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Objective: To analyze the relationship between D-lactate, intestinal fatty acid binding protein (I-FABP) and the severity as well as the prognosis of patients in intensive care unit (ICU)., Methods: Using a retrospective approach, the data derived from a prospective, randomized, single-blind, multicenter clinical study published earlier by our group were further analyzed to evaluate the effect of fat-modified enteral nutrition (EN) suspension on the intestinal barrier in ICU patients. In this study, a total of 141 patients were recruited from 7 ICUs in South China, and 15 healthy volunteers were included as healthy control group. Clinical data of patients were collected, including gender, age, disease severity related indicators such as acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), C-reactive protein (CRP) and initial ICU diagnosis, as well as prognostic indicators such as length of stay in ICU, length of stay in hospital and prognosis of patients at 28 days. To compare the difference of serum D-lactate and I-FABP between ICU patients and healthy control group on day 0 (the day before EN reached 500 mL) and day 5 (EN ≥ 2 092 kJ/d for 5 days). According to the hemodynamic and/or mechanical ventilation status on day 5 (compared with day 0), 141 patients were divided into the improvement group (101 cases) and the non-improvement group (40 cases), and the changes of D-lactate and I-FABP in the two groups were observed. Spearman correlation analysis was used to analyze the correlation between serum D-lactate, I-FABP and the severity of the disease, as well as the predictive value of dynamic changes of D-lactate and I-FABP on the prognosis of 28 days., Results: Compared with the healthy volunteers, the serum D-lactate and I-FABP levels of ICU patients on day 0 were significantly increased [D-lactate (mg/L): 10.82 (3.31, 25.48) vs. 6.63 (1.54, 17.70), I-FABP (ng/L): 519.60 (159.06, 1 362.14) vs. 84.40 (30.78, 108.57), both P < 0.01], and D-lactate and I-FABP on day 5 were both decreased compared with the levels on day 0, but still higher than the healthy volunteers. I-FABP in the improvement group was significantly lower than that in the non-improvement group on day 0, and there was no significant difference in D-lactate levels between the two groups, D-lactate and I-FABP in both groups were significantly lower on day 5 than those on day 0, and D-lactate and I-FABP in the improvement group on day 5 were significantly lower than those in the non-improvement group [D-lactate (mg/L): 7.61 (1.71, 27.22) vs. 9.38 (2.09, 20.56), I-FABP (ng/L): 378.65 (152.56, 864.62) vs. 521.21 (205.93, 1 413.11), all P < 0.05]. Correlation analysis showed that D-lactate was significantly positively correlated with APACHE II score and SOFA score on day 0 and day 5 (R 1 2 = 0.367, P < 0.001; R 2 2 = 0.240, P = 0.012); I-FABP was significantly positively correlated with APACHE II score on day 0 (R 2 = 0.264, P = 0.004); D-lactate on day 5 and I-FABP on day 0 and day 5 were significantly negatively correlated with prognosis on day 28 (R 1 2 = -0.203, P = 0.022; R 2 2 = -0.208, P = 0.023; R 3 2 = -0.211, P = 0.021). The area under curve (AUC) analysis showed that D-lactate on day 5 and I-FABP on day 0 and day 5 had independent predictive value for 28-day prognosis, with AUC of 0.634, 0.638 and 0.652, P values of 0.023, 0.024 and 0.017, 95% confidence intervals (95%CI) of 0.533-0.734, 0.523-0.754 and 0.525-0.778, respectively. When the cut-off values were 7.71 mg/L, 593.55 ng/L and 468.10 ng/L, the sensitivity were 51.5%, 68.5% and 75.3%, and the specificity were 91.0%, 60.0% and 60.0%, respectively., Conclusions: Serum D-lactate and I-FABP were increased significantly and decreased with the improvement of the condition, and these two molecular biomarkers have certain value in predicting the prognosis of ICU patients.

The present study was to investigate the effect of mesenteric lymph duct drainage on lung inflammatory response, histological alteration, and endothelial cell apoptosis in septic rats. Animals were randomly assigned into four groups: control, sham surgery, sepsis, and sepsis plus mesenteric lymph drainage. We used the colon ascendens stent peritonitis (CASP) procedure to induce the septic model in rats, and mesenteric lymph drainage was performed with a polyethylene (PE) catheter inserted into mesenteric lymphatic. The animals were sacrificed at the end of CASP in 6 h. The mRNA expression levels of inflammatory mediators were measured by qPCR, and the histologic damage were evaluated by the pathological score method. It was found that mesenteric lymph drainage significantly reduced the expression of TNF- α , IL-1 β , and IL-6 mRNA in the lung. Pulmonary interstitial edema and infiltration of inflammatory cells were alleviated by mesenteric lymph drainage. Moreover, increased mRNA levels of TNF- α , IL-1 β , IL-6 mRNA, and apoptotic rate were observed in PMVECs treated with septic lymph. These results indicate that mesenteric lymph duct drainage significantly attenuated lung inflammatory injury by decreasing the expression of pivotal inflammatory mediators and inhibiting endothelial apoptosis to preserve the pulmonary barrier function in septic rats., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Yongjun Liu et al.)

Objective: To observe the effects of 2-aminopurine (2-AP), a double-stranded RNA-dependent protein kinase (PKR) inhibitor, on organ function, plasma inflammatory factor expression and 7 days mortality in sepsis mice induced by cecal ligation puncture (CLP). Methods: Forty specific specific pathogen free C57BL/6 mice were randomly divided into sham group ( n= 10), CLP group ( n= 10), CLP+2-AP group ( n= 10) and 2-AP group ( n= 10). CLP was used to establish sepsis mice models.Peripheral blood serum was collected 24 hours after operation, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Cr), blood urea nitrogen (BUN) and inflammatory factors (IL-1β, IL-10 and TNF-α) were detected; peripheral blood and peritoneal lavage fluid were taken for bacterial clearance detection. Another 60 C57BL/6 mice were selected to observe the 7-day survival rate according to the above groups ( n= 15). Independent sample t test was used to compare the measurement data between groups. Results: The levels of ALT, AST, Cr and BUN in CLP Group and CLP+2-AP group were significantly higher than those in sham group (all P< 0.001). The levels of ALT and AST in CLP+2-AP group were significantly lower than those in CLP Group ( t= 27.88, 11.33, both P< 0.001); the levels of Cr and BUN in CLP+2-AP group were significantly lower than those in CLP Group ( t= 11.02, 7.15, both P< 0.001). Compared with sham group, the levels of pro-inflammatory (IL-1β and TNF-α) and anti-inflammatory (IL-10) cytokines in CLP group were significantly higher (all P< 0.001); the levels of IL-1β and IL-10 in CLP+2-AP group were significantly lower (all P< 0.001), but the levels of TNF-α in CLP+2-AP group were not significantly lower ( P= 0.33). The 7-day survival rate was 100% in sham group, 13.3% in CLP+2-AP group, 86.7% in 2-AP group and 20.0% in CLP+2-AP group. Inhibition of PKR activation slightly improved the trend of 7-days survival rate of CLP model mice (analysis by mantel Cox test, χ(2)=0.0012, P= 0.97). Conclusion: In sepsis mice model, inhibition of PKR activity can reduce the expression of inflammatory factors in plasma, decrease bacterial load in blood and abdominal cavity, and protect organ function, which could suggest that inhibition of PKR activity has potential application in sepsis treatment.

Objective: To investigate the relationship between plasma oxidative stress factors levels and organ damage parameters as well as prognosis in patients with sepsis., Methods: A case-control study was conducted. Twenty-five patients admitted to surgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from March to December in 2016 and diagnosed as sepsis were enrolled as study subjects. Another 15 patients without sepsis admitted to surgical ICU in the same period were enrolled as controls. General demographic data, main diagnoses, acute physiology and chronic health evaluation II (APACHE II) score within 24 hours, clinical laboratory indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), serum creatinine (SCr), blood urea nitrogen (BUN), C-reactive protein (CRP), procalcitonin (PCT), white blood count (WBC)] and oxidative stress indicators [superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO)] as well as length of ICU stay, total hospital stay and 28-day mortality were recorded. Spearman or Pearson correlation method was used to analyze the correlation between oxidative stress indicators and organ damage indicators as well as prognosis in patients with sepsis. Receiver operator characteristic (ROC) curve was plotted to evaluate the predictive value of oxidative stress indicators for 28-day mortality in patients with sepsis., Results: The length of ICU stay in sepsis group was significantly longer than that in non-sepsis group [days: 7.0 (5.5, 11.0) vs. 4.0 (1.0, 11.0), P < 0.05], and AST, BUN, CRP, PCT, plasma MDA and NO levels were significantly higher than those in non-sepsis group [AST (U/L): 50.76±19.53 vs. 28.53±14.02, BUN (mmol/L): 9.99±5.26 vs. 6.97±4.32, CRP (mg/L): 109.28±42.79 vs. 60.33±46.68, PCT (μg/L): 5.4 (0.3, 24.0) vs. 0.6 (0.1, 1.5), MDA (ng/L): 488.31±76.68 vs. 399.30±50.23, NO (ng/L): 5.08±0.89 vs. 4.42±0.88, all P < 0.05]. There was no significant difference in gender, age, APACHE II score, total hospital stay, 28-day mortality, ALT, SCr, WBC or plasma SOD activity between the two groups. The correlation analysis between oxidative stress parameters and organ damage parameters as well as prognosis in patients with sepsis showed that MDA and NO were positively correlated with SCr (r value was 0.426 and 0.431, respectively, both P < 0.05), and there was a positive correlation between MDA and NO (r = 0.990, P < 0.01); plasma SOD activity was negatively correlated with 28-day mortality (r = -0.468, P < 0.05), while MDA and NO levels were positively correlated with 28-day mortality (r value was 0.598 and 0.611, respectively, both P < 0.01). ROC curve analysis showed that plasma SOD, MDA and NO levels had a good independent predictive effect on 28-day mortality, the area under ROC curve (AUC) was 0.816±0.087, 0.904±0.078 and 0.912±0.071, and the best cut-off value was 40.76% (sensitivity 68.4%, specificity 100%), 487.93 ng/L (sensitivity 83.3%, specificity 89.5%) and 5.31 ng/L (sensitivity 83.3%, specificity 89.5%), respectively., Conclusions: The plasma levels of oxidative stress factors in patients with sepsis are significantly increased, which is closely related to organ damage and poor prognosis. The plasma SOD, MDA and NO levels can be used as independent bio-marker to predict the 28-day mortality of patients with sepsis.

Background: To investigate the effect of biliary tract external drainage (BTED) on inflammatory mediators and pathomorphism of intestine, liver, and lung in septic rats., Method: 48 SD rats (n = 8 per group) were randomized into six groups: control, sepsis, sepsis plus BTED, normal bile (obtained from eight healthy rats), and septic bile infusion for 6 hours respectively to test the effects of BTED bile infusion on cytokines' expression and tissue injury in the intestine, liver, and lung of septic/normal rats. Co-cultivation of intestinal epithelial cells (IEC-6) with bile for 12 hours was performed to evaluate the potential cytotoxicity of septic bile. Survival rate for sepsis plus BTED rats was detected compared with sepsis without BTED group (n = 20 per group) at 24, 48, and 72 hours, respectively., Results: BTED for 6 hours significantly reduced the mRNA expression levels of tumor necrosis factor alpha (TNF-α) and IL-1β (all p < 0.05 vs. sepsis group), whereas mRNA expression of TNF-α and IL-1β in the intestine was increased after 6 hours' septic bile infusion compared with normal bile infusion group (all p < 0.05). TNF-α concentration in septic bile was significantly higher than that in the control group (p < 0.001). Tissue injury was significantly attenuated after 6 hours' BTED., Conclusions: BTED can significantly restrain the mRNA expression of TNF-α and IL-1β in the intestine, liver, and lung and attenuate histological damage in septic rats.

Objective: To observe the effect of sepsis single-disease manage system on the improvement of sepsis treatment and the value in predicting mortality in patients with sepsis. Methods: A retrospective study was conducted. Patients with sepsis admitted to the Department of Surgical Intensive Care Unit of Sun Yat-Sen University First Affiliated Hospital from September 22, 2013 to May 5, 2015 were enrolled in this study. Sepsis single-disease manage system (Rui Xin clinical data manage system, China data, China) was used to monitor 25 clinical quality parameters, consisting of timeliness, normalization and outcome parameters. Based on whether these quality parameters could be completed or not, the clinical practice was evaluated by the system. The unachieved quality parameter was defined as suspicious parameters, and these suspicious parameters were used to predict mortality of patients with receiver operating characteristic curve (ROC). Results: A total of 1 220 patients with sepsis were enrolled, included 805 males and 415 females. The mean age was (59±17) years, and acute physiology and chronic health evaluation (APACHE Ⅱ) scores was 19±8. The area under ROC curve of total suspicious numbers for predicting 28-day mortality was 0.70; when the suspicious parameters number was more than 6, the sensitivity was 68.0% and the specificity was 61.0% for predicting 28-day mortality. In addition, the area under ROC curve of outcome suspicious number for predicting 28-day mortality was 0.89; when the suspicious outcome parameters numbers was more than 1, the sensitivity was 88.0% and the specificity was 78.0% for predicting 28-day mortality. Moreover, the area under ROC curve of total suspicious number for predicting 90-day mortality was 0.73; when the total suspicious parameters number was more than 7, the sensitivity was 60.0% and the specificity was 74.0% for predicting 90-day mortality. Finally, the area under ROC curve of outcome suspicious numbers for predicting 90-day mortality was 0.92; when suspicious outcome parameters numbers was more than 1, the sensitivity was 88.0% and the specificity was 81.0% for predicting 90-day mortality. Conclusion: The single center study suggests that this sepsis single-disease manage system could be used to monitor the completion of clinical practice for intensivist in managing sepsis, and the number of quality parameters failed to complete could be used to predict the mortality of the patients.

Hypoxia inducible factor-1α (HIF-1α) plays an essential role in hypoxia and inflammatory response. Oxygen metabolic dysfunction and cascade amplification of inflammatory response are prominent pathophysiological characteristics in sepsis induced acute lung injury (ALI). In this study, we started with septic mesenteric lymph injection model to investigate whether HIF-1α played a role in the pathogenesis of ALI induced by septic lymph. The data demonstrated that rats injected with septic lymph showed a significant higher Lung Injury Scale and MPO(myeloperoxidase) levels than that of rats injected with normal saline/lymph. ALI was associated with a higher degree of HIF-1α expression in the lungs infused by septic lymph. Intratracheal delivery of YC-1(3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole) significantly attenuated lung inflammatory damages. Furthermore, in vitro studies, human alveolar type II epithelial cell (A549)/human pulmonary microvascular endothelial cell (HPMEC) incubated by septic lymph showed dramatically decreased cell viability, higher levels of inflammatory cytokines (TNF-α, IL-6 and IL-1β) and excitation of HIF-1α expression (Immunofluorescence localization/RT-PCR test) simultaneously. Nevertheless, compared with the non-silencing cell lines, A549/HPMEC with HIF-1α gene silencing manifested increased viability and restrained cytokines' expression after incubation with septic lymph. These results indicate that HIF-1α expression can be induced and activated in rats during the acute lung inflammatory damages triggered by septic lymph injection and that lung inflammatory injuries occur via a HIF-1α-dependent pathway., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the efficacy of immunotherapy on septic patients with Ulinastatin plus Thymosin-alpha(1)., Methods: Seventy postoperative septic patients were divided into two groups at random: the immunotherapy group (n equal to 36) and the conventional therapy group (n=34). Patients in the immunotherapy group received intravenous Ulinastatin of 200 000 U, 3 times per day for 3 days, Ulinastatin of 100 000 U, 3 times per day for 4 days, and subcutaneous injection of Thymosin-alpha(1) of 1.6 mg, twice per day for 3 days, then once per day for 4 days. While conventional therapies such as antibiotics and fluid resuscitation were undertaken in both groups. The expression levels of serum tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), IgG, C3, T lymphocyte subsets, CD14+ monocyte human leukocyte antigen (locus) DR (HLA-DR) and patients'28-day survival rate of the two groups were observed and evaluated., Results: The survival rate was significantly higher in the immunotherapy group (63.9%; 23/36) compared with the conventional therapy group (41.2%; 14/34). The serum TNF-alpha levels [(1.38+/-0.50) ng/ml in the immunotherapy group vs (1.88+/-0.53) ng/ml in the conventional group, P less than 0.05] and the serum IL-10 levels [(217.52+/-15.71) ng/ml vs (101.53+/-16.57) ng/ml, P less than 0.05] were significantly different between the two groups. The serum IgG levels in the immunotherapy group [(17.65+/-6.81) g/L] were significantly higher than in the conventional group [(11.94+/-5.32) g/L]. There were also significant differences in the expression levels of CD4+ T lymphocyte (35%+/-13% in the immunotherapy group vs 21%+/-7% in the conventional group, P less than 0.05) and CD14+ monocyte HLA-DR (50%+/-5% in the former vs 35%+/-4% in the latter, P less than 0.05)., Conclusions: Immunotherapy with Ulinastatin plus Thymosin-alpha(1) can enhance the inflammatory response, improve the immune homeostasis, and increase the survival rate of septic patients.

Objective: To assess the role of heparin administration in the early stage of sepsis and its mechanism of action., Methods: This was a prospective study. One hundred and nineteen patients were enrolled in the study and were randomly divided into control group (64 cases) and therapy group (55 cases). Except the basic therapy of sepsis given to patients in both groups, the patients in the control group received normal saline, while the patients in the therapy group received heparin 2 mg.kg(-1).d(-1) with the aid of intravenous pump continuously after the onset of sepsis. The platelet count (PLT), D-dimer, and lactic acid in the blood were analyzed before therapy and on the 1st, 3rd, 5th and 10th day. The bleeding tendency was also observed. In every patient an acute physiology and chronic heath evaluation II (APACHE II) score was made., Results: Patients in both groups had a similar APACHE II score. The pathogenetic and therapeutic condition were similar in both groups. The rate of the active bleeding in the therapy group was lower significantly than that of the control group (12.5% vs. 5.4%, P < 0.05). The PLT of the therapy group decreased on the 1st day, but began to rise on the 3rd day gradually, and up to the same level of the admission day on the 10th day. The PLT of the control group decreased progressively every day (P < 0.05 or P < 0.01). D-dimer in the therapy group raised significantly on the 1st day, but lowered to normal level after 3 days. D-dimer in the control group went up progressively every day (all P < 0.01). Lactic acid in the therapy group went up significantly on the 1st day (P < 0.01), but it no longer rose after 3 days (all P > 0.05). The lactic acid level in the control group rose progressively every day (all P < 0.01). There were no significant differences for the PLT, D-dimer, and lactic acid between the two groups before therapy and on the 1st day (all P > 0.05). However, on the 3rd, 5th and 10th day, the PLT in the therapy group was significant higher than that of the control group, the D-dimer and the lactic acid level in the therapy group were significantly lower than that of the control group (P < 0.05 or P < 0.01)., Conclusion: The use of heparin at the earlier period of sepsis can inhibit the lowering of PLT and increase of D-dimer and lactic acid significantly, prevent microvascular thrombosis, improve the tissue perfusion, and decrease active bleeding.

Background: Because of the complicated pathological features after liver transplantation, severe sepsis is difficult to treat and often leads to death. This study was undertaken to analyze the role of orthotopic liver transplantation (OLT) in patients with severe sepsis and to evaluate the effect of the scoring system., Methods: Fifty-six patients conformed to the inclusion criteria. They were divided into two groups: non-OLT group (group A) and OLT group (group B). Besides the general data of the patients, the surveillance of blood lactate, the number of failed organs, acute physiology and chronic health evaluation II (APACHE II ) and multiple organ dysfunction score (MODS) were evaluated at the 1st, 3rd and 7th day after OLT., Results: The mortality during hospitalization was 30% in the non-OLT group and 57.6% in the other group. The level of blood lactate at the 1st day of OLT increased more significantly in the OLT group than in the non-OLT group (P<0.01). It was decreased but higher than that in the non-OLT group in the seven days after OLT. The number of failed organs in the OLT group was greater than that in the non-OLT group (P<0.01). The continuous score of APACHE II was not significantly different in the two groups. But the continuous MODS in the OLT group was higher than that in the non-OLT group (P<0.01), which was consistent with the number of failed organs., Conclusions: The persistently higher level of blood lactate during 7 days may be a dependent risk factor. Immunosuppression may be another risk factor for OLT patients. The mortality of OLT in patients with severe sepsis in 28 days is almost double that in non-OLT patients. The MODS score is better than the APACHE II score in the assessment of organ failure in OLT patients with severe sepsis. The standard scoring system could be improved or a new scoring system that includes the blood lactate score should be established for liver transplantation.