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Objective:To evaluate the value of preoperative serum miRNA-146a-5p expression in predicting postoperative delirium (POD) in the pediatric patients undergoing living donor liver transplantation.Methods:Eighty pediatric patients with congenital biliary atresia, aged 5-12 months, with body mass index of 4-10 kg, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective living donor liver transplantation in our hospital, were selected. Venous blood samples were collected at 1 day before surgery, and serum miRNA-146a-5p expression was detected by quantitative real-time polymerase chain reaction. The children′s cognitive function was evaluated using the Mini-Mental State Examination and the Modified Montreal Cognitive Assessment at 1 day before operation and at 1, 3 and 7 days after operation. The pediatric patients were divided into POD group and non-POD group according to whether POD occurred within 7 days after surgery. Multiple logistic regression analysis was used to evaluate the relationship between serum miRNA-146a-5p expression and POD, Pearson′s correlation analysis was used to analyze the correlation between miRNA-146a-5p and POD, and the receiver operating characteristic curves were used to evaluate the accuracy of serum miRNA-146a-5p concentrations in predicting the occurrence of POD.Results:There were 30 cases in POD group and 50 cases in non-POD group, and the incidence of POD was 38%. The results of multiple logistic regression analysis showed that down-regulated serum miR-146a-5p expression was an independent risk factor for POD in pediatric patients undergoing living donor liver transplantation ( P<0.05). The incidence of POD was negatively correlated with serum miRNA-146a-5p expression ( r=-0.658, P<0.001). The area under the receiver operating characteristic curve of serum miRNA-146a-5p expression in predicting POD was 0.870 in pediatric patients undergoing living donor liver transplantation, with a sensitivity of 0.825 and a specificity of 0.875. Conclusions:Preoperative serum miRNA-146a-5p expression has a certain predictive value for POD in the pediatric patients undergoing living donor liver transplantation.
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Objective:To evaluate the effect of patent foramen ovale (PFO) on the perioperative complications and survival rate in pediatric patients undergoing living donor liver transplantation.Methods:The medical records from pediatric patients of either sex with biliary atresia, aged<18 yr, who underwent living donor liver transplantation from January 2020 to January 2022, were retrospectively collected. The pediatric patients were divided into PFO group and non-PFO group according to the results of echocardiography before operation. The postreperfusion syndrome, acute lung injury, acute kidney injury, postoperative delirium and 1-year survival rate were recorded.Results:There was no significant difference in the incidence of postreperfusion syndrome, acute lung injury, acute kidney injury, postoperative delirium and one-year survival rate between PFO group and non-PFO group ( P>0.05). Conclusions:PFO has no obvious effect on the incidece of intraoperative and early postoperative complications and 1-year survival rate in pediatric patients undergoing living donor liver transplantation.
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Objective:To identify the risk factors for postreperfusion syndrome (PRS) during living donor liver transplantation in pediatric patients with biliary atresia.Methods:The clinical data from pediatric patients who underwent living donor liver transplantation from January 2020 to December 2021 in our hospital were retrospectively analyzed. The clinical data included: (1) general information of the pediatric patients such as age, gender, height and body weight; (2) preoperative data such as left ventricular ejection fraction, pediatric end-stage liver disease score, serum aminotransferase, aspartate aminotransferase, total bilirubin, International Normalised Ratio and creatinine concentrations, and whole blood Hb concentration; (3) intraoperative data such as vital signs and blood gas analysis parameters immediate before reperfusion, time of anhepatic phase, donor liver cold ischemia time, transplanted liver quality, time of surgery, anesthesia time, volume of urine, blood loss, amount of blood transfused, and amount of fresh frozen plasma transfused. The pediatric patients were divided into PRS group and non-PRS group according to whether intraoperative PRS occurred. Risk factors for PRS were analyzed using binary logistic regression analysis.Results:A total of 304 pediatric patients were finally enrolled, with 132 cases in PRS group and 172 cases in non-PRS group. The incidence of PRS was 43.4%. The results of logistic regression analysis showed that prolonged liver graft cold ischemic time ( OR=1.031, 95% confidence interval 1.021-1.042, P<0.001) and body temperature <36 ℃ immediately before reperfusion ( OR=3.095, 95% confidence interval 1.656-5.785, P<0.001) were risk factors for PRS. Conclusions:Body temperature immediately before reperfusion<36.0 ℃ and prolonged liver graft cold ischemic time are risk factors for PRS during living donor liver transplantation in pediatric patients with biliary atresia.
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Objective:To investigate the association between remnant cholesterol (RC) and the risk of diabetic retinopathy (DR) in middle-aged and older individuals with diabetes.Methods:Based on the Shanghai Nicheng Cohort Study database, the data of 1 255 individuals with diabetes aged 55-70 years at baseline (2013-2014) with complete fundus photographs and serum cholesterol data in Nicheng, Shanghai, were analyzed. Multinomial logistic regression models were used to evaluate risk ratios ( RRs) and their 95% confidence intervals ( CIs) between baseline RC level and incident DR. Results:The median age of the subjects was 61.9 years, and 60.4% were women. After a 4.6-year follow-up, 79 (6.3%) patients developed DR, including 50 (4.0%) mild non-proliferative DR and 29 (2.3%) referable DR (RDR). Multivariable logistic regression showed that each mmol/L increase of RC was associated with a 40% higher risk of RDR ( RR=1.40, 95% CI 1.03-1.90). Compared with the lowest tertile of RC (<0.63 mmol/L), the risk of RDR in the highest tertile (≥0.85 mmol/L) increased by 4.59 times ( RR=5.59, 95% CI 1.51-20.73). Conclusion:The RC level may help identify individuals at high risk of incident RDR in middle-aged and older Chinese adults with diabetes.
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Objective:To compare the myocardial protection in pediatric patients undergoing living-donor liver transplantation (LDLT) performed under propofol- versus desflurane-based anesthesia. Methods:Sixty American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ pediatric patients of both sexes, aged 5-24 months, weighing 5-15 kg, scheduled for elective LDLT under general anesthesia, were divided into 2 groups ( n=30 each) using a random number table method: propofol group (group P) and desflurane anesthesia group (group D). During anesthesia maintenance, propofol 5-10 mg·kg -1·min -1 was intravenously infused in group P, desflurane 0.65 MAC-1.30 MAC was inhaled in group D. At 5 min after induction of anesthesia, at 1 h of reperfusion, at the end of surgery, at 1, 2, 3, 7 and 14 days after surgery, and on the day of discharge, the concentrations of serum high-sensitivity cardiac troponin I, creatine kinase isoenzyme, N-terminal pro-B-type natriuretic peptide were determined by enzyme-linked immunosorbent assay, the occurrence of nausea and vomiting, agitation, and shivering, postoperative tracheal extubation time, intensive care unit stay time, and postoperative length of hospital stay were recorded within 24 h after surgery. Results:Compared with group P, the concentrations of serum high-sensitivity cardiac troponin I and creatine kinase isoenzyme were significantly decreased after surgery, the extubation time and intensive care unit stay time were shortened ( P<0.05), and no significant change was found in serum N-terminal pro-B-type natriuretic peptide concentrations, postoperative length of hospital stay and incidence of postoperative adverse effects at each time point in group D ( P>0.05). Conclusions:Desflurane has better myocardial protection than propofol in pediatric patients undergoing LDLT, which is helpful for early prognosis.
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The paper reports two cases of lipoprotein glomerulopathy (LPG) in children. The Sanger sequencing results in 2 cases indicated apolipoprotein E gene mutation[c.127 (exon3) C>T, p.R43C (p.Arg43Cys); c.494 (exon4) G>C, p.R165P (p.Arg165Pro),respectively]. Renal pathological presentation of two children showed that a large number of lipoprotein emboli were formed in the glomerular capillary loop, and the diagnosis of LPG was confirmed. The onset of LPG has no specific clinical manifestation, which is easy to be undiagnosed or misdiagnosed. Renal biopsy is a diagnostic means, glucocorticoid treatment is ineffective, and long-term lipid-lowering treatment may be required for LPG.
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Objective:To analyze the clinical and prognosis of primary membranous nephropathy (PMN) in children with positive glomerular M-type phospholipase A2 receptor (PLA2R).Methods:A total of 69 children diagnosed with PMN by renal biopsy admitted to the Department of Pediatrics of Eastern Theater Command General Hospital from January 2006 to December 2018 were retrospectively analyzed, including 40 males and 29 females, with an average age of 14.86 years.According to the immunofluorescence of renal pathology, they were divided into PLA2R positive group and PLA2R negative group.Pathological features between 2 groups were compared by the t test, Mann- Whitney U test and Chi- square test.Kaplan-Meier method was used to compare the long-term renal survival rate and cumulative remission rate between 2 groups. Results:A total of 69 pediatric PMN patients were included.The po-sitive rates of serum anti-PLA2R antibody and positive expression of PLA2R in renal tissues were 53.6% (37 cases) and 82.6% (57 cases), respectively.The proportion of children with clinical manifestations of large proteinuria [55 cases(96.5% ) vs.9 cases(75.0%), P=0.034] was significantly higher in the PLA2R positive group than that of the PLA2R negative group.Blood urea nitrogen level was significantly higher in the PLA2R positive group than that of PLA2R negative group[1.14(0.93, 1.54) mg/L vs.0.80 (0.44, 1.18) mg/L, P=0.049], while estimate glomerular filtration rate(eGFR) [162.26 (139.81, 185.53) mL/(min·1.73 m 2) vs.199.52 (157.58, 212.01) mL/(min·1.73 m 2), P=0.034] and serum IgG [3.58 (2.50, 5.43) g/L vs.5.14 (4.35, 6.03) g/L, P=0.016] were significantly lower.The cumulative remission rate was significantly higher in the PLA2R negative group than that of PLA2R positive group ( P<0.001). The 24 h urinary protein ≥50 mg/kg ( HR=0.119, 95% CI: 0.021-0.595, P=0.010)was an independent risk factor for renal prognosis, and PLA2R( HR=0.263, 95% CI: 0.125-0.551, P<0.001) and 24 h urinary protein ≥50 mg/kg ( HR=0.568, 95% CI: 0.125-0.551, P=0.041)were independent predictors of urinary protein remission.PLA2R ( HR=1.020, 95% CI: 0.698-1.682, P=0.656)was not associated with renal prognosis. Conclusions:The severity of PMN in children with positive PLA2R was higher than that in those with negative PLA2R.The long-term cumulative remission rate of PLA2R negative children with PMN was higher than that of PLA2R positive children.
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Objective:To evaluate the relationship between serum exosomes and microglial pyroptosis during brain injury in a young rat model of hepatic ischemia-reperfusion (I/R).Methods:Forty-six clean-grade healthy male Sprague-Dawley rats, aged 2-3 weeks, weighing 40-60 g, were allocated into 4 groups using a random number table method: sham operation group (group S, n=10), hepatic I/R group (group I/R, n=13), treatment with serum exosome in sham-operated young rat group (group S-Exosome, n=10), and treatment with serum exosomes in young rats with I/R group (group I/R-Exosome, n=13). The common trunk of the portal vein, left hepatic artery and bile duct was clamped for 60 min resulting in ischemia of 70% of the liver in anesthetized animals.After 6 h of reperfusion, the serum was collected to extract exosomes in S group and I/R group, and the serum exosome suspension 100 μl of S group and I/R group was injected through the tail vein in S-Exosome group and I/R-Exosome group, respectively.The expression of serum exosome marker proteins CD9 and CD81 was determined by Western blot in S group and I/R group.Serum and hippocampi were obtained from each group at 6 h after the corresponding treatment.The expression of NOD-like receptor protein 3 (NLRP3), gasdermin D (GSDMD), pro-caspase-1, cleaved-caspase-1, and apoptosis-associated speck-like protein containing CARD (ASC) in the hippocampus was detected using Western blot, and the expression of GSDMD in hippocampal tissues was determined by immunohistochemistry.The levels of interleukin-1beta (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) in serum and hippocampal tissues and S100β and NSE in serum were determined by enzyme-linked immunosorbent assay.In group I/R-Exosome, 3 rats were selected, and their serum exosomes were extracted, labeled with PKH26 red fluorescence and then injected via the tail vein, and the co-localization between exosomes and microglia was identified by immunofluorescence technique. Results:Compared with group S, the expression of serum CD9 and CD81 was significantly up-regulated in group I/R, the expression of NLRP3, GSDMD, cleaved-caspase-1 and ASC in hippocampal tissues was significantly up-regulated, the levels of IL-18, IL-1β and TNF-α in serum and hippocampal tissues and S100β and NSE in serum were increased in I/R and I/R-Exosome groups ( P<0.05), and no significant change was found in the parameters mentioned above in group S-Exosome ( P>0.05). The positive expression of GSDMD was significantly increased in I/R and I/R-Exosome groups ( P<0.05), no positive expression of GSDMD was found in S and S-Exosome groups ( P>0.05), and the results of immunofluorescence showed the co-localization between exosomes and microglia. Conclusions:The mechanism by which hepatic I/R induces brain injury may be related to serum exosomes-mediated microglial pyroptosis in young rats.
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Objective:To analyze the clinical and pathological characteristics in children diagnosed with primary focal segmental glomerulosclerosis (FSGS) after repeated renal biopsy.Methods:The clinicopathological data of children who ever experienced renal biopsy in Jinling Hospital from January 1, 2000 to December 31, 2020 were retrospectively reviewed. Clinical manifestations, pathological characteristics and treatment responses were analyzed.Results:Of the 34 enrolled patients, there were 22 males and 12 females. The median age of the first renal biopsy was 14 years old (1-18 years old), and the median interval between repeat renal biopsy and first renal biopsy was 6 months (1-151 months). Thirty-one showed nephrotic syndrome, of which 22 had microscopic hematuria, and 4 had elevated serum creatinine. Among the other 3 patients, 2 had hematuria and proteinuria, and 1 had proteinuria. In the first renal biopsy, 16 cases were diagnosed as minimal change disease, 14 cases were diagnosed as mesangial proliferative glomerulonephritis, 2 cases were diagnosed as IgA nephropathy, and 2 cases were diagnosed as IgM nephropathy. All 34 children showed poor responses to hormone and immunosuppressive therapies. The pathological features of the first renal biopsy in some patients were adhesion (2/34), decreased loop podocyte attachment (2/34), peripheral loop extension to the urinary pole (2/34), renal tubular reflux (4/34), capillary thrombosis (2/34) and IgM deposition (12/34).Conclusions:The initial diagnosis of FSGS is difficult, and the lesions are atypical and easily misdiagnosed. The patients have poor responses to hormone and immunosuppressive therapies. For patients with the pathological changes of adhesion, decreased loop podocyte attachment, peripheral loop extension to the urinary pole, renal tubular reflux, capillary thrombosis and IgM deposition, follow-up is required, and if necessary, repeat renal biopsy needs be performed to determine whether it is FSGS.
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Objective:To examine influencing factors for social support satisfaction among disabled elderly people at home in rural areas and to provide evidence for policies on further improving the level of social support and the quality of care for disabled elderly people.Methods:We conducted a self-administered questionnaire survey with 211 disabled elderly people, using a random sampling method in 6 villages and towns in the Southern, Northern and Guanzhong areas of Shaanxi province from June to October 2020.An ordinal logistic regression model was adopted to analyze influencing factors for social support satisfaction among the participants.Results:The survey results indicated that, of the 211 disabled elderly people, 49(23.22%)were unsatisfied with social support, 110(52.13%)were generally satisfied, and 52(24.65%)were satisfied.Ordinal logistic regression analysis showed that the degree of disability, the number of chronic diseases, with or without hospitalization in 2019, the most important daily caregiver, the time needed to the nearest medical institution, and relationships with family members were important factors influencing social support satisfaction for disabled elderly people(all P<0.05).For the elderly with disability, female, a low degree of disability, no hospitalization in 2019, the spouse as the most important caregiver, and a short time needed to the nearest medical institution tended to be associated with a high level of social support satisfaction( OR=2.07, 71.52, 30.75 and 19.22, respectively).Poor relationships with family members were associated with a low level of social support satisfaction( OR=0.39). Conclusions:The satisfaction of disabled elderly people with social support is at a moderate level.For elderly people with disability, the degree of disability, the number of chronic diseases, recent hospitalization, the most important daily caregivers, the time needed to the nearest medical institution, and relationships with family members are important influencing factors for social support satisfaction.
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Objective:To evaluate the effect of hepatic ischemia-reperfusion (I/R) rats-derived exosomes on microglial pyroptosis.Methods:Twenty clean-grade healthy male Sprague-Dawley rats, aged 2-3 weeks, weighing 20-50 g, were divided into 2 groups ( n=10 each) using a random number table method: sham operation group (group S) and hepatic I/R group (group I/R). The serum of rats in S group and I/R group was collected, and exosomes were isolated from the sera using differential centrifugations.Microglial cells were co-cultured with PKH26-labeled exosomes for 6 h. The intake of exosomes in microglial cells was determined using immunofluorescence staining.Primary microglial cells were seeded onto 6-well culture plates at a density of 5×10 5 cells/ml and were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), 10 7 cells/ml I/R-exosomes treated group (group 10 7), 10 8 cells/ml I/R-exosomes treated group (group 10 8), and 10 9 cells/ml I/R-exosomes treated group (group 10 9). Microglia in each group were co-cultured with the corresponding concentration of I/R-exosomes for 6 h. The expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cleaved-caspase-1 and gasdermin-D (GSDMD) was detected using Western blot.Primary microglial cells were divided into 3 groups ( n=24 each) by a random number table method: control group (group C), sham operation-exosomes treated group (group S-exosome) and I/R-exosomes treated group (group I/R-exosome). In S-exosome group and I/R-exosome group, exosomes 10 8 cells/ml in S group and I/R group were given, respectively, to incubate cells for 6 h. The expression of NLRP3, ASC and GSDMD mRNA was determined by real-time polymerase chain reaction, and the levels of interleukin-18 (IL-18), IL-1β and tumor necrosis factor-alpha (TNF-α) in the cell culture supernatant were measured by enzyme-linked immunosorbent assay. Results:The results from immunofluorescence staining showed that I/R-exosomes colocalized with microglia.The 10 8 cells/ml I/R-exosomes and 10 9 cells/ml I/R-exosomes up-regulated the expression of NLRP3, ASC, GSDMD and cleaved-caspase-1 in microglial cells ( P<0.01). Compared with group C and group S-exosome, the expression of NLRP3, ASC and GSDMD mRNA in microglial cells was up-regulated, and the levels of IL-18, IL-1β and TNF-α in the supernatant were elevated in group I/R-exosome ( P<0.01). Conclusions:Hepatic I/R rats-derived exosomes can promote microglial pyroptosis.
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Objective:To investigate the efficacy and safety of Rituximab (RTX) in treating children with refractory steroid-resistant nephrotic syndrome (SRNS).Methods:The clinical data of 10 children with refractory SRNS receiving RTX in the Department of Pediatrics, Jinling Hospital from September 2013 to March 2018 were analyzed retrospectively.Results:The age of onset of 10 children (including 5 males and 5 females) was (4.47±2.75) years old.The renal biopsy showed focal segmental glomerular sclerosis in 5 cases (50%), minimal change nephropathy in 3 cases (30%), IgM nephropathy in 1 case (10%), and mesangial proliferative glomerulonephritis in 1 case (10%). Ten children received RTX treatment (1 or 4 doses; 375 mg/m 2 once; maximum: 500 mg) at the age of (6.74±2.62) years old.There were 8 patients (80%) receiving a single dose of RTX, 1 patient (10%) receiving 3 doses, and 1 patient (10%) receiving 8 doses.The follow-up time was 11.93 (5.17, 25.66) months.The remission rates at the 3-month follow-up, 6-month follow-up and last follow-up were 30% (3 patients), 40% (4 patients), and 40% (4 patients), respectively.The 24-hour urinary proteinuria and serum albumin levels were improved in 10 children after RTX treatment, but there were no significant statistical difference(all P>0.05). No significant difference was found in humoral immunity and renal function before and after RTX treatment (all P>0.05). During the treatment and follow-up, 3 patients (30%) developed infusion reaction, 2 patients (20%) showed severe pulmonary infection, and 1 patient (10%) died of severe pulmonary infection. Conclusions:RTX is effective in treating some children with refractory SRNS, and a long-term follow-up should be conducted to prevent infection.
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Objective:To evaluate the effect of propofol postconditoning on retinoblastoma protein (Rb)-E2F1 signaling pathway in hippocampal neurons in a rat model of oxygen-glucose deprivation and restoration (OGD/R).Methods:Pregnant Wistar rats at 16-18 days of gestation were sacrificed, and the hippocampal neurons of fetal rats were obtained and primarily cultured for 7 days.The neurons were divided into 3 groups ( n=42 each) using a random number table method: control group (group C), OGD/R group (group O) and propofol postconditoning group (group P). In group O, the neurons were subjected to oxygen-glucose deprivation for 1 h, followed by restoration of oxygen-glucose.In group P, propofol (final concentration 1.2 μg/ml) was added immediately after restoration of oxygen and glucose, and the cells were cultured for 2 h and then the culture medium was replaced with plain culture medium.At 24 h of culture, the expression of p-Rb and E2F1 was determined by Western blot, and the cell cycle and apoposis rate were assessed by flow cytometry. Results:Compared with group C, the apoptosis rate was significantly increased, expression of p-Rb and E2F1 was up-regulated, the ratio of p-Rb nuclear/plasmosin protein and the proportion of neurons in G 0/G 1 phase were decreased, and the proportion of neurons in S and G 2/M phases was increased in O and P groups ( P<0.05). Compared with group O, the apoptosis rate was significantly decreased, expression of p-Rb and E2F1 was down-regulated, the ratio of p-Rb nuclear/plasmosin protein and the proportion of neurons in G 0/G 1 phase were increased, and the proportion of neurons in S and G 2/M phases was decreased in group P ( P<0.05). Conclusion:The mechanism by which propofol postconditioning decreases the apoptosis in hippocampal neurons is related to inhibiting Rb-E2F1 signaling pathway in a rat model of OGD/R.
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Objective:To determine the characteristics of changes in postoperative early lung ultrasound imaging in pediatric patients undergoing living-related liver transplantation.Methods:A total of 96 pediatric patients of both sexes, aged 3-24 months, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with Child-Pugh grade B or C, scheduled for elective living-related liver transplantation performed with the piggy back technique, were selected.At 24 h before surgery (T 0), at 24 h after surgery (T 1) and at 72 h after surgery (T 2), the condition of lung ultrasound was recorded.Ultrasound examination was performed using Color Doppler ultrasound diagnostic instrument with a linear array probe (frequency 7-13 MHz). The lung was divided into 12 areas, and each area of both lungs was scanned successively.The lung ultrasound score in each area was recorded.The results with the highest scores were considered as the ultrasound results of this area.The general conditions of the pediatric patients were recorded and the fluid volume (input minus output) per kilogram per minute was calculated. Results:Compared with the values at T 0, the scores for lung consolidation and the pulmonary edema in lateral area were significantly increased at T 1, and the scores for lung consolidation, pulmonary edema and pleural effusion in posterior area and total score for lung consolidation, pulmonary edema and pleural effusion in each area were increased at T 1, 2 ( P<0.05). Compared with the values at T 1, the scores for lung consolidation in posterior area and total score for lung consolidation in each area were significantly decreased, and the scores for pulmonary edema in lateral and posterior areas and total score for pulmonary edema in each area were decreased at T 2 ( P<0.05), and no significant change was found in the lung ultrasound scores in anterior area at each time point ( P>0.05). Compared with the values in anterior area, the scores for lung consolidation at each time point were significantly increased, scores for pulmonary edema at T 1, 2 were increased, and score for pleural effusion at T 1 was increased in lateral area, and scores for lung consolidation, pulmonary edema and pleural effusion at each time point were increased in posterior area ( P<0.05). Compared with the values in lateral area, the scores for lung consolidation, pulmonary edema and pleural effusion at each time point were significantly increased in posterior area ( P<0.05). Conclusion:Lung consolidation, pulmonary edema and pleural effusion tend to occur in the lateral and posterior areas of the lung at 1 day after living-related liver transplantation, and the complications are severer in posterior areas.The lung consolidation in the posterior region is alleviated than that in the anterior area, and the pulmonary edema in the lateral and posterior areas is alleviated than that in the anterior area.However, all of these indexes don′t return back to their preoperative status.
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Objective:To evaluate the role of Toll-like receptor 4(TLR4)/Src signaling pathway in activation of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasomes in hippocampus in a rat model of hepatic ischemia-reperfusion (I/R).Methods:Thirty-two clean-grade healthy Sprague-Dawley rats, aged 8 weeks, weighing 200 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), hepatic I/R group (HIR group), Toll-like receptor 4 (TLR4) inhibitor TAK-242 treatment group (TAK-242 group), and Src inhibitor PP2 treatment group (PP2 group). Hepatic I/R model was established by clamping hepatic vessels for 1.5 h followed by reperfusion in anesthetized rats.TAK-242 0.5 mg/kg was injected via the tail vein at 30 min before establishing the model in group TAK-242.PP2 0.03 mg/kg was intraperitoneally injected for 3 consecutive days before establishing the model in group PP2.The animals were sacrificed at 6 h of reperfusion, and hippocampal tissues were extracted for determination of interleukin-1β (IL-1β) and interleukin-18 (IL-18) contents (by enzyme-linked immunosorbent assay), malondialdehyde (MDA) content (by TBA method), superoxide dismutase (SOD) activity (using total superoxide dismutase assay), and expression of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), c-Src, pro caspase-1, cleaved caspase-1, TLR4 and phosphorylated Src (p-Src) (Western blot). Results:Compared with Sham group, the contents of IL-1β, IL-18 and MDA were significantly increased, the SOD activity was decreased, and the expression of NLRP3, cleaved caspase-1, ASC, TLR4 and p-Src was up-regulated in the other three groups ( P<0.05). Compared with HIR group, the contents of IL-1β, IL-18 and MDA were significantly decreased, the SOD activity was increased, and the expression of NLRP3, cleaved caspase-1, ASC, TLR4 and p-Src was down-regulated in TAK-242 group and PP2 group ( P<0.05). There was no significant difference in each index between TAK-242 group and PP2 group ( P>0.05). Conclusion:The mechanism underlying activation of NLRP3 inflammasomes in hippocampus is related to activating TLR4/Src signaling pathway in a rat model of hepatic I/R.
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Objective@#To investigate the clinical efficacy of combination therapy of selenium yeast and levothyroxine sodium in the treatment of type 2 diabetes mellitus complicated with chronic lymphocytic thyroiditis(CLT).@*Methods@#A total of 96 patients with type 2 diabetes mellitus complicated with CLT who admitted to Wenling Hospital of Traditional Chinese Medicine from June 2017 to December 2018 were randomly divided into control group and treatment group according to the digital table, with 48 patients in each group.On the basis of stable blood sugar control, the control group received routine treatment with levothyroxine sodium tablets.The treatment group was given selenium yeast on the basis of the control group.The blood glucose, thyroid, clinical efficacy within 3 months of treatment were recorded.@*Results@#The total effective rate of the study group was 95.83%(46/48), which was significantly higher than 68.75%(33/48) of the control group(χ2=12.080, P<0.05). The levels of blood sugar and glycosylated hemoglobin in the study group were significantly lower than those in the control group after treatment(all P<0.05), and the levels of C-peptide in the fasting and postprandial 2h were significantly higher than those in the control group(t=4.927-8.725, all P<0.05). After treatment, the serum selenium level in the study group was significantly higher than that in the control group(P<0.05), and the serum TPOAb and TGAb levels were significantly lower than those in the control group(t=17.264-27.032, all P<0.05). There were no statistically significant differences in serum TSH, FT3 and FT4 levels between the two groups(t=0.704-1.926, all P>0.05).@*Conclusion@#The clinical efficacy of selenium yeast and levothyroxine in the treatment of type 2 diabetes with CLT is significantly better than traditional treatment.
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Objective To investigate the clinical efficacy of combination therapy of selenium yeast and levothyroxine sodium in the treatment of type 2 diabetes mellitus complicated with chronic lymphocytic thyroiditis (CLT).Methods A total of 96 patients with type 2 diabetes mellitus complicated with CLT who admitted to Wenling Hospital of Traditional Chinese Medicine from June 2017 to December 2018 were randomly divided into control group and treatment group according to the digital table ,with 48 patients in each group.On the basis of stable blood sugar control,the control group received routine treatment with levothyroxine sodium tablets .The treatment group was given selenium yeast on the basis of the control group.The blood glucose, thyroid,clinical efficacy within 3 months of treatment were recorded.Results The total effective rate of the study group was 95.83%(46／48 ), which was significantly higher than 68.75%(33／48) of the control group (χ2 ＝12.080,P＜0.05).The levels of blood sugar and glycosylated hemoglobin in the study group were significantly lower than those in the control group after treatment (all P＜0.05),and the levels of C -peptide in the fasting and postprandial 2h were significantly higher than those in the control group(t＝4.927-8.725,all P＜0.05).After treatment,the serum selenium level in the study group was significantly higher than that in the control group ( P ＜0.05 ), and the serum TPOAb and TGAb levels were significantly lower than those in the control group ( t＝17.264-27.032,all P＜0.05).There were no statistically significant differences in serum TSH ,FT3 and FT4 levels between the two groups (t＝0.704-1.926,all P＞0.05). Conclusion The clinical efficacy of selenium yeast and levothyroxine in the treatment of type 2 diabetes with CLT is significantly better than traditional treatment.
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OBJECTIVE：To study the improvement effects of isopimpinelline on p-chlorophenylalanine（PCPA）-induced pineal injury model rats and its effect on expression of biological clock gene. METHODS ：Totally 60 rats were divided into blank control group（2％ polysorbate solution），model control group （2％ polysorbate solution），positive control group （melatonin，10 mg/kg） and isopimpinelline high-dose ，medium-dose and low-dose groups （3，1.5，0.75 mg/kg）. Except for blank control group ，rats in other groups were given PCPA intraperitoneally （450 mg/kg）to establish pineal injury model. After modeling finished ，they were given relevant medicine intragastrically ，once a day ，for consecutive 7 d. On the 6th day of administration ，the sleep latency and sleep duration of rats in each group were investigated by pentobarbital sodium coordination sleep test ；after last administration ， ELISA assay was used to determine the serum level of melatonin in rats. Fluorescence microscope and electron microscope were used to observe the pathological tissue and cell ultrastructure changes of the pineal gland. RT-qPCR was used to detect the mRNA expressions of biological clock gene Clock，Bmal1，Per1，Per2，Per3，Cry1，Cry2 in pineal gland of rats. RESULTS ：Compared with blank control group ，model control group had significantly longer sleep latency （P＜0.05）；serum melatonin ，mRNA expressions of Bmal1 and Per1 in pineal gland were significantly decreased （P＜0.05 or P＜0.01）while mRNA expression of Per3 was increased significantly （P＜0.05）. The pineal gland cell arrangement disorder ，nuclear pyknosis ，vacuolar degeneration increased and cell number decreased significantly ；mitochondria swollen ，cristae broken and pyknosis were observed. Compared with model control group ，the sleep latency of isopimpinelline high-dose group was shortened significantly （P＜0.05），sleep duration time was prolonged significantly （P＜0.05）；the levels of melatonin in serum ，mRNA expressions of Clock，Bmal1， Per1，Cry1 and Cry2 in pineal gland of rats were increased significantly （P＜0.05 or P＜0.01）. In isopimpinelline medium-dose group，the sleep latency was shortened significantly （P＜0.05）；the levels of melatonin in serum and mRNA expressions of Clock， Bmal1，Per1，Cry1，Cry2 in pineal gland were increased significantly （P＜0.05 or P＜0.01），while mRNA expression of Per3 was decreased significantly （P＜0.05）. In isopimpinelline low-dose group ，the levels of mRNA expressions of Clock，Bmal1，Per2 and Cry2 were increased significantly （P＜0.05），while mRNA expression of Per3 was decreased significantly （P＜0.05）. Cell arrangement disorder was improved and nuclear pyknosis vacuole degeneration was decreased to some extent in isopimpinelline groups；mitochondria swelled ，cristae fractured ，and pyknosis decreased to some extent. CONCLUSIONS ：Isopimpinelline can improve PCPA-induced pineal gland injury in rats ；it can up-regulate the expressions of positive regulators Clock，Bmal1 and negative regulators Per1，Per2，Cry1，Cry2，while down-regulate the expression of negative regulator Per3.
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Objective@#To evaluate the role of pyroptosis in brain injury in a rat model of hepatic ischemia-reperfusion (I/R).@*Methods@#Thirty clean-grade healthy male Sprague-Dawley rats of both sexes, aged 6-8 weeks, weighing 180-200 g, were divided into 3 groups (n=10 each) using a random number table method: sham operation group (group S, n=10), hepatic I/R plus dimethyl sulfoxide (DMSO) group (group I/R+ DMSO, n=10), and hepatic I/R plus caspase-1 inhibitor Ac-YVAD-cmk group (group I/R+ YVAD, n=10). Hepatic I/R was produced by occluding the left hepatic artery and portal vein for 90 min followed by 6-h reperfusion in anesthetized rats.At 2 h before reperfusion, Ac-YVAD-cmk 5 mg/kg was intraperitoneally injected in group I/R+ YVAD, and the equal volume of DMSO was given instead in group I/R+ DMSO.Hippocampal and cortical samples were obtained at the end of reperfusion for determination of reactive oxygen species (ROS) content (using DCFH-DA fluorescence probe), malondialdehyde (MDA) content (using thiobarbituric acid method), superoxide dismutase (SOD) activity (by xanthine oxidase method), expression of NLRP3, cleaved-caspase-1 and apoptosis-associated speck-like protein containing a CAR (ASC) (by Western blot), nucleotide-binding domain, leucine rich family (NLR) pyrin domain containing 3 (NLRP3) expression (by immunohistochemical staining), and concentrations of IL-1β, IL-18, S100-β protein and neuron-specific enolase (NSE) in serum (by enzyme-linked immunosorbent assay).@*Results@#Compared with group S, the contents of ROS and MDA in hippocampus and cortex were significantly increased, the activity of SOD in hippocampus and cortex was decreased, the expression of NLRP3, cleaved-caspase-1 and ASC was up-regulated, and the concentrations of IL-1β, IL-18, S-100β protein and NSE in serum were increased in group I/R+ DMSO (P<0.05). Compared with group I/R+ DMSO, the contents of ROS and MDA in hippocampus and cortex were significantly decreased, the activity of SOD in hippocampus and cortex was increased, the expression of NLRP3, cleaved-caspase-1 and ASC was down-regulated, and the concentrations of IL-1β, IL-18, S-100β protein and NSE in serum were decreased in group I/R+ YVAD (P<0.05).@*Conclusion@#Pyroptosis is involved in the pathophysiological mechanism of brain injury induced by hepatic I/R injury in rats.
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Objective To evaluate the role of pyroptosis in brain injury in a rat model of hepatic ischemia-reperfusion (I/R).Methods Thirty clean-grade healthy male Sprague-Dawley rats of both sexes,aged 6-8 weeks,weighing 180-200 g,were divided into 3 groups (n=10 each) using a random number table method:sham operation group (group S,n=10),hepatic I/R plus dimethyl sulfoxide (DMSO)group (group I/R+DMSO,n=10),and hepatic I/R plus caspase-1 inhibitor Ac-YVAD-cmk group (group I/R+YVAD,n=10).Hepatic I/R was produced by occluding the left hepatic artery and portal vein for 90 min followed by 6-h reperfusion in anesthetized rats.At 2 h before reperfusion,Ac-YVAD-cmk 5 mg/kg was intraperitoneally injected in group I/R+YVAD,and the equal volume of DMSO was given instead in group I/R+DMSO.Hippocampal and cortical samples were obtained at the end of reperfusion for determination of reactive oxygen species (ROS) content (using DCFH-DA fluorescence probe),malondialdehyde (MDA) content (using thiobarbituric acid method),superoxide dismutase (SOD) activity (by xanthine oxidase method),expression of NLRP3,cleaved-caspase-1 and apoptosis-associated speck-like protein containing a CAR (ASC) (by Western blot),nucleotide-binding domain,leucine rich family (NLR)pyrin domain containing 3 (NLRP3) expression (by immunohistochemical staining),and concentrations of IL-1β,IL-18,S100-β protein and neuron-specific enolase (NSE) in serum (by enzyme-linked immunosorbent assay).Results Compared with group S,the contents of ROS and MDA in hippocampus and cortex were significantly increased,the activity of SOD in hippocampus and cortex was decreased,the expression of NLRP3,cleaved-caspase-1 and ASC was up-regulated,and the concentrations of IL-1β,IL-18,S-100β protein and NSE in serum were increased in group I/R+DMSO (P＜0.05).Compared with group I/R+DMSO,the contents of ROS and MDA in hippocampus and cortex were significantly decreased,the activity of SOD in hippocampus and cortex was increased,the expression of NLRP3,cleaved-caspase-1 and ASC was down-regulated,and the concentrations of IL-1β,IL-18,S-100β protein and NSE in serum were decreased in group I/R+YVAD (P＜0.05).Conclusion Pyroptosis is involved in the pathophysiological mechanism of brain injury induced by hepatic I/R injury in rats.