PD-L1 expression and immune cells infiltration in primary tracheobronchial neoplasm.

BACKGROUND: Primary tracheobronchial neoplasm is rare yet poses a serious threat to life. Due to its low incidence, the immune microenvironment of such tumors remained unclear. This study aimed to clarify the expression of programmed death-ligand 1 (PD-L1) and infiltration of immune cells in primary tracheobronchial neoplasm, which might be useful for guiding treatment and evaluating clinical outcome. METHODS: We assessed retrospectively the expression of PD-L1 and infiltration in cells expressing CD8, CD16, CD68, CD163 and FOXP3 in 21 patients with primary tracheobronchial neoplasm who underwent surgery in Tangdu Hospital from January 2016 to July 2021. The expression of PD-L1 was assessed based on the tumor proportion score system. The density of immune cells was analyzed by automatic image analysis software. RESULTS: In this study, all of 16 participants with adenoid cystic carcinoma (ACC) had no expression of PD-L1, whereas 4/5 (80%) of those with squamous cell carcinomas (SCC) were positive for PD-L1 expression. Compared with ACC, the density of FOXP3+ cells in both the intratumoral region and peritumoral region was higher in SCC (P<0.01). The density of FOXP3+ cells was significantly higher than that of CD8+, CD16+, and CD163+ cells in SCC in the intratumoral region (P<0.01). In contrast, the density of FOXP3+ cells was significantly lower than that of CD8+, CD16+, and CD68+ cells in ACC in both the intratumoral region and peritumoral regions. The density of CD68+ cells was significantly higher than that of CD8+ cells (P<0.05) and CD163+ cells (P<0.01) in ACC in the intratumoral region. Furthermore, the tumors of patients with metastasis more commonly of immune-excluded status, in which the CD8+ cells accumulated in peritumoral region. CONCLUSIONS: This study demonstrated that the expression of PD-L1 in primary tracheobronchial neoplasm was mainly concentrated in patients with SCC. In the immune microenvironment of SCC, FOXP3+ cells were the dominant immune cells, while in the immune microenvironment of ACC, CD68+ cells were the main immune cells. Therefore, the immune microenvironment was significantly different in primary tracheobronchial neoplasm according to histology.

GPS2 promotes erythroid differentiation by control of the stability of EKLF protein.

Erythropoiesis is a complex multistage process that involves differentiation of early erythroid progenitors to enucleated mature red blood cells, in which lineage-specific transcription factors play essential roles. Erythroid Krüppel-like factor (EKLF/KLF1) is a pleiotropic erythroid transcription factor that is required for the proper maturation of the erythroid cells, whose expression and activation are tightly controlled in a temporal and differentiation stage-specific manner. Here, we uncover a novel role of G-protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor/silencing mediator of retinoic acid and thyroid hormone receptor corepressor complex, in erythrocyte differentiation. Our study demonstrates that knockdown of GPS2 significantly suppresses erythroid differentiation of human CD34+ cells cultured in vitro and xenotransplanted in nonobese diabetic/severe combined immunodeficiency/interleukin-2 receptor γ-chain null mice. Moreover, global deletion of GPS2 in mice causes impaired erythropoiesis in the fetal liver and leads to severe anemia. Flow cytometric analysis and Wright-Giemsa staining show a defective differentiation at late stages of erythropoiesis in Gps2-/- embryos. Mechanistically, GPS2 interacts with EKLF and prevents proteasome-mediated degradation of EKLF, thereby increasing EKLF stability and transcriptional activity. Moreover, we identify the amino acids 191-230 region in EKLF protein, responsible for GPS2 binding, that is highly conserved in mammals and essential for EKLF protein stability. Collectively, our study uncovers a previously unknown role of GPS2 as a posttranslational regulator that enhances the stability of EKLF protein and thereby promotes erythroid differentiation.

Evidence of efficacy of acupuncture in the management of low back pain: a systematic review and meta-analysis of randomised placebo- or sham-controlled trials.

OBJECTIVES: To assess the evidence for the efficacy of acupuncture for non-specific low back pain (NSLBP), compared with sham or placebo therapies. METHODS: We searched Cochrane CENTRAL to December 2016, and conducted searches from 1980 to December 2016 in PubMed, MEDLINE and Embase. There were no regional restrictions applied. We included only randomised controlled trials of adults with NSLBP. Placebo/sham procedures were required of the control interventions. The trials were combined using meta-analysis when the data reported allowed for statistical pooling. RESULTS: 14 trials (2110 participants) were included in the review, and 9 were included in the meta-analysis. Immediately after the acupuncture treatment we found statistically significant differences in pain reduction between acupuncture and sham or placebo therapy (standardised mean difference (SMD) -0.40, 95% CI -0.54 to -0.25; I2 7%; 753 participants; 9 studies), but there were no differences in function (weighted mean difference (WMD) -1.05, 95% CI -3.61 to 1.52; I2 79%; 462 participants; 4 studies). At follow-up, there were significant differences in pain reduction (SMD -0.46, 95% CI -0.82 to -0.09; I2 67%), but not in function (WMD -0.98, 95%CI -3.36 to 1.40; I2 87%). We conducted subgroup analyses both immediately after treatment and at follow-up. CONCLUSION: There is moderate evidence of efficacy for acupuncture in terms of pain reduction immediately after treatment for NSLBP ((sub)acute and chronic) when compared to sham or placebo acupuncture. REGISTRATION: PROSPERO registration no. CRD42017059438.

Effects of electroacupuncture stimulation at different spinal segmental levels in a rat model of diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is associated with high morbidity, mortality and economic cost. Studies have shown that acupuncture can improve many symptoms of DM. OBJECTIVES: To examine for differences in effects of electroacupuncture (EA) stimulation at Weiwanxiashu, BL15 and BL23 in the streptozotocin (STZ)-induced DM rat model, to help guide clinical selection of acupuncture points. METHODS: 90 male rats weighing 160±5 g were used. 12 rats were control fed (Normal group) and 78 were fed a high-fat high-sugar diet for 8 weeks and underwent intraperitoneal STZ injection to model DM. 60 animals that met modelling criteria were randomly divided into an untreated DM group and four groups receiving EA at Weiwanxiashu (DM+WWX group), BL15 (DM+BL15 group), BL23 (DM+BL23 group) or a non-traditional acupuncture point on the tail (DM+Tail group). Fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and insulin levels were determined and an oral glucose tolerance test (OGTT) performed. RESULTS: EA at Weiwanxiashu had a glucose-lowering effect on the 21st and 28th days, decreased TC, TG and LDL-C levels, increase insulin levels and improved glucose tolerance. EA at BL15 had a glucose-lowering effect on the7th, 14th and 21st days of intervention but did not impact lipids, insulin or OGTT parameters. EA at BL23 or on the tail had no significant effects. CONCLUSION: EA at Weiwanxiashu and BL15 had differential effects on metabolic markers in the STZ-induced rat model of DM. These effects may be explained neuroanatomically by variations in the segmental innervation of the tissues at these locations.

[Effect of Electroacupuncture at "Weiwanxiashu" (EX-B 3) on Islet Morphology and the Expression of Pancreatic Glucagon-like Peptide-1 Receptor in Type 2 Diabetes Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on pancreatic glucagon-like peptide-1 receptor (GLP-1 R), pancreatic and duodenal homeobox 1 (PDX-1) protein expression and blood glucose in type 2 diabetes rats, so as to explore the underlying mechanism of EA treatment in improving type 2 diabetes. METHODS: Sprague-Dawley rats were randomly divided into blank control group, model group, "Weiwanxiashu" (EX-B 3) group, "Xinshu" (BL 15) group, and "Shenshu" (BL 23) group, 12 rats in each group. Diabetes model was established by feeding the rat with high fat and high sugar diet combined with intraperitoneal injection of streptozotocin (35 mg/kg). All the EA groups received 2 Hz, 2 mA continuous wave treatment for 20 min everyday, 6 times per week lasting for 4 weeks. Fasting blood glucose was measured by Roche glucometer before and after treatment. Hematoxylin and eosin (HE) staining and Masson staining were used to detect pancreas morphology. GLP-1 R and PDX-1 protein expressions in the pancreas were detected by Western blot. RESULTS: Compared to the blank control group, fasting blood glucose was significantly increased in the model group(P<0.01), accompanied with shrunken islet area, reduced nucleus counts of islet ß cells, and compensatorily enlarged ß cell nucleus. Compared to the model group, EA intervention significantly reduced fasting blood glucose level only in the EX-B 3 group (P<0.05), partly restored pancreas morphology and nucleus counts of islet ß cells in the EX-B 3, BL 15, and BL 23 groups. Compared to the blank control group, GLP-1 R and PDX-1 expressions were decreased in the model group (P<0.01), while EA treatment could obviously increase GLP-1 R expression in the EX-B 3(P<0.01), BL 15 (P<0.01) and BL 23 (P<0.05) groups compared with the model group. The expression of GLP-1 R in the BL 15 group was the highest among the three EA groups (P<0.05,P<0.01), and that in the EX-B 3 group was higher than in the BL 23 group (P<0.05).There were no signifincant differences in the expression of PDX-1 protein among the three EA groups (P>0.05). CONCLUSIONS: EA treatment at EX-B 3 can reduce blood glucose via regulating pancreas function, increasing pancreatic GLP-1 R expression, and partly restoring the morphology of pancreas.

PI3K-GLUT4 Signal Pathway Associated with Effects of EX-B3 Electroacupuncture on Hyperglycemia and Insulin Resistance of T2DM Rats.

Objectives. To explore electroacupuncture's (EA's) effects on fasting blood glucose (FBG) and insulin resistance of type 2 diabetic mellitus (T2DM) model rats and give a possible explanation for the effects. Method. It takes high fat diet and intraperitoneal injection of streptozotocin (STZ, 30 mg/kg) for model preparation. Model rats were randomly divided into T2DM Model group, EA weiwanxiashu (EX-B3) group, and sham EA group (n = 12/group). EA (2 Hz continuous wave, 2 mA, 20 min/day, 6 days/week, 4 weeks) was applied as intervention. FBG, area under curve (AUC) of oral glucose tolerance test (OGTT), insulin resistance index (HOMA-IR), pancreatic B cell function index (HOMA-B), skeletal muscle phosphorylated phosphatidylinositol-3-kinase (PI3K), glucose transporter 4 (GLUT4), and membrane GLUT4 protein expression were measured. Results. EA weiwanxiashu (EX-B3) can greatly upregulate model rat's significantly reduced skeletal muscle PI3K (Y607) and membrane GLUT4 protein expression (P < 0.01), effectively reducing model rats' FBG and AUC of OGTT (P < 0.01). The effects are far superior to sham EA group. Conclusion. EA weiwanxiashu (EX-B3) can upregulate skeletal muscle phosphorylated PI3K protein expression, to stimulate membrane translocation of GLUT4 and thereby increase skeletal muscle glucose intake to treat T2DM.

[Effect of Acupuncture and Moxibustion Interventions on Ethological Changes and 5-HT/5-HIAA Levels in Prefrontal Cortex in Depression Rats].

OBJECTIVE: To observe the effect of acupuncture and moxibustion interventions on ethology and 5-HT/5-HIAA levels in the frontal cortex tissue in depression rats, so as to reveal their biological mechanisms underlying improvement of depression. METHODS: A total of 40 male SD rats were randomized into normal control, depression model, medication (Fluoxetine), acupuncture and moxibustion groups, with 8 rats in each group. The depression model was established by chronic unpredictable mild stress for 5 weeks. The interventions including acupuncture or moxibustion stimulation of "Baihui" (GV 20) and "Dazhui" (GV 14) for 20 min/d and intragastric administration of Fluoxetine (1.8 mg · kg⁻¹ · d⁻¹) beginning after 2 weeks of modeling for 3 weeks. The percentages of sucrose consumption was counted, the contents of 5-HT, hydroxyindole acetic acid (5-HIAA), tryptophan (Trp) in the prefrontal cortex tissue were assayed by radioimmunoassay, and the relative binding affinities (constant and capacity) of 5-HT1A receptor in the prefrontal cortex were measured by radioligand binding assay and Scatchard plot analysis in a computer. Results In comparison with the normal control group, the sucrose consumption percentage on the 35th day of modeling, the levels of cerebral cortical 5-HT, 5-HT/5-H1AA and 5-HT1A receptor binding constant were significantly down-regulated in the model group (P < 0.01, P < 0.05), and the cortical Trp content was obviously up-regulated in the model group (P < 0.01). Compared with the model group, the sucrose consumption percentage on the 35th day of modeling, and cortical 5-HT/5-HIAA in the medication, acupuncture and moxibustion groups, cortical 5-HT content in the medication group were significantly increased (P< 0.01, P < 0.05), and cortical 5-HIAA and Trp contents were obviously down-regulated in the three treatment groups (P < 0.01). No significant changes were found in the cortical 5-HT content after acupuncture and moxibustion, and in the high and lower affinity of 5-HTA receptor binding constant and binding capacity after medication, acupuncture and moxibustion interventions (P > 0.05). The effects of acupuncture and moxibustion interventions were comparable in increasing sucrose consumption percentage on the 35th day and 5-HT/5-HIAA, and in down-regulating cortical Trp content (P > 0.05). CONCLUSION: Both acupuncture and moxibustion can increase sucrose consumption (anti-depression) in depression rats, which may be closely associated withheir effects in up-regulating 5-HT/5-HIAA and down-regulating Trp content in the frontal cortex.

Wnt/Glycogen Synthase Kinase 3ß/ß-catenin Signaling Activation Mediated Sevoflurane Preconditioning-induced Cardioprotection.

BACKGROUND: Sevoflurane preconditioning (SP) has been shown to invoke potent myocardial protection in animal studies and clinical trials. However, the mechanisms underlying SP are complex and not yet well understood. We investigated the hypothesis that the cardioprotection afforded by SP is mediated via the Wnt/glycogen synthase kinase 3ß (GSK3ß)/ß-catenin signaling pathway. METHODS: Two models were established: a Langendorff perfused rat heart model and the H9C2 cell hypoxia/reoxygenation model. Both rats and H9C2 cells were randomly divided into 6 groups as follows: S group, ischemia-reperfusion (I/R) group, DMSO group, IWP group, SP group, and SP + IWP group. Hemodynamic parameters, lactate dehydrogenase (LDH) activity in coronary effluent and cell culture supernatant, and the infarct size were measured to evaluate myocardial ischemia-reperfusion injuries. To determine the activity of Wnt/GSK3ß/ß-catenin signaling pathway, the expressions of Wnt3a, phospho-GSK3ß, and ß-catenin were measured by Western blotting. RESULTS: SP improved cardiac function recovery, reduced infarct size (18 ± 2% in the SP group compared with 35 ± 4% in the I/R group; P < 0.05), decreased LDH activity in coronary effluent, and culture supernatant. IWP-2, an inhibitor of Wnt, abolished the cardioprotection by SP. In addition, Western blotting analysis demonstrated that the expressions of Wnt3a, phospho-GSK3ß, and ß-catenin significantly (P < 0.05) increased in the I/R group, compared with the S group; and compared to I/R group, SP significantly (P < 0.05) increased Wnt3a, phospho-GSK3ß, and ß-catenin expressions. Pretreatment with IWP-2 significantly (P < 0.05) abolished SP-induced Wnt/GSK3ß/ß-catenin signaling activation. CONCLUSIONS: The results showed for thefirst time that cardioprotection afforded by SP may be mediated partly via the Wnt/GSK3ß/ß-catenin signaling pathway.

[Effects of electroacupuncture at "Yishu" (EX-B 3) on the relative hormones of HPA axis in rats with type-2 diabetes mellitus].

OBJECTIVE: To observe the intervention effects of electroacupuncture at "Yishu" (EX-B 3) on rats with type-2 diabetes mellitus (T2DM), so as to provide experiment references for acupuncture to treat T2DM. METHODS: Among seventy male Wistar clean-grade rats, 8 rats were randomly selected into a control group; the rest rats were made T2DM model. Fifty-two rats which were successfully made T2DM model, according to randomized block method, were divided into a model group (10 rats), a medication group (10 rats), an electroacupuncture at "Shenshu" (BL 23) group (11 rats), an electroacupuncture at "Pishu" (BL 20) group (10 rats) and an electroacupuncture at "Yishu" (EX-B 3) group (11 rats). Seven days after successful establishment of model, the rats in the model group were fixed in the self-made rat bag without receiving any treatment; the rats in the medication group, according to body mass (10 mL/kg), were treated with intragastric administration of glimepiride; the rats in all the electroacupuncture groups were treated with electroacupuncture at "Shenshu" (BL 23), "Pishu" (BL 20) and "Yishu" (EX-B 3), respectively. The continuous wave was selected with a frequency of 15 Hz and a current intensity of 4 to 6 mA. The treatment was given 20 min per treatment, once a day, 5 treatments per week for continuous 4 weeks. Before the establishment of model and continuous 4 weeks after the intervention, blood samples were collected from rats' caudal vein, and fasting blood glucose (FBG) was measured with FBG device each week. After the last intervention, the rats were killed and hypothalamus, pituitary and adrenal gland were collected. The colorimetric method was applied to measure the contents of triglyceride (TG), cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C); radioimmunoassay was used to test the contents of glycated serum protein (GSP), fasting insulin (FINS), corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortin (CORT). RESULTS: Four weeks after the intervention, except that the rat's body mass in the normal group continued to increase, body mass in the model group, medication group and each electroacupuncture group were significantly reduced (P<0.01, P<0.05). Compared with the model group, the FBG in the electroacupuncture at "Pishu" (BL 20) group and electroacupuncture at "Yishu" (EX-B 3) group were obviously reduced (P<0.05, P<0.01); FBG in the electroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (both P<0.05). The contents of TG, HDL-C and LDL-C in the electroacupuncture at "Yishu" (EX-B 3) group were reduced (P<0.05, P<0.01), the content of TG was significantly lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (both P<0.05), the content of LDL-C was significantly lower than that in electroacupuncture at "Shenshu" (BL 23) group (P<0.05). Insulin sensitivity index (ISI) in the medication group, electroacupuncture at "Pishu" (BL 20) group and electroacupuncture at "Yishu (EX-B 3)" group were evidently increased (P<0.05, P<0.01); ISI in the medication group was lower than that in the electroacupuncture at "Yishu" (EX-B 3) group (P<0.05). The content of CRH in the electroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (P<0.05, P<0.01); the content of CORT in the electroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Pishu" (BL 20) group (both P<0.05). CONCLUSION: Electroacupuncture at "Yishu" (EX-B 3) could reduce the level of CORT to improve the insulin resistance in rats with T2DM, improve insulin sensitivity index, regulate blood lipid metabolism and relieve the hyperactivity of the HPA axis.

[Risk factors and early diagnosis of acute kidney injury in patients with sepsis].

OBJECTIVE: To analyze related risk factors of sepsis complicated acute kidney injury (AKI), and to explore the precaution equation for early clinical diagnosis. METHODS: A retrospective review of patients with sepsis complicating AKI admitted to intensive care unit (ICU) of Affiliated Hospital of Binzhou Medical University from April 2011 to April 2013 were enrolled. Fifty-eight sepsis patients without AKI were enrolled as control. Eleven indexes including age, mean arterial pressure (MAP) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, 24-hour urine volume, 24-hour net liquid intake score, serum creatinine (SCr) score, blood urea nitrogen (BUN), oxygenation index, blood lactic acid score and plasma albumin were collected as possible risk factors for AKI in sepsis patients. The risk factors and calculation of the critical value were analyzed by multiple factor logistic regression analysis. RESULTS: Nine factors with statistical significance for AKI in sepsis patients analyzed with univariate analysis were substituted in logistic regression model including MAP score, SOFA score, APACHEII score, 24-hour urine volume, 24-hour net liquid intake score, SCr score, BUN, oxygenation index, blood lactic acid score. After variable screening SCr score, MAP score, 24-hour net liquid intake score and blood lactic acid score were substituted in regression equation: Y=0.237X1 + 0.139X2 + 0.057X3 + 0.051X4 (X1, X2, X3, X4 typified SCr score, MAP score, blood lactic acid score and 24-hour net liquid intake score), F=125.897, P=0.000. The diagnostic cutoff appeared as 0.778. The sensitivity, the specificity, the Youden index, positive predictive value and negative predictive value were 80%, 100%, 0.8, 100% and 74%, respectively. CONCLUSIONS: SCr score, MAP score, blood lactic acid score and 24-hour net liquid intake score were risk factors of sepsis complicating AKI. When the value higher than 0.778 from regression equation Y=0.237X1 + 0.139X2 + 0.057X3 + 0.051X4, it hinted there was risk related to AKI in sepsis patients. The equation can help the clinicians diagnose sepsis and AKI earlier.

[The influence of volume load on prognosis of patients with sepsis induced acute kidney injury].

OBJECTIVE: To investigate the influence of volume load on the prognosis of patients with sepsis induced acute kidney injury (AKI). METHODS: A retrospective study was conducted. Patients with sepsis induced AKI from intensive care unit (ICU) of Binzhou Medical College Hospital from October, 2009 to September, 2011, were studied. 28-day mortality, 28-day renal-recovery rate, ICU stay days and mechanical ventilation rate were compared between negative fluid balance group and positive fluid balance group according to the fluid balance in first 72 hours. The influence of continuous renal replacement therapy (CRRT) on the volume load and the prognosis of patients with sepsis induced AKI were also studied. RESULTS: One hundred and sixty patients were enrolled. Compared with positive fluid balance group (n=79), 28-day-mortality [37.0% (30/81) vs. 68.4% (54/79), P<0.01], ICU stay time (10.1±4.9 days vs. 12.4±8.0 days, P<0.05) and mechanical ventilation rate [50.6% (41/69) vs. 68.4% (54/819), P<0.01] were lower in negative fluid balance group (n=81). According to Acute Kidney Injury Net (AKIN) staging standard, in stage 1, 2, and 3 of AKI (n=49, n=52, n=59), the day volume of first 72 hours of patients undergoing CRRT were lower than that of patients not undergoing CRRT (-10 ml vs. 716 ml, 324 ml vs. 778 ml, 521 ml vs. 1177 ml, all P<0.05). The 28-day mortality of patients undergoing CRRT was lower than that of patients not undergoing CRRT in stage 2 of AKI [38.7% (12/31) vs. 66.7% (14/21), P<0.05]. CONCLUSIONS: There is a relationship between fluid balance and prognosis of sepsis induced AKI, and 28-day-mortality can be reduced by negative fluid balance. CRRT can regulate fluid balance and improve the prognosis of sepsis induced AKI.

Genome­wide analysis of DNA methylation in rat lungs with lipopolysaccharide­induced acute lung injury.

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are associated with high morbidity and mortality in patients, however, the precise pathogenesis of ALI/ARDS remains unknown. Lipopolysaccharide (LPS) exhibits a number of critical functions and may be associated with the DNA methylation of genes in the lungs. In the present study a genome­wide analysis of DNA methylation was performed in rat lungs with LPS­induced ALI/ARDS. Normal and LPS­induced lung tissues with ALI were analyzed using methylated DNA immunoprecipitation and a rat DNA methylation promoter plus CpG island microarray and the candidate genes were validated by quantitative reverse transcriptase polymerase chain reaction (qRT­PCR). Aberrant DNA methylation of the promoter regions of 1,721 genes and the CpG islands of 990 genes was identified when normal lung tissues and lung tissues with LPS­induced ALI/ARDS were compared. These genes were commonly located on chromosomes 1, 3, 5, 7 and 10 (P<0.01). Methylation level and CpG density were compared and it was found that genes associated with high CpG density promoters had a high ratio of methylation. Furthermore, we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In addition, three genes (Mapk3, Pak1 and Rac2) were validated in the control and lung tissues with ALI by RT­PCR. The results indicate that aberrant DNA methylation of lung tissues may be involved in the pathophysiology of LPS­induced ALI/ARDS. Future studies are required to evaluate the therapeutic and prognostic value of the current novel observations in ALI/ARDS.

[The effect of early goal lactate clearance rate on the outcome of septic shock patients with severe pneumonia].

OBJECTIVE: To observe the clinical effects of 10%, 30% lactate clearance rate and early goal-directed therapy (EGDT) as 6-hour resuscitation goals directing treatment in septic shock patients with severe pneumonia. METHODS: In this randomized, perspective study, septic shock patients with severe pneumonia were divided into control group and experimental group, which included 10% lactate clearance rate group and 30% lactate clearance rate group, adopting random number method. The control group was treated with 6-hour EGDT strategy, and the experimental groups were treated with 10% lactate clearance rate protocol and 30% lactate clearance rate protocol respectively, beside the EGDT. RESULTS: There were 19 patients in control group, and 43 patients in experimental group, which included 22 patients in 10% lactate clearance rate group and 21 patients in 30% lactate clearance rate group. Patients were well matched by basic features. After 48 hours, the acute physiology and chronic health evaluation II (APACHE II ) score of both 10% lactate clearance rate group (13.76 ± 6.00, P < 0.05) and 30% lactate clearance rate group (13.60 ± 6.18, P < 0.05) were lower than that of control group (18.15 ± 6.62). There were no differences in time of mechanical ventilation (hours) between control group and experimental group (10% group 136.90 ± 100.02, 30% group 97.00 ± 75.20, control group 152.32 ± 96.51, P > 0.05). The length in intensive care unit (ICU, days) of 10% and 30% lactate clearance rate groups were significantly shorter than control group (10% group 7.94 ± 6.00, 30% group 7.51 ± 3.99, control group 11.31 ± 5.97, both P < 0.05). The three groups had no differences in 7-day mortality rate (10% group 18.18%, 30% group 14.29%, control group 21.05%, all P > 0.05), but the 28-day mortality of 10% and 30% lactate clearance rate groups were significantly lower than control group (10% group 36.36%, 30% group 28.57%, control group 63.16%), especially in 30% lactate clearance rate group (P < 0.05). CONCLUSION: For the septic shock patients with severe pneumonia, prompt archiving EGDT strategy and 6-hour lactate clearance more than 30% were associated with an optimal outcome.