analyze the influencing factors of all-cause death in PD patients. Multivariate logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the predictive value of mCCI and serum albumin levels on whether patients could maintain long-term PD.Results:Of the 183 patients included [males 106(57.9%), females 77(42.1%); (53.35±16.50) years old; 162 cases (88.5%) with hypertension, 55 cases (30.1%) with diabetes], 97 cases had PD duration for ≥5 years and 86 cases less than 5 years. The overall 5-year technical survival rate was 65.1%. At the beginning of PD, compared with the dialysis age≥5 years group, the patients in the dialysis age less than 5 years group had older age, higher mCCI, lower serum albumin level, and higher C-reactive protein (CRP) level (all P<0.05), but there were no significant differences in gender, education level, electrolyte, mean arterial pressure, high densitv lipoprotein (HDL), low-density lipoprotein (LDL) and PD adequacy index between the two groups (all P>0.05). Multivariate logistic regression analysis showed that increased age ( OR=1.022, 95% CI 1.000-1.043, P=0.046), increased mCCI ( OR=1.620, 95% CI 1.300-2.018, P<0.001) and decreased serum albumin ( OR=0.807, 95% CI 0.730-0.893, P<0.001) were independent predictors for the duration of PD<5 years. ROC curve analysis showed that the area under ROC curves ( AUC) of mCCI, serum albumin level and combined prediction probability of the two for the duration of PD<5 years were 0.647(95% CI 0.568-0.727), 0.655(95% CI 0.577-0.734), and 0.767(95% CI 0.700-0.835), respectively, indicating that the accuracy of combined parameters to predict survival outcome was higher than that of any single parameter. Multivariate Cox analysis showed that increased age ( HR=1.073, 95% CI 1.046-1.100, P<0.001), increased mCCI ( HR=1.198, 95% CI 1.044-1.375, P=0.010) and decreased serum albumin ( HR=0.904, 95% CI 0.843-0.969, P=0.004) were independent influencing factors for all-cause death in PD patients. Conclusions:Old age, high mCCI and low serum albumin level are influencing factors for dialysis age<5 years and all-cause death in PD patients. mCCI combined with serum albumin level can improve the accuracy of predicting the long-term dialysis in PD patients.
ABSTRACT
In recent years, morbidity of sepsis shows a rising trend and has become the leading cause of child death.Cardiac function suppression is the major cause of sepsis-related death.As a continuous inflammatory factor, damaged mitochondria can induce apoptosis of myocardium and lead to myocardial dysfunction.Mitophagy is one of the compensatory mechanisms for the inflammatory response caused by sepsis, and it can specifically remove damaged mitochondria caused by oxidative stress, calcium overload, and cell energy metabolism disorders, so as to maintain cell vitality and respiration, and to provide the body with sufficient ATP.The level of mitophagy in cardiomyocytes may be closely related to the outcome and prognosis of sepsis.The PINK1/Parkin and mitochondrial autophagy receptor (BNIP3L/NIX, FUNDC1, etc.) are the main mitophagy pathways.They can protect cardiomyocytes and improve repairing potential of myocardium by controlling the quality of mitochondria.This review focused on the research of progression on mitophagy regulatory mechanisms in recent years.It summarized the impact of mitophagy on myocardial of sepsis and the pathways of mitophagy, reviewed the mechanism of mitophagy on myocardial protection, provided some information for seeking molecules or target drugs on regulation of mitophagy and created new ideas for the prevention and treatment of myocardium damage induced by sepsis.
ABSTRACT
Objective@#To provide basis for early selection of drug intervention or surgical treatment for premature patent ductus arteriosus(PDA) by a dynamic monitoring of serum N-terminal pro-brain natriuretic peptide(NT-proBNP)levels with ultrasonic examination, so as to improve the prognosis of premature infants.@*Methods@#A total of 108 premature infants with gestational age less than 32 weeks and body weight less than 1.5 kg, within 24 h of birth were admitted to the Department of NICU, Harbin Children′s Hospital from June 2016 to December 2018.The serum NT-proBNP levels were measured at 3 d, 6 d, 9 d after birth, and echocardiography was performed at the same time.According to the results of echocardiography and clinical symptoms, infants were divided into haemodynamically significant PDA(hsPDA)(n=29), asymptomatic PDA(asPDA)(n=24)and non-PDA as control group(n=55). Among them, the hsPDA group was further divided into drug treatment group(n=21) and surgical treatment group(n=8). The surgical treatment group was those who failed 2 courses of oral ibuprofen treatment or had contraindications to drug treatment.Arterial catheter ligation was used for surgical treatment group on 9 to 21 days after birth.NT-proBNP levels were detected at 24 hours and 3 days after surgery, and echocardiography was performed at the same time.The levels of serum NT-proBNP were compared between the three groups and before and after the treatment, and the ROC curve of NT-proBNP was drawn to analyze its diagnostic value.@*Results@#(1) At 3 and 6 days after birth, serum NT-proBNP levels were 8 346 pg/ml and 3 340 pg/ml in the hsPDA group, and 2 536 pg/ml and 1 079 pg/ml in the asPDA group, 1 132 pg/ml and 879 pg/ml in the control group, respectively.The levels of NT-proBNP in the hsPDA group were significantly higher than those in the asPDA group(P<0.05), and the levels of NT-proBNP in the asPDA group were higher than those in the control group(P<0.05). At 9 days after birth, serum NT-proBNP levels were 2 231 pg/ml in the hsPDA group, 834 pg/ml in the asPDA group, and 808 pg/ml in the control group.The levels of serum NT-proBNP in the hsPDA group were significantly higher than those in the asPDA group and the control group (P<0.05). There was no significant difference between the asPDA group and the control group (P>0.05). (2)At 3, 6, and 9 d after birth, serum NT-proBNP levels were 9 000 pg/ml, 8 989 pg/ml, 9 000 pg/ml in the surgical treatment group, and 3 741 pg/ml, 2 544 pg/ml and 1 032 pg/ml in the drug treatment group, respectively.The levels of serum NT-proBNP in the surgical treatment group were significantly higher than those in the drug treatment group (P<0.05). The serum NT-proBNP levels in both drug treatment group and surgical treatment group were significantly lower than those before treatment (P<0.05). At 3 d after the operation, the serum NT-proBNP level was 941 pg/ml in the surgical treatment group and 736 pg/ml in the drug treatment group.There was no significant difference between the two groups (P>0.05). (3)At 3 d after birth, the area under the ROC curve of serum NT-proBNP was 0.91 (95%CI 0.865-0.964), and the sensitivity and specificity of NT-proBNP to diagnose hsPDA at 2 343.5 pg/ml were 93.1% and 73.41.% respectively.@*Conclusion@#NT-proBNP level monitoring can be used as a sensitive indicator for early identification of hsPDA, and it has a clinical significance for intervention strategy and intervention time selection.
ABSTRACT
Objective To provide basis for early selection of drug intervention or surgical treatment for premature patent ductus arteriosus(PDA) by a dynamic monitoring of serum N-terminal pro-brain natri-uretic peptide(NT-proBNP)levels with ultrasonic examination,so as to improve the prognosis of premature infants. Methods A total of 108 premature infants with gestational age less than 32 weeks and body weight less than 1. 5 kg,within 24 h of birth were admitted to the Department of NICU,Harbin Children′s Hospital from June 2016 to December 2018. The serum NT-proBNP levels were measured at 3 d,6 d,9 d after birth, and echocardiography was performed at the same time. According to the results of echocardiography and clin-ical symptoms,infants were divided into haemodynamically significant PDA(hsPDA)(n＝29),asymptomatic PDA(asPDA)(n＝24)and non-PDA as control group(n＝55). Among them,the hsPDA group was further divided into drug treatment group(n＝21) and surgical treatment group(n＝8). The surgical treatment group was those who failed 2 courses of oral ibuprofen treatment or had contraindications to drug treatment. Arterial catheter ligation was used for surgical treatment group on 9 to 21 days after birth. NT-proBNP levels were de-tected at 24 hours and 3 days after surgery,and echocardiography was performed at the same time. The levels of serum NT-proBNP were compared between the three groups and before and after the treatment,and the ROC curve of NT-proBNP was drawn to analyze its diagnostic value. Results (1) At 3 and 6 days after birth,serum NT-proBNP levels were 8 346 pg/ml and 3 340 pg/ml in the hsPDA group,and 2 536 pg/ml and 1 079 pg/ml in the asPDA group,1 132 pg/ml and 879 pg/ml in the control group,respectively. The levels of NT-proBNP in the hsPDA group were significantly higher than those in the asPDA group(P<0. 05),and the levels of NT-proBNP in the asPDA group were higher than those in the control group(P<0. 05). At 9 days after birth,serum NT-proBNP levels were 2 231 pg/ml in the hsPDA group,834 pg/ml in the asPDA group, and 808 pg/ml in the control group. The levels of serum NT-proBNP in the hsPDA group were significantly higher than those in the asPDA group and the control group (P<0. 05). There was no significant difference between the asPDA group and the control group (P>0. 05). (2)At 3,6,and 9 d after birth,serum NT-proBNP levels were 9 000 pg/ml,8 989 pg/ml,9 000 pg/ml in the surgical treatment group, and 3 741 pg/ml, 2 544 pg/ml and 1 032 pg/ml in the drug treatment group,respectively. The levels of serum NT-proBNP in the surgical treatment group were significantly higher than those in the drug treatment group (P<0. 05). The serum NT-proBNP levels in both drug treatment group and surgical treatment group were significantly lower than those before treatment ( P < 0. 05 ). At 3 d after the operation, the serum NT-proBNP level was 941 pg/ml in the surgical treatment group and 736 pg/ml in the drug treatment group. There was no signifi-cant difference between the two groups (P>0. 05). (3)At 3 d after birth,the area under the ROC curve of serum NT-proBNP was 0. 91 (95%CI 0. 865-0. 964),and the sensitivity and specificity of NT-proBNP to diagnose hsPDA at 2 343. 5 pg/ml were 93. 1% and 73. 41.% respectively. Conclusion NT-proBNP level monitoring can be used as a sensitive indicator for early identification of hsPDA,and it has a clinical signifi-cance for intervention strategy and intervention time selection.
ABSTRACT
Objective To investigate the effect of 1α, 25-dihydroxyvitamin D3 [1α,25-(OH)2 D3] on tumor necrosis factor-α ( TNF-α) induced activation of human umbilical vein endothelial cells ( HUVECs ) . The mechanism involved in this process was also studied. Methods HUVECs were cultured and treated with TNF-α( 40 ng/ml), 1α,25-(OH)2D3(10-8 mol/L), and SN50 as indicated. Vascular cell adhesion molecule (VCAM) and E-selectin were used as markers of endothelial activation, which were detected by Western blotting and realtime PCR (RT-PCR). NF-κB signaling pathway was investigated to study the mechanism. Western blotting, RT-PCR, immunofluorescence assay, and chromatin immunoprecipitation ( ChIP ) method were used to evaluate the effects of 1α,25-( OH) 2 D3 on its early activation, nuclear transport, and binding to VCAM and E-selectin promoters. Results (1) Western blotting and RT-PCR showed that TNF-α could significantly up-regulate the expression of VCAM and E-selectin in HUVECs, which can be inhibited by specific NF-κB blocker SN50. 1α,25-( OH) 2 D3 down-regulated the expression of VCAM and E-selectin induced by TNF-α. ( 2 ) Western blotting showed that TNF-α induces I-κBαphosphorylation, thereby activating NF-κB p65 subunit. Immunofluorescence showed that 1α, 25-( OH ) 2 D3 significantly inhibited the nuclear translocation of NF-κB p65 subunit. ChIP analysis revealed that 1α,25-( OH) 2 D3 inhibited the binding of NF-κB p65 to VCAM and E-selectin promoters and thus affected gene expression. Conclusions TNF-αenhanced the expression of E-selectin and VCAM in HUVECs via NF-κB signaling pathway. 1α,25-( OH) 2 D3 may inhibit NF-κB early activation, nuclear transport and the binding of NF-κB p65 to VCAM and E-selectin promoters, thereby inhibiting TNF-α-induced endothelial cell activation.
ABSTRACT
Objective To explore the potential mechanisms of low density lipoprotein receptor (LDLr) in high glucose peritoneal dialysis solution (PDS)-induced peritoneal fibrosis.Methods Human peritoneal mesothelial cells (PMCs) were applied.In pre-experiment,human PMCs were cultured with 1.5％ PDS,2.5％ PDS and 4.25％ PDS for 6 h,12 h and 24 h.4.25％ mannitol was used as high osmotic pressure control.In formal experiment,PMCs were divided into the control group (treated with phosphate buffer saline) and the high glucose PDS group (treated with 4.25％ PDS for 24 h).Morphological change of PMCs was observed by inverted microscope.The mRNA and protein expressions of extracellular matrix proteins such as α-smooth muscle actin (α-SMA),fibroblast specific protein-1 (FSP-1) and collagen Ⅰ in PMCs were respectively measured by real-time PCR and Western blotting.The lipid accumulation was observed by oil red O staining and filipin staining,and the content of intracellular cholesterol ester was detected by high-performance liquid chromatography.The co-expression of the sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) with golgin was observed with immunofluorescent staining.The mRNA and protein expressions of LDLr,SREBP-2 and SCAP were respectively detected by real-time PCR and Western blotting.The mRNA and protein expressions of mammalian target of rapamycin (mTOR),eukaryotic initiation factor 4E-binding protein 1 (4EBP1),and p70 S6 kinase (S6K1) were respectively detected by real-time PCR and Western blotting.Results (1) Compared with the 1.50％ PDS stimulation,4.25％ PDS for 24 h intervention significantly increased the expression of LDLr in PMCs (P ＜ 0.05),and high osmotic pressure control at 6 h,12 h and 24 h had no statistical difference (P ＞ 0.05).(2) Compared with those in the control group,in high glucose PDS group PMCs showed notable elongation consistent with the morphology of myofibroblasts,the expressions of α-SMA,FSP-1 and collagen Ⅰ were increased (all P ＜ 0.05),and the intracellular cholesterol were enhanced (P ＜ 0.05).Meanwhile,the co-expression of SCAP with golgin was enhanced,and the mRNA and protein expressions of LDLr,SREBP-2 and SCAP were up-regulated in high glucose PDS group (all P ＜ 0.05).Further,the mRNA and protein phosphorylation of mTOR,4EBP1 and S6K1 were increased (all P ＜ 0.05).Conclusions The disruption of LDLr feedback regulation is involved in high glucose PDS-mediated cholesterol accumulation in PMCs by mammalian target of rapamycin complex 1 (mTORC1) pathway,which promotes the accumulation of extracellular matrix and peritoneal fibrosis.
ABSTRACT
Objective To study the effect of WeChat follow-ups on the self-management ability and satisfaction of demand of the patients with home peritoneal dialysis. Methods We established a WeChat platform to implement the follow-ups to the patients with home peritoneal dialysis in our hospital. Sixty patients with regular peritoneal dialysis were enrolled. On the basis of the routine follow-ups at outpatient visits,telephone and family visits,the WeChat follow-ups were carried out.The comparison was carried out on the self-management ability and satisfaction of demand before the implementation and six months after the implementation. Results The total score and the scores on each dimension of the patients'self-management ability after the implementation were all significantly higher than those before the implementation (P<0.01).The patients'satisfaction of demand after the implementation was superior to the one before the implementation (P<0.01). Conclusion WeChat follow-ups improve the patients' ability in self-management and satisfaction of the patients'demand.
ABSTRACT
Objective To investigate clinical feature,therapy and prognosis of 63 (rhabdomyolysis,RM) patients.Methods Retrospective analysis was used for the 63 patients who were from Nanjing from Janurary 2010 to August of 2016.Results Clinical history:the pathogenic factors mainly contained eating lobster,excessive exercise,lipid-lowering drugs,and minority patients were induced by infection,cardiac defibrillation,alcohol,and unexplained factors.Clinical features:most patients presented different degree of muscle soreness and weakness,and urine color of soy sauce;and few patients manifested a fever,respiratory distress and sound hoarse.Of which 11 RM patients concurrent acute kidney injury (AKI),there was no obvious bias of pathogenic factors among 11 patients.Clinical examination:the data was described by median,including creatine kinase 6 400 U/L,aspartate aminotransferase 399 U/L,lactate dehydrogenase 816 U/L,α-hydroxybutyric acid 445 U/L,and myoglobin 1 200 ng/ml.Creatine kinase and myoglobin were selected to measure muscle injure,there was no significant difference among the groups (P ＞ 0.05).Renal tubular injury index such as urincosmotic pressure,urine retinol-binding protein and N-acetyl-beta-D-glucosaminidase (NAG) enzyme,the abnormal percentage were 62.5％,50％,and 47.6％.Treatment:patients without complications through resting,water infusion,urine alkalization,were cured;and 11 cases of patients with AKI,1 case gave up,5 cases underwent hemodialysis,and 5 cases underwent conservative treatment,creatinine decreased to the basic level.Conclusions Among different pathogenic factors of RM,there were no obvious differences in clinlcal symptom,muscle damage degree,and whether the coexistence of AKI and prognosis.The understanding of RM,early diagnosis and treatment would prevent AKI and improve the prognosis.
ABSTRACT
Objective To explore the clinical manifestations, electroencephalographic characteristics and therapeutic effect of drugs in children with Jeavons syndrome. Methods The clinical and electroencephalographic characteristics and thera-peutic effect of drugs were analyzed in 4 children with Jeavons syndrome. Results Among the four children there were 3 female and 1 male. The age at the onset of the disease was from 1 to 6 years. The typical clinical manifestations of this disease were brief, fast and repeated eyelid myoclonia (EM) with or without absence seizure. The typical electroencephalography (EEG) in two patients showed 3-6 Hz generalized spike and waves and polyspikes burst, and the eye closure and intermittent photic stimu-lation helped to induce discharges and clinical events. The typictal EEG in the other two patients showed 3.0-3.5 Hz generalizedδslow wave rhythm burst. The drugs of choice for treatment was sodium valproate monotherapy in two cases, levetiracetam in one case, sodium valproate combined with levetiracetam in one case. During the follow-up, seizures were controlled in one case, decreased in frequency in two cases and were still frequent in one case. Conclusions Jeavons syndrome is one of the idiopathic and generalized epileptic syndromes and characterized by EM with or without absence seizure. Video EEG monitoring plays an important role in the diagnosis of this disease. Sodium valproate and levetiracetam were effective for this disease.
ABSTRACT
ObjectiveToexploretheeffectof ceremideonprocess of peritoneal mesothelial cells(PMCs) apoptosis induced by peritoneal dialysis solution(PDS).Methods PMCs were cultured with normal DMEM,1.5％ PDS and 4.25％ PDS.4.25％ mannitol was used as high osmotic pressure control.Ceremide were detected by LC-MS-MS.Flow cytometry was used in apoptosis analysis.Bax,p53 and bcl-2 protein expressions were detected by Western blotting.Results (1) PDS caused the increase of intracellular ceremide in PMCs,and normal and high osmotic pressure controls had no such effect.As the acidic sphigomyelinase inhibitor,desipramine significantly inhibited the production of ceramide induced by 4.25％ PDS [(56.08±12.24) μg/L vs (91.25:t:15.89) μg/L,P＜0.01]. (2) Compared with 1.5％ PDS,4.25％ PDS stimulated PMCs apoptosis (26.65％±6.21％ vs 4.04％±1.86％,P＜0.01),up-regulated bax and p53 proteins expression (P＜0.01),and down-regulated bcl-2 protein exprssion(P＜0.05).Desipramine obviously inhibited the apoptosis induced by 4.25％ PDS,decreased bax and p53 proteins expression,increased bcl-2 protein expression(P＜0.05).Exogenous C2-ceremide reversed the effect of desipramine(P＜0.05).Conclusion The increase of intracellular ceremide may play an important role in the PMCs apoptosis induced by high glucose PDS.
ABSTRACT
In this review,firstly,it has been discussed the mechanisms of Chinese herbal medicine ameliorating glomerulosclerosis and renal interstitial fibrosis during the progression of chronic renal failure (CRF) by improving glomerular hemodynamics turbulence, podocyte injury, transforming growth factor (TGF)-beta over-expression, hyperlipidemia, macrophage infiltration, tubular epithelial myofibroblast transdifferentiation, and nephrotoxicity of proteinuria. Secondly,it has been reported the clinical effects of Chinese herbal medicine improving renal function and some clinical complications in the patients with progressive CRF through various treatments including oral administration or coloclysis of Chinese herbal medicine, oral administration combined with coloclysis of Chinese herbal medicine, and colonic dialysis combined with coloclysis of Chinese herbal medicine. Finally,it has been reviewed the beneficial influences of Chinese herbal medicine on metabolic dysequilibrium of calcium and phosphonium, microinflammatory state, and uremic toxins in patients with uremia.
Subject(s)
Animals , Humans , Drugs, Chinese Herbal , Therapeutic Uses , Kidney , Metabolism , Pathology , Kidney Failure, Chronic , Drug Therapy , Transforming Growth Factor beta , MetabolismABSTRACT
Objective To investigate the effects of extracellular-signal regulated kinase (ERK) on hypoxic-ischemic brain damage of neonatal rats.Methods The hypoxic-ischemic brain damage model of neonatal Wistar rats was established as following:first the right common carotid artery of the rats was ligated;2 h after operation,the rats began to inhale 8%-oxygen oxygen-nitrogen gas mixture lasting for 2 h.Rats were randomly divided into three groups:sham-group,hypoxic-ischemic group and ERK inhibitor PD98059 group (the rats were injected PD98059 2 mg/kg 10 min before the ligation).Six hours after the models were done,hippocampi and cortex of the ligation side of rats in the three groups were collected,and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured.Apoptosis of neuron was assessed by TUNEL staining.The expression of ERK1,ERK 2,Bcl-2 and Bax were examined by Western blot.The differences among the groups were analyzed with ANOVA and q test.Results Compared with the sham-group,the MDA level [(342.9± 10.8) μmol/L vs (181.5± 17.0) μmol/L,q= 6.35,P＜0.01) and the apoptosis rate of neuron [(18.80±1.37)% vs (3.53±0.34)%,q=6.06,P＜0.01) of hypoxic-ischemic group was higher,and SOD level was lower [(34.8±4.3) U/ml vs (63.4±4.3) U/ml,q=4.99,P＜0.01].While the apoptosis rate of neuron [(15.53±0.64) %] and MDA level [(252.0± 17.1) μmol/L] of PD98059 group were lower than those of hypoxic-ischemic group(q=3.87 and 5.28,P＜0.01respectively),the SOD level [(51.5 ± 3.8) U/ml] was higher than that of hypoxic-ischemic group (q=4.17,P＜0.01).There were no differences of ERK1 and ERK2 expressions among the three groups.The phosphorylated ERK1 and ERK2 levels of hypoxic-ischemic group were higher than those of sham-group (q=3.82 and 4.08,P＜0.01) and PD98059 group (q=4.79 and 5.12,P＜0.01).The expression of Bcl-2 and Bax of hypoxic-ischemic group were higher than those of sham-group (q=3.55 and 3.42,P＜0.01).Compared with hypoxic-ischemic group,Bcl-2 expression (q=3.71,P＜0.01) of PD98059 group was higher,and Bax expression (q=5.86,P ＜ 0.01) was lower.Conclusions ERK is involved in hypoxic-ischemic brain damage of neonatal rats through regulating the expression of apoptosis protein.
ABSTRACT
ObjectiveTo observe the influence of calcium - sensing receptor (CaSR) on Fas/Fas ligand (Fas L) pathway during anoxia/reoxygenation (A/R)- induced cardiomyocytes apoptosis in neonatal rat. MethodsSingle cells were dissociated from minced hearts of 2 - day - old Wistar rats with a 0. 25％ solution of crude trypsin and then cultured as monolayers at a density of 5 x 104cells/cm2 in DMEM medium equilibrated with humidified air containing 5％ CO2 at 37C. Three days after the cells were seeded, the cultured cardiomyocytes were randomly divided into three groups. ( 1 ) control group: cardiomyocytes were continuously cultured for 26 hours in DMEM medium.(2) A/R group: cardiomyocytes underwent anoxia for 2 hours and reoxygenation for 24 hours.(3) GdCl3 group: 300μmol/L GdCl3 was added to the culture medium at the beginning of reoxygenation. Apoptosis of cardiomyocytes was assessed by flow cytometer and morphological alterations were observed with transmission electron microscope.The expression of CaSR, Fas and Fas L were analyzed by Western blot.Results The result of flow cytometer showed that cardiomyocytes apoptosis was 12. 18％ ± 1.54％ in A/R group,and was higher than that in the control group (P ＜0. 01 ). At the same time, mitochondrial cristae dissolution and disappearance could be detected. Compared with A/R group, GdCl3, a specific activator of CaSR, further enhanced cardiomyocytes apoptosis to 20. 25％ + 2. 87％ ( P ＜ 0. 01 ), along with an increment in CaSR, Fas and Fas L expressions ( P ＜ 0. 05 ). ConclusionCaSR is closely involved in cardiomyocytes apoptosia during anoxia/reoxygenation. CaSR could induce apoptosis of neonatal rat cardiomyocytes through Fas/Fas L receptor pathway.
ABSTRACT
Objective To investigate the technique and effect of tunneled cuffed catheter as long-term hemodialysis access and the prevention of its related complications.Methods Permcath cuffed dual lumen catheter wag implanted in patients by the standard Seldinger technique,that a guidewire wss inserted into deep central vein, following by the insertion of the cuffed catheter through a peel-away sheath.The catheter related complications were observed.Urea reduce rate(URR),the Kt/V,the normalized protein catabolic rate(nPCR)and the time-averaged BUN concentration(TACurea)were measured as the index of the effect of hemodislysis.The effects were compared to those of arteriovenous fistula(AVF)within the same period(in 20 cases).Results In the total of 25 patients, 23 catheters were implanted in the internal jugular vein (21 cases at right,two at left side),one in the subclavian vein and one in the external jugular vein.Except for that one case died of cerebral infarction,all patients were using the catheter in well condition.Catheter related thrombosis or underfed occurred in 4 cases for 9 times, which became fluent after thrombolytic therapy or the adjustment of catheters.Catheter related infections occurred in 2 cases,and were successfully treated with anti-inflammation therapy.The average URR was 71.03%,Kt/V was 1.29,TAC urea was 12.74 mmol/L,and nPCR was 0.93 g/(kg·d)in all 25 patients,which was not significant different compared to patients with AVF((URR 72.46%,Kt/V 1.31,TACurea 12.86 mmol/L,nPCR 0.94 g/(kg·d)).Conclusions Cuffed dual lumen catheter for long-term aecegs in persistent hemodialysis has good effect on hemodialysis. Good catheter implanting technique and prevention of complications may improve the application of the catheter.
ABSTRACT
Objective Calcium-sensing receptor(CaSR)belongs to the family C of G-protein coupled receptors.This study was carried out to observe the influence and mechanism of CaSR on anoxia/reoxygenation(A/R)-induced cardiomyocytes apoptosis.Methods The model of A/R injury was established through anoxia for 2 hours and reoxygenation for 24 hours in cultured cardiomyocytes of neonatal rats.Cardiomyocytes were randomly divided into three groups:control group,A/R group and GdCl3 group(300μmol/L GdCl3 was added to the culture medium at the beginning of reoxygenation).Apoptosis of cardiomyocytes was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).The expression of CaSR,cysteine-requiring aspartate protease(caspase)-3,9 and cytochrom c (Cytc)were analyzed by Western blot.Results The TUNEL showed that cardiomyocytes apoptosis was 17%±3% in A/R group,and was higher than that in the control group.At the same time,expression of CaSR in A/R group was markedly increased in response to control group.Compared with A/R group,GdCl3,a specific activator of CaSR,further enhanced cardiomyocytes apoptosis to (28±4)% and decreased the ability of cardiomyocytes to (51.2±6.8)%,along with an increment in CaSR,caspase-3,caspase-9 and Cytc expressions.Conclusion CaSR is involved in anoxia/reoxygenation-induced apoptosis of neonatal rat cardiomyocytes through Cytc-caspase-3 pathway.
ABSTRACT
In the trials of multi-glycoside of Tripterygium wilfordii (GTW) in the field of pharmacodynamics, some clinical characteristics and symptoms, such as proteinuria, hematuria,joint pain, and skin damage, could be improved in the patients with various diseases including proliferative glomerulonephritis, lupus nephritis, rheumatoid arthritis, psoriasis and other immune-related diseases. In this review, it has been also reported to discuss the effects of GTW and Triptolide (T4), which is a bioactive component in GTW on anti-inflammatory, immunosuppression, and protection of epithelial cell in kidney. On the other hand, it is possible to have some beneficial effects on organ transplant rejection, tumor growth and anti-fertility.
Subject(s)
Animals , Humans , Biomedical Research , Drug Therapy , Drugs, Chinese Herbal , Pharmacokinetics , Therapeutic Uses , Pharmacology , Tripterygium , ChemistryABSTRACT
AIM: To explore the effects and possible mechanism of exogenous spermine on the apoptosis of primary cultured neonatal cardiomyocytes induced by simulated ischemia-reperfusion (I/R) injury. METHODS: To establish a model of simulated I/R, the primary cultured neonatal rat cardiomyocytes were incubated in ischemia-mimetic solution (under the conditions of hypoxia plus serum deprivation) for 2 h, and re-incubated the cells in normal culture medium for 24 h. The apoptotic cell death was assayed by flow cytometry. The morphological alterations of the cells were observed under transmission electron microscope. The transcription and expression of Fas and FasL were determined by the methods of RT-PCR, Western blotting and immunofluorescence. RESULTS: The cells exposed to I/R underwent significant apoptosis, and the percentage of apoptotic cells was 27.4%±1.8%, much higher than that in normal group (5.7%±0.3%). In I/R group the evident histopathological changes were observed and the myocardial transcription and expression of Fas and FasL were significantly upregulated. Compared to normal group, mRNA expression of Fas and FasL increased 2.2 folds and 2.4 folds, respectively, and their proteins increased 1.7 folds and 1.9 folds at 24 h of reperfusion respectively (P<0.01). Pretreatment with 10 μmol/L spermine significantly inhibited apoptosis of I/R injured cells, and the percentage of apoptotic cells was 21.7%±1.3% (P<0.01, as compared to I/P group). Spermine also suppressed the expression of Fas and FasL significantly (P<0.05 or P<0.01, as compared to I/P group). CONCLUSION: Spermine plays anti-apoptotic effect on the cultured neonatal myocardial cells under the condition of I/R injury by suppressing the expression of Fas/FasL.