Objective To evaluate the effect of electro-acupuncture (EA) at Zusanli (ST-36) and Neiguan (PC6) acupoints on endotoxic shock (ES)-induced myocardial injury in rabbits and the role of heme oxygenase-1 (HO-1).Methods Sixty healthy male New Zealand white rabbits,aged 2 months,weighing 1.5-2.0 kg,were randomly assigned into 6 groups (n =10 each) using a random number table:sham operation group (group S) ; heme oxygenase-1 inhibitor zinc protoporphyrin-Ⅸ (ZnPP-Ⅸ) group (group Z) ; group ES; EA + ES group (group EES); sham EA + ES group (group SEES); EA + ES + ZnPP-Ⅸ group (group EESZ).The rabbits were anesthetized with intravenous 20％ urethane 5 ml/kg.Right common carotid artery was cannulated for BP monitoring.Ear vein was cannulated for drug administration.ES was induced with lipopolysaccharide (LPS) 5 mg/kg injected intravenously in ES,EES,SEES and EESZ groups,while the equal volume of normal saline was given in S and Z groups.ES was confirmed by decrease in MAP to 75 ％ of the baseline value.ZnPP-Ⅸ 10 μmol/kg (in 1 ml of NaHCO3 50 mmol/L) was injected intraperitoneally at 2 h after LPS or normal saline administration in EESZ and Z groups,while the equal volume of NaHCO3 was injected intraperitoneally in the other groups.In EES and EESZ groups,bilateral 30 min EA stimulation (0.2-0.6 ms,2/100 Hz,2-3 mA) of ST36 and PC6 was performed once a day on days 1-4 before induction of ES and on the day of induction of ES (from the onset of LPS injection until the end of induction of ES).In SEES group,electro-stimulation was performed at the points 0.5 cm lateral to the acupoints of ST36 and PC6 and the method was similar to those previously described in group EES.Blood samples were taken from the right common carotid artery at 6 h after LPS or normal saline administration for measurement of serum tumor necrosis factor-alpha (TNF-α),creatine kinase (CK),and lactic dehydrogenase (LDH) levels.Then the rabbits were sacrificed by exsanguination,and the myocardial tissues were removed for microscopic examination of the pathological changes which were scored and for determination of HO-1 protein (by Western blot) and mRNA (using fluorescence quantitative PCR) expression.Results Compared with group S,the pathological scores and concentrations of serum TNF-α,CK,and LDH were significantly increased,and the expression of HO-1 protein and mRNA was up-regulated in ES,EES,SEES and EESZ groups (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group Z (P ＞ 0.05).Compared with group ES,the pathological scores and concentrations of serum TNF-α,CK,and LDH were significantly decreased,and the expression of HO-1 protein and mRNA was up-regulated in group EES (P ＜ 0.05),while no significant change in the parameters mentioned above was found in SEES and EESZ groups (P ＞ 0.05).Compared with group EES,the pathological scores and concentrations of serum TNF-α,CK,and LDH were significantly increased,and the expression of HO-1 protein and mRNA was down-regulated in group EESZ (P ＜ 0.05).Conclusion EA at ST-36 and PC6 acupoints can attenuate ES-induced myocardial injury in rabbits and upregulation of HO-1 expression and inhibition of inflammatory responses may be involved in the mechanism.

Objective To evaluate the effects of electroacupuncture (EA) at Zusanli and Chize on sepsisinduced acute lung injury (ALI) in patients.Methods Sixty patients with sepsis-induced ALI/respiratory distress syndrome,aged 43-78 yr,weighing 49-89 kg,with their APACHE-Ⅱ scores of 16-23 and oxygenation index of 125-256 mm Hg,were randomly divided into 3 groups (n =20 each):conventional therapy group (group S),conventional therapy + acupuncture at non-acupoint group (group SNE) and conventional therapy + acupuncture at acupoint group (group SE).Bilateral Huantiao and Chize points were stimulated with electric stimulator (frequency 2/50 Hz,wave length 300μs,starting at a voltage of 0 and increasing by 0.1 mA every time until the maximal tolerance level was reached) for 30 min once a day for 5 days based on the conventional therapy in group SE.In group SNE,EA was performed at the non-acupoint based on the conventional therapy and the parameters of EA were same as those previously mentioned in group SE.Before EA stimulation (T1) and at 3 and 5 days after the end of EA stimulation (T2-3),arterial blood samples were taken for blood gas analysis,oxygenation index (OI) was calculated,and APACHE-Ⅱ] scores were assessed.Venous blood samples were collected at T1 and T3 for detection of TNF-α and IL-10 concentrations in the broncho-alveolar lavage fluid (BALF) and serum (by ELISA).Results Compared with the baseline value at T1,OI was significantly increased and APACHE-Ⅱ scores were decreased at T2 and T3,and TNF-α concentrations in the BALF and serum were decreased and IL-10 concentrations in the BALF and serum were increased at T3 in the three groups (P ＜ 0.05 or 0.01).The OI was significantly higher and APACHE-Ⅱ scores were lower at T3 than at T2 in the three groups (P ＜ 0.05).Compared with group S,the OI was significantly increased at T2 and T3,APACHE-Ⅱ scores and TNF-α concentrations in the BALF and serum were decreased at T3,and IL-10 concentrations in the BALF and serum were increased at T3 in group SE (P ＜0.05 or 0.01),and no significant changes were found in the parameters mentioned above in group SNE (P ＞0.05).There were no significant differences in the incidence and survival rate of multiple organ dysfunction syndrome among the three groups (P ＞ 0.05).Conclusion EA at Zusanli and Chize is helpful in mitigating sepsisinduced ALI in patients,and regulation of the balance between proinflammatory factors and anti-inflammatory factors and inhibition of inflammatory responses may be involved in the mechanism.

Objective To evaluate the role of activator protein-1 (AP-1 ) in electro-acupuncture (EA )-induced up-regulation of heme oxygenase-1 (HO-1 ) expression in lung tissues in a rabbit model of endotoxic shock .Methods Seventy healthy male New Zealand white rabbits ,aged 2 months ,weighing 1.5-2.0 kg ,were randomly divided into 7 groups ( n=10 each ) using a random number table :normal control group (group C ) , endotoxic shock-induced acute lung injury (ALI ) group (group ALI ) , EA + ALI group (group EL ) , non-acupoint+EA+ ALI group (group NEL ) , curcumin (HO-1 inhibitor ) group (group Cur ) , dimethyl sulfoxide group (group D ) ,and EA+ALI+curcumin group (group ELC ) .Bilateral 15 min EA stimulation of Zusanli and Feishu (according to atlas of animals acupoints ) was performed (frequency 15Hz ) once a day for 5 consecutive days before lipopolysaccharide (LPS ) administration in EL and ELC groups ,while in group NEL ,EA stimulation was performed at non-acupoints located 0.5 cm lateral to Zusanli and Feishu acupoints with the same parameters . The animals were anesthetized with urethane and tracheostomized .The animals kept spontaneous breathing .Right internal carotid artery was cannulated for blood pressure monitoring . Ear vein was cannulated for drug administration .At 5 days after EA stimulation ,curcumin 25 mg/kg (in 0.5 ml of 0.1% dimethyl sulfoxide ) was injected in Cur and ELC groups ,0.1% dimethyl sulfoxide 0.5 ml was injected in D group ,and the equal volume of normal saline was given in the other groups .LPS 5 mg/kg (in 2 ml of 0.9% normal saline ) was injected intravenously at 30 min after administration in ALI ,EL ,NEL and ELC groups ,while the equal volume of normal saline was given in the other three groups .Endotoxic shock was confirmed by decrease in mean arterial pressure to 75% of the baseline value within 2 h after LPS injection .Blood samples were collected from the common carotid artery at 6 h after LPS or normal saline administration and the rabbits were then sacrificed .The lungs were removed for microscopic examination and the pathological changes were scored .The wet/dry lung weight ratio (W/D ratio ) was calculated .The malondialdehyde (MDA ) content and superoxide dismutase (SOD ) activity in lung tissues were detected ,and the expression of HO-1 mRNA ,HO-1 ,c-Jun mRNA and c-Jun in lung tissues was determined by Western blot .Results Compared with group C ,the pathological score ,W/D ratio and MDA content were significantly increased ,and the SOD activity was decreased in ALI ,EL ,NEL and ELC groups ,the expression of HO-1 mRNA ,HO-1 ,c-Jun mRNA and c-Jun was up-regulated in groups ALI ,EL and NEL ( P<0.05 ) ,while no significant change was found in the expression of c-Jun mRNA and c-Jun in group ELC ( P>0.05) .There was no significant difference in the parameters mentioned above between Cur and D groups ( P>0.05 ) .Compared with group ALI ,the pathological score ,W/D ratio and MDA content were significantly decreased ,and SOD activity was increased ,and the expression of HO-1 mRNA and HO-1 was up-regulated in EL and ELC groups ( P<0.05) ,the expression of c-Jun mRNA and c-Jun was up-regulated in group EL ,while down-regulated in group ELC ( P<0.05) ,and no significant change was found in the parameters mentioned above in group NEL ( P>0.05) .The pathological score ,W/D ratio and MDA content were significantly higher ,and the SOD activity and expression of HO-1 mRNA ,HO-1 ,c-Jun mRNA and c-Jun were lower in group ELC than in group EL ( P<0.05) .Conclusion EA up-regulates HO-1 expression through activating AP-1 during endotoxic shock-induced ALI in rabbits ,thus protecting the lung .

Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative acute lung injury (ALI) in the pediatric patients undergoing living-related liver transplantation.Methods:Sixty pediatric patients of either sex, aged 4-24 months, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with New York Heart Association (NYHA) class Ⅰ or Ⅱ, with Child-Pugh B or C, scheduled to undergo elective left external lobe piggyback living-related liver transplantation, were divided into 2 groups ( n=30 each) using a computer-generated table of random numbers: control group (group C) and TEAS group (group T). In group T, bilateral Zusanli (ST36), Neiguan (PC6), and Feishu (BL13) acupoints were stimulated with disperse-dense waves at the initial intensity of 0.5 mA and frequency of 2/15 Hz, the current intensity was gradually increased until local slight muscle shaking appeared, and continuous stimulation lasted for 30 min at a 30-min interval (a cycle) until the end of operation. TEAS was performed for 30 min at the same time every day up to 1 week after surgery. Stimulus locations in group C were selected at 0.5 cm lateral to the acupoints, and the electrodes with inert medium were attached to the location, with no effective current output from acupuncture treatment instrument. The peak inspiratory pressure, plateau pressure, and pulmonary compliance were recorded before skin incision (T 0), at 30 min after portal vein occlusion (T 1), at 1 h after portal vein opening (T 2), at the end of operation (T 3), and the difference between peak inspiratory pressure and plateau pressure was calculated. Blood samples from the jugular vein were collected at T 0-3 to determine the levels of plasma club cell protein 16 (CC16), surfactant protein D (SP-D), soluble receptor for advanced glycation end products (sRAGE), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) by enzyme-linked immunosorbent assay. Blood samples from the radial artery were collected at T 0-3 for blood gas analysis, PaO 2 and A-aDO 2 were recorded, and oxygenation index (OI) and respiratory index (RI) were calculated. The indwelling time of postoperative tracheal tube and length of ICU stay were also recorded. The lung injury was assessed and scored using ultrasound at 48 h after surgery. The occurrence of ALI within 1 week after operation was also recorded. Results:Compared with baseline at T 0, OI was significantly decreased, RI was increased, and plasma IL-10 concentrations were increased at T 2, 3, and the plasma concentrations of TNF-α, CC16, sRAGE and SP-D were increased at T 1-3 in both groups ( P<0.05). Compared with group C, OI was significantly increased, RI was decreased, the plasma concentrations of sRAGE were decreased, and the plasma concentrations of IL-10 were increased at T 2, 3, and the concentrations of plasma TNF-α, CC16 and SP-D were decreased at T 1-3, the indwelling time of postoperative tracheal tube and length of ICU stay were shortened, the ultrasound score of lung injury was decreased ( P<0.05), and no significant change was found in the incidence of ALI in group T ( P>0.05). Conclusions:TEAS can alleviate ALI in the pediatric patients after living-related liver transplantation.

OBJECTIVEBy clarifying the natural history of chronic hepatitis B, to evaluate its long-term therapeutic outcome, antiviral drugs efficacy and economic significance.

METHODSA cohort of 183 (mean age of 31.75?.03 years, male/female ratio: 152:31) chronic hepatitis B patients with biopsy-proven and 247 cases of general population as control were followed up by retrospective cohort study. The follow-up time was 11.81?.08 years. This study was focused on long-term clinical outcome including the rate of liver cirrhosis, hepatocellular carcinoma and death, the long-term effect of antiviral drugs and prognostic factors.

RESULTSIn chronic hepatitis B patients, 22 (12.02%) developed liver cirrhosis, 12 (6.56%) hepatocellular carcinoma, and 20 (10.93%) died. The cumulative survival probabilities were 97.27%, 91.62%, and 84.47% in 5, 10, and 15 years, respectively. The cumulative probabilities of HCC were 0.00%, 3.19%, and 11.56% in 5, 10, and 15 years, respectively. In 247 control subjects, 6 (2.43%) died, none of them developed cirrhosis or HCC. The rates of death, liver cirrhosis, and HCC in hepatitis B patients were markedly different (P<0.005) compared with controls. The overall mortality of hepatitis B patients was 4.50 folds of the general population. Cox multiple regression analysis showed that old age, severe histological injury, and the positive HBeAg were closely related to liver cirrhosis, while old age, severe histological injury, and male were major factors leading to death. The independent variable of predicted HCC was not found.

CONCLUSIONSThe long-term outcome of hepatitis B is poor.

Adolescent ; Adult ; Aging ; physiology ; Carcinoma, Hepatocellular ; epidemiology ; etiology ; Cohort Studies ; Female ; Follow-Up Studies ; Hepatitis B e Antigens ; physiology ; Hepatitis B, Chronic ; complications ; epidemiology ; mortality ; Humans ; Liver Cirrhosis ; epidemiology ; etiology ; Liver Failure ; physiopathology ; Liver Neoplasms ; epidemiology ; etiology ; Male ; Middle Aged ; Regression Analysis ; Retrospective Studies ; Risk Factors ; Sex ; Survival Rate

PURPOSE: We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children. METHODS: This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children. RESULTS: The maternal G allele of IL-13 130 (rs20541) was significantly (P=0.001) associated with decreased IgE in children in the Karelian population (Pooling Finnish and Russian children), as well as in Finnish (P=0.030) and Russian children (P=0.018). The IgE levels were significantly (P=0.001) higher in Russian children whose mothers were homozygous for the G allele of the IL-4Ra 50 (rs1805010) SNP than that in Russian children of mothers who were AG heterozygotes or AA homozygotes. After accounting for children's genotypes, we observed interactive effects on children's IgE for maternal IL-13 130 genotypes (P=0.014) and maternal IL-4Ra 50 genotypes (P=0.0003) with "Western or Eastern" lifestyles/environments. With the adjustment for multiple comparisons using a false discovery rate (FDR) of 0.05, the interactive effect of the maternal IL-4Ra50 SNP was significant. CONCLUSION: Maternal genetic variants in IL-4/IL-13 pathway genes, such as IL-13 130 and IL-4Ra50, influenced IgE levels in school children that were independent of the children's genetic effects. These effects differ in "Western or Eastern" environments.
Alleles ; Child ; Genotype ; Heterozygote ; Homozygote ; Humans ; Hypersensitivity ; Immunoglobulin E* ; Interleukin-13 ; Interleukin-4 ; Mothers ; Polymorphism, Single Nucleotide

PURPOSE: We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children. METHODS: This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children. RESULTS: The maternal G allele of IL-13 130 (rs20541) was significantly (P=0.001) associated with decreased IgE in children in the Karelian population (Pooling Finnish and Russian children), as well as in Finnish (P=0.030) and Russian children (P=0.018). The IgE levels were significantly (P=0.001) higher in Russian children whose mothers were homozygous for the G allele of the IL-4Ra 50 (rs1805010) SNP than that in Russian children of mothers who were AG heterozygotes or AA homozygotes. After accounting for children's genotypes, we observed interactive effects on children's IgE for maternal IL-13 130 genotypes (P=0.014) and maternal IL-4Ra 50 genotypes (P=0.0003) with "Western or Eastern" lifestyles/environments. With the adjustment for multiple comparisons using a false discovery rate (FDR) of 0.05, the interactive effect of the maternal IL-4Ra50 SNP was significant. CONCLUSION: Maternal genetic variants in IL-4/IL-13 pathway genes, such as IL-13 130 and IL-4Ra50, influenced IgE levels in school children that were independent of the children's genetic effects. These effects differ in "Western or Eastern" environments.
Alleles ; Child ; Genotype ; Heterozygote ; Homozygote ; Humans ; Hypersensitivity ; Immunoglobulin E* ; Interleukin-13 ; Interleukin-4 ; Mothers ; Polymorphism, Single Nucleotide

OBJECTIVETo observe the effect of the decomposition products of necrotic tissues from wounds on the serum levels of inflammation factors in comparison with endotoxin.

METHODSThirty adult New Zealand rabbits were randomly divided into 3 groups and received injections of saline, necrotic tissue homogenate or endotoxin. From each rabbit, blood samples (2 ml) were collected from the central artery of the ears at 0, 2, 6, 12, 24, 30, 36, 48, and 60 h after the injection for measurement of serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and IL-6.

RESULTSThe serum level of TNF-α, IL-1 and IL-6 in the rabbits increased 2-4 h after injection of the necrotic tissue homogenate and reached the peak level at 12 h, followed by a gradual reduction since 36 h. No obvious changes in the levels of the inflammatory factors were found in saline group (P<0.01). Compared with endotoxin, necrotic tissue homogenate resulted in an early increment (2-4 h vs 5-6 h) and significantly higher peak levels (at 30 h) of the inflammation factors (P<0.05). Curve fitting showed a distinct difference between necrotic tissue homogenate and endotoxin in their effect on the inflammatory factors.

CONCLUSIONThe necrotic tissue decomposition products contain toxic substances that possess a different toxicity profile from endotoxin, and their toxicity can be even stronger.

Animals ; Endotoxins ; adverse effects ; Inflammation ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Necrosis ; Rabbits ; Tumor Necrosis Factor-alpha ; blood ; Wounds and Injuries ; blood ; pathology

Objective:To evaluate the effect of esketamine on postoperative acute lung injury (ALI) in pediatric patients undergoing living donor liver transplantation.Methods:Sixty pediatric patients of either sex with biliary atresia, aged 0-36 months, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, with cardiac function grade I or Ⅱ, with Child-Pugh grade B or C, undergoing living donor liver transplantation, were divided into 2 groups ( n=30 each) using a computer-generated table of random numbers: control group (group C) and esketamine group (group S). Combined intravenous-inhalational anesthesia was performed with propofol and sevoflurane in both groups, and in addition esketamine was intravenously infused continuously after induction in group S. After anesthesia induction (T 0), at 60 min after start of surgery (T 1), at 10 min after anhepatic phase (T 2), at 60 min after portal vein opening (T 3), and immediately after abdominal closure (T 4), central venous blood samples were collected for determination of the serum concentrations of Clara cell secretory protein 16, surface active protein D, soluble receptor for advanced glycation end-products, high mobility group protein B1, interleukin-1beta and tumor necrosis factor-alpha (using enzyme-linked immunosorbent assay), concentrations of malondialdehyde (using TBA method), and activity of superoxide dismutase (using hydroxylamine method). The dynamic lung compliance was recorded from T 0 to T 4. Blood samples were taken from the radial artery at T 0 and 24 h after surgery (T 5) for blood gas analysis, and oxygenation index and respiratory index were calculated. Lung ultrasound scores were recorded at 24 h before surgery and T 5. The postoperative mechanical ventilation time and duration of intensive care unit stay were recorded. The occurrence of ALI within 7 days after liver transplantation was observed. Results:Compared with group C, the serum concentrations of Clara cell secretory protein 16, surface active protein D, soluble receptor for advanced glycation end products, high mobility group protein B1, interleukin-1beta, tumor necrosis factor-alpha and malondialdehyde were significantly decreased, and the activity of superoxide dismutase was increased at T 3, 4, the oxygenation index was increased and respiratory index was decreased at T 3-T 5, lung ultrasound C score and B score were decreased at T 5, the postoperative mechanical ventilation time and duration of intensive care unit stay were shortened, and the incidence of ALI was decreased in group S ( P<0.05). Conclusions:Esketamine can alleviate postoperative ALI in pediatric patients undergoing living donor liver transplantation.

Objective:To compare the effects of different anesthesia methods on perioperative lung injury in pediatric patients with biliary atresia undergoing living donor liver transplantation.Methods:Ninety-one American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ pediatric patients with biliary atresia, regardless of gender, aged 0-36 months, with cardiac function grade of Ⅰ or Ⅱ and Child-Pugh grade of B or C, undergoing elective living donor liver transplantation, were selected. According to the anesthesia method, the pediatric patients were divided into 3 groups: propofol-based anesthesia group (P group, n=30), sevoflurane-based anesthesia group (S group, n=30) and propofol-sevoflurane-based anesthesia group (PS group, n=31). Group P received intravenous infusion of 1% propofol 9-15 mg·kg -1·h -1. In group S, sevoflurane was inhaled and the end-tidal concentration was maintained at 2.6%-4.0%.In PS group, 1% propofol 9-15 mg·kg -1·h -1 was intravenously infused and sevoflurane was inhaled, maintaining an end-tidal concentration at 1.0%-2.5%. Remifentanil 0.1-1.0 μg·kg -1·min -1 was intravenously infused during operation for analgesia, and cisatracurium besylate 1-2 μg·kg -1·min -1 was intravenously infused to maintain muscle relaxation in three groups. Immediately after anesthesia induction (T 0), at 60 min after start of surgery (T 1), at 10 min of anhepatic phase (T 2), at 60 min after portal vein opening (T 3), and immediately after abdominal closure (T 4), the concentrations of serum Clara cell secretory protein 16 (CC16), surfactant protein (SP-D), soluble receptors for advanced glycation end products (s-RAGE), high mobility group protein B1 (HMGB1), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were measured using enzyme-linked immunosorbent assay method, and lung compliance (Cdyn) was simultaneously recorded. At T 0-T 4 and 24 h after surgery (T 5), the arterial blood gas analysis was performed to calculate the oxygenation index (OI) and respiratory index (RI). Lung ultrasound scores (LUS scores) were assessed at 24 h before surgery and T 5. The occurrence of pulmonary complications was recorded within 7 days after surgery. The survival was observed for 6 months after surgery. Results:There were no statistically significant differences in serum concentrations of CC16, SP-D and s-RAGE concentrations and LUS scores at different time points between group S and group P ( P>0.05). Compared with S group and P group, the serum CC16 concentrations at T 3 and s-RAGE concentrations at T 3, 4 were significantly decreased, and the C and B scores were decreased at T 5 in PS group ( P<0.05). There were no statistically significant differences in the concentrations of serum HMGB1, IL-1β and TNF-α, Cydn and incidence of ALI/ARDS, pulmonary infection, pleural effusion, and atelectasis within 7 days after surgery among the three groups( P>0.05). The 6-month survival rate was 100% in the three groups. Conclusions:Propofol-sevoflurane-based anesthesia has a better efficacy in reducing perioperative lung injury than propofol-based anesthesia and sevoflurane-based anesthesia in the perioperative period of liver transplantation.