Zhiqiang Yuan

Effects of early enteral feeding on the prevention of enterogenic infection in severely burned patients

The aim of the study was to analyse the effects of early enteral feeding on the prevention of enterogenic infection in severely burned patients. A total of 22 patients with severe burns were randomly divided into an early enteral feeding group (EF) and a delayed enteral feeding group (DF). The levels of serum endotoxin and TNF-alpha were dynamically detected in the members of both groups, and two unmetabolized sugars (lactulose and mannitol) were orally administered to these patients 1, 3 and 5 days postburn. Intestinal permeability was evaluated by detecting the concentrations of lactulose and mannitol in the urine and the lactulose-mannitol ratio (L/M) ratio. The levels of serum endotoxin and TNF-alpha in severely burned patients were significantly higher than in normal subjects (P<0.01). The endotoxin level was positively related to the TNF-alpha level (rEF=0.93, P<0.01; rDF=0.80, P<0.05). The urinary lactulose levels in both groups were significantly higher than in normal (P<0.01), the urinary mannitol levels showed no obvious changes (P>0.05). The urinary L/M ratios in both groups were significantly higher than in normal subjects (P<0.01). The urinary L/M ratio was positively related to the serum endotoxin level (r=0.95, P<0.01). The urinary lactulose levels and the urinary L/M ratios in the EF group were significantly lower than in the DF group (P<0.01). The levels of serum endotoxin and TNF-alpha in the EF group were significantly lower than in the DF group (P<0.01). It is suggested that intestinal permeability was markedly higher after burns than normal, and was positively related to the gut-derived endotoxemia. Early enteral feeding may decrease intestinal permeability, preserve the intestinal mucosal barrier and have a beneficial effect on the reduction of enterogenic infection.

HSP70 protects intestinal epithelial cells from hypoxia/reoxygenation injury via a mechanism that involves the mitochondrial pathways

Though recent studies have reported the importance of several endogenous cytoprotective factors including heat shock protein 70 (HSP70) that protect intestinal epithelial cells (IECs) from the effects of stress and injury, the exact mechanism of HSP70 underlying cytoprotection against hypoxia/reoxygenation induced IEC injury remains unclear. The present study was designed to investigate the possible mechanisms by which HSP70 protected IECs against hypoxia/reoxygenation injury and focused on the effects of HSP70 on IEC apoptosis induced by hypoxia/reoxygenation injury. Recombinant adenoviruses (Ad-HSP70) were transfected into the intestinal epithelial cell line in vitro and then suffered from 90 min of hypoxia followed by 60 min of reoxygenation. The LDH leaking, apoptosis, and mitochondrial membrane potential (Psi(m)) were evaluated after hypoxia/reoxygenation. The expression of HSP70, cytochrome c and Bcl-2 protein was determined by Western blot or immunofluorescence analysis. The results show that HSP70 protein was highly expressed in the IECs at 48h following Ad-HSP70 transfection. HSP70 overexpression could reduce LDH leakage and cell apoptosis in IECs following hypoxia/reoxygenation injury. Furthermore, the overexpression of HSP70 significantly reversed the decrease of mitochondrial membrane potential and the release of mitochondrial cytochrome c in IECs during hypoxia/reoxygenation. HSP70 overexpression was also associated with the increasing expression of Bcl-2 protein in IECs during hypoxia/reoxygenation. We conclude that HSP70 protects IECs against hypoxia/reoxygenation induced apoptosis through increasing Bcl-2 expression, which in turn could inhibit the mitochondria-related apoptotic pathway that involves the disruption of the Psi(m) and release of cytochrome c from mitochondria.

Inhalation injury in southwest China—The evolution of care

AIM This study aims to review the changes in management of inhalation injury and the associated reduction in mortality over the past 2 decades. METHODS The records of burn patients with inhalation injury hospitalised in our institute from 1986 to 2005 were retrospectively analysed. The incidence of inhalation injury and the associated mortality were analysed. Meanwhile, the relationship of inhalation injury with age, total burn area, tracheostomy intubation and mechanical ventilation were studied. RESULTS The incidence of inhalation injury was 8.01% in the total 10 608 hospitalised burn patients during the 20 years surveyed. Inhalation injury was always associated with large-sized burn and was more common in adults. The incidence of tracheostomy and mechanical ventilation increased from 39.46 and 30.28% in the period from 1986 to 1995 to 70.12 and 39.74% from 1996 to 2005, respectively. The overall mortality of inhalation-injured burn patients was 15.88% compared with 0.82% of the non-inhalation group. The mortality of the burn patients with inhalation injury dropped from 25.29% during the first 10 years to 11.71% during the second decade (p<0.01). Mortality secondary to inhalation injury as the lead cause decreased from 14.56 to 6.29% (p<0.01). CONCLUSION The care of inhalation injury has made significant progress over the past 2 decades. The early diagnosis of inhalation injury, early airway control and pulmonary function assistance with mechanical ventilation contribute to the reduction of mortality.

Fluid resuscitation for major burn patients with the TMMU protocol

BACKGROUND Fluid resuscitation is one of the critical treatments for the major burn patient in the early phases after injury. We evaluated the practice of fluid resuscitation for severely burned patients with the Third Military Medical University (TMMU) protocol, which is most widely used in many regions of China. METHODS Patients with major burns (>30% total body surface area (TBSA)) presenting to Southwest Hospital, Third Military Medical University, between January 2005 and October 2007, were included in this study. Fluid resuscitation was initiated by the TMMU protocol. RESULTS A total of 71 patients were (46 adults and 25 children) included in this study. All patients survived the first 48 h after injury smoothly and none developed abdominal compartment syndrome or other recognised complications associated with fluid resuscitation. The average quantity of fluid infused was 3.3-61.33% more than that calculated based on the TMMU protocol in both adult and paediatric groups. The average urine output during the first 24h after injury was about 1.2 ml per kg body weight per hour in the two groups, but reached 1.2 ml and 1.7 ml during the second 24h in adult and pediatric groups, respectively. CONCLUSION This study indicates that the TMMU protocol for fluid resuscitation is a feasible option for burn patients. Individualised resuscitation - guided by the physiological response to fluid administration - is still important as in other protocols.

Yeast from burn patients at a major burn centre of China

AIM This study presents fungi and their characteristics identified from burn patients at a major Chinese burn centre. METHODS All burns patients admitted to our Burn Research Institute from 2003 to 2006 inclusive were included in this study. Once fungal infection was suspected clinically, samples including wound tissue, blood, urine, stool and sputum were harvested for the culture of yeast. The sensitivities of the identified yeast were determined and the positive samples and cases were analysed. RESULTS Out of a total of 3909 cases, 467 patients were clinically suspected of fungal infection, of which 1970 samples were taken for yeast culture. A total of 38 samples and 36 patients tested positive. The three most positive samples were urine, blood and catheter. Candida tropicalis was identified as the most common yeast type (42.1%), followed by Candida albicans (31.6%), Candida famata (T. Famata) (10.5%) and Candida glabrata (T. Glabrata) (7.9%). Except for C. galbrata, most of the yeast strains found in the study were sensitive to the routine antimycotic agents. There were eight deaths in the 36 positive patients. As much as 83.3% of the positive cases suffered burns of more than 50% total body surface area (TBSA) and half of the positive cases were greater than 80% TBSA. A total of 78.95% of the positive samples were taken from patients after 2 weeks post-burn injury. CONCLUSION A profile of the fungi isolated from burn patients in a major Chinese burn centre is presented.

Heat shock protein 90β inhibits apoptosis of intestinal epithelial cells induced by hypoxia through stabilizing phosphorylated Akt

Intestinal epithelial cell (IEC) apoptosis induced by hypoxia compromise intestinal epithelium barrier function. Both Akt and Hsp90 have cytoprotective function. However, the specific role of Akt and Hsp90β in IEC apoptosis induced by hypoxia has not been explored. We confirmed that hypoxia-induced apoptosis was reduced by Hsp90β overexpression but enhanced by decreasing Hsp90β expression. Hsp90β overexpression enhanced BAD phosphorylation and thus reduced mitochondrial release of cytochrome C. Reducing Hsp90β expression had opposite effects. The protective effect of Hsp90β against apoptosis was negated by LY294002, an Akt inhibitor. Further study showed that Akt phosphorylation was enhanced by Hsp90β, which was not due to the activation of upstream PI3K and PDK1 but because of stabilization of pAkt via direct interaction between Hsp90β and pAkt. These results demonstrate that Hsp90β may play a significant role in protecting IECs from hypoxia-induced apoptosis via stabilizing pAkt to phosphorylate BAD and reduce cytochrome C release. [BMB Reports 2013;46(1): 47-52]

Characteristics of burn deaths from 2003 to 2009 in a burn center: A retrospective study

Mortality remains one of the most important end-point quality control parameters to evaluate a burn care system. We retrospectively reviewed the characteristics and multiple organ dysfunction syndrome (MODS) patterns of burn deaths in our center from January 2003 to December 2009. The mortality rate during this time period was 2.3%. Fifty-six patients died, including 49 males and 7 females. The mean survival time was 28.45 ± 24.60 days. The burn percentage was (76.70 ± 26.86) % total burn surface area (TBSA), with (27.74 ± 24.95) % deep-partial thickness burns and (46.88 ± 33.84) % full-thickness burns. Inhalation injury was diagnosed in 36 (64.29%) patients. Patients who had undergone an operation, particularly in the first week post-burn, had a significantly longer survival time. An average of 5.50 ± 1.35 malfunctioning organs per patient and a mean sequential organ failure assessment (SOFA) score of 13.91 ± 3.65 were observed. The most frequently malfunctioning organs were involved in the respiratory, hematologic, circulatory, and central nervous systems. Most of the organ damage occurred during the first week post-burn, followed by 4 weeks later, with relatively less organ damage observed in the third week. Among patients with a TBSA over 50%, non-survivors had larger burn sizes (particularly larger full-thickness burns) and a higher incidence of inhalation injury compared with survivors; non-survivors were also more likely to have microorganism-positive blood and sputum cultures. In conclusion, burn deaths are related to a higher burn percentage, inhalation injury, MODS, and infection. Early operation may help improve survival duration.

Astragaloside-IV Alleviates Heat-Induced Inflammation by Inhibiting Endoplasmic Reticulum Stress and Autophagy

Background: Thermal injury is the main cause of pulmonary disease in stroke after burn and can be life threatening. Heat-induced inflammation is an important factor that triggers a series of induces pathological changes. However, this mechanism underlying heat-induced inflammation in thermal inhalation injury remains unclear. Studies have revealed that astragaloside-IV (AS-IV), a natural compound extracted from Astragalus membranaceus, has protective effects in inflammatory diseases. Here, we investigated whether the protective effects of AS-IV occur because of the suppression of heat-induced endoplasmic reticulum (ER) stress and excessive autophagy Methods: AS-IV was administered to Wistar rats after thermal inhalation injury and 16HBE140-cells were treated with AS-IV. TNF-α, IL-6, and IL-8 levels were determined by ELISA and real-time PCR. ER stress and autophagy were determined by western blot. Autophagic flux was measured by recording the fluorescence emission of the fusion protein mRFP-GFP-LC3 by dynamic live-cell imaging. Results: AS-IV had protective effects against heat-induced reactive oxygen species production and attenuated ER stress. AS IV alleviated heat-induced excessive autophagy in vitro and in vivo. Excessive autophagy was attenuated by the PERK inhibitor GSK2656157 and eIF2α siRNA, suggesting that heat stress-induced autophagy can activate the PERK-eIF2α pathway. Beclin 1 and Atg5 siRNAs inhibited the upregulation of the inflammatory cytokines TNF-α, IL-6, and IL-8 after heat exposure. Conclusions: Thus, AS-IV may attenuate inflammatory responses by disrupting the crosstalk between autophagy and the PERK-eIF2α pathway and may be an ideal agent for treating inflammatory pulmonary diseases.

Burn Serum Increases Staphylococcus aureus Biofilm Formation via Oxidative Stress

Staphylococcus aureus is a common pathogen isolated from burn patients that can form biofilms on burn wounds and implanted deep vein catheters, which often leads to refractory infections or even biofilm-related sepsis. As biofilm formation is usually regulated by environmental conditions, we hypothesized that serum composition may be altered after burn injury, potentially affecting the ability of infecting bacteria to form biofilms. As predicted, we observed that serum from burn-injured rats increases biofilm formation by S. aureus and also induces bacterial aggregation and adherence to human fibronectin and fibrinogen. Analysis of potential regulatory factors revealed that exposure to burn serum decreases expression of the quorum-sensing agr system and increases mRNA levels of some biofilm inducers such as sarA and icaA. In addition, we also observed that burn serum imposes oxidative stress and increases expression of key oxidoreductase genes (sodA, sodM, katA, and ahpC) in S. aureus. Importantly, the ability of burn serum to enhance biofilm formation and bacterial cell aggregation can be abrogated by treatment with an antioxidant. Taken together, these findings indicate that burn serum increases S. aureus biofilm formation via elevated oxidative stress, and may lead to novel strategies to control biofilm formation and infection in burn patients.

A 5-year Survey Reveals Increased Susceptibility to Glycopeptides for Methicillin-Resistant Staphylococcus aureus Isolates from Staphylococcus aureus Bacteremia Patients in a Chinese Burn Center

Methicillin-resistant Staphylococcus aureus (MRSA) infections are prevalent in burn wards, and are especially serious in S. aureus bacteremia (SAB) patients. Glycopeptides and daptomycin are effective against MRSA infections, but MIC creeps can reduce their efficacy. Our object was to perform a molecular epidemiological investigation of S. aureus isolates in our burn center and to evaluate MICs for antimicrobials against SAB-associated MRSA isolates. A total of 259 S. aureus isolates, obtained from August 2011 to July 2016, were used in this study. Multiple molecular typing was used for molecular epidemiological analysis. E-tests were used to determine MICs of vancomycin, teicoplanin, and daptomycin for SAB-associated MRSA isolates. MIC values were stratified by collection date or source and compared. Spearmans test was used to analyze MICs correlations amongst tested antimicrobials. ST239-MRSA-III-t030-agrI clone was found to be dominant in both SAB and non-SAB patients, and significantly more in SAB patients (P < 0.0001). SAB-MRSA isolates exhibited decreased MICs for vancomycin, teicoplanin, and daptomycin during the 5-year period. Compared to those isolated from catheters or wounds, SAB-MRSA isolates from the bloodstream were less susceptible to vancomycin and daptomycin, but more susceptible to teicoplanin. MICs Correlation was found only between vancomycin and daptomycin in MRSA isolates from the bloodstream (rho = 0.250, P = 0.024). In conclusion, our results suggest that MRSA infections are still serious problems in burn centers. In contrast to most other studies, we observed increased susceptibility to glycopeptides and daptomycin against SAB-associated MRSA in our center from 2011 to 2016, suggesting the use of glycopeptides does not lead to MIC creeps. Isolates from different sites of the body may exhibit different levels of susceptibility and change trend over time for different antimicrobials, antimicrobials selection for MRSA infections should be considered comprehensively.