Serum Lactic Acid Research Articles

Serum Proteomics Identifies Biomarkers Associated With the Pathogenesis of Idiopathic Pulmonary Fibrosis

The heterogeneity of idiopathic pulmonary fibrosis (IPF) limits its diagnosis and treatment. The association between the pathophysiological features and the serum protein signatures of IPF currently remains unclear. The present study analyzed the specific proteins and patterns associated with the clinical parameters of IPF based on a serum proteomic dataset by data-independent acquisition using MS. Differentiated proteins in sera distinguished patients with IPF into three subgroups in signal pathways and overall survival. Aging-associated signatures by weighted gene correlation network analysis coincidently provided clear and direct evidence that aging is a critical risk factor for IPF rather than a single biomarker. Expression of LDHA and CCT6A, which was associated with glucose metabolic reprogramming, was correlated with high serum lactic acid content in patients with IPF. Cross-model analysis and machine learning showed that a combinatorial biomarker accurately distinguished patients with IPF from healthy individuals with an area under the curve of 0.848 (95% CI = 0.684–0.941) and validated from another cohort and ELISA assay. This serum proteomic profile provides rigorous evidence that enables an understanding of the heterogeneity of IPF and protein alterations that could help in its diagnosis and treatment decisions.

Effect of Levosimendan on the Prognosis of Cardiac Surgery in Patients with Cardiac Insufficiency

Objective: To retrospectively analyze the effect of levosimendan on the survival and prognosis of cardiac surgery patients with LVEF<40%. Methods: The clinical data of 224 patients with preoperative LVEF<40% were retrospectively analyzed. According to different treatment schemes, the patients were divided into levosimendan group (n=60) and non-levosimendan group (n=164). The control group was treated with routine treatment, and the observation group was treated with levosimendan on the basis of routine treatment. Then a multivariate logistic regression model with a propensity score analysis was used to limit biases and finally the data of 40 patients in each group were selected for analysis. Results: Hemodynamic data showed that the cardiac index, LVEF and PAOP of patients in levosimendan group were significantly improved. The concentration of serum lactic acid in the levosimendan group was lower than that in the control group (P<0.05). At the same time, postoperative ICU and hospital stay were significantly reduced in levosimendan group (P<0.05), Logistics regression analysis showed that levosimendan was the only protective factor for Low cardiac output syndrome (LCOS) (HR=4.33; 95% confidence interval: 1.27-14.78; P=0.019). Conclusion: Levosimendan can better improve hemodynamics and reduce postoperative ICU time and hospital stay. The use of it tends to decrease the incidence of LCOS significantly.

Lactic Acidosis Related to Pharmacotherapy and Human Diseases.

Lactic acidosis represents one of the most common conditions that can compromise the health of intensive care unit (ICU) patients, increasing the mortality of patients with high levels of Lactate who do not receive a proper treatment within the first 6 h of hospitalization. There are two enantiomers of lactic acid: L-lactic acid (when the concentration increases, it can lead to a state of severe acidemia risking cardiovascular collapse, causing an increase in mortality in ICU patients) and D lactic acid (produced in the human organism by microbiota and its production increases during some pathological status). Generally, increased levels of serum lactic acid could be due to numerous factors, including hypoxia (caused for example by septic/cardiogenic/hypovolemic or obstructive shock), specific pathologies (e.g., liver disease), use of some drugs (e.g., metformin), presence of toxins, and trauma. Since the underlying cause could be fatal for the ICU patient, it is important to understand the root of this clinical status with a view to correct it and prevent the risk of a poor clinical outcome. Prevention and early treatment are the keys to control the negative clinical consequences. The aim of this review is to revise the scientific literature for further confirmation about the importance of early identification of acidotic statuses and to underline how an early diagnosis can prevent the worst clinical outcome, especially for ICU patients who are more fragile compared to the general population.

Poor expression of miR-195-5p can assist the diagnosis of cerebral vasospasm after subarachnoid hemorrhage and predict adverse outcomes.

Patients with spontaneous subarachnoid hemorrhage (SAH) may develop refractory arterial cerebral vasospasm (CVS), which is the leading cause of death in SAH patients. This study explored the clinical diagnostic value of serum miR-195-5p levels in CVS after SAH (SAH + CVS) and its relationship with the prognosis of SAH + CVS. A total of 110 patients with spontaneous SAH were divided into the SAH group (N=62) and SAH + CVS group (N=58), with 60 healthy subjects as controls. The clinical data of blood glucose, blood sodium fluctuation, and serum lactic acid were recorded. miR-195-5p serum level was detected by RT-qPCR and its diagnostic value on SAH + CVS was analyzed by receiver operating characteristic curve. Serum levels of PDGF/IL-6/ET-1 and their correlation with miR-195-5p were analyzed using RT-qPCR, enzyme-linked immunosorbent assay, and Pearson's method. The patient prognosis was evaluated by Glasgow Outcome Scale. The effect of miR-195-5p levels on adverse prognosis was analyzed by Kaplan-Meier method and Cox regression analysis. miR-195-5p was lowly expressed in the serum of SAH patients and lower in SAH + CVS patients. Serum miR-195-5p level assisted the diagnosis of SAH and SAH + CVS and was negatively correlated with PDGF/IL-6/ET-1 levels and was an independent risk factor together with ET-1 and blood glucose for SAH + CVS. miR-195-5p low expression predicted a higher cumulative incidence of adverse outcomes and was an independent predictor of adverse outcomes. Poor expression of miR-195-5p can assist the diagnosis of SAH + CVS and predict higher adverse outcomes.

Development of Intestinal Injury and Restoration of Weaned Piglets under Chronic Immune Stress.

This study aimed to investigate the effects of lipopolysaccharide (LPS)-induced chronic immune stress on intestinal morphology and function, immune system, oxidative status, and mitochondrial function in piglets. Fifty healthy Duroc × Landrace × Yorkshire piglets (21 ± 2 days old, barrow, 6.98 ± 0.14 kg body weight) were selected and randomly allotted to five groups, which were slaughtered at 0 (0 group), 1, 5, 9, and 15 d of LPS injection. The results showed that compared with the piglets without LPS injection, LPS injection significantly impaired the intestinal morphology and permeability at 1, 5, and 9 d, as manifested by the increased serum lactic acid and decreased ratio of villus height to crypt depth (p < 0.05). Moreover, intestinal inflammation and oxidative and mitochondrial injury were caused at 1 d, as manifested by upregulated IL-6 mRNA expression, increased malondialdehyde content, and impaired mitochondrial morphology (p < 0.05). However, these parameters were restored to levels identical to 0 group at 9~15 d, accompanied by significantly increased antioxidant capacity, enhanced protein expression of CD3+ and CD68+, and upregulated mRNA abundance of genes related to mitochondrial biogenesis and functions (p < 0.05). Collectively, these results suggest that the intestinal injury of piglets caused by chronic immune stress could be self-repaired.

Application of Different Continuous Renal Replacement Therapy Hemofilter in Patients with Septic Shock Complicated with Acute Renal Injury.

We aimed to compare the clinical effects of continuous renal replacement therapy (CRRT) with different hemofilters in patients with septic shock and acute kidney injury (AKI). Thirty patients with septic shock complicated with AKI admitted to The Fourth Affiliated Hospital of Anhui Medical University from 2018-2020 were selected and divided into the control and observation groups. The control group was treated with CRRT using the conventional ST-100 hemofilter. The observation group was treated with CRRT using the oXiris hemofilter for 48 hours, followed by CRRT with the conventional ST-100 hemofilter. Infection indexes, sepsis-related organ failure assessment (SOFA), changes in corresponding organ function indexes, duration of each treatment, and death were compared between the two groups during CRRT. The white blood cells (WBC) count, high-sensitivity C-reactive protein (hs-CRP), and procalcitonin (PCT) levels were significantly decreased in the oXiris group 48 hours after CRRT (P= 0.048, 0.036, 0.031, respectively). After 48 hours of CRRT, SOFA score, serum lactic acid, and norepinephrine dose in the oXiris group were significantly lower than those in the control group (P= 0.039, 0.002, 0.021, respectively). The use time of vasoactive drugs and the treatment time of CRRT in the oXiris group was significantly shortened (P= 0.031 and 0.029, respectively). However, there were no significant differences in mechanical ventilation duration, intensive care unit (ICU) hospitalization time, total hospitalization time, ICU mortality, and in-hospital mortality. For patients with septic shock complicated by AKI, CRRT treatment with the oXiris hemofilter could effectively clear inflammatory cytokine levels and quickly correct hemodynamic disorders, thus accelerating the recovery of organ function.

Effect of herbal cake-separated moxibustion on behavioral stress reactions and blood lactic acid level and muscular AMPK/PGC-1α signaling in rats with chronic fatigue syndrome

To observe the effect of herbal cake-separated moxibustion (HCSM) on serum lactic acid (BLA) level and AMPK/PGC-1α signaling pathway in the quadriceps femoris in chronic fatigue syndrome (CFS) rats, so as to explore its mechanisms underlying improvement of CFS. According to the random number table, 50 SD rats were divided into blank control, model, HCSM, sham HCSM and medication (herbal medicine gavage) groups, with 10 rats in each group. The CFS model was established by using chronic restraint and exhaustive swimming, alternately, once daily for 21 days. The herbal cake was made of Xiaoyao Powder (Mental Ease Powder, composed of [Danggui (Radix Angelicae Sinensis), Baishao (Radix Paeoniae Alba), Chaihu (Radix Bupleuri), Fuling (Poria), Baizhu (Rhizoma Atractylodis, Macrocephalae), etc.]. The HCSM was applied to "Shenque" (CV8), "Guanyuan "(CV4), bilateral "Zusanli" (ST36) and "Qimen" (LR14), 5 moxa-cones for each acupoint, once daily for 10 days. For sham HCSM, the excipient was instead of herbal cake, and the same 5 moxa-cones was given as the HCSM group. Rats of the medication group received gavage of Xiaoyao Powder suspension (60 mg·kg-1), once daily for 10 days. The open field test and tail suspension test were conducted for determining the animals' locomotor activity. The blood sample was taken from the abdominal aorta under anesthesia for assaying the levels of serum BLA, chemokine ligand CXCL9 and β-endorphin (EP) by ELISA. Bilateral quadriceps femoris were sampled for observing histopathological changes after staining with conventional H.E. technique, and for detecting the expression levels of phosphorylated AMP-activated protein kinase (p-AMPK) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) by using immunohistochemistry. Compared with the blank control group, the number of rearing and horizontal grid-crossing times, struggling times of tail suspension test were significantly decreased (P<0.05), and the immobility time was obviously prolonged (P<0.05) in the model group. Compared with the model group, both HCSM and medication groups had a significant increase of rearing, horizontal grid-crossing times and struggling times (P<0.05), and the immobility time had a significant decrease (P<0.05). But there were no significant differences in the total movement distance among the 5 groups (P>0.05), and in the 5 indexes of behavioral measurements between the HCSM and medication groups (P>0.05). The sham HCSM could also evidently increase the struggling times and reduce the immobility time (P<0.05). The contents of serum BLA, CXCL9 and β-EP were obviously higher in the model group than in the blank control group (P<0.05), as well as remarkably lower in the HCSM and medication groups than in the model group (P<0.05). Whereas the expression levels of muscular p-AMPK and PGC-1α were considerably lower in the model group than in the blank control group (P<0.05), and significantly increased in both HCSM and medication groups relevant to the model group (P<0.05). Compared with the sham HCSM group, the contents of BLA, CXCL9 and β-EP in serum of the HCSM group and contents of CXCL9, β-EP in medication group were significantly decreased (P<0.05), and the protein expressions of p-AMPK and PGC-1α in quadriceps femoris in both HCSM and medication groups were significantly increased (P<0.05). H.E. staining showed smaller intercellular space, uneven cytoplasmic staining in some muscle fibers, nucleus pyknosis and condensation, and inflammatory cell infiltration in the model group, which was milder in both HCSM and medication groups. HCSM can mitigate the stress behavioral state in CFS rats, which may be related with its functions in lowering the levels of serum BLA, CXCL9 and β-EP, and activating AMPK/PGC-1α signaling pathway (balancing energy metabolism) in the quadriceps femoris.

Association between septic patient mortality and blood survivin concentrations

ObjectiveSurvivin is a member of inhibitors of apoptosis proteins family. There are not data about the association between mortality of septic patients and blood survivin concentrations. Therefore, the objective of this study was to determine whether exist that association. DesignObservational and prospective study. SettingThree Spanish Intensive Care Units. PatientsPatients with sepsis or septic shock according to Sepsis-3 Consensus criteria. InterventionsSerum survivin concentrations were determined at moment of sepsis diagnosis. Main variable of interestMortality at 30 days. ResultsA total of 204 patients were included in the study, of which 75 (36.8%) died in the first 30 days. Lower age (p<0.001), serum lactic acid levels (p=0.001), rate of septic shock (p=0.001) and SOFA (p<0.001), and higher serum survivin levels (p=0.001) exhibited surviving (n=129) than non-surviving patients (n=75). We found in multiple logistic regression analysis an association between serum survivin concentrations and mortality independently of SOFA, lactic acid, age, INR, activated partial thromboplastin time (aPTT) and empiric antimicrobial treatment adequate (OR=0.968; 95% CI=0.946–0.990; p=0.005), and also independently of APACHE-II, lactic acid, platelet, INR, aPTT and empiric antimicrobial treatment adequate (OR=0.966; 95% CI=0.943–0.989; p=0.004). ConclusionsThere is an association between septic patient mortality and low blood survivin concentrations.

CARDIOGENIC SHOCK AND CRITICAL ILLNESS-RELATED CORTICOSTEROID INSUFFICIENCY: DID STEROIDS MAKE MY HEART GO ON?

CARDIOGENIC SHOCK AND CRITICAL ILLNESS-RELATED CORTICOSTEROID INSUFFICIENCY: DID STEROIDS MAKE MY HEART GO ON?

Impact of Paper Mill Effluent on Carbohydrate Metabolism of Freshwater Snake Headed Fish, Channa punctatus (Bloch, 1793)

The snake-headed fish, Channa sp. Bloch (Actinoptrygii: Channidae) is animportant component of inland fishery in the Indian subcontinent and one of the fashionable commercial fish. The industrialized effluents’ accomplishment to the aquatic ecosystem is one of the foremost causes of environmental pollution, and its hazardous influence on the exposed edible fishes may be a serious threat to human health. The present investigation has been designed to study the effects of sublethal concentrations of paper mill effluent on the serum glucose, serum lactic acid, liver glycogen, and liver lactic acid contents of Channa punctatus (Bloch) after in vitro exposure for96 hours. The investigation recorded a significant increase in serum glucose, serum lactic acid, and liver lactic acid contents with a significant quantitative decline in liver glycogen among effluent exposed fishes were recorded during the investigation. Thus the authors supposed to propose that the carbohydrate metabolism of freshwater snake-headed fish, C. punctatus affected during effluent exposure based on their experimental findings.

Antifatigue effect of naringin on improving antioxidant capacity and mitochondrial function and preventing muscle damage.

The aim of this study was to explore effects of naringin (Nar) on antifatigue ability; the weight-loaded and non-loading swimming tests were performed. Compared with the control group, dietary supplementation of Nar significantly prolonged the weight-loaded swimming time to exhaustion of mice (P < 0.01). Nar significantly reduced the serum lactic acid (LD) level (P < 0.05) and lactate dehydrogenase (LDH) activity (P < 0.001), while increased the serum non-esterified free fatty acids (NEFA) level (P < 0.001). In addition, Nar significantly increased the liver glycogen and muscle glycogen contents (P < 0.05) and the phosphoenolpyruvate carboxykinase (PEPCK) (P < 0.01) and glucokinase (GCK) mRNA levels (P < 0.001) in liver and gastrocnemius (GAS) muscle. Furthermore, Nar significantly improved the antioxidant capacity, mitochondrial function, and muscle mitochondrial fatty acid β-oxidation (P < 0.05), and decreased inflammation and muscle damage-related gene expression (P < 0.05). These findings suggested that Nar can improve antifatigue effect by enhancing antioxidant capacity and mitochondrial function and preventing muscle damage.

Evaluation of Lactate Dehydrogenase and Gamma Glutamyl Transferase Among Pregnant Women with Hypertensive Disorders and Their Association with Disease Severity in Jimma Medical Center, Ethiopia

Background & Objective: Pregnancy-induced hypertensive disorders (PIHD) are the main reasons for maternal and perinatal mortality, as they complicate 10% of pregnancies worldwide. Serum lactic acid dehydrogenase (LDH) and gamma-glutamyl transferase (GGT) are possible markers reflecting the occurrence of pregnancy-associated complications like preeclampsia and eclampsia. There is a paucity of data with conflicting results showing serum LDH and GGT on PIHD in Ethiopia. This investigation aimed to assess the serum LDH and GGT levels in pregnant women with PIHD along with their correlation with the severity of the disease at Jimma Medical Center (JMC), Ethiopia.Materials & Methods: This hospital-based comparative cross-sectional study was undertaken from August 03 to September 27, 2020, in JMC. A total of 97 study participants were recruited. Serum GGT and LDH levels were determined using a fully automated Roche Cobas 6000 chemistry analyzer. The data were analyzed using SPSS 25.0. One-way ANOVA and independent samples t-test were employed to compare serum GGT and LDH levels with categories of PIHD.Results: The significantly highest mean serum levels of LDH (580.9±193.8 U/L) and GGT (86.1±29.2 U/L) were observed in eclamptic women compared to gestational hypertensive (276.7±60.7 and 38.3±16.9 U/L) and preeclamptic patients (353±132.8 and 48.8±29.9 U/L), respectively. Both serum GGT and LDH levels were found to correlate with the severity of preeclampsia, respectively significantly.Conclusion: Serum LDH and GGT were found to be at the highest levels in eclamptic than preeclamptic and gestational hypertensive women. Blood pressure, gestational age, and severity of hypertensive disorders of pregnancy were predictor variables associated with serum GGT and LDH.

The Relationship Between COVID-19 Disease Severity and Zonulin Levels.

IntroductionZonulin is a protein that plays a role in the reversible regulation of epithelial permeability. As zonulin is released in large amounts into the intestinal lumen, it disrupts the integrity of the tight junctions and causes continuous migration of antigens to the submucosa. Consequently, it can trigger inflammatory processes and severe immune reactions. In severe cases, SARS-CoV-2 may have a major impact on the clinical manifestations of the disease by directly or indirectly affecting intestinal cells and triggering systemic inflammation. Therefore, our study aimed to investigate the role of one of the possible mediators, zonulin, in the severity of the COVID-19 infection.Methods Thirty COVID-19 patients and 35 healthy controls were included in the study. Blood samples were taken from the patients on the 1st, 4th, and 8th days of hospitalization. Serum zonulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Complete blood count (white blood cell [WBC], neutrophil, lymphocyte, and platelet), biochemical parameters (serum lactic acid dehydrogenase [LDH], erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], D-dimer, ferritin, fibrinogen levels) were determined and chronic systemic disease states of the patients were assessed.Results Serum zonulin levels were notably higher in the healthy control group compared to the patient group (p=0.003). Although there was an increase in the zonulin values by time in hospitalization, this rising was not significant. Conversely, ESR and CRP levels were significantly higher in the patient group (p<0.001). There was no significant difference between the two groups regarding gender, age, and WBC counts.Conclusion The serum zonulin levels of COVID-19 patients with the mild clinical course were lower than the healthy control group. Moreover, serum zonulin levels were not correlated with ESR, CRP, and other inflammation markers. Our results suggest that low serum zonulin levels in COVID-19 patients might represent a mild disease course.

Risk Factor Analysis of Hepatic Encephalopathy and the Establishment of Diagnostic Model.

To identify laboratory diagnostic indicators of hepatic encephalopathy (HE), the present study established a HE diagnostic model to explore the diagnostic value of serum homocysteine, lactic acid, procalcitonin, and bile acid levels in HE identification. 371 patients with liver cirrhosis were selected as research objects, who were admitted to the Department of Hepatic Diseases, Affiliated Hospital of Northwest Minzu University from August 2019 to August 2020. The Spearman correlation results indicated that between lactic acid, procalcitonin, bile acid, serum homocysteine, and HE, the coefficients were -0.15, 0.41, 0.29, and -0.19, respectively. Univariate and multivariate analysis methods were adopted for inpatient analysis to identify the influencing factors of HE occurrence, and the diagnosis of the HE identification model was subsequently constructed. The univariate logistic regression showed that risk of developing HE increased as bile acid level (P = 0.00434) and serum homocysteine (P = 0.058) increased. Multivariate logistic regression diagnostic model of bile acid level and serum homocysteine revealed that the AUC value of the area under the ROC curve was 0.7201, indicating that the diagnostic model produced a satisfactory evaluation effect. The model formula referred logistic (P) = −2.4544 + 0.0117 bile acid levels + 0.0198 serum homocysteine. In this study, the HE diagnostic model was established using logistic regression analysis, which could benefit patients in early HE differential diagnosis. Particularly, combined detection of serum homocysteine and bile acid levels was considered to be more significant.

Elevated serum lactic acid level is an independent risk factor for the incidence and mortality of sepsis-associated acute kidney injury

To explore the effect of serum lactic acid (Lac) level on acute kidney injury (AKI) in patients with sepsis and whether Lac level affects the in-hospital mortality of patients with sepsis-associated AKI. A retrospective cohort study was conducted. Clinical data of patients with sepsis admitted to the internal intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from March 2014 to June 2019 and the ICU of the Second Affiliated Hospital of Guangxi Medical University from January 2017 to June 2020 were collected. According to the first quartile of Lac within 24 hours of admission to ICU, the patients were divided into Lac ≤ 1.4 mmol/L group (group Q1), Lac 1.5-2.4 mmol/L group (group Q2), Lac 2.5-4.0 mmol/L group (group Q3), and Lac ≥ 4.1 mmol/L group (group Q4). The incidence of sepsis-associated AKI after admission to ICU and hospital mortality were compared among four groups. The effect of elevated Lac on the incidence and mortality of sepsis-associated AKI was investigated by binary Logistic regression analysis. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of Lac on the incidence and mortality of sepsis-associated AKI, and the cut-off value was obtained to analyze the incidence and death risk of sepsis-associated AKI at different Lac levels. A total of 655 sepsis patients were enrolled, of which 330 patients (50.4%) developed AKI and 325 patients (49.6%) did not. Among 330 patients with sepsis-associated AKI, 134 (40.6%) died and 196 (59.4%) survived. With the increase of Lac level, the incidence of sepsis-associated AKI increased gradually (34.5%, 41.0%, 58.4%, 66.3%, respectively, in group Q1-Q4), meanwhile, the in-hospital mortality also increased gradually (23.4%, 29.2%, 33.1%, 43.4%, respectively, in group Q1-Q4), the differences were statistically significant (both P < 0.01). Compared with the non-AKI group, the Lac level in the AKI group was significantly increased [mmol/L: 3.08 (1.84, 5.70) vs. 1.91 (1.20, 3.10), P < 0.01]. After adjustment for factors such as gender (male), site of infection (abdominal cavity), vasoactive drugs, basal mechanical ventilation, mean arterial pressure (MAP), basal renal insufficiency, uric acid, procalcitonin (PCT), platelet count (PLT), basal serum creatinine (SCr) and basal estimated glomerular filtration rate (eGFR), and other influencing factors, multivariate Logistic regression analysis showed that elevated Lac was an independent risk factor for sepsis-associated AKI [odds ratio (OR) = 1.096, 95% confidence interval (95%CI) was 1.022-1.175, P = 0.010]. Compared with the survival group, the Lac level in the death group was significantly increased [mmol/L: 3.55 (2.00, 6.76) vs. 3.00 (1.70, 4.50), P < 0.01]. After adjusting for age, diabetes, vasoactive drugs, basal eGFR, and other factors, multivariate Logistic regression analysis suggested that increased Lac was an independent risk factor for in-hospital mortality in sepsis-associated AKI patients (OR = 1.074, 95%CI was 1.004-1.149, P = 0.037). ROC curve analysis showed that the area under the ROC curve (AUC) of Lac for predicting the incidence and mortality of sepsis-associated AKI was 0.653 (95%CI was 0.611-0.694) and 0.593 (95%CI was 0.530-0.656, both P < 0.01), respectively, and the cut-off values were 2.75 mmol/L (sensitivity was 57.8%, specificity was 69.2%) and 5.95 mmol/L (sensitivity was 56.7%, specificity was 83.7%). When the Lac ≥ 2.75 mmol/L, the risk of sepsis-associated AKI was 2.772 times higher than that of < 2.75 mmol/L (OR = 2.772, 95%CI was 1.754-4.380, P < 0.001). When the Lac ≥ 5.95 mmol/L, the patients with sepsis-associated AKI had a 2.511 times higher risk of in-hospital death than those with Lac < 5.95 mmol/L (OR = 2.511, 95%CI was 1.378-4.574, P = 0.003). Elevated Lac level is an independent risk factor for the incidence and mortality of sepsis-associated AKI. When Lac ≥ 2.75 mmol/L, the risk of AKI in patients with sepsis increased by 1.772 times; when Lac ≥ 5.95 mmol/L, the risk of in-hospital death in patients with sepsis related AKI increased by 1.511 times.

Neural excitotoxicity and the toxic mechanism induced by acute hypoxia in Chinese mitten crab (Eriocheir sinensis)

Hypoxia can induce neural excitotoxicity in mammals, but this adverse effect has not been investigated in aquatic animals to date, especially in crustaceans. This study explored the induction effect and toxic mechanism of acute hypoxia stress (1.0±0.1mg dissolved oxygen /L) for 24h on neural excitotoxicity in juvenile Chinese mitten crab, Eriocheir sinensis. The results showed that hemolymph glucose and serum lactic acid content were significantly increased, and the mRNA expression of crustacean hyperglycemic hormone and hypoxia-inducible factor 1α were significantly up-regulated in the hypoxia group compared with control. RNA-Seq results confirmed that acute hypoxia stress had a more significant impact on carbohydrate metabolism than lipid and protein metabolism. In addition, the TUNEL assay showed that the apoptosis rate of nerve cells was significantly higher in the hypoxia group than in the control, and similar trends were observed in the expression of apoptosis-related genes. RNA-Seq results also showed that acute hypoxia stress-induced neuronal apoptosis by regulating multiple apoptosis-related pathways. Moreover, free glutamate and GABA contents in the nerve tissue of thoracic ganglia were significantly higher in the hypoxia group than in the control group. Furthermore, the mRNA expression of NMDA related receptors was significantly up-regulated in the hypoxia group compared with the control. Similar trends were observed in the expression of calcium-dependent degrading enzymes and endogenous antioxidant-related proteins or enzymes. Meanwhile, the mRNA expression level of high-affinity neuronal glutamate transporter in the hypoxia group was significantly up-regulated compared with the control, whereas the vesicular glutamate transporter was significantly down-regulated. Furthermore, NMDA-R antagonists (MK-801 and Ro25-6981) injection showed that NMDA-R served as the bridge and core position of glutamate-induced neural neurotoxicity. This study provides a new perspective and theoretical guidance for exploring the regulation of hypoxic tolerance in E. sinensis.

High mortality rate of septic patients with high blood granzyme B concentrations

Granzyme B could be released from cytotoxic T lymphocytes producing apoptosis activation. The objective of our study was to determine whether an association between septic patient mortality and blood granzyme B concentrations exist. We recruited septic patients admitted in 3 Intensive Care Units. We recorded mortality at 30 days and we determined serum granzyme B concentrations at moment of sepsis diagnosis. We found higher rate of history of diabetes mellitus (P = 0.02), serum granzyme B concentrations (P < 0.001), age (P = 0.001), serum lactic acid levels (P = 0.001) and sepsis-related organ failure assessment (P < 0.001) exhibited non-surviving patients (n = 67) than surviving ones (n = 110). We found in multiple logistic regression analysis an association of serum granzyme B concentrations with mortality (odds ratio = 1.223; 95% confidence interval = 1.104-1.355; P < 0.001) controlling for diabetes mellitus, sepsis-related organ failure assessment, lactic acid and age. That we know, our study is the first reporting the existence of an association of high serum granzyme B concentrations with high septic patients mortality.

Lotic Environment Affects Morphological Characteristics and Energy Metabolism of Juvenile Grass Carp Ctenopharyngodon idella

This study investigated the effect of a lotic environment on morphological characteristics and energy metabolism in juvenile grass carp Ctenopharyngodon idella. The fish were stocked in the lotic environment and forced to swim for 12 h per day for 4 weeks at three water current velocities of 0.5, 2, and 4 body length s−1 (Bl s−1). The control fish were stocked in the lentic environment with water current velocities of 0 Bl s−1. The results showed that lotic environment significantly increased body weight, body length, and condition factor of grass carp. The first principal component (PC1) characterized by measured overall body size suggested that fish in a lotic environment had body stoutness and wider tail stalk. Standard metabolic rate (SMR), maximum metabolic rate (MMR), and aerobic swimming performance (Ucrit) were elevated with the increased water flow and positively correlated with PC1. The 4 Bl s−1 group showed significantly decreased contents of serum glucose and muscular glycogen, and a significantly increased level of serum lactic acid. The mRNA expression levels of AMP-activated protein kinase-phosphorylate PPAR γ coactivator 1 α-nuclear respiratory factor 1 (AMPK-PGC1α-NRF1) pathway-related genes were significantly upregulated in red muscle of grass carp in the lotic environment. Water flow environment at 4 Bl s−1 significantly increased ratios of metabolic enzymes (lactate dehydrogenase/citrate synthase) and cytochrome c oxidase/citrate synthase) in the muscle. The relationship between morphological characteristics and metabolic capacity suggested that the body size of grass carp in a lotic environment was shaped to promote energy metabolism. The study identified the evidence of the mechanism and relationship of the trade-off between energy and morphology in grass carp.

Risk stratification and prognostic value of serum neutrophil gelatinase-associated lipocalin (sNGAL) in sepsis patients.

Sepsis is a host response with life-threatening organ dysfunction caused by an infection. Although the overall mortality rate has increased from 30% to 37% by the surviving sepsis campaign, it is still not acceptable. Early identification, accurate stratification and appropriate intervention can improve the prognosis. In this study we assessed the risk stratification and prognostic value of serum neutrophil gelatinase-associated lipocalin (sNGAL) as a biomarker in sepsis patients. A total of 112 sepsis patients (38 patients with sepsis, 41 patients with severe sepsis, 33 patients with septic shock) and 25 healthy controls were enrolled in this study. Serum samples of all patients were collected and frozen before testing. Basic patient information was collected, including age, gender, primary infection, complications, and so on. Results of serum calcitonin, lactic acid, and SOFA score were followed up for 28 days. Levels of serum procalcitonin (PCT), serum lactate, Sequential Organ Failure Assessment (SOFA) score and sNGAL of sepsis patients were significantly higher (p<0.05) than those of controls. The sNGAL level in sepsis patients who were alive on the 28th day of follow-up was significantly lower (p<0.05) than that of sepsis patients who had died before the 28th day of follow-up. Multiple logistic regression analysis showed that sNGAL-0h and lactates were independent risk factors of death due to sepsis within 28 days. At cut-off value of 250 ng/mL, the sensitivity and specificity sNGAL-0h predicting the 28-day mortality in septic patients were 0.838 and 0.827, respectively. The sNGAL level in sepsis patients with acute kidney injury (AKI) was significantly higher (p<0.05) than in sepsis patients without AKI. Serum NGAL may contribute to the assessment of the severity of sepsis. Serum NGAL and lactate can be independent risk factors for 28-day mortality in sepsis patients. Serum NGAL has potential of predicting septic-AKI.

Obesity and Mitochondrial Function in Children: A case–control study

OBJECTIVES: Childhood obesity has increased over the past years worldwide. Therefore, changes in mitochondrial function as the risk factors of obesity in children need to consider. AIM: The study aimed to evaluate the connection between obesity and mitochondrial function in obese children. PATIENTS AND METHODS: This study was a case–control study conducted in the primary school children in Mosul city. The study included 100 children, with an age ranged from 6 to 12 years. Fifty child with obesity (BMI ≥ 95th percentile) for children enrolled in this work and compared to 50 control with BMI &lt;95th percentile. Mitochondrial function assessed by measurement of serum lactic acid, lactate/pyruvate ratio, and L-carnitine and mt-DNA copy number. RESULTS: Serum lactate and the lactate/pyruvate ratio were significantly higher in obese children than in the control group, while serum pyruvate levels in children with obesity are not significantly different from those in the control group. Serum levels of L-carnitine and mt-DNA copy number significantly reduced in obese children comparison to the control group. CONCLUSION: Changes of mitochondrial function may be involved in obesity of children.