Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Purpose: To determine the non-contrast computer tomography imaging features of pyonephrosis and evaluate the predictive value of Hounsfield units (HUs) in different hydronephrotic region slices. Materials and Methods: We retrospectively reviewed data from patients with hydronephrosis who had renal-ureteral calculi. All patients were categorized into pyonephrosis and simple hydronephrosis groups. Baseline characteristics, the mean HU values in the maximal hydronephrotic region (uHU) slice, and the range of uHU in different slices (△uHU) were compared between the two groups. Univariate and multivariate analyses were performed to identify risk factors for pyonephrosis. Results: Among the 181 patients enrolled in the current study, 71 patients (39.2%) were diagnosed with pyonephrosis. The mean dilated pelvis surface areas were comparable between patients with pyonephrosis and simple hydronephrosis (822.61 ㎟ vs.877.23 ㎟ , p=0.722). Collecting system debris (p=0.022), a higher uHU (p=0.038), and a higher △uHU (p<0.001) were identified as independent risk factors for pyonephrosis based on multivariate analysis. The △uHU sensitivity and specificity were 88.7% and 86.4%, respectively, at a cutoff value of 6.56 (p<0.001), whereas the sensitivity and specificity for detecting pyonephrosis at a uHU cutoff value of 7.96 was 50.7% and 70.9%, respectively (p=0.003). Conclusions Non-contrast computer tomography was shown to accurately distinguish simple hydronephrosis from pyonephrosis in patients with obstructive uropathy. Evaluation of the △uHU in different slices may be more reliable than the uHU acquired from a single slice in predicting pyonephrosis.

The biosynthesis and maturation of proteins are primarily regulated by the endoplasmic reticulum in its physiological state. Thus, the disruption of physiological homeostasis initiates the buildup of unfolded and misfolded proteins in the endoplasmic reticulum, resulting in endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). One of the important pathways by which UPR maintains intracellular homeostasis under ERS is activating protein kinase R-like endoplasmic reticulum kinase (PERK). The activation of the PERK pathway stimulates eukaryotic translation initiation factor 2 subunit-α (eIF2α) phosphorylation and the selective translation of active transcription factor 4 (ATF4), and PERK induces cell apoptosis by directly binding to the promoter of pro-apoptotic transcription factor C/EBP homologous protein (CHOP). This signaling pathway is also one of the important mechanisms by which UPR participates in the regulation of hematological malignancies and immune cells in a tumor microenvironment. This article provides an overview of advancements in research into the PERK-eIF2α-ATF4-CHOP signaling pathway in hematological malignancies and the potential therapeutic benefits of targeting this signaling pathway.

Non-muscle myosin heavy chain 9-related disease (MYH9-RD) is an autosomal dominant disease caused by the mutations of the MYH9 gene encoding the non-muscle mysoin heavy chain ⅡA and leads to abnormal accumulation of myosin in cells. These further causes functional disorders of the blood, eye, ear, kidney, and liver systems. MYH9-RD displays heterogeneous kidney involvement and outcomes, but doctors still lack understandings of the mechanism and treatment strategies, owing to difficulty of conducting renal biopsies. Here, we report a case of MYH9-RD with tail fragments heterozygous mutation, which renal pathology is presented as glomerular minor lesion. Moreover, we reviewed related relevant to strengthen clinical diagnosis and understanding of MYH9-RD.

Objective To compare the effect of palliative mitral valve surgeries and medication therapies for secondary non-ischemic mitral regurgitation. Methods The clinical data of patients with non-ischemic functional mitral regurgitation treated in our hospital between 2009 and 2019 were retrospectively analyzed. Patients with a left ventricular ejection fraction (LVEF)＜40% underwent a dobutamine stress test, and a positive result was determined when the LVEF improved by more than 15% compared to the baseline value. Positive patients were divided into a surgery group and a medication group. The surgery group underwent surgical mitral valve repair or replacement, while the medication group received simple medication treatment. Follow-up on survival and cardiac function status through outpatient or telephone visits every six months after surgery, and patients underwent cardiac ultrasound examination one year after surgery. The main research endpoint was a composite endpoint of all-cause death, heart failure readmission, and heart transplantation, and the differences in cardiac function and cardiac ultrasound parameters between the two groups were compared. Results Ultimately 41 patients were collected, including 28 males and 13 females with an average age of 55.5±11.1 years. Twenty-five patients were in the surgery group and sixteen patients in the medication group. The median follow-up time was 16 months, ranging 1-96 months. The occurrence of all-cause death in the surgery group was lower than that in the medication group (HR=0.124, 95%CI 0.024-0.641, P=0.034). The difference between the two groups was not statistically significant in the composite endpoint (HR=0.499, 95%CI 0.523-1.631, P=0.229). The New York Heart Association (NYHA) grade of the surgery group was better (NYHA Ⅰ-Ⅱ accounted for 68.0% in the surgury group and 18.8% in the medication group, P<0.01) as well as the grade of mitral valve regurgitation (87.5% of the patients in the medication group had moderate or above regurgitation at follow-up, while all the patients in the surgery group had moderate below regurgitation, P<0.01). There was no statistical difference in preoperative and follow-up changes in echocardiograph parameters between the two groups (P＞0.05). Conclusion For non-ischemic functional mitral regurgitation, if the cardiac systolic function is well reserved, mitral valve surgery can improve survival and quality of life compare to simple medication therapy.

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.