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Objective:To evaluate the influencing factors of carotid-femoral pulse wave velocity (CF-PWV) and its value to predict outcomes in peritoneal dialysis (PD) patients.Methods:Eligible patients undergoing PD in Renji Hospital of Shanghai Jiao Tong University between August 2016 and July 2018 were recruited and prospectively followed up until death, PD cessation, or to the end of the study. CF-PWV was measured by an arterial pulse wave velocity meter to assess arterial stiffness (July 31, 2020). Overhydration was measured by bioimpedance spectroscopy. The patients were divided into CF-PWV≤10 m/s group and CF-PWV>10 m/s group according to the measured value of CF-PWV. The influencing factors of elevated CF-PWV were analyzed by multivariate logistic regression. Survival curves were generated using the Kaplan-Meier method and multivariate Cox proportional hazards models were used to analyze the difference for all-cause mortality and cardiovascular disease (CVD) mortality between the two groups.Results:A total of 224 PD patients were enrolled, including 133 males (59.4%). The age was (55.2±13.4) years old, and median PD vintage was 22.3(6.5, 59.3) months. Among them, 47(21.0%) patients were comorbid with diabetes, and 37(16.5%) patients had CVD history. The median CF-PWV was 9.6(8.4, 11.4) m/s for the cohort, and 105(46.9%) participants had CF-PWV over 10 m/s. Compared with CF-PWV≤10 m/s group, CF-PWV>10 m/s group patients had older age, increased percentage of diabetes and CVD (all P<0.05). Multivariate logistic analysis showed that increased age ( OR=1.070, 95% CI 1.043-1.099, P<0.001), diabetes ( OR=3.693, 95% CI 1.646-8.287, P=0.002) and higher overhydration ( OR=1.238, 95% CI 1.034-1.483, P=0.020) were independent influencing factors for elevated CF-PWV in PD patients. After followed up for 37.4(25.6, 41.7) months, 24 patients died, including 19 cases of CVD-related deaths. Kaplan-Meier survival analysis showed that all-cause mortality and CVD mortality were significantly higher in the CF-PWV>10 m/s group than those in CF-PWV≤10 m/s group (Log-rank χ2=6.423, P=0.011; Log-rank χ2=6.243, P=0.012, respectively). Multivariate Cox proportional hazards models showed that increased age was an independent influencing factor for both all-cause mortality and CVD mortality ( HR=1.057, 95% CI 1.010-1.107, P=0.018; HR=1.062, 95% CI 1.009-1.118, P=0.022). Conclusions:Increased arterial stiffness is relatively common in PD patients. Higher CF-PWV in PD patients is associated with increased age, diabetes and higher overhydration, and it is probably a valuable predictor of outcome in PD patients.
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Objective:To observe whether endoplasmic reticulum stress and NOD-like receptor protein 3 (NLRP3) inflammasome activation were involved in severe heat stroke induced intestinal mucosal injury and to investigate the potential protective effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA).Methods:Thirty male BALB/c mice were randomly (random number) assigned to 3 groups: the control group, heat stroke group (HS), and 4-PBA pretreatment group (4-PBA+HS, 4-PBA 120 mg/kg, intraperitoneal injection). Mice in the control group were placed at room temperature, while mice in the HS group and 4-PBA+HS group were placed in a prewarmed chamber [temperature (35.5±0.5) °C, humidity (60.0±5.0)%]. A rectal temperature (Tc) that reached 42 °C was considered to indicate severe heat stroke. The concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) in intestinal homogenate were analyzed by a colorimetric method, serum interleukin-1β (IL-1β) and interleukin-18 (IL-18) were assessed by ELISA, intestinal histopathology was evaluated by hematoxylin and eosin (HE) staining, intestinal ultrastructure was observed by electron microscopy, and the protein expression of GRP78, CHOP, NLRP3 and cleaved caspase-1 were analyzed by Western blot. Data were statistically analyzed by ANOVA test and LSD- t multiple comparison test if homogeneous variance, or analyzed by Welch test and Dunnett's T3 multiple comparison test if heterogeneous variance. Results:The concentration of MDA in the HS group was increased ( t=14.243, P<0.01), while SOD was decreased compared with that in the control group ( t=7.781, P<0.01), and the concentrations of serum IL-1β and IL-18 were significantly elevated ( t=12.664, P<0.01; t=16.240, P<0.01). Under light microscopy, extensive destruction of small intestinal villi and inflammatory cell infiltration were observed in the intestines of mice with severe heat stroke. Transmission electron microscopy showed that endoplasmic reticulum structures were significantly expanded, and mitochondria were vacuolated in the intestines of mice with severe heat stroke. Compared with those in the control group, the protein expression levels of GRP78, CHOP, NLRP3 and cleaved caspase-1 in the small intestine were elevated in the HS group ( t=14.824, P <0.01; t=12.667, P<0.01; t=9.298, P<0.01; and t=6.588, P=0.001). Compared with those in the HS group, mice in the 4-PBA pretreatment group exhibited reduced concentrations of MDA ( t=9.167, P<0.01), increased SOD ( t=6.077, P<0.01) , and reduced serum IL-1β and IL-18 levels ( t=4.889, P= 0.001; t=5.693, P<0.01). In addition, 4-PBA pretreatment significantly alleviated the pathological disruption and ultrastructural damage to small intestine tissues. Moreover, 4-PBA pretreatment reduced GRP78, CHOP , NLRP3 and cleaved caspase-1 protein expression ( t=9.080, P<0.01; t=7.152, P<0.01; t=4.249, P=0.005; t=3.650, P=0.011). Conclusions:Endoplasmic reticulum stress and NLRP3 inflammasome are involved in intestinal mucosal injury induced by severe heat stroke. 4-PBA plays a protective role by alleviating endoplasmic reticulum stress and NLRP3 inflammasome activation.
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Objective:To investigate the predictive value of peritoneal protein clearance (Pcl) for cardiovascular events and cardiovascular mortality in peritoneal dialysis (PD) patients.Methods:Eligible PD patients were prospectively enrolled from January 2014 to April 2015 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University. All patients were followed up until death, withdrawing from PD, transferring to other centers, or the end of study period (October 1, 2018). The patients were divided into high Pcl group and low Pcl group by the median Pcl, and the differences of related indicators between the two groups were compared. A multiple linear regression model was used to analyze the influencing factors of Pcl. The Kaplan-Meier method and Log-rank test were used to compare the cumulative survival rates of patients between the two groups. A multivariate Cox regression model was used to estimate the risk of cardiovascular events and cardiovascular mortality in relation to Pcl in PD patients.Results:A total of 271 patients were enrolled, with 135 males (49.8%), age of (56.92±0.84) years old and a median PD duration of 38.77(19.00, 63.10) months. There were 70 patients (25.8%) comorbiding with diabetes and 81 patients (29.9%) with cardiovascular diseases (CVD). The median Pcl of this cohort was 67.93(52.31, 88.36) ml/d. Compared with the low Pcl group (Pcl<67.93 ml/d), the high Pcl group (Pcl≥67.93 ml/d) had older age, and greater proportion of CVD, body mass index (BMI), pulse pressure, brain natriuretic peptide, mass transfer area coefficient of creatinine (MTACcr), and lower serum albumin (all P<0.05). There was no significant difference in gender, dialysis duration, proportion of diabetes, proportion of angiotensin converting enzyme inhibitor and angiotensin receptor blocker, proportion of continuous ambulatory PD, high sensitivity C reactive protein, fluid removal including 24 h urine volume and 24 h ultrafiltration, and residual renal function between the two groups (all P>0.05). Multiple linear regression analysis showed that serum albumin ( β=-0.388, P<0.001), BMI ( β=0.189, P<0.001), and MTACcr ( β=0.247, P<0.001) were independently related to lg(Pcl). During the study period, 55 patients experienced one or more cardiovascular events and 39 patients had cardiovascular mortality. According to Kaplan-Meier analysis, cardiovascular mortality in the high Pcl group was higher than that of low Pcl group (Log-rank χ2=6.902, P=0.009). Multivariate Cox regression analysis showed that, high lg(Pcl) was an independent influencing factor of cardiovascular events in PD patients ( HR=7.654, 95% CI 1.676-34.945, P=0.009). Conclusions:Serum albumin, BMI and MTACcr are independently associated with Pcl, and Pcl is an independent predictor of cardiovascular events in PD patients.
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Objective To investigate the role of BMP-2/Smad signaling pathway in the osteogenic differentiation of human aortic smooth muscle cells (HASMCs) caused by hyperphosphatemia -induced calcium phosphate (CaP) crystals.Methods High-phosphate medium was incubated at 37℃ for 3 days.CaP crystals and supernatant were isolated by ultracentrifugation.Scanning electron microscope and energy dispersive X-ray spectroscopy were performed for analysis of physicochemical characteristics of CaP crystals.HASMCs were cultured in vitro,and divided into high-phosphate,control,crystals and supernatant groups.Calcification was visualized by Alizarin red staining.Calcium loads in cells were quantified by o-cresolphthalein complexone method.Protein expression of bone morphogenetic protein-2 (BMP-2),Runt-related transcription factor 2 (RUNX2),osteopontin (OPN),phospho-Smad1/5/9 (p-Smad1/5/9) were quantified by Western blotting.After knockdowns of BMP-2 and Smad1 with small hairpin RNA (shRNA) interfering respectively in HASMCs,protein expressions were measured by Western blotting.Results High-phosphate medium induced the formation of CaP crystals.Compared with the cells in control group,CaP crystals significantly induced HASMCs calcification,increased calcium loads and up-regulated the levels of BMP-2,RUNX2 and OPN proteins (all P ＜ 0.05).After the addition of CaP crystals into HASMCs,the level of p-Smad 1/5/9 protein peaked at 30 min (P ＜ 0.05).After BMP-2 was knocked down in HASMCs,the expression of p-Smad1 caused by CaP crystals was blocked completely,and the expressions of RUNX2 and OPN caused by CaP crystals were reduced significantly (all P ＜ 0.05).After Smad1 was knocked down in HASMCs,the expressions of RUNX2 and OPN caused by CaP crystals were decreased significantly (all P ＜ 0.05).Conclusions Hyperphosphatemia-induced CaP crystals promoted osteogenic differentiation of HASMCs through the BMP-2/Smad signaling pathway.
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Objective To investigate the factors affecting the efficacy of leflunomide combined with medium/low dose corticosteroids in the treatment of progressive IgA nephropathy (IgAN).Methods Clinical and pathological parameters were collected retrospectively in patients of primary IgAN with proteinuria＞ 1.0 g/24 h and chronic kidney disease (CKD) stage 1-3 treated with leflunomide combined with medium/low dose corticosteroids in Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University from Jan 2005 to Dec 2010.According to the treatment effects,patients were divided into complete remission group and non-complete remission group.The biochemical and pathological indexes of the two groups were compared.Results A total of 42 patients were included.The remission rates at 3,6,9 and 12 months were 62％,64％,67％ and 74％,respectively.Seventeen (40.5％) and fourteen (33.3％) patients achieved complete and partial remission after one-year treatment,and the remission rate remained stable within one year after withdrawal of drugs.The 24hour proteinuria was 1.50 (0.67,2.66) g,which was significantly reduced compared with the baseline 2.44 (1.36,3.74) g (P ＜ 0.01).The decrease rate was 31.3％.There was a slight decrease in proteinuriawithin one year after withdrawal of drugs.Estimated glomerular filtration rate (eGFR) remained stable during the treatment and a year of follow-up.No serious adverse event was observed during the followup period.Among 31 responder patients,6(19.4％) patients relapsed.Logistic multivariate regression analysis suggested that the degree of renal interstitial inflammatory infiltration was an independent predictor of complete remission with one-year treatment of leflunomide combined with medium / low dose corticosteroids (HR=0.067,95％ CI 0.008-0.535,P=0.011).Conclusions IgAN treated with leflunomide and medium/low dose corticosteroids can achieve remission in early stage,and the remission rate remains stable after withdrawal of drugs.It is a safe option for the treatment of IgAN.Renal interstitial inflammatory infiltration is an independent predictor of complete remission.
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Objective To investigate the incidence of left ventricular hypertrophy (LVH) in peritoneal dialysis (PD) patients with different hydration statuses,and analyze the risk factors of LVH in PD patients.Methods PD patients in Renji Hospital,Shanghai Jiao Tong University School of Medicine from September 2016 to January 2017 were enrolled.Demographic data of patients were collected and biochemical parameters were measured.Hydration status index overhydration (OH) was measured by bioimpedance spectroscopy,and LVH was diagnosed by echocardiography.Logistic regression was used to analyze the risk factors of LVH.Results A total of 113 PD patients aged 58.98(48.89,65.33) years with median PD duration 46.20(18.08,72.75) months were enrolled in present study,among whom 60 patients (53.1％) had LVH.OH ＞ 1.1 L was detected in 80 patients (70.8％),among whom 34 patients (42.5％) had subclinical overhydration (SCOH).LVH was however diagnosed in 33(71.7％) clinical overhydrated (COH) patients and 17(50.0％) SCOH patients (n=34).In the normal hydrated (OH≤1.1 L) patients (n=33),LVH was detected in 10 patients (30.3％).Multivariate logistic regression showed that high OH (OR=1.730,95％CI 1.274-2.348,P ＜ 0.001) and low hemoglobin (OR=0.965,95％CI 0.940-0.991,P=0.008) were the independent risk factors of LVH.Conclusions LVH is common in PD patients,especially in overhydrated patients.High OH and low hemoglobin were the independent risk factors of LVH.
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Objective To investigate the expression of miR-424* in 2 and 4 Gy X-ray irradiated A549 cells in vitro and in vivo,as well as in clinical lung tissues and serum sample of non-small cell lung cancer(NSCLC) patients,and to explore its potential role in the diagnosis and prognosis of lung cancer.Methods A549 cells were irradiated with 2 and 4 Gy X-rays,and some of irradiated cells were injected into nude mice through tail vein.Real time quantitative PCR (RT-qPCR) assay was employed to detect the expression of miR-424 * in 2 and 4 Gy X-ray irradiated A549 cells in vitro and in vivo,as well as in clinical lung tissues and serum sample of lung cancer patients.Results Compared with the control group,the expression of miR-424* was up-regulated significantly in X-ray irradiated A549 cells at 1,2,12,24 and 48 hpost irradiation,respectively (2 Gy:t =-45.886--6.709,P ＜0.05;4 Gy:t =-29.087--7.833,P ＜ 0.05).Furthermore,the expression of miR-424 * was up-regulated in the lung and serum of nude mice with injection of 0,2 and 4 Gy X-ray irradiated A549 cells,compared with control group (fold change was 9.72,8.58 and 4.7 with 2 Gy irradiation and 11.93,9.22 and 8.99 with 4 Gy irradiation,t=-13.243,-12.409,-9.833 in lung andt=-6.436,-3.052,-3.609 in serum,respectively,P ＜ 0.05).Out of 11 tissue samples of NSCLC patients,6 were detected with up-regulated miR-424* expression,and no significant discrepancy of miR-424* expression was detected in two type of NSCLC tissue samples.On the contrary,43 serum samples were detected with up-regulated miR-424* expression out of 84 serum samples (51.20％) of NSCLC patients (fold change range 1.97 to 17.71),and significant discrepancy of miR-424* expression was shown in two subtypes of NSCLC serum samples [adenocarcinoma:39.10％ (18/46) and squamous carcinoma:65.8％ (25/38)],as well as in serum samples of NSCLC patients with radiotherapy [41.5％ (22/53)] and without radiotherapy [67.7％ (21/31)] (t=5.919,5.387,P ＜0.05,respectively).Conclusions 2 and 4 Gy X-ray irradiation could up-regulate the expression of miR-424* in A549 cells,which might be correlated with the enhanced metastasis of A549 cells induced by X-ray in vivo and in vitro.Furthermore,the expression of miR-424* was up-regulated in over 50％ of the tissue and serum samples of NSCLC patients,which might be correlated with the diagnosis of NSCLC subtype and prognosis of radiotherapy.
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Objective To investigate the microbiological trends and antibiotic susceptibility of peritoneal dialysis(PD)-related peritonitis (PDAP).Methods All patients who developed PDAP between 2004 and 2015 in Renji Hospital,Shanghai Jiao Tong University School of Medicine were enrolled.Demographic data,results of dialysate pathogen culture and drug susceptibility test were recorded.The trend of peritonitis incidence was measured by Poisson regression and the chi-square test or Fisher exact test method was used to compare the composition of causative organisms and their antimicrobial susceptibilities over time.Results During the study period,a total of 711 episodes of PDAP were occurred in 386 patients.The culture positive rate of pathogens rose from 52.0％ in 2004 to 77.0％ in 2015 (P ＜ 0.001).The distribution of causative organisms of the culture positive peritonitis was gram-positive bacteria (270,59.5％),followed by gram-negative bacteria (129,28.4％),polymicrobial(39,8.6％),fungi (15,3.3％) and mycobacteria (1,0.2％).From 2004 to 2015,the incidence of peritonitis decreased from 0.214 to 0.160 episodes/patient·year (P=0.034).The incidence of coagulase-negative staphylococcus peritonitis decreased from 0.049 to 0.027 episodes/patient · year (P=0.025),while others had no significant change;A significant decline was observed in the sensitivity of Gram-positive strains to the first generation cephalosporin and ampicillin/sulbactam in 2010-2015 group compared with those in 2001-2009 group (61.3％ vs 88.2％,P ＜ 0.001;61.7％ vs 85.5％,P=0,001),whereas the sensitivity to vancomycin remained the same.The sensitivity of Gram-negative strains to ceftazidime and amikacin showed no significant change.As for the gram-positive peritonitis treated with cefradine as empirical treatment,compared with those in 2004-2009 group,in 2010-2015group the proportion of patients requiring to change their treatment regime was significantly higher,and the treatment course was longer.Conclusions A gradual decline is observed in the incidence of PDAP and the culture positive rate of pathogens improves.Peritonitis caused by coagulase-negative staphylococcus decreases overtime.The present empirical treatment protocols may need re-evaluation considering the decreased rate of the first generation cephalosporin sensitivity in recent years.
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Objective · To explore influencing factors associated with the hydration status in peritoneal dialysis (PD) patients.Methods · Eligible PD patients treated in Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine from September 2016 to January 2017 were enrolled.Demographic data of patients were collected and biochemical indexes were measured.Their peritoneal transport characteristics and dialysis adequacy were evaluated.Hydration status index overhydration (OH) value was measured with bioimpedance spectroscopy.Multivariate linear regression was used to analyze the independent factors associated with the OH.Results · A total of 147 PD patients with a median age of 58.52 years and a median PD duration of 43.03 months were enrolled.Of them,90 (61.2％) were male,21(14.3％) were accompanied by diabetes mellitus,and 107 (72.8％)were overhydrated (OH＞1.1L).Compared to those with normal hydration status (OH ≤ 1.1 L),the overhydrated patients had higher proportion of diabetes,BSA,Charlson comorbidity score,brain natriuretic peptide (BNP),4 h D/Pcr,and 24 h dialysate protein,and lower tKt/V,serum albumin than the normal hydrated patients (all P＜0.05).Multivariate linear regression showed that comorbid diabetes mellitus (P=0.000),higher 4h D/Pcr (P=0.000),and lower serum albumin level (P=0.001) were independent relevant factors for the increase of OH.Conclusion· Overhydration is common in PD patients.Comorbid diabetes mellitus,higher 4 h D/Pcr,and lower serum albumin are independent relevant factors for the hydration status in PD patients.
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Objective To investigate the expression of miR-520d-3p in 2 and 4 Gy X-ray irradiated A549 cells, serum samples of non-small cell lung cancer (NSCLC) patients and its significance. Methods Real time quantitative PCR (RT-qPCR) was employed to detect the expression miR-520d-3p in 2 and 4 Gy X-ray irradiated A549 cells in vitro. Besides, 0, 2 and 4 Gy X-ray irradiated A549 cells were used to prepare animal model of nude mice lung metastasis through mainline. The expressions of miR-520d-3p and lung tissue of nude mice were detected, and the serum samples of NSCLC patients were collected to test the expression of miR-520d-3p . Results Compared with the control group ( 0 Gy ) , the expression of miR-520d-3p was up-regulated significantly in 2 and 4 Gy X-ray irradiated A549 cells after 48 hours (1.00±0.03, 1.47±0.10, 1.84 ±0.09 respectively), and there was a significant difference (F= 94.350, P= 0.000). Furthermore, compared the control group with injection after 10 weeks, the expressions of miR-520d-3p in nude mice lung tissue in 0, 2 and 4 Gy X-ray irradiated groups were increased (2.33 ±0.13, 8.24 ±0.25, 3.46 ±0.14, respectively) (F=1.787, P= 0.227), and the expressions in serum were increased (11.43±2.30, 10.22±4.62, 8.99 ±3.67, respectively) (F= 1.547, P= 0.246). Out of 20 serum samples of NSCLC patients (including 10 cases of adenocarcinoma, 10 cases of squamous carcinoma ), 11 cases (55%) were detected with up-regulated miR-520d-3p expression. Conclusions 2 and 4 Gy X-ray could increase the expression of miR-520d-3p of A549 cells in vitro and in vivo, which might be correlated with the enhanced invasion and metastasis of A549 cells induced by X-ray in vitro and in vivo. Furthermore, the expressions of miR-520d-3p were increased significantly in over 50%serum samples of NSCLC patients, which might be a new marker for the diagnosis of NSCLC.
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Objective To explore the effect of soluble tyrosine kinase 2 fusion protein (sTie-2-Fc) on peritoneal angiogenesis, solute transport and ultrafi]tration capacity in uremic rats undergoing peritoneal dialysis (PD). Methods Thirty-two male Wistar rats were randomly divided into sham-operation group, uremic group, uremic PD group, and sTie-2-Fc group (all n=8).Uremic PD group and sTie-2-Fc group received intraperitoneal infusion of 3 ml/100 g of peritoneal dialysis fluid (PDF) containing 4.25% glucose twice daily for 4 weeks. Rats in sTie-2-Fc group were infused with PDF supplemented with 1 μg sTie-2-Fc. Before the rats were sacrificed, a peritoneal equilibration test (PET) was performed to evaluate the peritoneal solute transport and ultrafiltration capacity, and omenta was obtained for anti-CD31 immunohistochemical staining to determine the vessel density. Results Compared to their counterparts in sham-operation group,rats in uremic group had higher 2 h-dialysate to plasma creatinine concentration ratio (D/Pcr, 0.78±0.05 vs 0.70±0.09, P=0.028), lower 2 h to initial dialysate glucose concentration ratio (D/D0, 0.69±0.05 vs 0.76±0.07, P=0.033), decreased peritoneal ultrafiltration [UF, (2.29±0.50) ml vs (4.58±1.64) ml, P=0.005], and increased omental vessel density [(5.8±3.0)/HP vs (1.6±0.5)/HP, P＜0.01]. When compared to uremic group, rats in uremic PD group showed higher D/Pcr (0.89±0.05 vs 0.78±0.05, P=0.001), lower D/D0 (0.47±0.09 vs 0.69±0.05, P＜0.01), decreased UF [(0.40±0.59) ml vs (2.29±0.50) mi, P=0.005] and more omental vessels [(16.7±1.2)/HP vs (5.8±3.0)/HP, P＜0.01]. Improved peritoneal UF [(1.56±0.48) ml vs (0.40±0.59) mi, P=0.014] and decreased omental vessels [(9.2± 1.2)/HP vs (16.7 ± 1.2)/HP, P＜0.01] were observed in rats treated with sTie-2-Fc compared with those in uremic PD group, however, the differences of D/Pcr (0.87±0.06 vs 0.89±0.05, P=0.122) and D/D0 (0.60±0.11 vs 0.47±0.09, P=0.06) between these two groups did not reach statistical significance. Conclusion sTie-2-Fc preserves peritoneal ultrafiltration capacity and ameliorates peritoneal angiogenesis caused by uremia and exposure to bioincompatibal PDF.