Significado biológico y utilidad clínica del lactato en la sepsis / Biological significance and clinical utility of lactate in sepsis

La sepsis es un problema global de salud y la progresión hacia el shock séptico se asocia con un incremento marcado de la morbimortalidad. En este escenario, el aumento del lactato plasmático demostró ser un indicador de gravedad y un predictor de mortalidad, y suele interpretarse casi exclusivamente como marcador de baja perfusión tisular. Sin embargo, últimamente se produjo un cambio de paradigma en la exégesis del metabolismo y propiedades biológicas del lactato. En efecto, la adaptación metabólica al estrés, aun con adecuado aporte de oxígeno, puede justificar la elevación del lactato circulante. Asimismo, otras consecuencias fisiopatológicas de la sepsis, como la disfunción mitocondrial, se asocian con el desarrollo de hiperlactatemia sin que necesariamente se acompañen de baja perfusión tisular. Interpretar el origen y la función del lactato puede resultar de suma utilidad clínica en la sepsis, especialmente cuando sus niveles circulantes fundamentan las medidas de reanimación.

Sepsis is a global health problem; progression to septic shock is associated with a marked increase in morbidity and mortality. In this setting, increased plasma lactate levels demonstrated to be an indicator of severity and a predictor of mortality, and are usually interpreted almost exclusively as a marker of low tissue perfusion. However, a recent paradigm shift has occurred in the exegesis of lactate metabolism and its biological properties. Indeed, metabolic adaptation to stress, even with an adequate oxygen supply, may account for high circulating lactate levels. Likewise, other pathophysiological consequences of sepsis, such as mitochondrial dysfunction, are associated with the development of hyperlactatemia, which is not necessarily accompanied by low tissue perfusion. Interpreting the origin and function of lactate may be of great clinical utility in sepsis, especially when circulating lactate levels are the basis for resuscitative measures.

Lactate and Lactate Clearance Are Predictive Factors for Mortality in Patients with Extracorporeal Membrane Oxygenation

ABSTRACT Introduction: Findings of inadequate tissue perfusion might be used to predict the risk of mortality. In this study, we evaluated the effects of lactate and lactate clearance on mortality of patients who had undergone extracorporeal membrane oxygenation (ECMO). Methods: Patients younger than 18 years old and who needed venoarterial ECMO support after surgery for congenital heart defects, from July 2010 to January 2019, were retrospectively analyzed. Patients successfully weaned from ECMO constituted Group 1, and patients who could not be weaned from ECMO were in Group 2. Postoperative clinics and follow-ups of the groups including mortality and discharge rates were evaluated. Results: There were 1,844 congenital heart surgeries during the study period, and 55 patients that required ECMO support were included in the study. There was no statistically significant difference between the groups regarding demographics and operative variables. The sixth-, 12th-, and 24th-hour lactate levels in Group 1 were statistically significantly lower than those in Group 2 (P=0.046, P=0.024, and P<0.001, respectively). There were statistically significant differences regarding lactate clearance between the groups at the 24th hour (P=0.009). The cutoff point for lactate level was found as ≥ 2.9, with 74.07% sensitivity and 78.57% specificity (P<0.001). The cutoff point for lactate clearance was determined as 69.44%, with 59.26% sensitivity and 78.57% specificity (P=0.003). Conclusion: Prognostic predictive factors are important to initiate advanced treatment modalities in patients with ECMO support. In this condition, lactate and lactate clearance might be used as a predictive marker.

Performance Evaluation of Geometrically Different Pediatric Arterial Cannulae in a Pediatric Cardiopulmonary Bypass Model

ABSTRACT Objective: To define a reference chart comparing pressure drop vs. flow generated by a set of arterial cannulae currently utilized in cardiopulmonary bypass conditions in pediatric surgery. Methods: Cannulae from two manufacturers were selected considering their design and outer and inner diameters. Cannula performance was evaluated in terms of pressure drop vs. flow during simulated cardiopulmonary bypass conditions. The experimental circuits consisted of a Jostra HL-20 roller pump, a Quadrox-i pediatric oxygenator (Maquet Cardiopulmonary AG, Rastatt, Germany), and a custom pediatric tubing set. The circuit was primed with lactated Ringer's solution only (first condition) and with human packed red blood cells added (second condition) to achieve a hematocrit of 30%. Cannula sizes 8 to 16 Fr were inserted into the cardiopulmonary bypass circuit with a "Y" connector. The flow was adjusted in 100 ml/min increments within typical flow ranges for each cannula. Pre-cannula and post-cannula pressures were measured to calculate the pressure drop. Results: Utilizing a pressure drop limit of 100 mmHg, our results suggest a recommended flow limit of 500, 900, 1400, 2600, and 3100 mL/min for Braile arterial cannulae sizes 8, 10, 12, 14, and 16 Fr, respectively. For Medtronic DLP arterial cannulae sizes 8, 10, 12, 14, and 16 Fr, the recommended flow limit is 600, 1100, 1700, 2700, and 3300 mL/min, respectively. Conclusion: This study reinforces discrepancies in pressure drop between cannulae of the same diameter supplied by different manufacturers and the importance of independent translational research to evaluate components' performance.

Acute physiological responses to "recovery intermittent hypoxia" in hiit / Respuestas agudas a la "hipoxia intermitente de recuperación" en el hiit / Respostas fisiológicas agudas à "hipóxia intermitente de recuperação" no hiit

ABSTRACT Introduction: Traditional intermittent hypoxia training improves sport performance after short periods of exposure, but acute exposure to intermittent hypoxia leads to decreased training intensity and technical quality. The solution to overcome these negative effects may be to perform efforts in normoxia and the intervals between efforts in hypoxia, maintaining the quality of training and the benefits of hypoxia. Objective: This study aimed to evaluate the acute physiological responses to hypoxia exposure during recovery between high intensity efforts. Materials and methods: Randomized, one-blind, placebo-controlled study. Sixteen men performed a graded exercise test to determine their maximal intensity and two sessions of high-intensity interval training. The training intervals could be in hypoxia (HRT), FIO2: 0.136 or normoxia (NRT), FIO2: 0.209. During the two-minute interval between the ten one-minute efforts, peripheral oxygen saturation (SpO2), heart rate (HR), blood lactate ([La]), blood glucose ([Glu]) were constantly measured. Results: There were differences in HR (TRN = 120 ± 14 bpm; TRH = 129 ± 13 bpm, p < 0.01) and SpO2 (TRN = 96.9 ± 1.0%; TRH = 86.2 ± 3.5%, p < 0.01). No differences in [La] and [Glu] TRN (4.4 ± 1.7 mmol.l-1; 3.9 ± 0.5 mmol.l-1) and TRH (5.2 ± 2.0 mmol.l-1; 4.0 ± 0.8 mmol.l-1, p = 0.17). Conclusion: The possibility of including hypoxia only in the recovery intervals as an additional stimulus to the training, without decreasing the quality of the training, was evidenced. Level of Evidence II; Randomized Clinical Trial of Minor Quality.

RESUMEN Introducción: El entrenamiento tradicional en hipoxia intermitente mejora el rendimiento deportivo tras cortos periodos de exposición, sin embargo, la exposición aguda a la hipoxia intermitente conduce a una disminución de la intensidad del entrenamiento y de la calidad técnica. La solución para superar estos efectos negativos puede ser realizar los esfuerzos en normoxia y los intervalos entre esfuerzos en hipoxia, manteniendo la calidad del entrenamiento y los beneficios de la hipoxia. Objetivo: Este estudio pretendía evaluar las respuestas fisiológicas agudas a la exposición a la hipoxia durante la recuperación entre esfuerzos de alta intensidad. Materiales y métodos: Estudio aleatorizado, a ciegas y controlado con placebo. Dieciséis hombres realizaron una prueba de ejercicio graduado para determinar su intensidad máxima y dos sesiones de entrenamiento por intervalos de alta intensidad. Los intervalos de entrenamiento podían ser en hipoxia (HRT), FIO2: 0,136 o normoxia (NRT), FIO2: 0,209. Durante el intervalo de dos minutos entre los diez esfuerzos de un minuto, se midieron constantemente la saturación periférica de oxígeno (SpO2), la frecuencia cardiaca (FC), el lactato en sangre ([La]) y la glucemia ([Glu]). Resultados: Hubo diferencias en la FC (TRN = 120 ± 14 lpm; TRH = 129 ± 13 lpm, p < 0,01) y la SpO2 (TRN = 96,9 ± 1,0%; TRH = 86,2 ± 3,5%, p < 0,01). No hubo diferencias en [La] y [Glu] TRN (4,4 ± 1,7 mmol.l-1; 3,9 ± 0,5 mmol.l-1) y TRH (5,2 ± 2,0 mmol.l-1; 4,0 ± 0,8 mmol.l-1, p = 0,17). Conclusión: Se evidenció la posibilidad de incluir hipoxia sólo en los intervalos de recuperación como estímulo adicional al entrenamiento sin disminuir la calidad del mismo. Nivel de Evidencia II; Ensayo Clínico Aleatorizado de Baja Calidad.

RESUMO Introdução: O treinamento de hipóxia intermitente tradicional melhora o desempenho esportivo após curtos períodos de exposição, porém a exposição aguda à hipóxia intermitente leva à diminuição da intensidade do treinamento e da qualidade técnica. A solução para superar esses efeitos negativos pode ser realizar esforços em normóxia e os intervalos entre os esforços em hipóxia, mantendo a qualidade do treinamento e os benefícios da hipóxia. Objetivo: Este estudo teve como objetivo avaliar as respostas fisiológicas agudas à exposição de hipóxia durante a recuperação entre esforços de alta intensidade. Materiais e métodos: Estudo aleatório e one-blinded, com efeito placebo controlado. Dezesseis homens realizaram um teste de exercício graduado para determinar sua intensidade máxima e duas sessões de treinamento intervalado de alta intensidade. Os intervalos de treinamento podem ser em hipóxia (TRH), FIO2: 0,136 ou normóxia (TRN), FIO2: 0,209. Durante os dois minutos de intervalo entre os dez esforços de um minuto, foram medidos constantemente a saturação periférica de oxigênio (SpO2), frequência cardíaca (FC), lactato sanguíneo ([La]), glicemia ([Glu]). Resultados: Houve diferenças na FC (TRN = 120 ± 14 bpm; TRH = 129 ± 13 bpm, p <0,01) e SpO2 (TRN = 96,9 ± 1,0%; TRH = 86,2 ± 3,5%, p <0,01). Sem diferenças em [La] e [Glu] TRN (4,4 ± 1,7 mmol.l-1; 3,9 ± 0,5 mmol.l-1) e TRH (5,2 ± 2,0 mmol.l-1; 4,0 ± 0,8 mmol.l-1, p = 0,17). Conclusão: Evidenciou-se a possibilidade de incluir a hipóxia apenas nos intervalos de recuperação como um estímulo adicional ao treinamento, sem diminuir a qualidade do treinamento. Nível de Evidência II; Estudo Clínico Randomizado de Menor Qualidade.

Mechanism of catalpol regulating Th17 cell differentiation by interfering PKM2/LDHA expression / 中国药房

OBJECTIVE To investigate the mechanism of catalpol affecting the differentiation of helper T cell 17 （Th17） by interfering the expressions of pyruvate kinase M2 （PKM2） and lactate dehydrogenase A （LDHA）. METHODS The naive CD4+ T cells were selected from the spleen of C57BL/6 mice， and were differentiated into Th17 cells by adding directional differentiation stimulants for 72 hours. At the same time， the cells were treated with 0 （directed control）， 20， 40 and 80 μg/mL catalpol. The flow cytometry was used to detect the proportion of Th17 cell differentiation in cells； the colorimetric method was adopted to detect the levels of pyruvate and lactate in cell culture supernatant； mRNA expressions of retinoid-related orphan nuclear receptor gamma t （RORγt）， PKM2 and LDHA were detected by qRT-PCR method； Western blot was used to detect the expression levels of PKM2， LDHA， signal transducer and activator of transcription 3 （STAT3）， and phosphorylated STAT3 （p-STAT3） proteins in cells. RESULTS Compared with the directed control group， after 72 hours of treatment with 20， 40， 80 μg/mL catalpol， the differentiation ratio of Th17 cells were decreased by 6.74%， 8.41%， 9.24%， and the levels of pyruvate and lactate in the cell culture supernatant， the mRNA expressions of PKM2， LDHA and RORγt as well as the protein expressions of PKM2 and LDHA and the phosphorylation of STAT3 were significantly reduced （P＜0.05）. CONCLUSIONS Catalpol can reduce the glycolysis level by down-regulating the expressions of PKM2 and LDHA， thereby inhibiting the differentiation of Th17 cells.

Lactate dehydrogenase as a hematopoietic stem cell mobilization biomarker in autologous transplantation

ABSTRACT Introduction: Pre-apheresis peripheral blood CD34+ cell count (PBCD34+) is the most important predictor of good cell mobilization before hematopoietic stem cell transplantation, albeit flow cytometry is not always immediately available. Identification of surrogate markers can be useful. The CD34+ cells proliferate after mobilization, resulting in elevated lactate dehydrogenase (LDH) activity and correlating with the PBCD34+ count. Objective: To determine the LDH cut-off value at which adequate CD34+ cell mobilization is achieved and its diagnostic yield. Materials and methods: A total of 103 patients who received an autologous stem cell transplantation (ASCT) between January 2015 and January 2020 were included. Demographic and laboratory characteristics were obtained, including complete blood count, pre-apheresis PBCD34+ and LDH levels. Receiver operating characteristic (ROC) curves were performed to identify the optimal serum LDH activity cut-off points for ≥ 2 and ≥ 4 × 106 cells/kg post-mobilization CD34+ count and their diagnostic yield. Results: A post-mobilization serum LDH cut-off value of 462 U/L yielded a sensitivity (Se) = 86.8% (positive predictive value [PPV] = 72.7%), a pre- and post-mobilization serum LDH difference cut-off value of 387 U/L, an Se = 45.7% (PPV = 97%) and an LDH ratio of 2.46, with an Se = 47.1% (PPV = 97%) for an optimal mobilization count (CD34+ ≥ 4 × 106). Conclusion: The LDH measurement represents a fast and affordable way to predict PBCD34+ mobilization in cases where flow cytometry is not immediately available. According to the LDH diagnostic yield, it could be used as a surrogate marker in transplant centers, supporting the CD34+ count, which remains the gold standard.

Lactate and pH values in newborns with a history of acute fetal distress / Valores de lactato y pH en recién nacidos con antecedente de sufrimiento fetal agudo

Abstract Background: Acute fetal distress (AFD) is a condition that requires timely diagnosis because it generates hypoxia, acidosis, and even intrauterine death. This study aimed to determine lactate and pH values in the umbilical cord in full-term newborns (NBs) with a history of AFD. Methods: We conducted a cross-sectional study in full-term NBs of mothers with at least one perinatal, neonatal, or gasometric AFD antecedent. Neonatal morbidity was considered: if 1-min Apgar ≤ 6, or advanced neonatal maneuvers, or neonatal intensive care unit (NICU) admissions were necessary. The cutoff points were lactate > 4mmol/L and pH < 7.2. Results: Of 66 NBs, 33.3% of mothers presented at least one antecedent for developing AFD; 22.7% presented hypertensive pregnancy disease, 13.6% oligohydramnios, and 63.6% other factors. Perinatally, 28.7% required advanced neonatal resuscitation maneuvers and 7.5% admission to the NICU. In the gasometry, the lactate and pH values for the neonatal morbidity of the NBs' group were 4.726 ± 1.401 and 7.293 ± 0.056, respectively, versus 2.240 ± 0.318 and 7.359 ± 0.022 (p < 0.05) for the group without associated neonatal morbidity. Conclusions: Lactate values in the umbilical cord increased by 25%, and pH decreased by one percent in NBs with a history of AFD and associated morbidity.

Resumen Introducción: El sufrimiento fetal agudo (SFA) es una condición que amerita un diagnóstico oportuno debido a que genera hipoxia, acidosis e incluso la muerte intrauterina. El objetivo de este estudio fue determinar los valores de lactato y pH en cordón umbilical en recién nacidos de término con antecedente SFA. Métodos: Se llevó a cabo un estudio transversal, en recién nacidos a término, de madres que tuvieron al menos un antecedente para SFA de tipo perinatal, neonatal o gasométrico. Se consideró morbilidad neonatal cuando presentaron Apgar al minuto ≤ 6, o requirieron maniobras avanzadas de reanimación neonatal, o ingreso a Unidad de Cuidados Intensivos Neonatales (UCIN). El punto de corte fue > 4 mmol/L para los valores de lactato y pH < 7.2. Resultados: De un total de 66 recién nacidos, el 33.3% de las madres presentaron al menos un antecedente para desarrollar SFA; el 22.7% presentó enfermedad hipertensiva del embarazo, el 13.6%, oligohidramnios, y el 63.6%, otros factores. El 28.7% requirieron maniobras avanzadas de la reanimación neonatal y el 7.5%, el ingreso a la UCIN. En la gasometría, el valor de lactato y pH para el grupo de recién nacidos con morbilidad neonatal fue de 4.726 ± 1.401 y 7.293 ± 0.056 respectivamente, versus 2.240 ± 0.318 y 7.359 ± 0.022 (p < 0.05) para el grupo sin morbilidad neonatal asociada. Conclusiones: Se observó un incremento del 25% de los valores de lactato en cordón umbilical y una disminución del 1% del pH en los recién nacidos con antecedente de SFA y morbilidad asociada.

Correlation of Venous to Arterial Carbon Dioxide Partial Pressure Difference with other Cardiac Output Indices in Patients Undergoing Intracardiac Repair for Tetralogy of Fallot

Background: Clearance of tissue carbon dioxide by circulation is measured by venous to arterial carbon dioxide partial pressure difference (AVCO2 ) and is correlated with cardiac output (CO) in critically ill adult patients. This study aimed to correlate AVCO2 with other CO indices like arteriovenous oxygen saturation difference (AVO2 ), central venous oxygen saturation (ScVO2 ), and serum lactate in pediatric patients undergoing intracardiac repair (ICR) for tetralogy of Fallot (TOF). Methods: We conducted a prospective observational study in 50 patients, of age 5months to 5 years, undergoing ICR for TOF and analyzed AVO2 , AVCO2 , ScVO2 , and lactate from arterial and venous blood gas pairs obtained at different time intervals from admission to pediatric intensive care unit(PICU)(T0 ), at 6 h (T1 ), 12 h (T2 ), 24 h (T3 ), and 48 h (T4 ) postoperatively. Bivariate correlations were analyzed using Pearson for parametric variables. Results: Admission AVCO2 was not correlated with AVO2 (R2 = 0.166, P = 0.246), ScVO2 (R2 = ?2.2, P = 0.124), and lactate (R2 = ?0.07, P = 0.624). At T1 , AVCO2 was correlated with AVO2 (R2 = 0.283, P = 0.0464) but not with ScVO2 (R2 = ? 0.25, P = 0.079) and lactate (R2 = ?0.07, P = 0.623). At T2 , T3 and T4 , AVCO2 was correlated with AVO2 (R2 = 0.338,0.440 & 0.318, P = 0.0162, 0.0013, and 0.024), ScVO2 (R2 = ? 0.344, ? 0.488, and ?0.366; P = 0.0143, <0.0001, and 0.017), and lactate (R2 = 0.305, 0.467 and 0.607; P = 0.0314, 0.00062 and <0.0001). AVCO2 was negatively correlated with ScVO2 . No correlation observed between admission AVCO2 and mechanical ventilation duration. Two nonsurvivors had higher value of admission AVCO2 compared to survivors. Conclusion: AVCO2 is correlated with other CO surrogates like AVO2 , ScVO2 , and lactate in pediatric patients undergoing ICR for TOF.

Lactate acid level and prognosis of neonatal necrotizing enterocolitis: a retrospective cohort study based on pediatric-specific critical care database

Abstract Objective To investigate the relationship between lactate acid level and hospitalization mortality in neonatal necrotizing enterocolitis (NEC). Method Paediatric-specific critical care database collected clinical data from the intensive care unit of Children's Hospital Affiliated to Zhejiang University Medical College from 2010 to 2018. Clinical and laboratory examination information of NEC patients was collected and divided into the death group and discharge group to find out the risk factors affecting the prognosis through univariate and multivariate analysis. Results Among 104 NEC neonates, the admission age was 7.5 days and the weight was 2.03 kg. Comparing the death group with the discharge group, there were significant differences in therapeutic regimen, pH, serum albumin, total protein, creatinine and lactate acid. Multivariate and threshold effect analysis showed that lactate acid had a linear correlation with hospital mortality, and newborns who died in the hospital had much higher lactate levels than those who were discharged. The mortality of NEC newborns increased by 40-45% for every 1 mmol/L increase in lactate acid level. Conclusions There was a correlation between lactate acid level and hospital mortality in newborns with NEC, and lactate acid level was an important index to evaluate the prognosis of NEC.

CORRELATION OF SERUM FERRITIN AND LDH ON CRITICALLY ILL PATIENTS OF COVID-19 DISEASE DURING 1ST AND 2ND WAVE OF COVID 19 PANDEMIC IN TERTIARY CARE HOSPITAL, INDIA

In both the earlier waves of COVID-19 variants, severe and fatal respiratory disease like acute respiratory distress syndrome (ARDS) became more fatal in population with comorbid conditions. Therefore, early identi?cation of severe COVID-19 is very important for individual's precise management, including antiviral, oxygen support and intensive care unit (ICU) management. First case of COVID-19 got reported in the medical record of India on 30th January 2020 in a student who had returned from Wuhan, China. In 2020 and 2021 it was found that individuals with increased serum ferritin and LDH level landed up with severe and very severe COVID-19 if not treated timely and correctly. So correlation between S. Ferritin and LDH in 1st and 2nd wave was required to evaluate the condition of patients who remained admitted in critical care unit with or without comorbid conditions. This is hospital based cross- sectional observational study on 50-50 (total-100) critically ill patients admitted during 2020 and 2021 respectively. We found that In 2020 during the 1st wave serum LDH and serum Ferritin levels were signi?cantly high with the mean value of 481.65 U/L and 532.56 ng/ml respectively and in 2021 during 2nd wave serum LDH and serum Ferritin levels were again signi?cantly high with the mean value of 488.43 U/L and 667.27 ng/ml respectively. In 2020 patients with comorbid conditions showed S. LDH and Ferritin mean value of 543.47 U/L and 582.63 ng/ml respectively and in 2021 during 2nd wave it showed S.LDH and Ferritin levels mean value of 672.72 U/L and 727.38 ng/ml respectively. Both in?ammatory markers were signi?cantly more increased in the critically ill patients who presented with co-morbidities. This study will provide improved con?dence to health workers working in remote areas and COVID-19 hospitals in predicting transfer of COVID-19 patients to tertiary care hospitals for critical care management at the earliest.

Lactic Acid Inhibits the Cytotoxicity of NK-92 Cells via Activating the Lactate Receptor GPR81

Aims: Lactate acid functions as not only an energy source but a signaling molecule through the lactate receptor GPR81 under physiological conditions. However, the pathological role of lactic acid in the tumor microenvironment remains unclear, particularly for immune cells. Methodology: NK-92 cells were treated with L-lactic acid solutions at final concentrations of 10, 20, 30, and 40 mM, and its cell viability and cytotoxicity on A549 cells and A375 cells were evaluated by CCK8 assay and crystal violet assay, respectively. Furthermore, qPCR was used to assess the expression of GPR81 and cytotoxicity-related genes in NK-92 cells treated with antagonist and agonist. And their relationship between lactate/GPR81 pathway and cytotoxicity-related genes were analyzed by Pearson’s correlation. Results: The viability of NK-92 cells was inhibited by L-lactic acid with increasing concentration. Additionally, the cytotoxic activity against tumor cells of NK-92 cells treated with L-lactic acid decreased with increasing concentration. Moreover, qPCR results demonstrated that GPR81 can be activated by lactic acid or agonist (3,5-DHBA) and downregulate the expression cytotoxicity-related genes which included FASLG gene(Fas Ligand),TNF-? gene(Tumor necrosis factor-?), INFG gene (Interferon-?), RPF1 gene (Perforin 1), GZMA gene (Granzyme A), GZMB gene (Granzyme B), GZMH gene (Granzyme H), GAMK gene (Granzyme K) and GZMM gene (Granzyme M). And the expression of GPR81 returned to near-control level when treated with L-lactic acid in the presence of antagonist (3-OBA), the expression of cytotoxicity-related genes did as well. Pearson’s correlation analysis of cytotoxicity-related genes with GPR81 revealed that their correlation coefficient seems negative. Conclusion: Lactic acid can activate the GPR81 to downregulate the expression of cytotoxicity-related genes, subsequently lower the cytotoxicity of NK-92 cells.

Efficacy of mouse nerve growth factor combined with edaravone in the treatment of carbon monoxide poisoning and its influence on oxygen free radical-related indicators / 中国医师进修杂志

Objective:To investigate the therapeutic effect of the combination of mouse nerve growth factor and edaravone in the treatment of carbon monoxide poisoning and its effect on patients′ cognitive function, lactic acid clearance rate, and related indicators of oxygen free radicals.Methods:A selection of 158 patients with carbon monoxide poisoning in the Huxi Hospital Affilliated Jining Medical College from May 2017 to June 2020 were divided into study group (80 cases) and control group (78 cases) according to the treatment plan. Both groups were given conventional treatment. On this basis, the control group was given edaravone, and the study group was given mouse nerve growth factor combined with edaravone, both of which were treated for 2 weeks. The clinical efficacy of the two groups was compared with those before treatment and 1 week and 2 weeks after treatment. Neurological impairment score (NIHSS), disease severity score (APACHE Ⅱ), cognitive function score (MMSE), serum inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP)], oxygen free radical related indicators [lipid peroxide (LPO), superoxide dismutase (SOD), gluten Glutathione peroxidase (GSH-PX), malondialdehyde (MDA)] levels, blood lactic acid levels before treatment and lactic acid clearance rates after 12 h, 24 h, 72 h treatment, and statistics of adverse reactions and 30-day mortality.Results:The total effective rate of the study group was higher than that of the control group after 2 weeks of treatment [95.00% (76/80) vs. 78.21% (61/78)] ( P<0.05); NIHSS and APACHEⅡ scores of the study group after 1 week and 2 weeks of treatment Lower than the control group: (6.08 ± 1.15) points vs. (8.94 ± 1.71) points, (4.58 ± 0.74) points vs. (6.32 ± 0.93) points and (6.79 ± 1.03) points vs. (8.02 ± 1.47) points, (5.94 ± 1.47) points vs. (7.25 ± 0.94) points, the MMSE score was higher than that of the control group: (22.09 ± 4.35) points vs. (19.34 ± 5.32) points, (26.05 ± 2.37) points vs. (22.47 ± 4.64) points ( P<0.05) After 1 and 2 weeks of treatment, the serum TNF-α, IL-6, CRP, LPO and MDA levels in the study group were lower than those in the control group: (22.62 ± 4.12) ng/L vs. (29.43 ± 4.68) ng/L and (18.21 ± 2.09) ng/L vs. (24.37 ± 3.16) ng/L, (39.67 ± 4.35) ng/L vs. (52.14 ± 5.48) ng/L and (34.83 ± 3.75) ng/L vs. (41.07 ± 4.09) ng/L, (12.63 ± 1.85) mg/L vs. (17.02 ± 2.47) mg/L and (8.27 ± 1.16) mg/L vs. (11.05 ± 1.62) mg/L, (11.06 ± 1.28) μmol/L vs. (15.97 ± 1.85) μmol/L and (8.24 ± 1.12) μmol/L vs. (12.97 ± 1.40) μmol/L, (7.15 ± 1.16) μmol/L vs. (9.02 ± 1.47) μmol/L and (6.12 ± 0.96) μmol/L vs. (7.84 ± 1.25) μmol/L, the levels of SOD and GSH-PX were higher than those in the control group ( P<0.05); the lactate clearance rate in the study group was higher than that in the control group after 12, 24 and 72 h of treatment: (18.49 ± 3.63)% vs. (14.62 ± 2.95)%, (23.19 ± 4.20)% vs. (17.42 ± 3.57)%, (29.86 ± 6.37)% vs. (25.38 ± 5.21)% ( P<0.05); the incidence of adverse reactions in the study group during treatment Compared with the control group, there was no significant difference ( P>0.05); there was no significant difference in the 30-day mortality between the study group and the control group ( P>0.05). Conclusions:The combination of mouse nerve growth factor and edaravone in the treatment of carbon monoxide poisoning can reduce the severity of disease and neurological deficits, improve cognitive function and lactate clearance rate, reduce inflammation and oxidative stress, improve efficacy, and have good safety.

The predicting indices for the outcome of refractory septic shock in preterm infants / 中国新生儿科杂志

Objective:To study the predictive value of vasoactive-inotropic score (VIS), fluid overload (FO) and lactate level for the outcome of preterm infants with refractory septic shock.Methods:Preterm infants diagnosed with refractory septic shock and required hydrocortisone treatment in our Department from January 2016 to December 2021 were analyzed retrospectively. Preterm infants were assigned into three gestational age groups (<28 weeks, 28-31 weeks, 32-36 weeks). According to the outcome of the disease, the children were further divided into good prognosis group and poor prognosis group. The relationship between the maximum VIS, FO and the mean lactic acid before hydrocortisone and the outcome of refractory septic shock was analyzed by receiver operating characteristic (ROC) curve, the cut-off point of ROC curve was calculated to obtain the predictive efficacy of the three indicators for the outcome of refractory septic shock in preterm infants.Results:A total of 50 preterm infants with refractory septic shock and received hydrocortisone treatment were enrolled, including 20 in the good prognosis group and 30 in the poor prognosis group. There were no significant differences in the maximum VIS, FO and mean lactic acid before hydrocortisone treatment between the two groups of gestational age of <32 weeks ( P> 0.05). The maximum VIS, FO and mean lactic acid of gestational age of 32-36 weeks in the poor prognosis group were higher than those in the good prognosis group, VIS: 56.1±15.7 vs. 37.1±12.9, FO (%): 108.2 (78.6,137.7) vs. 55.5 (10.3, 100.7), and mean lactic acid (mmol/L): 8.3 (4.6, 12.0) vs. 4.8 (-0.8, 10.5), all P<0.05. The area under the ROC curve of the mean lactic acid was the largest, the cut-off value was 4.1 mmol/L, and the Youden index was 1.732. Conclusions:VIS, FO and lactate level are difficult to be used for determining the outcome of refractory septic shock in preterm infants of <32 weeks. While the mean lactic acid has the best predictive performance in preterm infants of 32-36 weeks.

Predictive value of Pcv-aCO 2 on left ventricular ejection fraction in myocardial infarction / 中华急诊医学杂志

Objective:To investigate the relationship between central venous-arterial blood carbon dioxide partial pressure difference (Pcv-aCO 2) and left ventricular ejection fraction(LVEF) in acute myocardial infarction. Methods:Clinical data of patients with acute myocardial infarction admitted to the Intensive Care Unit of Fujian Provincial Hospital from November 2019 to October 2021 were retrospectively analyzed. LVEF was measured by bedside echocardiogram. The patients were divided into the normal LVEF group (LVEF ≥ 52%) and decreased LVEF group (LVEF < 52%) according to LVEF. The differences in general information and hemodynamic parameters between the two groups were compared. The normality of the above data was tested by the Jarque-Bera test. Correlation analysis of hemodynamic indices with LVEF was performed. Binary logistic regression was used to analyze the risk factors associated with the decrease in LVEF. The feasibility of diagnosing LVEF decline with Pcv-aCO 2 was assessed using receiver operating characteristic (ROC) curve. Results:Seventy-two patients with acute myocardial infarction were included for analysis, including 25 patients in the normal LVEF group and 47 patients in the decreased LVEF group. Pcv-aCO 2 was significantly higher in the decreased LVEF group than that in the normal LVEF group [(7.13±1.19) mmHg vs. (5.41±1.23) mmHg, P<0.01]. There was a negative correlation between LVEF and Pcv-aCO 2 ( rs= -0.740, P<0.01). The area under the ROC curve for Pcv-aCO 2 was 0.849 (95% CI: 0.758-0.939, P<0.01). The binary logistic regression analysis showed that Pcv-aCO 2 was an independent risk factor for decreased LVEF ( OR=2.251, 95% CI: 1.326-3.820). Conclusions:To a certain extent, the increase of Pcv-aCO 2 can predict the decrease of LVEF in acute myocardial infarction.

Predictive value of lactate clearance rate combined with syndecan-1 in patients with septic shock and ARDS / 中华急诊医学杂志

Objective:To observe the changes of lactate clearance rate (LCR) and serum polyligandosan-1 (SDC-1) in patients with septic shock complicated with acute respiratory distress syndrome (ARDS) and to evaluate its prognostic value.Methods:Patients with septic shock and ARDS who were admitted to the Respiratory Intensive Care Unit (RICU) of Zhengzhou Central Hospital Affiliated to Zhengzhou University from February 2021 to April 2022 were selected as subjects. The patients were divided into the survival group and death group according to their 28-day survival status. General clinical data and related indicators of patients in the two groups were collected and compared. The related factors influencing the 28-day death of patients with septic shock and ARDS were screened, and receiver operating characteristic (ROC) curve was drawn to evaluate the individual and combined forecast value of LCR and SDC-1 for the prognosis of patients with septic shock and ARDS.Results:Compared with the survival group, sequential organ failure score (SOFA) and acute physiology and chronic health status score Ⅱ(APACHE Ⅱ) at admission to RICU, the levels of 24 h Lac, 6 h SDC-1, 24 h SDC-1 and 72 h SDC-1 in the death group increased significantly (all P< 0.05), and the levels of 6 h LCR, 24 h LCR, 6 h OI, 24 h OI and 72 h OI significantly decreased (all P<0.05). Spearman correlation analysis showed that SDC-1 at 6 h, 24 h and 72 h was significantly negatively correlated with OI at corresponding time points (all P<0.05), and LCR at 6 h and 24 h was significantly positively correlated with OI at corresponding time points (all P<0.05). Multivariate Logistic regression analysis showed that SOFA score, 24 h LCR, 24 h SDC-1 and 72 h SDC-1 were the risk factors of 28-d death in patients with septic shock and ARDS (all P<0.05). The areas under ROC curve of each related factor were SOFA score, 24 h LCR, 24 h SDC-1 and 72 h SDC-1, which could predict the prognosis (all P<0.05). 24 h LCR combined with 24 h SDC-1 had the maximum area under the curve (AUC=0.805, 95% CI: 0.691-0.920, with a sensitivity of 75.0% and a specificity of 74.4%). Conclusions:24 h LCR, 24 h SDC-1 and 72 h SDC-1 are the risk factors of the 28-day death of patients with septic shock and ARDS. 24 h LCR combined with 24 h SDC-1 can improve the test efficiency compared with the single indicator.

Expression and Significance of Lactate Dehydrogenase A in Renal Cell Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo analyze the expression of Lactate dehydrogenase A（LDHA） in both renal cell carcinoma （RCC） tissue and RCC cell lines， and to investigate the impact of LDHA expression on the progression of RCC. MethodsFrom June 2018 to June 2022， totally 52 cases of RCC tissue samples and 49 cases of para-cancerous tissue samples were collected through surgical procedures from our hospital. LDHA expression was detected using immunohistochemistry （IHC）. The expression levels of LDHA in vitro were also detected in the normal human proximal tubule epithelial cell line HK-2 and renal cell carcinoma cell lines A498， Caki-2， ACHN， and 786-O by using qRT-PCR and Western blot. A recombinant plasmid carrying LDHA-shRNA was constructed and then transfected into 786-O cells to down-regulate the expression of LDHA. Tumor proliferative capacity was monitored using CCK-8 assay， clonal formation assay and EdU assessments. Additionally， cell glycolytic activity was assessed through glucose uptake assay， lactate secretion assay， and ECAR analysis. ResultsIHC analysis revealed significantly higher expression of LDHA in RCC tissue compared to adjacent tissues（P<0.05）. Furthermore， RCC tissues with higher TNM stage exhibited greater expression of LDHA than those with lower TNM stage （P<0.05）. The results of qRT-PCR and Western blot demonstrated that the expression of LDHA in each RCC cell line was significantly higher than that in HK-2（P<0.05）. After blocking the expression of LDHA in 786-O， there was a significant down-regulation of cell proliferation and glycolysis capacity （P<0.05）. ConclusionsThe expression of LDHA in RCC tissue and RCC cell lines is significantly overexpressed compared with normal one， particularly in those with higher TNM stage. Knockdown of the expression of LDHA significantly suppresses cell proliferation and aerobic glycolysis capacity in 786-O.

Lactate-induced up-regulation of PLEKHA4 promotes proliferation and apoptosis of human glioma cells / 南方医科大学学报

OBJECTIVE@#To investigate the effect of lactic acid-induced upregulation of PLEKHA4 expression on biological behaviors of glioma cells and the possible molecular mechanism.@*METHODS@#GEO database and GEPIA2 website were used to analyze the relationship between PLEKHA4 expression level and the pathological grade of glioma. A specific PLEKHA4 siRNA was transfected in glioma U251 and T98G cells, and the changes in cell proliferation ability were assessed by real-time cell analysis technology and Edu experiment. The colony-forming ability of the cells was evaluated using plate cloning assay, and cell cycle changes and cell apoptosis were analyzed with flow cytometry. The mRNA expression of PLEKHA4 was detected by PCR in glioma samples and controls and in glioma cells treated with lactic acid and glucose. Xenograft mice in vivo was used to detect tumor formation in nude mice; Western blotting was used to detect the expressions of cyclinD1, CDK2, Bcl2, β-catenin and phosphorylation of the key proteins in the MAPK signaling pathway.@*RESULTS@#The results of GEO database and online website analysis showed that PLEKHA4 was highly expressed in glioma tissues and was associated with poor prognosis; PLEKHA4 knockdown obviously inhibited the proliferation and attenuated the clone-forming ability of the glioma cells (P < 0.05). Flow cytometry showed that PLEKHA4 knockdown caused cell cycle arrest in G1 phase and promoted apoptosis of the cells (P < 0.01). PLEKHA4 gene mRNA expression was increased in glioma samples and glioma cells after lactate and glucose treatment (P < 0.01). PLEKHA4 knockdown, tumor formation ability of nude mice decreased; PLEKHA4 knockdown obviously lowered the expression of cyclinD1, CDK2, Bcl2 and other functional proteins, inhibited the phosphorylation of ERK and p38 and reduced the expression of β-catenin protein (P < 0.01).@*CONCLUSION@#PLEKHA4 knockdown inhibited the proliferation of glioma cells and promoted apoptosis by inhibiting the activation of the MAPK signaling pathway and expression of β-catenin. Lactic acid produced by glycolysis upregulates the expression of PLEKHA4 in glioma cells.

Effect of Lactate on Immune Cells in Tumor Microenvironment and Progress of Related Target Therapy / 肿瘤防治研究

The relationship between tumor metabolism and immunity is complex and diverse. To date, the role of tumor-specific metabolic reprogramming in shaping the specific tumor microenvironment in tumor immunotherapy remains unclear. Lactic acid is the main product of glycolysis, and the aerobic glycolysis of tumor cells causes lactic acid to accumulate in the microenvironment. Recent studies have shown that the accumulation of lactic acid in the tumor microenvironment hinders anti-tumor immunity, especially affects the function, differentiation, and metabolism of immune cells, and participates in tumor immune escape, thus promoting tumor. This article reviews the effects of lactate accumulation in the tumor microenvironment on dendritic cells, T cells, NK cells, tumor-associated macrophages, and myeloid-derived suppressor cells. Targeted intervention of lactate production and efflux by tumor cells is expected to become a new strategy for tumor immunotherapy.

Predictive value of serum lactate dehydrogenase on prognosis of patients with paraquat poisoning / 中华劳动卫生职业病杂志

Objective: To investigate the predictive value of serum lactate dehydrogenase (LDH) in the prognosis of patients with paraquat (PQ) poisoning, and to provide evidence for early prognosis assessment. Methods: In February 2022, 50 patients with PQ poisoning who completed serum LDH detection admitted to the Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University from January 2012 to December 2021 were selected as the observation group, and 50 healthy physical examination personnel were randomly selected as the control group. Patients with PQ poisoning were divided into survival group and death group according to the prognosis, and the differences of blood routine routine, liver and kidney function and other indicators in the first admission between the two groups were compared. Multivariate logisitic regression model was established, ROC curve was drawn, and the influencing factors of prognosis of patients with PQ poisoning were analyzed. Results: Compared with the control group, the white blood cell count (WBC), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), LDH, glucose (GLU) and creatinine (Cr) in observation group were significantly increased, while albumin (ALB) and total cholesterol (TC) were significantly decreased (P<0.05). Univariate analysis showed that WBC, elevated LDH (>247 U/L), TBil, ALT, AST and Cr were significantly different between PQ poisoning survival group and death group (P<0.05). Multivariate logisitic regression analysis showed that elevated serum LDH was an independent risk factor for the prognosis of PQ poisoning patients (OR=9.95, 95%CI: 1.34-73.82, P=0.025). The area under the ROC curve of LDH was 0.811 (95%CI: 0.692-0.930). When the cut-off value was 340 U/L, the sensitivity was 0.889 and the specificity was 0.719. Log-rank test showed that there was a statistically significant difference in survival rate between the normal LDH group and the elevated LDH group (P=0.001) . Conclusion: Serum LDH has a good predictive value in evaluating the prognosis of patients with PQ poisoning. Elevated LDH is a risk factor for poor prognosis of patients with PQ poisoning.

Effect of Liangfang Wenjing Decoction on expression of key glycolytic enzymes in uterus and ovaries of rats with coagulating cold and blood stasis syndrome / 中国中药杂志

This study aimed to investigate the relationship between coagulating cold and blood stasis syndrome and glycolysis, and observe the intervention effect of Liangfang Wenjing Decoction(LFWJD) on the expression of key glycolytic enzymes in the uterus and ovaries of rats with coagulating cold and blood stasis. The rat model of coagulating cold and blood stasis syndrome was established by ice-water bath. After modeling, the quantitative scoring of symptoms were performed, and according to the scoring results, the rats were randomly divided into a model group and LFWJD low-, medium-and high-dose groups(4.7, 9.4, 18.8 g·kg~(-1)·d~(-1)), with 10 in each group. Another 10 rats were selected as the blank group. After 4 weeks of continuous administration by gavage, the quantitative scoring of symptoms was repeated. Laser speckle flowgraphy was used to detect the changes of microcirculation in the ears and uterus of rats in each group. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of uterus and ovaries of rats in each group. The mRNA and protein expressions of pyruvate dehydrogenase kinase 1(PDK1), hexokinase 2(HK2) and lactate dehydrogenase A(LDHA) in the uterus and ovaries of rats were examined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. The rats in the model group showed signs of coagulating cold and blood stasis syndrome, such as curl-up, less movement, thickened veins under the tongue, and reduced blood perfusion in the microcirculation of the ears and uterus, and HE staining revealed a thinning of the endometrium with disorganized arrangement of epithelial cells and a decrease in the number of ovarian follicles. Compared with the model group, the treatment groups had alleviated coagulating cold and blood stasis, which was manifested as red tongue, reduced nail swelling, no blood stasis at the tail end as well as increased blood perfusion of the microcirculation in the ears and uterus(P<0.05 or P<0.01). Among the groups, the LFWJD medium-and high-dose groups had the most significant improvement in coagulating cold and blood stasis, with neatly arranged columnar epithelial cells in uterus, and the number of ovarian follicles was higher than that in the model group, especially mature follicles. The mRNA and protein expressions of PDK1, HK2, LDHA in uterus and ovaries were up-regulated in the model group(P<0.05 or P<0.01), while down-regulated in LFWJD medium-and high-dose groups(P<0.05 or P<0.01). The LFWJD low-dose group presented a decrease in the mRNA expressions of PDK1, HK2 and LDHA in uterus and ovaries as well as in the protein expressions of HK2 and LDHA in uterus and HK2 and PDK1 in ovaries(P<0.05 or P<0.01). The therapeutic mechanism of LFWJD against coagulating cold and blood stasis syndrome is related to the down-regulation of key glycolytic enzymes PDK1, HK2 and LDHA, and the inhibition of glycolytic activities in uterus and ovaries.