Protective effect of modified Huangqi Chifeng decoction on immunoglobulin A nephropathy through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway.

OBJECTIVE: To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction (, MHCD) in immunoglobulin A nephropathy (IgAN) rats. METHODS: To establish the IgAN rat model, the bovine serum albumin, lipopolysaccharide, and carbon tetrachloride 4 method was employed. The rats were then randomly assigned to the control, model, telmisartan, and high-, medium-, and low-dose MHCD groups, and were administered the respective treatments via intragastric administration for 8 weeks. The levels of 24-h urinary protein, serum creatinine (CRE), and blood urea nitrogen (BUN) were measured in each group. Pathological alterations were detected. IgA deposition was visualized through the use of immunofluorescence staining. The ultrastructure of the kidney was observed using a transmission electron microscope. The expression levels of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-ß1 (TGF-ß1) were examined by immunohistochemistry and quantitative polymerase chain reaction. Levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB) P65, were examined by immunohistochemistry, Western blotting, and quantitative polymerase chain reaction. RESULTS: The 24-h urine protein level in each group increased significantly at week 6, and worsen from then on. But this process can be reversed by treatments of telmisartan, and high-, medium-, and low-dose of MHCD, and these treatments did not affect renal function. Telmisartan, and high-, and medium-dose of MHCD reduced IgA deposition. Renal histopathology demonstrated the protective effect of high-, medium-, and low-dose of MHCD against kidney injury. The expression levels of MCP-1, IL-6, and TGF-ß1 in kidney tissues were downregulated by low, medium and high doses of MHCD treatment. Additionally, treatment of low, medium and high doses of MHCD decreased the protein and mRNA levels of TLR4, MyD88, and NF-κB. CONCLUSIONS: MHCD exerted nephroprotective effects on IgAN rats, and MHCD regulated the expressions of key targets in TLR4/MyD88/NF-κB signaling pathway, thereby alleviating renal inflammation by inhibiting MCP-1, IL-6 expressions, and ameliorating renal fibrosis by inhibiting TGF-ß1 expression.

Special mechanical ventilation:heliox ventilation and partial liquid ventilation / 中国小儿急救医学

Neonatal mortality has been significantly decreased because of the development of neo-natal respiratory support techniques. Nevertheless,constant and high frequency ventilators have some limita-tions to solve all problems in neonatal respiratory failure. Special mechanical ventilation,mainly including he-liox and partial liquid ventilation,provides new respiratory support for newborn infants. The clinical signifi-cance of heliox and partial liquid ventilation need further investigation.

Clinical value of amplitude integrated EEG in early diagnosis and prognosis of neonatal asphyxia / 重庆医学

Objective To investigate the clinical value of amplitude integrated electroencephalogram on early diagnosis and prognosis evaluation of brain injury caused by neonatal asphyxia.Methods A total of 34 full-term asphyxiated neonates(asphyxia group)hospitalized in NICU of our hospital from January 2015 to September 2015 were selected;meanwhile,34 full-term healthy infants(control group)of the same term were selected.All cases were monitored for the activities of aEEG background,sleep-awakening cycle(SWC)and epileptic activity(SA)within 6 hours after birth.Meanwhile,the relationships between various indexes and asphyxia degree and brain injury were analyzed.Results The electroencephalogram of the asphyxia group was 52.9％and the rate of SWC was 58.8％,which were lower than those of the control group,and the difference had statistic significance(P<0.05).Meanwhile,neonates with epileptic activity in asphyxia group accounted for 11.8％,which was higher than that of control group significantly(P<0.05).Conclusion The AEEG changes of neonates at early period after birth are closely related to perinatal asphyxia and brain injury after asphyxia.The application of amplitude integrated electroencephalogram has an important significance on early diagnosis of neonatal asphyxia.

Nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure for preterm infants with respiratory distress syndrome: a meta-analysis and up-date.

OBJECTIVE: To evaluate whether nasal intermittent positive pressure ventilation (NIPPV) would decrease the requirement for endotracheal ventilation compared with nasal continuous positive airway pressure(NCPAP) for preterm infants with respiratory distress syndrome (RDS) and compare the related complications between these two noninvasive variations of respiratory support METHODS: A search of major electronic databases, including Medline (1980-2013) and the Cochrane Central Register of Controlled Trials, for randomized controlled trials that compared NIPPV versus NCPAP for preterm infants with RDS was performed. MAIN RESULTS: Six randomized controlled trials met selection criteria (n = 1,527). The meta-analyses demonstrated significant decrease in the need for invasive ventilation in the NIPPV group (RR:0.53; 95% CI, 0.33-0.85). In the subgroup of infants who received surfactant also demonstrated a significant rate of failure of nasal support in the NIPPV group (RR:0.57; 95% CI 0.42-0.78). However, the subgroup of infants whose gestational age (GA) ≤ 30 weeks or birth weight (BW) < 1,500 g showed no difference between the two groups (RR:0.59; 95% CI 0.27-1.26); and the subgroup of infants whose GA > 30 weeks or BW > 1,500 g also showed no difference between the two groups (RR:0.63; 95% CI 0.29-1.39). No differences in other outcome variables were observed between the two groups. CONCLUSIONS: Among preterm infants with RDS, there was a significant decrease in the need for invasive ventilation in the NIPPV group as compared with NCPAP group, especially for the infants who received surfactant. However, NIPPV could not decrease the need for invasive ventilation both in the subgroup of infants whose GA ≤ 30 weeks or BW < 1,500 g and the subgroup of infants with BW of >30 weeks or BW > 1,500 g. It is limited to analysis the primary outcome generally. Larger trials of this intervention are needed to assess the difference in this primary outcome and the related complications between both forms of noninvasive respiratory support.

Clinical study on intratracheal instillation of sodium nitroprusside for treating persistent pulmonary hypertension of newborn / 重庆医学

Objective To investigate the therapeutic effect and safety of the intratracheal instillation of sodium nitroprusside for treating persistent pulmonary hypertension of newborn (PPHN) .Methods The intratracheal instillation of sodium nitroprusside was used to 19 cases of PPHN under the mechanical ventilation ,and the pulmonary arterial mean pressure(PAMP) ,arterial mean pressure(AMP) ,transcutaneous oxygen saturation(TcSaO2 ) of the right upper and left lower limb at the basic state ,30 ,60 ,120min after intratracheal instillation of sodium nitroprusside were respectively measured and compared .Results Among 19 cases of PPHN ,17 cases had the primary lung disease .Of 17 cases ,14 cases(82 .35% ) had significant decrease of PAMP after intratracheal instillation of sodium nitroprusside ,which was most significant at 30min after therapy and the difference was statistically significant compared with before therapy [(21 .30 ± 4 .200)mm Hg vs .(30 .30 ± 4 .20)mm Hg ,P0 .05] .Conclusion The intratracheal instillation of sodium nitroprusside is the safe ,effective and economic method for treating PPHN .

Effects of limited fluid resuscitation on systemic inflammatory responses in rats with traumatic hemorrhagic shock: a comparison with unlimited fluid resuscitation / 中华麻醉学杂志

Objective To evaluate the effects of limited fluid resuscitation on systemic inflammatory responses in rats with traumatic hemorrhagic shock through comparing with unlimited fluid resuscitation.Methods Sixty pathogen-free male Sprague-Dawley rats,aged 2-3 months,weighing 250-290 g,were randomly divided into 6 groups (n =10 each) using a random number table:sham operation group (group S),no fluid resuscitation group (group NF),unlimited fluid resuscitation group (group ULF),limited crystalloid fluid resuscitation group (group LR),and limited colloid fluid resuscitation groups (group LSG and group LHES).Traumatic uncontrolled hemorrhagic shock was induced by withdrawal of blood from the femoral artery at 2.5 mL/100 g over a 20-minute period,followed by tail amputation at 10 min after the end of blood withdrawal.At 10 min after the end of blood withdrawal,fluid resuscitation was performed.Lactated Ringer's solution (ULF and LR groups),4 ％ succinylated gelatin (group LSG),or 6 ％ hydroxyethyl starch 130/0.4 (group LHES) was infused intravenously.The initial infusion rate was 2 ml · kg-1 · min-1.The target MAP was maintained at 50 mm Hg in rats with limited fluid resuscitation,while at 80 mm Hg in rats with unlimited fluid resuscitation.After 60 min of fluid resuscitation,bleeding in the tail was stopped by ligation and fluid infusion was replaced with blood resuscitation.After 60 min of blood resuscitation,180 main of observation was started.At 10 min after catheterization of the femoral artery and vein (T0),10 min after the end of blood withdrawal (T1),the end of fluid resuscitation (T2),the end of blood resuscitation (T3),and the end of observation (T4),arterial blood samples were collected to measure hematocrit (Hct)and concentrations of plasma tumor necrosis factor-alpha (TNF-α),interleukin (IL)-6,and IL-10.Blood samples were collected from the femoral artery at T2 for determination of the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) and activity of nuclear factor-kappaB (NF-κB) in monocytes.The amount of blood loss from the tail and volume of fluid infused were also recorded.Another 120 Sprague-Dawley rats were randomly divided into 6 groups (n =20 each) and resuscitation was performed according to the method previously described.The rats were observed for 72 h survival rate.Results Compared with group S,Hct was significantly decreased,the concentrations of plasma TNF-α,IL-6,and IL-10 and activity of NF-κB were increased,and the expression of TLR4,and MyD88 in monocytes was up-regulated in the other groups (P ＜ 0.05).Compared with group NF,the concentrations of plasma TNF-α and IL-6 and NF-κB activity were significantly increased,and the concentration of plasma IL-10 and Hct were decreased,and the expression of TLR4 and MyD88 in monocytes was up-regulated in ULF,LR and LSG groups,and the concentrations of plasma TNF-α and IL-6 were significantly increased,the concentration of plasma IL-10 and Hct were decreased in group LHES (P ＜ 0.05).Compared with group ULF,the concentrations of plasma TNF-α and IL-6 and NF-κB activity were significantly decreased,the concentration of plasma IL-10 and Hct were increased,the survival rate was higher,the expression of TLR4 and MyD88 in monocytes was down-regulated,and the amount of blood loss from the tail was decreased and the volume of fluid infused was reduced in LSG,LHES and LR groups (P ＜ 0.05).Compared with group LR,the concentrations of plasma TNF-α and IL-6 and NF-κB activity were significantly decreased and the expression of TLR4 and MyD88 in monocytes was down-regulated (P ＜ 0.05),and no significant change was found in the concentration of plasma IL-10 in group LHES (P ＞ 0.05),and the volume of fluid infused was reduced and the survival rate was increased (P ＜ 0.05),and no significant change was found in the amount of blood loss from the tail in LSG and LH-ES groups (P ＞ 0.05).Conclusion Compared with unlimited fluid resuscitation,limited fluid resuscitation exerts less effect on systemic inflammatory responses in rats with traumatic hemorrhagic shock,especially when resuscitation with 6％ hydroxyethyl starch 130/0.4 is performed,and inhibition of TLR4/NF-κB signaling pathway is involved in the mechanism.

Glycochenodeoxycholate induces rat alveolar epithelial type II cell death and inhibits surfactant secretion in vitro.

Bile acid-induced lung injury has become an important topic for neonatologists after the discovery of a high incidence of infant respiratory distress syndrome complicated from maternal intrahepatic cholestasis. To explore the molecular pathway of bile acid-induced lung injury, we investigated the cytotoxicity of the glycochenodeoxycholate (GCDC) to alveolar epithelial type II cells (AECII), as the main component of bile acid. The results demonstrated that glycochenodeoxycholate induced oxidative stress, mitochondrial damage, and increased caspase activity in the primary cultured AECII. Moreover, ROS scavengers and caspase inhibitors could rescue cell death induced by GCDC in rat AECII. Our results also indicated that GCDC inhibited AECII surfactant secretion. In conclusion, this study suggested that cell death prevention and cell therapy should be considered as therapeutic strategies for infant respiratory distress syndrome complicated from maternal intrahepatic cholestasis.

Effects of ketamine on MAC_(BAR) of sevoflurane in patients undergoing abdominal surgery / 中华麻醉学杂志

ObjectiveTo evaluate the effects of ketamine on the minimum alveolar concentration of scvoflurane for blunting adrenergic responses to skin incision (MAC_(BAR)) in patients undergoing abdominal surgery. Methods Forty-four ASA Ⅰ or Ⅱ patients aged 30-60 yr undergoing elective abdominal surgery were randomly divided into 2 groups (n=22 each) : control group (group K_0) and ketamine group (group K_1). Anesthesia was induced with propofol 2 mg/kg and fentanyl 3 μg/kg. Tracheal intubation was facilitated with cisatracurium 0.15 mg/kg. The patients were mechanically ventilated. Anesthesia was maintained with sevoflurane inhalation (the initial end-tidal concentration 3% ). Ketamine at 14 μg·kg~(-1)·min~(-1) was infused at the same time in group K,. The patients' response to skin incision was described as positive if MAP or HR increased by≥15%. If the response was positive, the end-tidal concentration of sevoflurane for the next patient was increased by 0.5%, while if negative, decreased by 0.5% . ResultsThe MAC_(BAR) of scvoflurane was 3.25 % (95 % confidence interval 3.05%-3.45%) in group K_0, and 2.20% (95% confidence interval 1.96%-2.44%) in group K~1. The MAC_(BAR) of sevoflurane was significantly lower in group K~1 than in group K_0 (P<0.05). Conclusion Ketamine infusion at 14 μg·kg~(-1)·min~(-1) can reduce MAC_(BAR) of sevoflurane and enhance the inhibitory effect of sevoflurane on the stress response.

Establishment of the oxidative damage model in brain of PD rats induced by L-DOPA with microdialysis technique / 中国药理学通报

Aim To establish the model of oxidative damage in brain of Parkinsons disease(PD)rats induced by levodopa(L-DOPA)with microdialysis technique.Methods PD model rats were induced by intracerebral injection of 6-hydroxyl dopamine(6-OHDA)and were perfused in brain with L-DOPA by using microdialysis technique.Salicylic acid can capture hydroxyl radicals in brain,then yield 2,3-dihydroxy benzyl acid(2,3-DHBA)and 2,5-dihydroxy benzyl acid(2,5-DHBA).Extracelluler dopamine(DA)and its metabolites,2,3-DHBA and 2,5-DHBA in striatum of rats were measured by HPLC-ED before and after L-DOPA treatment.Results Both 2,3-DHBA and 2,5-DHBA in model group were significantly higher than those in control group at 6 and 7 time points respectively(P