The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogramming-related parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC). METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Affiliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82)and a survival group(n=38).Healthy adult volunteers(n=40)of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogramming-related parameters(lactate dehydrogenase[LDH],lactate and pyruvate),neuron-specific enolase(NSE)and interleukin 6(IL-6)were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score and Sequential Organ Failure Assessment(SOFA)score were calculated.The Cerebral Performance Category(CPC)score was recorded on day 28 after ROSC. RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1)significantly increased and were higher in the non-survivors than in the survivors on admission(all P＜0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE Ⅱ score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P＜0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC)of 0.904[95％confidence interval[95％CI]:0.851-0.957])with 96.8％specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95％CI:0.911-0.989)with 94.7％specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested. CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive efficacy of LDH during the first week was superior to others.

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogramming-related parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC). METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Affiliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82)and a survival group(n=38).Healthy adult volunteers(n=40)of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogramming-related parameters(lactate dehydrogenase[LDH],lactate and pyruvate),neuron-specific enolase(NSE)and interleukin 6(IL-6)were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score and Sequential Organ Failure Assessment(SOFA)score were calculated.The Cerebral Performance Category(CPC)score was recorded on day 28 after ROSC. RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1)significantly increased and were higher in the non-survivors than in the survivors on admission(all P＜0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE Ⅱ score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P＜0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC)of 0.904[95％confidence interval[95％CI]:0.851-0.957])with 96.8％specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95％CI:0.911-0.989)with 94.7％specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested. CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive efficacy of LDH during the first week was superior to others.

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogramming-related parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC). METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Affiliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82)and a survival group(n=38).Healthy adult volunteers(n=40)of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogramming-related parameters(lactate dehydrogenase[LDH],lactate and pyruvate),neuron-specific enolase(NSE)and interleukin 6(IL-6)were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score and Sequential Organ Failure Assessment(SOFA)score were calculated.The Cerebral Performance Category(CPC)score was recorded on day 28 after ROSC. RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1)significantly increased and were higher in the non-survivors than in the survivors on admission(all P＜0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE Ⅱ score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P＜0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC)of 0.904[95％confidence interval[95％CI]:0.851-0.957])with 96.8％specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95％CI:0.911-0.989)with 94.7％specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested. CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive efficacy of LDH during the first week was superior to others.

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogramming-related parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC). METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Affiliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82)and a survival group(n=38).Healthy adult volunteers(n=40)of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogramming-related parameters(lactate dehydrogenase[LDH],lactate and pyruvate),neuron-specific enolase(NSE)and interleukin 6(IL-6)were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score and Sequential Organ Failure Assessment(SOFA)score were calculated.The Cerebral Performance Category(CPC)score was recorded on day 28 after ROSC. RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1)significantly increased and were higher in the non-survivors than in the survivors on admission(all P＜0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE Ⅱ score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P＜0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC)of 0.904[95％confidence interval[95％CI]:0.851-0.957])with 96.8％specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95％CI:0.911-0.989)with 94.7％specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested. CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive efficacy of LDH during the first week was superior to others.

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogramming-related parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC). METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Affiliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82)and a survival group(n=38).Healthy adult volunteers(n=40)of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogramming-related parameters(lactate dehydrogenase[LDH],lactate and pyruvate),neuron-specific enolase(NSE)and interleukin 6(IL-6)were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score and Sequential Organ Failure Assessment(SOFA)score were calculated.The Cerebral Performance Category(CPC)score was recorded on day 28 after ROSC. RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1)significantly increased and were higher in the non-survivors than in the survivors on admission(all P＜0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE Ⅱ score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P＜0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC)of 0.904[95％confidence interval[95％CI]:0.851-0.957])with 96.8％specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95％CI:0.911-0.989)with 94.7％specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested. CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive efficacy of LDH during the first week was superior to others.

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogramming-related parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC). METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Affiliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82)and a survival group(n=38).Healthy adult volunteers(n=40)of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogramming-related parameters(lactate dehydrogenase[LDH],lactate and pyruvate),neuron-specific enolase(NSE)and interleukin 6(IL-6)were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score and Sequential Organ Failure Assessment(SOFA)score were calculated.The Cerebral Performance Category(CPC)score was recorded on day 28 after ROSC. RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1)significantly increased and were higher in the non-survivors than in the survivors on admission(all P＜0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE Ⅱ score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P＜0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC)of 0.904[95％confidence interval[95％CI]:0.851-0.957])with 96.8％specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95％CI:0.911-0.989)with 94.7％specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested. CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive efficacy of LDH during the first week was superior to others.

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogramming-related parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC). METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Affiliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82)and a survival group(n=38).Healthy adult volunteers(n=40)of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogramming-related parameters(lactate dehydrogenase[LDH],lactate and pyruvate),neuron-specific enolase(NSE)and interleukin 6(IL-6)were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score and Sequential Organ Failure Assessment(SOFA)score were calculated.The Cerebral Performance Category(CPC)score was recorded on day 28 after ROSC. RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1)significantly increased and were higher in the non-survivors than in the survivors on admission(all P＜0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE Ⅱ score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P＜0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC)of 0.904[95％confidence interval[95％CI]:0.851-0.957])with 96.8％specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95％CI:0.911-0.989)with 94.7％specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested. CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive efficacy of LDH during the first week was superior to others.

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogramming-related parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC). METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Affiliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82)and a survival group(n=38).Healthy adult volunteers(n=40)of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogramming-related parameters(lactate dehydrogenase[LDH],lactate and pyruvate),neuron-specific enolase(NSE)and interleukin 6(IL-6)were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score and Sequential Organ Failure Assessment(SOFA)score were calculated.The Cerebral Performance Category(CPC)score was recorded on day 28 after ROSC. RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1)significantly increased and were higher in the non-survivors than in the survivors on admission(all P＜0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE Ⅱ score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P＜0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC)of 0.904[95％confidence interval[95％CI]:0.851-0.957])with 96.8％specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95％CI:0.911-0.989)with 94.7％specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested. CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive efficacy of LDH during the first week was superior to others.

Objective To determine the surgical procedures and effects of ultra-distal tibial intramedullary nails combined with blocking screws in treatment of distal tibial fractures.Methods From April 2008 to September 2012,21 cases of distal tibial fractures were treated with ultra-distal tibial intramedullary nails combined blocking screws.All fractures were statically locked and closed using undreamed technique.For relatively simple fracture,blocking screws were considered when the reduction and stability was not satisfied after the insertion of intramedullary nails; for severe comminuted fractures,blocking screws were inserted directly under C-arm fluoroscopy.Partial weight-bearing was permitted 3 weeks after surgery.Quality of reduction,fracture union,and function assessment were measured at follow-up.Results No skin necrosis and soft tissue and bone infections occurred after a mean follow-up of 17.5 months (range,12-22 months).All fractures were healed with an average healing time of 12 months (range,8-26 months).X-ray findings revealed the fracture of ＜ 5° angulation on coronal and sagittal planes.There was no deformation or breakage of blocking screws and intramedullary nails.According to the criteria of Tormetta,the results were excellent in 19 cases and good in 2.Conclusion Blocking screws assists reduction and improve the fixation stability by narrowing the canal in treatment of distal tibial fractures and expands the application of intramedullary nails.