Effect of breastfeeding on the development of infection-related diseases during hospitalization in late preterm infants in 25 hospitals in Beijing, China / 中国当代儿科杂志

OBJECTIVE@#To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases.@*METHODS@#Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases.@*RESULTS@#A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, @*CONCLUSIONS@#Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.

Effects of adipose-derived stem cells and non-methylated CpG-oligodeoxynucleotides on peripheral blood CD4CD25regulatory T cells in young mice with food allergy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effects of adipose-derived stem cells (ADSC) and non-methylated CpG-oligodeoxynucleotides (CpG-ODN) on the expression of peripheral blood CD4CD25regulatory T (Treg) cells in young mice with food allergy, as well as their immune intervention effects.</p><p><b>METHODS</b>A total of 40 female BALB/c mice were randomly divided into control group, allergic group, ADSC treatment group, and CpG-ODN treatment group, with 10 mice in each group. A mouse model of food allergy was established by intraperitoneal injection and intragastric administration of ovalbumin (OVA) for sensitization and challenge. The mice in the control group were treated with normal saline at the same dose; the mice in the ADSC treatment group were given intraperitoneal injection of ADSC (1×10cells for each mouse) before and after OVA challenge, and those in the CpG-ODN treatment group were given intraperitoneal injection of non-methylated CpG-ODN solution (40 μg for each mouse) at 1 hour before challenge by gavage. The allergic symptom scores were determined for each group after model establishment. ELISA was used to measure the serum level of OVA-IgE. Flow cytometry was used to measure the percentage of peripheral blood CD4CD25Treg cells. Hematoxylin and eosin staining was used for the pathological analysis of the jejunum.</p><p><b>RESULTS</b>The allergic group had significantly higher allergic symptom scores and serum level of OVA-IgE than the control group (P<0.05). There were no significant differences in the allergic symptom score and the serum level of OVA-IgE between the ADSC treatment group and the CpG-ODN treatment group (P>0.05), but these two groups had significantly lower allergic symptom scores and serum level of OVA-IgE than the allergic group and significantly higher allergic symptom scores and serum level of OVA-IgE than the control group (P<0.01). The allergic group had a significantly lower percentage of peripheral blood CD4CD25Treg cells than the control group (P<0.05). The ADSC treatment group and the CpG-ODN treatment group had a significantly higher percentage of peripheral blood CD4CD25Treg cells than the allergic group (P<0.05); there were no significant differences between these two groups or between them and the control group (P>0.05). Pathological results showed structural damage and edema in the jejunal villi, a large number of eosinophils, and lymphocyte infiltration in the allergic group, while the ADSC treatment group and the CpG-ODN treatment group had less structural damage and edema in the jejunal villi, a lower number of eosinophils, and less lymphocyte infiltration.</p><p><b>CONCLUSIONS</b>ADSC and non-methylated CpG-ODN have a certain effect in the treatment of food allergy and can increase the percentage of peripheral blood CD4CD25Treg cells and reduce the level of OVA-IgE. They may be associated with the induction of immune tolerance and these two treatment have comparable effects. Detailed mechanisms of action still need further investigation.</p>

Effect of high mobility group box protein 1 on the Kupffer cells of rats with severe burn and the role of receptor for advanced glycation end products in the process / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the effect of high mobility group box protein 1 (HMGB1) on the production of pro-inflammatory cytokines by Kupffer cell (KC) of rats with severe burn and the role of receptor for advanced glycation end products (RAGE) in the process.</p><p><b>METHODS</b>Model of 30% TBSA full-thickness burn was reproduced in 32 SD rats through immersing the back in 98°C water for 12 s. KC (32 samples) was isolated from rat liver 24 h after injury and inoculated in 24-well plate in the concentration of 1×10(6) cell per well. (1) Cells were divided into control group (cultured with 1 mL PBS) and HMGB1 group (stimulated with 100 ng/mL HMGB1 in the volume of 1 mL) according to the random number table, with 8 samples in each group. At post culture hour (PCH) 48, the expression of RAGE (denoted as grey value ratio) was detected with Western blotting. (2) Another portion of cells were divided into control group (cultured with 1 mL PBS), HMGB1 group (treated with 100 ng/mL HMGB1 in the volume of 1 mL), HMGB1 + anti-RAGE antibody group (treated with 100 ng/mL HMGB1 in the volume of 1 mL after being pre-incubated with 20 µg/mL anti-RAGE monoclonal antibody in the volume of 1 mL for 2 hours), HMGB1 + recombinant rat RAGE/Fc chimera (rrRAGE/Fc) group (treated with the mixture of 100 ng/mL HMGB1 in the volume of 0.5 mL and 5 µg/mL rrRAGE/Fc in the volume of 0.5 mL which were pre-incubated for 2 hours) according to the random number table, with 8 samples in each group. At PCH 48, the protein levels of TNF-α and IL-1β in supernatant were determined with enzyme-linked immunosorbent assay, while the mRNA expression of TNF-α and IL-1β (denoted as grey value ratio) were determined with Northern blotting. Data were processed with one-way analysis of variance, t test, and LSD test.</p><p><b>RESULTS</b>(1) The expression of RAGE in HMGB1 group (1.036 ± 0.101) was significantly higher than that of control group at PCH 48 (0.191 ± 0.024, t = -23.158, P = 0.000). (2) In HMGB1 group, HMGB1 + anti-RAGE antibody group, and HMGB1 + rrRAGE/Fc group, the contents of TNF-α in supernatant were respectively (10.59 ± 1.39), (9.91 ± 1.68), (11.51 ± 2.27) ng/mL; the contents of IL-1β in supernatant were respectively (2.49 ± 0.33), (2.08 ± 0.32), (2.42 ± 0.42) ng/mL; the mRNA levels of TNF-α in cells were respectively 0.311 ± 0.009, 0.301 ± 0.047, 0.326 ± 0.016; the mRNA levels of IL-1β in cells were respectively 0.237 ± 0.021, 0.244 ± 0.041, 0.245 ± 0.013. There were no statistically significant differences in the above indexes among these three groups (with P values all above 0.05). Their levels were all significantly higher than those of control group [with contents of TNF-α and IL-1β in supernatant respectively (2.69 ± 0.14), (0.43 ± 0.05) ng/mL, and mRNA levels of TNF-α and IL-1β in cells respectively 0.140 ± 0.022, 0.077 ± 0.005, P values all below 0.01].</p><p><b>CONCLUSIONS</b>HMGB1 can induce the production of pro-inflammatory cytokines TNF-α and IL-1β from the KC in rats with severe burn. However, RAGE does not play a predominant role in this process.</p>

Unplanned decannulation of tracheotomy tube in massive burn patients: a retrospective case series study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Unplanned extubation is associated with adverse outcomes in intensive care unit. The massive burn patient differs from other critically ill patients in many ways. However, little is known about the unplanned decannulation (UD) in Burn Intensive Care Unit. This paper describes the special features of the circumstances and outcome of UD of tracheotomy tube in massive burn patients.</p><p><b>METHODS</b>A case series study was performed between January 1999 and December 2008 and UD of tracheotomy tube was analyzed retrospectively. A total of 21 patients with 29 UD events were identified. Demographic data, diagnosis, intervention, UD events and outcome of UD patients were collected. Differences in proportions were compared using the chi-square (χ(2)) or Fisher's exact test.</p><p><b>RESULTS</b>Patients with UD were often burned with head and neck (67%) and combined with inhalation injury (62%). The majority of them (76%) were transferred patients, occurred early (55%) and were accidental UD (79%). UD events tended to happen in day shift (90%) and to be associated with the medical procedure that was performing by caregivers at besides (79%). Loose of the stabilizing rope, medical procedure and tracheotomy malposition were the main causes of UD. Early UD and reintubation failure were associated with patients' death.</p><p><b>CONCLUSIONS</b>UD happened to massive burn patients can lead to patient death. Careful management of respiratory tract was essential for massive burn patients.</p>

Role of angiotensin II-angiotensin II type 1 receptor pathway in the production of proinflammatory cytokines in macrophage / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the role of angiotensin II (AngII)-angiotensin II type 1 receptor (AT1R) pathway in the production of proinflammatory cytokines in macrophage, and to analyze its mechanisms.</p><p><b>METHODS</b>RAW264.7 macrophages were cultured in vitro in DMEM nutrient medium containing 10% FBS, and then they were divided into control group (ordinary culture for 6 hours without any stimulation), ZD7155 group (pretreated with 38 µmol/L AT1R-specific inhibitor ZD7155 for 1 hour, then cultured with fresh nutrient solution for 6 hours), AngII group (cultured with 0.01 µmol/L AngII for 6 hours), and ZD7155 + AngII group (pretreated with 38 µmol/L AT1R-specific inhibitor ZD7155 for 1 hour, then cultured with 0.01 µmol/L AngII for 6 hours) according to the random number table. Contents of TNF-α and IL-1β in the supernatant were measured by ELISA. Expressions of TNF-α mRNA and IL-1β mRNA were determined by RT-PCR. Activity of NF-κB and AP-1 were examined by electrophoretic mobility shift assay. Data were processed with one-way analysis of variance.</p><p><b>RESULTS</b>Compared with those in AngII group [(119 ± 14), (105 ± 17) pg/mL, respectively], the levels of TNF-α and IL-1β in the supernatant in control group [(24 ± 11), (24 ± 6) pg/mL, with F value respectively 1.62, 8.03, P values all below 0.01], ZD7155 group [(22 ± 11), (25 ± 8) pg/mL, with F value respectively 1.62, 4.52, P values all below 0.01], and ZD7155 + AngII group [(45 ± 13), (62 ± 11) pg/mL, with F value respectively 1.16, 2.29, P < 0.05 or P < 0.01] were all obviously decreased. The expressions of TNF-α mRNA and IL-1β mRNA, and activity of NF-κB and AP-1 showed the similar changes as above: (1) The levels of TNF-α mRNA and IL-1β mRNA in AngII group were all higher than those in control group (with F value respectively 7.59, 3.38, P < 0.05 or P < 0.01), ZD7155 group (with F value respectively 10.66, 2.24, P values all below 0.05), and ZD7155 + AngII group (with F value respectively 5.10, 5.09, P values all below 0.01). (2) Activity of NF-κB and AP-1 was respectively 69 027 ± 2502, 36 752 ± 2055 in AngII group, all higher than those in control group (45 709 ± 1203, 20 325 ± 2695, with F value respectively 4.32, 1.72, P values all below 0.01), ZD7155 group (46 303 ± 1897, 21 951 ± 2517, with F value respectively 1.74, 1.50, P values all below 0.01), and ZD7155 + AngII group (38 271 ± 690, 22 365 ± 3797, with F value respectively 13.13, 3.41, P values all below 0.01).</p><p><b>CONCLUSIONS</b>AngII can mediate activation of transcription factor NF-κB and AP-1 via combination of AT1R, thereby contributing to the production and release of proinflammatory cytokines TNF-α and IL-1β in macrophage.</p>

Mechanisms of HIV envelope-induced T lymphocyte apoptosis / 中国病毒学·英文版

Infection by the human immunodeficiency virus (HIV) is characterized by a progressive depletion of CD4 T lymphocytes, which leads to dysfunction of the immune system. Although a variety of mechanisms may contribute to the gradual T cell decline that occurs in HIV-infected patients, abnormal apoptosis of infected or bystander T lymphocytes is an important event leading to immunodeficiency. The HIV envelope glycoprotein plays a crucial role in HIV associated apoptosis through both death receptor-mediated and mitochondria-dependent pathways. This review summarizes current knowledge of Env-mediated T lymphocyte apoptosis.

Observation on short and long-term effects of cervical spondylotic radiculopathy treated with abdominal acupuncture plus Long's bone-setting manipulation / 中国针灸

<p><b>OBJECTIVE</b>To compare the short and long-term therapeutic effects on cervical spondylotic radiculopathy (CSR) treated with simple Long's bone-setting manipulation, abdominal acupuncture and abdominal acupuncture plus Long's bone-setting manipulation.</p><p><b>METHODS</b>One hundred and eighty cases of CSR were randomly allocated into abdominal acupuncture plus bone-setting group (combined therapy group), bone-setting group and abdominal acupuncture group, 60 cases in each group. In combined therapy group, the abdominal acupuncture and Long's bone-setting were applied in combination. Abdominal acupuncture was applied to Zhongwan (CV 12), Guanyuan (CV 4), Shiguan (KI 18), Shangqu (KI 17), etc. Long's manipulation, such as bone-setting in head-upward posture and bone-setting in head-lateral posture, was adopted. In bone-setting group and abdominal acupuncture group, Long's bone-setting manipulation and abdominal acupuncture were adopted simply and respectively. The clinical therapeutic effects were compared after 2 courses of treatment (short-term) and 1-month after treatment (long-term) among groups.</p><p><b>RESULTS</b>The short and long-term curative and markedly effective rates in combined therapy group were 80.7% (46/57) and 68.4% (39/57) respectively, which were better than those of 63.64% (35/55), 30.9% (17/55) in bone-setting group and 58.9% (33/56), 50.0% (28/56) in abdominal acupuncture group, separately (all P < 0.05). Moreover, the long-term curative and markedly effective rate in abdominal acupuncture group was superior to that in bone-setting group (P < 0.05).</p><p><b>CONCLUSION</b>Abdominal acupuncture plus Long's bone-setting manipulation has significant efficacy of either short or long-term on CSR, which is superior to the efficacy of either simple abdominal acupuncture or Long's bone-setting manipulation and indicates superimposed effect. Hence, it is one of the better approaches in CSR treatment.</p>

Role of angiotensin II type 1 receptor in activation of nuclear factor-kappaB and activator protein-1 in lung of mice with acute lung injury / 中华烧伤杂志

<p><b>OBJECTIVE</b>To explore the role of angiotensin II type 1 (AT1) receptor in activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) in lung of mice with LPS-induced acute lung injury (ALI).</p><p><b>METHODS</b>Eighty-eight BABL/c mice were divided into control group (n = 8), LPS group (n = 40), and LPS + AT1 receptor antagonist ZD7155 group (n = 40) according to the random number table. Puncture of trachea was done in all mice. Mice in LPS + ZD7155 group were intraperitoneally injected with 10 mg/kg ZD7155. Mice in LPS and control groups were intraperitoneally injected with normal saline in the same volume as that of ZD7155. Thirty minutes later, 1 mg/mL LPS was dripped into trachea of mice in LPS and LPS + ZD7155 groups (2 mg/kg). Normal saline in the same volume as that of LPS was dripped into trachea of mice in control group. Lung tissue samples of mice in LPS and LPS + ZD7155 groups were harvested at post dripping hour (PDH) 1, 3, 6, 12, and 24. Lung tissue sample of mice in control group was harvested at PDH 24. Expression of AT1 receptor was determined with Western blot. AP-1 and NF-kappaB activity in lung tissue was detected with electrophoretic mobility shift assay. Data were processed with one-way analysis of variance.</p><p><b>RESULTS</b>The relative expression amount of AT1 receptor protein in lung tissue of mice in LPS group at each time point was increased obviously as compared with that of mice in control group (0.69 +/- 0.28, F = 9.356, with P values all below 0.01), and it peaked at PDH 6 (3.44 +/- 0.90), while that of mice in LPS + ZD7155 group was less than that in LPS group at each time point (F = 9.356, with P values all below 0.01). NF-kappaB activity in mice lung was markedly increased in LPS group at each time point as compared with mice in control group (5.47 +/- 0.08, F = 26.443, with P values all below 0.05), and its peak value in LPS group was found at PDH 3 (52.33 +/- 3.25). While NF-kappaB activity in mice of LPS + ZD7155 group was obviously lower than that in LPS group at each time point (F = 26.443, with P values all below 0.05). AP-1 activity in lung was enhanced significantly in LPS group at each time point as compared with that in control group (2.5 +/- 0.4, F = 34.685, with P values all below 0.05), and the activity peaked at PDH 6 (73.3 +/- 9.5) in LPS group. The activity was obviously weaker in mice in LPS + ZD7155 group as compared with that in LPS group at each time point (F = 34.685, with P values all below 0.05).</p><p><b>CONCLUSIONS</b>AT1 receptor contributes to LPS-induced ALI through activating NF-kappaB and AP-1 in lung tissue.</p>

Repair of deep burn and traumatic wounds in lower extremities with combined transplantation of multiple pedicled skin flaps / 中华烧伤杂志

<p><b>OBJECTIVE</b>To summarize the clinical experience in repair of deep burn and traumatic wounds with combined transplantation of different types of pedicled skin flaps in lower extremities.</p><p><b>METHODS</b>Two hundred and thirty-six patients with 271 deep wounds in lower extremities after burn or trauma were repaired with muscular skin flaps, local fascial flaps and island flaps with vascular pedicle (more than 20 types) in our department from Jan. 1998 to Sept. 2008.</p><p><b>RESULTS</b>Complete necrosis of skin flaps occurred in 1 case, congestion and necrosis over the edge of skin flaps occurred in 3 cases, which were healed after grafting, and other skin flaps survived well with soft texture. Skin flaps were too bulky in 26 cases, among them 17 cases were thinned, and the appearance of other skin flaps were satisfactory. In 68 patients with functional region injury were recovered to certain extent without contracture.</p><p><b>CONCLUSIONS</b>Skin flaps with pedicles, multiple transplantations if necessary, can repair deep wounds satisfactorily in lower extremities after deep burn or trauma injury.</p>

Interaction between p38 mitogen-activated protein kinase signal transduction pathway and NF-kappaB/IkappaB system on the proinflammatory cytokines release after burn trauma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the interaction between p38 mitogen-activated protein kinase signal transduction pathway and nuclear factor (NF)-kappaB/IkappaB system on the proinflammatory cytokines release after burn trauma.</p><p><b>METHODS</b>Human monocyte line THP-1 were incubated with serum from eight healthy controls, burn sera, burn sera pretreatment with SB203580, and burn sera pretreatment with pyrrolidine dithiocarbamate (PDTC). After 24 hours incubation with serum, tumor necrosis factor (TNF)-alpha and interleukin-1beta (IL-1beta) levels in THP-1 culture supernatants were measured by ELISA. The activities of p38 MAPK and expressions of IkappaBalpha in THP-1 were measured by Western blot analysis. The EMSA method was used to characterize the binding activities of NF-kappaB and activating protein (AP)-1 in THP-1.</p><p><b>RESULTS</b>In comparison with normal controls, burn sera resulted in a significant higher level release of TNF-alpha and IL-1beta in THP-1 [(7.30 +/- 0.84) ng/ml vs (2.20 +/- 0.28) ng/ml, P < 0.05; (2.88 +/- 0.38) ng/ml vs (0.81 +/- 0.14) ng/ml, P < 0.05], which were significantly inhibited by pretreatment with SB203580 or PDTC. Burn sera showed increased activities of p38 MAPK and AP-1 in THP-1 (4728 +/- 582 vs 1291 +/- 163, P < 0.05; 946 +/- 137 vs 361 +/- 40, P < 0.05), which were abolished by pretreatment with SB203580 but not PDTC. The expression of IkappaBalpha in THP-1 incubated with burn sera was significantly decreased than those incubated with control sera (1211 +/- 115 vs 2658 +/- 318, P < 0.05), which were abolished by pretreatment with PDTC but not SB203580. Burn sera also leaded to an increased activity of NF-kappaB in THP-1 (1636 +/- 170 vs 317 +/- 32, P < 0.05), which were abolished by pretreatment with PDTC but not SB203580.</p><p><b>CONCLUSIONS</b>There are no direct interaction between p38 MAPK signal transduction pathway and NF-kappaB/IkappaB pathway. These two pathways, which regulate the production of TNF-alpha and IL-1beta in monocyte following burn trauma, are parallel and independent.</p>

Activation of nuclear factor-kappaB signaling pathway in rat gastric mucosa during stress ulceration / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the time course of nuclear factor-kappaB (NF-kappaB) activation in the process of stress ulcer formation.</p><p><b>METHODS</b>Model of stress ulcer was reproduced by subjecting male Sprague-Dawley rats to water-immersion restraint (WIR) stress. At indicated time after the beginning of WIR stress, animals were sacrificed and cytoplasmic and nuclear protein and total RNA were prepared from gastric corpus mucosal tissues. DNA-binding activity of NF-KB was assessed as an index of NF-kappaB activation with electrophoretic mobility shift assay. Degradation of IkappaBalpha and IkappaBbeta, the inhibitory proteins of NF-kappaB, was analyzed by Western blot analysis. Expression of NF-kappaB dependent genes including tumor necrosis factor-alpha (TNF-alpha) , interleukin-1beta (IL-1beta), cytokine-inducible neutrophil chemoattractant-1 ( CINC-1), intercellular adhesion molecule-1 (ICAM-1), and inducible nitric oxide synthase (iNOS) was detected with Northern blot analysis.</p><p><b>RESULTS</b>WIR stress induced a rapid biphasic activation of gastric mucosal NF-kappaB within 15 min of the beginning of stress, peaking at 45 min and 360 min. Compared with baseline, NF-kappaB activation by stress was increased (10.6 +/- 1.3) and (8.9 +/- 1.2) fold at 45 min and 360 min, respectively (P < 0.01). Antibody supershift assays revealed that p50/p65 heterodimer was the major active component of mucosal NF-kappaB. Western blot analysis showed that degradation of IkappaBalpha and IkappaBbeta occurred at first and second wave of NF-kappaB activation. Corresponding with the rapid and persistent activation of NF-kappaB, the levels of TNF-alpha, IL-1beta, CINC-1 and ICAM-1 mRNA in gastric mucosa were markedly increased 15 to 30 min after stress, respectively. Up-regulation of iNOS mRNAs was observed 30 to 90 min after stress, and the expression of all of these genes was increased consistently until the end of stress.</p><p><b>CONCLUSION</b>NF-kappaB activation is an early event and may play an important role in proinflammatory gene over-expression in rat gastric mucosa during WIR stress.</p>

Role of p38MAPK signal transduction pathway in Kupffer cells production of TNF-alpha and IL-1beta in severely burned rats / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway in the Kupffer cells production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in severely burns rats.</p><p><b>METHODS</b>Male health adult Sprague-Dawley rats were randomized into four groups: sham burn rats given vehicle, sham burn rats given the p38 MAP kinase inhibitor SB203580, rats given a 30% total body surface area (TBSA) full-thickness burn and fluid resuscitation plus vehicle, and burn rats given injury and fluid resuscitation plus SB203580. Rats from each group were killed at 24 h after burn or sham burn and Kupffer cells (KCs) were isolated. After 18 h incubation, KCs next were stimulated with 50 ng/ml of LPS for 18 h. After stimulation, supernatants were removed for analysis of TNF-alpha and IL-1beta levels by ELISA. The TNF-alpha and IL-1beta mRNA expressions (by quantitative real-time RT-PCR) and the activities of p38 MAPK and JNK (by Western blot analysis) in KCs were examined.</p><p><b>RESULTS</b>Eighteen hours after 50 ng/ml LPS stimulation, KCs from burn rats released significantly higher levels of TNF-alpha and IL-1beta than did shams. The mRNA levels of TNF-alpha and IL-1beta in KCs increased significantly postburn. Western blot analysis suggested that expression of phosphorylated p38 MAPK and JNK were increased in KCs harvested from burn group after stimulation with LPS compared with those from sham group. In vivo administration of SB203580 markedly suppressed both the release of TNF-alpha and IL-1beta and the mRNA expressions of TNF-alpha and IL-1beta in KCs from both sham and burn rats. p38 MAPK activity in KCs was abolished by administration with SB203580, whereas JNK was not.</p><p><b>CONCLUSIONS</b>p38 MAPK signal transduction pathway mediates KCs production of proinflammatory cytokines TNF-alpha and IL-1beta in severely burned rats.</p>

The modulating role of p38 mitogen-activated protein kinase in the expression of tumor necrosis factor-alpha in hepatic cells and its role in hepatic injury in severely burned rats / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate The modulating role of p38 mitogen-activated protein kinase (MAPK) in the expression of tumor necrosis factor-alpha in hepatic cells and its role in hepatic injury in severely burned rats.</p><p><b>METHODS</b>Twenty-four adult healthy male SD rats were randomly divided into three groups (8 rats in each group): sham group, burn group, and burn with SB203580 group. A rat model of full-thickness burn injury covering 30% total body surface area (TBSA) was reproduced. The specific inhibitor of p38MAPK (SB203580 in 10 mg/kg) was given to the rats in the burn with SB203580 group at 15 minutes and 12 hours after burn. The serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured at 24 postburn hours (PBHs). The TNF-alpha mRNA expression in the liver was determined by real-time reverse transcription polymerase chain reaction, and the expression levels of p38MAPK and phosphor-p38MAPK in the liver were determined by Western blot analysis.</p><p><b>RESULTS</b>The serum levels of AST and ALT, and the expression of TNF-alpha mRNA in liver cells were significantly higher in burn group than those in sham and SB203580 groups (P < 0.05 or 0.01), but there was no difference between the two latter groups. It was indicated by Western blot results that there was no difference of p38MAPK expression in rat liver among the three groups (P > 0.05). The phospho-p38MAPK expression ratio among sham, burn and burn with SB203580 groups was 1.00:3.90:1.10. The phospho-p38MAPK expression was significantly lower in burn with SB203580 group than that in burn group (P < 0.01), but there was no significant difference compared with that in sham group (P > 0.05).</p><p><b>CONCLUSION</b>The postburn activated p38MAPK in rat liver after severe burn injury enhances the expression of TNF-alpha mRNA and participates in the development of postburn hepatic injury.</p>

Activation of p38 MAPK signal transduction pathway by burn serum and the expression of VCAM-1 in HUVECs induced by NF-kappaB / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the influence of burn serum on the expression of vascular cell adhesion molecule-1 (VCAM-1) of human umbilical vein endothelial cells (HUVECs) andits signal transduction mechanism.</p><p><b>METHODS</b>HUVECs cultured in vitro were employed for the experiment, and were divided into normal control (NC, with addition of normal serum), burn serum (BS, with addition of burn serum), SB203580 (with addition of 10 micromol/L SB203580 treatment 1 hour before burn serum treatment) and PDTC [with 10 mmol/L pyrrolidine dithiocarbamate (PDTC) 1 hour before burn serum treatment] groups. Protein and mRNA expression of VCAM-1 in HUVECs was measured by flow cytometry and reverse transcription polymerase chain reaction (RT-PCR) respectively at 0, 6, 12, 24 and 36 hours after burn serum treatment. The expression of VCAM-1 on HUVEC surface and the soluble VCAM-1 (sVCAM-1) content in HUVECs culture supernatants were measured by ELISA at 24 hours after the serum stimulation. Adherence of peripheral blood mononuclear leukocytes (PBMC) adherence to HUVECs was also observed in vitro.</p><p><b>RESULTS</b>The expression of VCAM-1 mRNA increased obviously in BS group after the burn serum stimulation and reached peak level at 24 post stimulation hour (PSH), and it decreased thereafter. The above expression was significantly decreased in SB203580 and PDTC groups at 24 PSH, but there was no difference compared with normal control (P > 0.05). The VCAM-1 expression on the membrane of HUVEC was evidently higher in BS group (66.5 +/- 6.2) than that in NC group (19.1 +/- 1.9, P < 0.05) at 24 PSH, but it was decreased significantly in SB203580 (21.7 +/- 2.3) and PDTC (23.1 +/- 2.4) groups and there was no significant difference compared with NC group (P > 0.05), and which was evidently lower than that in BS group (P < 0.05). The VCAM-1 content in the supernatant of BS group (125 +/- 10 ng/L) was obviously higher than that in NC (23 +/- 3 ng/L), SB203580 (27 +/- 5 ng/L) and PDTC (29 +/- 5 ng/L) groups. (P < 0.05). The number of PBMCs adherent to HUVECs in BS group [(197 +/- 11)%] was much larger than that in NC group [(100 +/- 4)%], SB203580 group [(113 +/- 7)%] or PDTC group [(97 +/- 112)%] at 24 PSH (P < 0.05), but no difference between NC group and SB203580, PDTC groups (P > 0.05).</p><p><b>CONCLUSION</b>Burn serum can enhance the expression of VCAM-1 in HUVECs through p38 MAPK signaling pathway, and the activation of NF-kappaB was also involved in this process.</p>

Role of p38 mitogen-activated protein kinase signal transduction pathway in the acute lung injury of severely burned rats / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway in the acute lung injury of severely burned rats.</p><p><b>METHODS</b>Forty-eight adult healthy rats were randomly divided into three groups: sham group, burn control group, and burn + SB203580 group. A third-degree burns over 30% total body surface area rat model was used and pulmonary capillary permeability, lung water content, pulmonary histology and p38 MAPK activity were measured at 24 hours postburn.</p><p><b>RESULTS</b>Burn trauma resulted in increased pulmonary capillary leakage permeability (42.5 +/- 4.7 vs. 12.1 +/- 1.4, P < 0.01), elevated lung water content (P < 0.05), and worsen histologic condition. There was a significant activation of p38 MAPK at 24 hours postburn compared with control. SB203580 inhibited the activation of p38 MAPK, reduced the pulmonary capillary leakage permeability (24.7 +/- 2.9 vs. 42.5 +/- 4.7, P < 0.01), decreased lung water content, and prevented burn-mediated lung injury.</p><p><b>CONCLUSION</b>The activation of p38 MAPK is one important aspect of the signaling event that contributes to burn-induced lung injury.</p>

Mechanism of p38 mitogen-activated protein kinase in postburn acute pulmonary injury in scalded rats / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway in the production of the proinflammatory factors such as tumor necrosis factor (TNF-alpha) and interleukin 1beta (IL-1beta) in lungs and in the pulmonary endothelial cell injury in severely scalded rats.</p><p><b>METHODS</b>Forty eight adult healthy SD rats were randomly divided into three groups with 16 rats in each group, i.e. sham, burn and burn with SB203580 treatment groups. The changes in the TNF-alpha and IL-1beta contents in serum and bronchoalveolar lavage fluid (BALF), the von Willebrand factor (vWF) contents in plasma and pulmonary microvessels and pulmonary activating protein (AP-1) activity were determined at 24 postburn hours (PBH).</p><p><b>RESULTS</b>Compared with those in sham group, the TNF-alpha and IL-1beta contents in serum and BALF and the vWF content in plasma (194.2% +/- 28.3% vs 93.2% +/- 14.3%) at 24 PBH in burn group increased significantly (P < 0.01), whereas vWF content in pulmonary microvessel decreased obviously (1.1 +/- 0.3 vs 3.3 +/- 0.4, P < 0.01). In addition, the pulmonary AP-1 activity also increased at 24 PBH. Nevertheless, all the above indices improved obviously in burn with SB203580 (inhibitor of p38 MAPK signal transduction pathway) treatment group when compared with those in burn group.</p><p><b>CONCLUSION</b>AP-1 might mediate the production of proinflammatory factors, such as TNF-alpha and IL-1beta in lungs leading to pulmonary vascular endothelial injury, after being activated by activated p38 MAPK.</p>